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Biomedical subjects

O Taguchi

Publications and source records attributed to O Taguchi.

At least 55 records · Page 3Linked to original sources

The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis.

The aim of this study was to determine whether low-dose inhalation of nitric oxide (NO) improves pulmonary haemodynamics and gas exchange in patients with stable idiopathic pulmonary fibrosis (IPF). The investigation included 10 IPF patients breathing spontaneously. Haemodynamic and blood gas parameters were measured under the following conditions: 1) breathing room air; 2) during inhalation of 2 parts per million (ppm) NO with room air; 3) whilst breathing O2 alone (1 L.min-1); and 4) during combined inhalation of 2 ppm NO and O2 (1 L.min-1). During inhalation of 2 ppm NO with room air the mean pulmonary arterial pressure (Ppa 25 +/- 3 vs 30 +/- 4 mmHg) and the pulmonary vascular resistance (PVR 529 +/- 80 vs 699 +/- 110 dyn.s.cm-5) were significantly (p < 0.01) lower than levels measured whilst breathing room air alone. However the arterial oxygen tension (Pa,O2) did not improve. The combined inhalation of NO and O2 produced not only a significant (p < 0.01) decrease of Ppa (23 +/- 2 vs 28 +/- 3 mmHg) but also, a remarkable improvement (p < 0.05) in Pa,O2 (14.2 +/- 1.2 vs 11.7 +/- 1.0 kPa) (107 +/- 9 vs 88 +/- 7 mmHg)) as compared with the values observed during the inhalation of O2 alone. These findings suggest that the combined use of nitric oxide and oxygen might constitute an alternative therapeutic approach for treating idiopathic pulmonary fibrosis patients with pulmonary hypertension. However, further studies must first be carried out to demonstrate the beneficial effect of oxygen therapy on pulmonary haemodynamics and prognosis in patients with idiopathic pulmonary fibrosis and to rule out the potential toxicity of inhaled nitric oxide, particularly when used in combination with oxygen.

Administration, Inhalation↗

Arterial endothelin-1 level in pulmonary emphysema and interstitial lung disease. Relation with pulmonary hypertension during exercise.

This study was undertaken to assess the arterial plasma levels of endothelin-1 (ET-1) and their relationship with pulmonary haemodynamic and gas exchange variables during exercise in patients with emphysema and interstitial lung disease (ILD). Incremental cycle ergometry was performed in all patients up to maximal capacity. At rest, arterial ET-1 levels were higher in emphysema (1.86 +/- 0.35 pg.mL-1; p < 0.02) and ILD (1.75 +/- 0.25 pg.mL-1; p < 0.03) patients than in controls (1.35 +/- 0.18 pg.mL-1). Emphysema (2.08 +/- 0.26 versus 1.70 +/- 0.40 pg.mL-1) and ILD (1.98 +/- 0.21 versus 1.67 +/- 0.02 pg.mL-1) patients with pulmonary hypertension (PH) presented significantly (p < 0.05) higher arterial ET-1 levels than those without. At rest, arterial ET-1 levels were significantly correlated with mean pulmonary arterial pressure (Ppa) in both ILD (r = 0.8, p = 0.01) and emphysema (r = 0.5, p = 0.03) patients. During exercise, the arterial ET-1 levels were significantly correlated with arterial oxygen (Pa,O2) (r = -0.6, p = 0.04), alveolar-arterial oxygen difference (r = 0.8, p = 0.01), and Ppa (r = 0.6, p = 0.04) in ILD patients, but not in those with emphysema. In brief, the results of this study suggest that arterial endothelin-1 is markedly increased in interstitial lung disease and emphysema patients, and that, it is related to the exercise-induced exacerbation of pulmonary hypertension in patients with interstitial lung disease, but not in those with emphysema.

Aged↗

Improvement of exercise performance with short-term nasal continuous positive airway pressure in patients with obstructive sleep apnea.

We examined the effects of nasal continuous positive airway pressure (CPAP) on exercise performance in patients with obstructive sleep apnea (OSA). Six patients were treated with nasal CPAP on seven successive days and underwent overnight sleep studies and multiple sleep latency test (MSLT) at the beginning and after the last day of the treatment. The subjects also performed incremental exercise testing using a bicycle ergometer followed by 0-w, 25-w, 50-w,--(3 minutes each) until maximum level. Arterial oxygen pressure, arterial carbon dioxide pressure at rest while awake, apnea/ hypopnea index, longest apnea duration, the lowest percutaneous oxygen saturation measured by a pulse oximeter and the value of MSLT were significantly improved after nasal CPAP. Moreover, maximal oxygen consumption was significantly increased from 1841 ml/min +/- 350 to 2125 ml/min +/- 351 (p < 0.05); however, other cardiorespiratory parameters did not change significantly. The improvement of exercise performance by short-term nasal CPAP treatment in OSA patients may correlate with the improvement of sleepiness.

Adult↗

Circulating intercellular adhesion molecule-1 in patients with lung cancer.

Recently, abnormal expression of a great variety of adhesion molecules has been reported in malignancy. Of these adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) has been suggested to play an important role in the process of tumor invasion and distant metastasis. The purpose of this investigation was to assess the peripheral blood levels of soluble ICAM-1 and the effect of cytotoxic therapy upon these circulating molecules in a cohort of patients with lung cancer. This study comprised 19 lung cancer patients hospitalized in our institution (males 16 and females 3, mean age 60 years old). Serum concentration of soluble ICAM-1 was measured using a commercially available enzyme immunoassay test kit. These measurements were done before the initiation of any therapy and on day 5 of chemotherapy. Samples taken from healthy volunteers were available for comparison. Soluble ICAM-1 serum concentration was significantly higher (p < 0.0001) in the cancer patients as compared to that of the control group. Serum levels of ICAM-1 were more significantly (p < 0.02) elevated in patients with advanced stages of disease. This study suggests the presence of an increased expression of circulating adhesion molecules in lung cancer. The concentration of this adhesion molecule was correlated with the clinical stage of the malignant disease, but did not change significantly after multidrug cytotoxic therapy.

Adenocarcinoma↗

[Low dose inhalation of nitric oxide in chronic obstructive pulmonary diseases].

We studied the effect of inhalation of various concentrations of nitric oxide (NO)(2 ppm, 5 ppm, and 10 ppm) on the pulmonary circulation and on arterial oxygenation in 11 patients with stable chronic obstructive pulmonary disease. Inhalation of 2 ppm of NO resulted in values of mean pulmonary arterial pressure significantly lower than those measured while breathing room air only (24.1 +/- 1.7 vs 20.7 +/- 1.7 mmHg, p < 0.00001). The decrease in pulmonary artery pressure associated with inhalation of 2 ppm NO was only slightly less than the decrease associated with 10 ppm; the difference between the two was not considered to be clinically relevant. The pulmonary vascular resistance was significantly lower during inhalation of 2 ppm NO than during inhalation of room air only (495 +/- 40 vs 382 +/- 34 dyne.sec/cm5, p < 0.00001); the effects of inhaling 2 ppm and 10 ppm did not differ significantly. the partial pressure of oxygen in arterial blood was significantly lower after inhalation of 2 ppm NO than of baseline (61.1 +/- 2.3 vs 57.6 +/- 2.2 mmHg, p < 0.01). These results show that inhalation of NO worsens arterial oxygenation in patients with chronic obstructive pulmonary disease.

Administration, Inhalation↗

[A case of amyloidosis of the tracheobronchial tree and inferior nasal concha].

A 50-year-old man resented at a local medical clinic with nasal obstruction. He was treated but did not improve. He then consulted our institution. Chest X-ray disclosed infiltrative shadows in the basal region of the left lung. A computed tomography scan of the lung showed marked thickening of the airway walls extending from the trachea to both bronchial trees and obstructive changes in the left lower lobe of the lung. On bronchoscopic examination the bronchial mucosa was reddened and edematous with a pinhole bronchial obstruction in one region. Congo red staining of biopsy samples taken from the bronchial mucosa showed deposition of an amorphous substance. Tracheobronchial amyloidosis was diagnosed. The amyloid material was resistant to potassium permanganate and tested positive for lambda-chain of L immunoglobulin. Otorrhinolaryngological examination disclosed a tumor in the inferior nasal concha as the cause of his nasal obstruction. The nasal tumor was resected and AL lambda-type amyloidosis was diagnosed pathologically. Tracheobronchial and inferior nasal concha amyloidosis is an extremely rare pathological condition. The patient was followed for one year and remain asymptomatic without treatment.

Amyloidosis↗

Roles of basigin, a member of the immunoglobulin superfamily, in behavior as to an irritating odor, lymphocyte response, and blood-brain barrier.

Basigin is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Using the knockout mouse lacking the basigin gene (Bsg), we analyzed the function of basigin in adult mice lacking the gene [Bsg (-1-)]. Although histochemical studies on the localization of basigin (also called HT7 and neurothelin) strongly indicated that it is involved in the function of the blood-brain barrier, basigin knockout mice showed only a little difference, if any, to wild-type mice in the function of the blood brain-barrier. The mitogenic response of lymphocytes upon mixed lymphocyte reaction was greater in Bsg (-1-) mice. Finally, Bsg (-1-) mice repeatedly visited filter paper impregnated with acetic acid or isozine, indicating an abnormality in either reception of the odor or behavior as to it.

Animals↗

Serial transplantation in SCID mice of an epidermodysplasia verruciformis-associated squamous cell carcinoma without alteration of its histological and virological features.

An epidermodysplasia verruciformis-associated squamous cell carcinoma was xenografted to a SCID mouse, and the resultant tumor was transplanted through mice for 10 generations. Histological and virological features, with replication of about a thousand copies of the papillomavirus DNA, were the same in both the original carcinoma and the transplanted tumors.

Animals↗

High plasma level of plasmin-alpha 2-plasmin inhibitor complex is predictor of poor prognosis in patients with lung cancer.

The occurrence of thrombotic complications is commonly associated with poor prognosis in patients with malignancy. However, the prognostic significance of the subclinical activation of the clotting system, frequently observed in cancer patients, is unknown. The purpose of the present study was to evaluate the value of the pre-thrombotic state for predicting survival of lung cancer patients. This investigation comprised 70 lung cancer patients without clinical or laboratory diagnosis of intravascular coagulation. There were 49 cases with non-small and 21 with small cell carcinomas. Samples taken in controls were available for comparison. The clotting system was assessed measuring thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP). The independent value of these clotting markers to predict survival was evaluated in relation with previously well-established prognostic factors for lung cancer patients. Plasma concentration of each parameter was significantly higher in cancer patients as compared to that of controls. The plasma level of PAP was a predictor of survival independently from the stage of disease, sex, age, histological type, performance status, tumor size and the presence of distant metastasis. Discriminant analysis of PAP plasma concentration identified 2 groups with significant difference in survival rate in all patients, cases in advanced stages of disease and in those with small and non-small cell lung cancer. The results of the present study showed prognostic significance of the subclinical activation of the clotting system, particularly of the fibrinolytic pathway, in lung cancer. Newly developed markers of fibrinolysis might be potentially applicable for predicting outcome in malignancy.

Adult↗

Administration of anti-interleukin-2 receptor alpha antibody in vivo induces localized autoimmune disease.

Neonatal thymectomy (Tx) of mice at day 3 after birth (Tx-3), but not day 7 (Tx-7), induces organ-localized autoimmune diseases such as oophoritis and gastritis. Lesions in Tx-3 mice can be prevented by injection of splenic CD4+ cells from syngeneic normal mice, and this CD4+ population with suppressor activity is activated extrathymically by self antigens. Since it is speculated that these CD4+ T suppressor cells (Ts) express the interleukin-2 receptor (IL-2R) as an activated T cell population, an attempt was made to eliminate these Ts from the developing immune system of Tx-7 mice and normal mice by i.p. injection of anti-IL-2R alpha monoclonal antibodies. Interestingly, organ-localized autoimmune disease with quite similar characteristics to those observed after neonatal Tx developed in not only Tx-7 mice, but also normal mice. The results thus indicate that CD4+ cells expressing IL-2R alpha play an important role, as Ts in the periphery, in maintaining immune tolerance.

Animals↗

Protein C activation in NIDDM patients.

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 +/- 3.8 vs 3.0 +/- 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 +/- 2.6 vs 35.3 +/- 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 +/- 0.6 vs 8.6 +/- 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 +/- 2.9 vs 23.4 +/- 2.6%, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.

Adult↗

Urothelial transformation into functional glandular tissue in situ by instructive mesenchymal induction.

It is generally believed that adult tissue is terminally differentiated. The ureter is derived from the metanephric diverticulum which, along with the derivatives of the metanephric mesoderm, forms the kidney. In our experiments, the left ureters of adult male athymic mouse hosts were severed below the kidney, and mesenchyme from neonatal rat seminal vesicles (SVM) was grafted to the cut end of the ureter, thus bringing adult mouse ureter epithelium (URE) in contact with neonatal rat SVM. After four to eight weeks, the in situ tissue recombinants were harvested, and the epithelial secretory proteins recovered. In 5 of 11 cases, an induction occurred, resulting in an in situ transformation of the non-glandular transitional epithelium of the adult mouse ureter into the simple columnar epithelium of the seminal vesicle (SV). Functional cytodifferentiation was examined in these neonatal rat SVM + adult mouse URE tissue recombinants using antibodies against SV-specific secretory (SVS) proteins of the mouse and rat. From the cut end of the ureter, the adult URE was induced to undergo SV morphogenesis, to express SV cytodifferentiation, and to produce the complete spectrum of major SVS proteins characteristic of the mouse. The induced seminal vesicle epithelium (SVE) also expressed androgen receptors (AR) which are not seen in urothelial tissue. Staining with Hoechst dye 33258, which can distinguish cells of mouse and rat origin, further demonstrated that the induced SVE was indeed of mouse origin and not a contaminant of the inducing rat SVM. in addition, neonatal mouse vaginal mesenchyme was grafted in situ beneath the bladder mucosa of adult male mice, and the host animals were killed after three months. The vaginal mesenchyme implanted into the bladders induced prostate-like acini, indicating that the above reprogramming of adult organs in situ is not an isolate occurrence. These results set a precedent for the "recreation" of new vital organs, such as the kidney, in situ by demonstrating that adult epithelial cells retain a developmental plasticity equivalent to their undifferentiated fetal counterparts and are capable of being reprogrammed in situ to express a completely new morphological, biochemical, and functional phenotype.

Animals↗

Mouse models of autoimmune disease suggest that self-tolerance is maintained by unresponsive autoreactive T cells.

Multiple organ-localized autoimmune diseases, such as thyroiditis and gastritis, spontaneously develop in BALB/c nu/nu (nude) mice receiving embryonic rat thymus grafts (TG) under their renal capsules (TG nude mice). When thyroid was grafted into the rat thymus of TG nude mice, development of autoimmune thyroiditis, but not other diseases, was completely prevented. However, when such mice received thyroid antigen plus complete Freund's adjuvant (CFA), severe autoimmune thyroiditis developed, suggesting that some thyroid-specific autoreactive T cells migrate into the periphery, but remain unresponsive. Development of autoimmune diseases, including thyroiditis, in TG nude mice was prevented by a single intraperitoneal injection of splenic CD4+ cells from normal BALB/c mice and also from mice with intrathymic thyroid grafts, indicating that thyroid-specific suppressor T cells are present in normal mice and that such T cells are neither deleted nor inactivated by the intrathymic thyroid grafts, in contrast to autoreactive T cells. Thus clonal deletion in the thymus, and clonal anergy and/or ignorance in the periphery, of autoreactive cells is important to maintain immune tolerance to organ-specific antigen, but CD4 suppressor T cells may play a more important role in tolerance, and the failure of education of this population may cause autoimmune diseases in the TG nude mouse model.

Animals↗

Peptide-mediated suppression of experimental autoimmune uveoretinitis in mice: development of a peptide vaccine.

Experimental autoimmune uveoretinitis (EAU) is an animal model of antigen-specific, Th cell-mediated, organ-specific autoimmune disease. EAU is induced by immunization of B10.A mice with interphotoreceptor retinoid-binding protein (IRBP). Pre-treatment with synthetic peptide 518-529 derived from IRBP prevented IRBP-mediated EAU. This was accompanied by augmentation of the IRBP-specific IgG1 antibody (Th2) response and down-regulation of the IRBP-specific IgG2a (Th1) response. Consistent with this is the observation that two of two T cell lines established from p518-529-primed mice produced Th2-type cytokines (IL-4 and IL-10), whereas three of three T cell lines obtained from IRBP-primed mice produced Th1-type cytokines (IL-2 and IFN-gamma). Together this suggests the possibility that p518-529 priming causes a shift from a Th1-to a Th2-dominated immune response, thereby playing a pivotal role in the prevention of IRBP-mediated EAU. Furthermore, co-transfer of cells from a CD4+ p518-529-specific T cell line prevented the development of EAU after adoptive transfer of spleen cells from mice with EAU into normal mice. These findings contribute to our understanding of the mechanism of EAU, particularly with respect to the down-regulation of Th1-initiated inflammation, and may prove valuable for designing a peptide vaccine for EAU in the future.

Adoptive Transfer↗

Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea.

BACKGROUND: Cyclical changes in systemic blood pressure occur during apnoeic episodes in patients with obstructive sleep apnoea (OSA). Although several factors including arterial hypoxaemia, intrathoracic pressure changes, and disruption of sleep architecture have been reported to be responsible for these changes in blood pressure, the relative importance of each factor remains unclear. This study assessed the role of hypoxaemia on the increase in blood pressure during apnoeic episodes. METHODS: The blood pressure in apnoeic episodes during sleep and the blood pressure response to isocapnic intermittent hypoxia whilst awake were measured in 10 men with OSA. While asleep the blood pressure was measured non-invasively using a Finapres blood pressure monitor with polysomnography. The response of the blood pressure to hypoxia whilst awake was also measured while the subjects intermittently breathed a hypoxic (5% or 7% oxygen) gas mixture. Each hypoxic gas exposure was continued until a nadir arterial oxygen saturation (nSaO2) of less than 75% was reached, or for a period of 100 seconds. The exposure was repeated five times in succession with five interposed breaths of room air in each run. RESULTS: The mean (SD) increase in blood pressure (delta MBP) during apnoeic episodes was 42.1 (17.3) mm Hg during rapid eye movement (REM) sleep and 31.9 (12.5) mm Hg during non-REM sleep. The delta MBP during apnoeic episodes showed a correlation with the decrease of nSaO2 (delta SaO2) (r2 = 0.30). The change in blood pressure in response to intermittent hypoxia whilst awake was cyclical and qualitatively similar to that during apnoeic episodes. Averaged delta MBP at an SaO2 of 7% and 5% oxygen was 12.6 (5.7) and 13.4 (3.6) mm Hg, respectively, whereas the averaged delta MBP at the same delta SaO2 during apnoeic episodes was 38.4 (15.5) and 45.2 (20.5) mm Hg, respectively. CONCLUSIONS: The blood pressure response to desaturation whilst awake was about one third of that during apnoeic episodes. These results suggest that factors other than hypoxia may play an important part in raising the blood pressure during obstructive sleep apnoea.

Adult↗