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Biomedical subjects

Shinji Nakao

Publications and source records attributed to Shinji Nakao.

At least 73 records · Page 4Linked to original sources

Role of fibrinolysis in tissue-factor-induced disseminated intravascular coagulation in rats - an effect of tranexamic acid.

We clarified the role of fibrinolysis in tissue-factor (TF)-induced rat disseminated intravascular coagulation (DIC) using tranexamic acid (TA). TA suppressed the elevation in D-dimer levels normally observed following TF-induced DIC, and an increase in organ dysfunction was seen. Enhanced fibrinolysis plays an important role in preventing the development of organ failure in TF-induced DIC.

Animals↗

[Comparison of the bronchodilator effect of salbutamol between pressure metered dosed inhaler and dry powder inhaler in patients with stable bronchial asthma].

Recently, dry powder inhaler (DPI) was more available than pressure metered dosed inhaler (pMDI) for the inhalation therapy of the respiratory disease. But there are differences in the lung deposition of the drug in these devices. We investigated the bronchodilator effect of salbutamol inhalation with two device, pMDI and Tubuhaler on the stable 8 asthmatic patients. The time course of FEV1 had a no significant difference between two devices. DeltaAUC (=difference between area under the curve for time course of increase in FEV1 via pMDI and via DPI) and Deltamax FEV1 (=difference between maximum increases in FEV1 following inhalation of salbutamol via pMDI and DPI) were defined as the index of difference of bronchodilator effect between the two devices. PMDI was more effective on improving the pulmonary function in subjects with severely decreased FEV1 and FEV1% than DPI. These results may reflect the correlation of inspiratory flow rate and drug deposition. PMDI is still useful on the part of asthmatic patients with decreased pulmonary function.

Adult↗

[A case of successful desensitization therapy for isoniazid-induced pneumonitis].

A 65-year-old man was admitted to hospital for treatment of pulmonary tuberculosis. He was treated with isoniazid (INH), rifampicin (RFP), ethambutol (EB), and pyrazinamide (PZA). On the 14th day, he developed a fever and interstitial pneumonia, which improved promptly after discontinuation of the antituberculous drugs. Drug lymphocyte stimulation tests against INH, RFP and PZA were negative. However, the provocation test on INH (only) was positive, leading to a diagnosis of pneumonitis caused by INH. We then tried desensitization of INH over a period of two weeks, which was successful and occurred without any clinical event. In the past, five cases of INH-induced pneumonitis were reported, but desensitization of INH did not occur in any. We conclude that physicians should be aware not only of paradoxical reactions but also of drug-induced pneumonitis when a new pulmonary infiltrate develops in the course of tuberculosis treatment. Furthermore, drug desensitization may be possible in some cases of drug-induced pneumonitis.

Aged↗

Polyclonal hematopoiesis maintained in patients with bone marrow failure harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells.

Although a minor population of paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells is often detected in patients with aplastic anemia (AA) and refractory anemia (RA), the significance of such cells in the pathophysiology of bone marrow (BM) failure remains obscure. We therefore examined clonality in peripheral blood granulocytes from 118 female patients with AA or myelodysplastic syndrome using the X chromosome inactivation pattern. Clonality, defined as a clonal population accounting for 35% or more of total granulocytes, was confirmed in 22 of 68 (32.4%) AA patients, in 13 of 44 (29.5%) RA patients, in all 4 RA with excess blasts (RAEB) patients, and in 4 patients with PNH. When the frequency of patients with granulocyte clonality was compared with respect to the presence of increased PNH-type cells, the frequency was significantly lower in AA patients with (PNH+; 21.2%) than without (PNH-; 42.9%) increased numbers of PNH-type cells (P =.049). Clonality was absent in granulocytes from the 15 PNH+ RA patients but present in 13 of 29 (44.8%) PNH- RA patients (P =.0013). The absence of clonality in AA and RA patients before treatment was strongly associated with positive response to immunosuppressive therapy (without clonality, 74.4%; with clonality, 33.3%; P =.0031) in all patients as well as in PNH+ patients (without clonality, 96.2%; with clonality, 66.6%, P =.026). These results suggest that AA and RA with a minor population of PNH-type cells are benign types of BM failure with immune pathophysiology that have little relationship to clonal disorders such as RAEB or acute myeloid leukemia.

Adolescent↗

Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disorder simultaneously affecting both B and T cells after allogeneic bone marrow transplantation.

Post-transplantation lymphoproliferative disorder (PTLD) is usually an aberrant proliferation of EBV-infected B cells. We report the case of a 31-year-old man with severe aplastic anemia who suffered PTLD 42 days post-BMT from an unrelated donor. At the onset of PTLD, peripheral blood lymphocytes were comprised of 40% CD20(+) cells, 3% CD4(+) cells, and 56% CD8(+) cells. A highly sensitive in situ hybridization (ISH) method was used to detect EBV-encoded small non-polyadenylated RNA 1 (EBER-1) in 33.9% of sorted CD20(+) cells, 4.4% of CD4(+) cells, and 1.4% of CD8(+) cells. Each T-cell fraction contained less than 0.034% of contaminated EBV-infected B cells. Clonal proliferation of both B and T cells was demonstrated by Southern blotting. The patient did not respond to donor leukocyte infusion and died due to deterioration of PTLD. At autopsy, examination of multiple organs revealed B-cell (rather than T-cell) infiltration. This case clearly indicates that EBV can simultaneously infect B and T cells and can induce clonal proliferation of both lymphocyte subsets in severely immunocompromised patients.

Adult↗

Persistent remission after immunosuppressive therapy of hairy cell leukemia mimicking aplastic anemia: two case reports.

Some patients with hairy cell leukemia (HCL) manifest pancytopenia and bone marrow hypoplasia without an apparent increase in atypical cells, so their disease resembles severe aplastic anemia at onset. We treated 2 HCL patients, who were initially diagnosed with aplastic anemia, with antithymocyte globulin (ATG) in combination with cyclosporine or antilymphocyte globulin (ALG). Both patients obtained partial remission in response to the immunosuppressive therapy and did not need transfusion treatment for more than 3 years. Sustained improvement of hematopoiesis in such B-cell malignancies after ATG/ ALG therapy suggests that the mechanisms underlying successful immunosuppressive therapy for aplastic anemia may involve B-cell suppression, inhibiting hematopoietic stem cells.

Anemia, Aplastic↗

Bronchodilator effects of intravenous olprinone, a phosphodiesterase 3 inhibitor, with and without aminophylline in asthmatic patients.

AIMS: There is no evidence demonstrating the clinical usefulness of phosphodiesterase (PDE) inhibitors in the treatment of asthma, although PDE3 and 4 inhibitors have received much attention for the treatment of bronchial asthma. We compared the bronchodilator effects of intravenously administered olprinone, a selective PDE3 inhibitor, and aminophylline, a nonselective PDE inhibitor, both alone and concomitantly. METHODS: In 12 patients with mild stable asthma, we compared the acute bronchodilator effects of the following two drugs, alone and together using a double-blind crossover design: intravenous administration of olprinone, 30 micro g min-1; aminophylline, 2.25 mg min-1; and olprinone plus aminophylline over a total period of 150 min. RESULTS: Mean maximal increase (95% confidence interval) in the FEV1 was 7.8% (2.4, 13.2), 17.1% (10.0, 24.2), 16.6% (11.2, 22.0), and 1.0% (-1.1, 3.1) during infusion of aminophylline, olprinone, aminophylline and olprinone, and saline, respectively. The magnitude of bronchodilatation produced by olprinone was greater than that by aminophylline. The combination of aminophylline and olprinone did not produce any greater bronchodilatation than olprinone alone. Olprinone alone or in combination with aminophylline lowered diastolic blood pressure, and increased heart rate. CONCLUSIONS: These results suggest that the intravenous administration of PDE3 inhibitors exhibits a bronchodilatory effect. There are no additive or synergistic effects of administration of olprinone and aminophylline at the same time.

3',5'-Cyclic-AMP Phosphodiesterases↗

A case of hypersensitivity pneumonitis caused by Humicola fuscoatra.

A 51-year-old housewife with hypersensitivity pneumonitis caused by Humicola fuscoatra is reported. The diagnosis was made by an inhalation challenge with H. fuscoatra antigen. She was admitted for diagnosis and treatment of a fever and productive cough. Auscultation of her lungs revealed inspiratory fine crackles. Her chest CT showed diffuse miliary nodules in a centri-lobular distribution with patchy ground glass opacities. Findings of transbronchial lung biopsy and BAL fluid were compatible with a hypersensitivity pneumonitis. Her symptoms worsened on returning home, which suggested the existence of some aetiological agent in the subject's house. H. fuscoatra, Penicillium decumbens and Aspergillus versicolor were isolated from a number of rooms. High titres of serum anti H. fuscoatra, P. decumbens and A. versicolor were detected. Inhalation challenge tests with both P. decumbens and A. versicolor antigen were negative, in contrast to that with H. fuscoatra which was positive. Based on these results, we advised the patient to cleanse her entire house. Since cleaning, her symptoms have not worsened upon returning home. This is the first report of hypersensitivity pneumonitis caused by H. fuscoatra antigen.

Alveolitis, Extrinsic Allergic↗

Congenital predisposition to spontaneous intracranial hypotension: a case report.

Dural rupture, cerebrospinal fluid leakage, and spontaneous intracranial hypotension may complicate significant or minimal spinal trauma and cause chronic headache with a positional component. While such cases typically reflect no pre-existing predilection, we encountered a patient whose cervicothoracic anatomy appeared to predispose him to this complication.

Adult↗

Pathophysiology of disseminated intravascular coagulation (DIC) progresses at a different rate in tissue factor-induced and lipopolysaccharide-induced DIC models in rats.

Tissue factor (TF) and lipopolysaccharide (LPS) are frequently used to induce disseminated intravascular coagulation (DIC) in experimental animal models. Although the pathophysiology of DIC may differ depending on which agent is used for induction, previous studies on models of DIC have not distinguished which DIC-inducing agent was used. In the present paper, we evaluate the characteristics of TF-induced and LPS-induced DIC using two types of DIC models, with special reference to selected hemostatic parameters and pathological findings within the kidney. Male Wistar rats were administered TF (3.75 U/kg; sustained infusion for 4 h) or LPS (30 mg/kg; sustained infusion for 4 h) via the tail vein, and blood sampling was performed at 0, 1, 3, 4, 5, 7, 9, 11, and 28 h. Judging from changes in the levels of thrombin-antithrombin complex, fibrinogen levels, and platelet counts, it is reasonable to conclude that the severity of both types of experimental DIC is similar with regard to hemostatic activation and consumption coagulopathy. A marked elevation in the level of D-dimer was noted without any organ dysfunction or much fibrin deposition in the kidney upon administration of TF. However, a markedly prolonged period of elevation in plasminogen activator inhibitor activity, a prolonged depression in antithrombin III activity, severe organ failure, and a markedly prolonged period of fibrin deposition in the kidney was observed following LPS administration. A modest number of the rats from the TF-induced DIC model died during the experimental period, whereas a large number of rats died during LPS-induced DIC, especially after 9 h. Since the time course of the pathophysiology differed remarkably among the TF-induced and LPS-induced DIC models in rats, we recommend that TF-induced and LPS-induced DIC be approached as distinct models in order to determine the implications of their experimental and clinical use.

Animals↗

The molecular mechanism of arsenic trioxide-induced apoptosis and oncosis in leukemia/lymphoma cell lines.

The mechanisms of As(2)O(3)-induced apoptosis are very complex. In the present study, we investigated the molecular mechanism of As(2)O(3) in vitro at low concentration (0.25-2.0 micro M) on three human leukemia/lymphoma cell lines: HL-60, RL and K562. As(2)O(3) inhibited the growth of these cell lines significantly. During As(2)O(3) treatment, two forms of cell death, apoptosis in HL-60 and RL and oncosis in K562, were found by morphological study. In HL-60 and RL, cell cycle analysis showed, at a distinct SubG1 region, that CD95 and CD95 ligand (CD95L) expression was upregulated, caspase 8 and caspase 3 were activated, and Bcl-2 protein expression was downregulated. On the other hand, in K562, the cell cycle was arrested at the G2+M phase, CD95/CD95L expression was upregulated, caspase 8 and caspase 3 were activated, but Bcl-2 expression was not changed as compared with untreated cells. These findings suggest that the CD95/CD95L pathway is involved in cell killing by As(2)O(3). Using anti-CD95 IgG monoclonal antibody (anti-CD95 MoAb) or specific caspase inhibitor ZVAD-fmk to block the CD95 pathway, the cell death induced by As(2)O(3) was partially blocked in each cell line. These results suggest that As(2)O(3) inhibits the growth of these leukemia/lymphoma cell lines by inducing apoptosis or oncosis that is partially mediated by the CD95/CD95L pathway.

Acute Disease↗

[A case of broncho-pulmonary aspergillosis complicated by bronchial asthma attack].

A 55-year-old man was hospitalized for the treatment of severe asthma. However, his condition improved with steroid chemotherapy under artificial ventilation, but high fever and multiple patchy shadows of the lung that were not responsive to antibiotics appeared. We detected aspergillus hyphae, probably inhaled with a quantity of dust in the attic of his workplace, in the sputum. We diagnosed invasive broncho-pulmonary aspergillosis complicated with allergic broncho-pulmonary aspergillosis. His condition improved with anti-fungal drug treatment. We consider that the causes of invasive broncho-pulmonary aspergillosis in this case were massive inhalation of aspergillus conidia, artifical ventilation and steroid chemotherapy.

Anti-Inflammatory Agents↗

[Non-myeloablative stem cell transplantation for non-malignant hematologic disorders].

Although non-myeloablative stem cell transplantation(NST) was originally developed to induce graft-versus-malignancy effect, the new transplant modality is now being applied for treatment of non-malignant disorders such as aplastic anemia(AA) and paroxysmal nocturnal hemoglobinuria due to its low toxicities. NST may be preferable than conventional transplantation when an AA patient has complications due to hemochromatosis such as heart failure and diabetes mellitus, and severe infections. We treated three aplastic anemia patients complicated by various organ failures, with a conditioning regimen consisting of fludarabine (Flu), cyclophosphamide(CY), and antithymocyte globulin (ATG). Engraftment promptly occurred in all patients without accompanying severe graft-versus-host disease or organ damages. Successful induction of complete chimerism and a low incidence of toxicities warrant a further clinical trial using the Flu + CY + ATG regimen.

Anemia, Aplastic↗

[Nonmyeloablative allogeneic peripheral blood stem cell transplantation of renal cell carcinoma].

We presented three cases with refractory metastatic renal cell carcinomas who underwent nonmyeloablative allogeneic peripheral blood stem cell transplantation(PBSCT). A fludarabine and cyclophosphamide-based regimen was used. Complete donor-T-cell chimerism was established at day 94, 40, 52 after PBSCT in each case. GVHD occurred at day 183, 53, 75. In Case 1 and Case 3 apparent GVT effects reduced the metastases at day 212, 261 and let them live longer than expected. Case 2 died at day 69 before GVT effect appeared, because the case was so-called rapid growth type. Histological examinations in Case 1 and Case 3 showed infiltration of lymphocytes disrupting the foci of renal cell carcinomas which was considered as findings of GVT effects.

Aged↗

[Influence of smoking on longitudinal decline in one-second forced expiratory volume in clinically healthy Japanese men: a longitudinal study].

We prospectively studied 2140 clinically healthy men to assess the influence of smoking on longitudinal decline in one-second forced expiratory volume (FEV1.0). All the subjects had annual medical checks including pulmonary function tests from 1995 to 1999. The mean values +/- standard deviations of annual decreases in FEV1.0 (slope) were 22 +/- 49 mL/year in non-smokers, 26 +/- 52 mL/year in former smokers, and 33 +/- 57 mL/year in current smokers (p < 0.01; non-smokers vs. current smokers). The adjusted slope (slope divided by predicted value of FEV1.0, per year) in current smokers was also greater than that in non-smokers (p < 0.01). Multiple regression analysis revealed that initial age, height, FEV1.0, and smoking status were significant parameters for determining the slope. This study clearly showed that smoking is an important risk factor foracceleration of the aging-related longitudinal decline in pulmonary function in Japanese men.

Adult↗

Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin 10 and interferon gamma may be critical mediators for the development of autologous GVHD.

Administration of the immunosuppressive drug cyclosporine A (CsA) following autologous stem cell transplantation paradoxically elicits a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with autoreactive CD8(+) T cells that recognize major histocompatibility complex (MHC) class II determinants in association with a peptide from the invariant chain. To investigate the potential role of cytokines and chemokines in autologous GVHD, interleukin 2 (IL-2), IL-4, IL-10, interferon gamma (IFN-gamma), and macrophage inflammatory protein-1alpha (MIP-1alpha) gene expression in peripheral blood mononuclear cells (PBMCs) was determined in 36 patients treated with CsA following transplantation and correlated with the induction of cytolytic activity against autologous phytohemagglutinin-stimulated lymphocytes (PHA-blasts) and the breast cancer cell line (T47D). The determination of gene expression by real-time polymerase chain reaction (PCR) revealed that IL-10 mRNA levels by PBMCs in patients with autologous GVHD were 29-fold higher than in healthy individuals. IFN-gamma (4-fold), IL-2 (3-fold), and MIP-1alpha (44-fold) mRNA levels were also increased in GVHD-induced patients compared with healthy individuals. The ability of PBMCs to lyse autologous PHA-blasts and T47D tumor cells exhibited an identical temporal relationship with expression of IL-10 and IFN-gamma during autologous GVHD. Moreover, the susceptibility to autologous GVHD as assessed in 75 patients was significantly associated with the IL-10(-1082) G/G polymorphic alleles, allelic variants in the promoter region that govern IL-10 production. These findings indicate that IL-10 may play an unexpected but critical role in autologous GVHD and could be utilized to enhance a graft-versus-tumor effect after transplantation. Interestingly, polymorphisms in the IL-10 promoter region may also explain differences in the susceptibility of patients to autologous GVHD induction.

Adolescent↗