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Biomedical subjects

Shinji Nakao

Publications and source records attributed to Shinji Nakao.

At least 19 recordsLinked to original sources
PubMed2007

Roles of DRB1 *1501 and DRB1 *1502 in the pathogenesis of aplastic anemia.

OBJECTIVE: Although a number of reports have documented a significantly increased incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the immune mechanisms of AA remains unclear. We herein clarify the difference between DRB1( *)1501 and DRB1( *)1502, the two DRB1 alleles that determine the presentation of HLA-DR15, in the pathophysiology of AA. MATERIALS AND METHODS: We investigated the relationships of the patients( *) HLA-DRB1 allele with both the presence of a small population of CD55(-)CD59(-) (PNH-type) blood cells and the response to antithymocyte globulin (ATG) plus cyclosporin (CsA) therapy in 140 Japanese AA patients. RESULTS: Of the 30 different DRB1 alleles, only DRB1( *)1501 (33.6% vs 12.8%, p(c) < 0.01) and DRB1( *)1502 (43.6% vs 24.4%, p(c) < 0.01) displayed significantly higher frequencies among the AA patients than among a control. AA patients possessing HLA-DR15 tended to be old, and especially, the frequency of DRB1( *)1502 in patients 40 years of age and older (52.4%) was markedly higher than that in those younger than 40 years old (16.2%, p(c) < 0.01). Only DRB1( *)1501 was significantly associated with the presence of a small population of PNH-type cells and it also showed a good response to ATG plus CsA therapy in a univariate analysis. A multivariate analysis showed only the presence of a small population of PNH-type cells to be a significant factor associated with a good response to the immunosuppressive therapy (p < 0.01). CONCLUSIONS: Although both DRB1( *)1501 and DRB1( *)1502 contribute to the development of AA, the methods of contribution differ between the two alleles.

Adolescent↗
PubMed2006

Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia.

To identify novel autoantibodies in acquired aplastic anemia (AA), we screened the sera of patients with AA possessing small populations of paroxysmal nocturnal hemoglobinuria (PNH)-type cells for the presence of antibodies (Abs) which recognize proteins derived from a leukemia cell line, UT-7. Immunoblotting using proteins derived from lysates or culture supernatants of UT-7 cells revealed the presence of IgG Abs specific to an 80-kDa protein. Peptide mass fingerprinting identified this 80-kDa protein as moesin. Enzyme-linked immunosorbent assay (ELISA) using recombinant moesin showed high titers of antimoesin Abs in 25 (37%) of 67 patients with AA. Moesin was secreted from several myeloid leukemia cell lines other than UT-7, such as OUN-1 and K562, as an exosomal protein. The presence of antimoesin Abs was significantly correlated with the presence of PNH-type cells and antidiazepam-binding inhibitor-related protein-1 (DRS-1) Abs. Patients with AA that did not show any of these 3 markers tended to respond poorly to immunosuppressive therapy. These findings suggest that a B-cell response to moesin, possibly derived from hematopoietic cells, frequently occurs in patients with AA and that detection of antimoesin Abs in combination with other markers may be useful in diagnosing immune pathophysiology in patients with AA.

Adult↗
PubMed2006

Pulmonary sarcoidosis with usual interstitial pneumonia distributed predominantly in the lower lung fields.

Nodular and reticular opacities were detected in both lower lung fields of a 75-year-old man in 2000. Bronchoscopy revealed pulmonary sarcoidosis. In 2002, nodular and reticular opacities were shown in the right upper lobe, and video-assisted thoracoscopic surgery was performed. The histological findings revealed usual interstitial pneumonia (UIP)-like lesions, whereas non-caseous granulomas were not detected. In the present case of pulmonary sarcoidosis, nodular and reticular opacities were predominantly distributed in both lower lung fields, and the histological findings obtained by video-assisted thoracoscopic surgery showed UIP-like lesions. These findings may enlighten the assist in understanding of the process of development of pulmonary sarcoidosis.

Aged↗
PubMed2006

Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host disease: a case report.

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogenic bone marrow transplantation. Even with aggressive treatment, cGVHD is associated with a significant degree of morbidity and mortality. cGVHD resembles autoimmune disorder, particularly systemic sclerosis (SSc). Sarpogrelate hydrochloride (SH) is an antagonist of the 5-hydroxytryptamine2A (5HT2A) receptor and has been reported to be effective in the treatment of systemic sclerosis (SSc) patients with Raynaud phenomenon. We used SH to treat a cGVHD patient, and we measured plasma PDGF and total TGF-beta levels. After SH treatment, his plasma PDGF and total TGF-beta levels decreased, and he noticed improvement in his skin pigmentation. In the present case, SH may have improved the skin lesion by inhibiting the synthesis of PDGF and TGF-beta.

Adult↗
PubMed2006

Bronchial asthma showing reduction in FEV1 after inhalation of Qvar.

The administration of Qvar (a hydrofluoroalkane-134a beclomethasone dipropionate; HFA-BDP) is highly useful for the treatment of patients with asthma. However, we found in a case of bronchial asthma that replacing the prior inhaled corticosteroids with Qvar resulted in temporary dyspnea and reduction in forced expiratory volume in 1 second (FEV1). Qvar contains beclomethasone dipropionate combined with absolute ethanol and an alternative to fluorocarbon. The patient had complicated alcohol-induced asthma. FEV1 decreased markedly and immediately after Qvar inhalation. The Qvar placebo is free of beclomethasone but contains other ingredients (ethanol and fluorocarbon). FEV1 did not decrease after the Qvar placebo, Aldecin inhalation, and Qvar inhalation orally treated with atropine before inhalation of Qvar. It seems unlikely that the components of Qvar (except beclomethasone) are responsible for the reduction in FEV1 observed immediately after inhalation of Qvar. These findings would be noteworthy when using Qvar for Japanese patients with asthma known to have a relatively high frequency of the complication of alcohol-induced asthma.

Administration, Inhalation↗
PubMed2006

A case of acute hypersensitivity pneumonitis associated with an oil fan heater.

We report here a case of acute hypersensitivity pneumonitis induced by an oil fan heater. A 57-year-old man was admitted to our hospital because of fever, nonproductive cough, and dyspnea. Paeccilomyces variotii and Paeccilomyces nivea were identified from an oil fan heater in his house. The result of an environmental challenge test was positive. Intradermal reaction and precipitin results to sugar antigen of those fungi were positive only in the patient. This is the first described case of acute hypersensitivity pneumonitis caused by an oil fan heater.

Alveolitis, Extrinsic Allergic↗
PubMed2006

Immunoglobulin preparations attenuate organ dysfunction and hemostatic abnormality by suppressing the production of cytokines in lipopolysaccharide-induced disseminated intravascular coagulation in rats.

OBJECTIVE: We attempted to clarify the effect of immunoglobulin concentrates on the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) model. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6 to 7 wks and weighing 160 to 170 g. INTERVENTIONS: Two kinds of experiments were performed. In the first, experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100 mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after which immunoglobulin infusion was continued for a further 4 hrs. In the second, experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1 hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the first experiment and at 1, 5, and 10 hrs in the second one. MEASUREMENT AND MAIN RESULTS: Similar results were observed in the two experiments. Consumption coagulopathy and hemostatic activation were attenuated, especially when immunoglobulin was administered before LPS infusion. Plasma levels of creatinine and alanine aminotransferase were significantly depressed by coadministration of immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS-induced DIC model, but this deposition was reduced by immunoglobulin. In the first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the second, plasma levels of IL-6 were significantly suppressed by immunoglobulin. CONCLUSION: It was concluded that plasma levels of TNF and IL-6 could be significantly suppressed by immunoglobulin in the LPS-induced DIC model. Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin deposition in this model were all ameliorated by immunoglobulin.

Alanine Transaminase↗
PubMed2006

No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats.

OBJECTIVE: Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC). DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6-7 wks, and weighing 160-170 g. INTERVENTIONS: Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs. MEASUREMENTS AND MAIN RESULTS: Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group. CONCLUSIONS: There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.

Animals↗
PubMed2006

Treatment of primary central nervous system lymphoma with induction of complement-dependent cytotoxicity by intraventricular administration of autologous-serum-supplemented rituximab.

We describe an immunocompetent 19-year-old man with CD20-positive primary central nervous system (CNS) lymphoma refractory to chemotherapy and irradiation. After intraventricular administration of rituximab, a chimeric anti-CD20 monoclonal antibody, supplemented with autologous serum, a remarkable response developed to the CNS parenchymal lymphoma. Cytotoxicity assays showed that untreated patient's serum with rituximab, but not that of heat-inactivated patient's serum with rituximab or rituximab alone, induced potent rituximab-mediated cytotoxicity against tumor cells in the patient's cerebrospinal fluid, suggesting induction of complement-dependent cytotoxicity against CNS lymphoma.

Adult↗
PubMed2006

Mycophenolate mofetil is effective and well tolerated in the treatment of refractory acute and chronic graft-versus-host disease.

We enrolled 11 patients with refractory graft-versus-host disease (GVHD) in a prospective trial evaluating the efficacy of mycophenolate mofetil (MMF). Four (67%) of the 6 patients with acute GVHD and all 5 patients with chronic GVHD responded to MMF. Ten (91%) of the 11 patients were able to decrease steroid use (median decrease, 86%; range, 25%-100%). After a median follow-up of 18 months (range, 1-65 months), 7 patients (64%) remained alive. The adverse events were infectious complications (36%), diarrhea (27%), and neutropenia (18%); the only patient discontinuing MMF did so because of grade 4 neutropenia. This preliminary study suggests that MMF is a well-tolerated agent and has a beneficial effect in the treatment of refractory acute and chronic GVHD.

Acute Disease↗
PubMed2006

Successful treatment of minimal residual disease-positive Philadelphia chromosome-positive acute lymphoblastic leukemia with imatinib followed by reduced-intensity unrelated cord blood transplantation after allogeneic peripheral blood stem cell transplantation.

We describe a 35-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic sibling donor peripheral blood stem cell transplantation (PBSCT) and entered a second complete remission. Upon detection of BCR-ABL transcripts after PBSCT, the patient received imatinib, leading to molecular remission. Following the failure of donor leukocyte infusions, she underwent reduced-intensity unrelated cord blood transplantation (RI-UCBT), and has continued durable molecular remission for more than 30 months without substantial graft-versus-host disease. Because of a lack of adverse effects of imatinib on transplantation outcome, a treatment strategy consisting of molecular monitoring-guided initiation of imatinib followed by RI-UCBT may be promising in the management of Ph+ ALL after allogeneic SCT.

Adult↗
PubMed2006

Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure.

Although increased blood cell deficiency of glycosyl phosphatidylinositol-anchored membrane proteins has often been detected in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), the clinical significance of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells remains to be elucidated. We established a sensitive flow cytometric assay capable of detecting less than 0.01% of CD59-CD55- blood cells in a sample and used the assay to examine a large number of patients with bone marrow failure. An increase in the proportion of PNH-type cells was detectable in approximately 60% of all AA patients and in 20% of all refractory anemia (RA)-MDS patients. The increase was undetectable in patients with RA with an excessive number of blasts, acute myelogenous leukemia, multiple myeloma, or systemic lupus erythematosus. Our study showed that the presence of an increased number of PNH-type cells was predictive of a good response to immunosuppressive therapy and a favorable prognosis among patients with recently diagnosed AA and RA. A sensitive flow cytometric analysis for detection of a small population of PNH-type cells in peripheral blood cells is one of the most important examinations in the management of bone marrow failure.

Anemia, Aplastic↗
PubMed2005

Inhaled lysophosphatidylcholine provokes bronchoconstriction in guinea pigs in vivo.

Lysophosphatidylcholine is increased in the airway of bronchial asthma, but its role is not clear. We investigated the role of lysophosphatidylcholine in asthma in anaesthetized, mechanically ventilated guinea pigs. Pressure at the airway opening was measured as an index of bronchial response. Increasing doses of lysophosphatidylcholine (1--10 mg/ml) were inhaled and then bronchoalveolar lavage was carried out. 100 and 200 microg/ml methacholine were inhaled 10 min after inhalation of 2.5 mg/ml lysophosphatidylcholine, 10 mg/ml dipalmitoyl phosphatidylcholine and 10 mg/ml glycerophosphocholine, all of which per se did not change the pressure at the airway opening. Effect of 1.0 microg/kg salbutamol, or 60 mg/kg diphenhydramine on the lysophosphatidylcholine-induced increase in the pressure at the airway opening was investigated. Inhalation of lysophosphatidylcholine dose-dependently increased the pressure at the airway opening and increased bronchial responsiveness to methacholine. On the other hand, inhalation of dipalmitoyl phosphatidylcholine decreased the pressure at the airway opening and decreased bronchial responsiveness to methacholine. Intravenously administered salbutamol, but not diphenhydramine, prevented the lysophosphatidylcholine-induced increase in the pressure at the airway opening. The percentage of leukocytes in bronchoalveolar lavage fluid did not change significantly at least within 20 min after the lysophosphatidylcholine inhalation. Lysophosphatidylcholine causes bronchoconstriction and enhances bronchial responsiveness without inducing leukocyte infiltration in the airway, suggesting that lysophosphatidylcholine may be a new bronchoconstrictor mediator in bronchial asthma.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia.

We investigated the clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells in patients with acquired aplastic anemia (AA). We quantified CD55-CD59- granulocytes and red blood cells (RBCs) in peripheral blood from 122 patients with recently diagnosed AA and correlated numbers of PNH-type cells and responses to immunosuppressive therapy (IST). Flow cytometry detected 0.005% to 23.1% of GPI-AP- cells in 68% of patients with AA. Sixty-eight of 83 (91%) patients with an increased proportion of PNH-type cells (PNH+) responded to antithymocyte globulin (ATG) + cyclosporin (CsA) therapy, whereas 18 of 39 (48%) without such an increase (PNH-) responded. Failure-free survival rates were significantly higher (64%) among patients with PNH+ than patients with PNH- (12%) at 5 years, although overall survival rates were comparable between the groups. Numbers of PNH-type and normal-type cells increased in parallel among most patients with PNH+ who responded to IST, suggesting that these cells are equally sensitive to immune attack. These results indicate that a minor population of PNH-type cells represents a reliable marker of a positive IST response and a favorable prognosis among patients with AA. Furthermore, immune attack against hematopoietic stem cells that allows PNH clonal expansion might occur only at the onset of AA.

Adolescent↗
PubMed2005

Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs.

BACKGROUND: Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs. METHODS: Measurement of number of coughs elicited by increasing concentrations of capsaicin (10(-6) and 10(-4) M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs. RESULTS: Percentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals. CONCLUSION: The results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs.

Journal Article↗
PubMed2005

Peripheral neuropathy associated with chronic natural killer cell lymphocytosis.

We report a patient with steroid-responsive peripheral neuropathy which developed with chronic natural killer cell lymphocytosis (CNKL). A 70-year-old female with a 2-week history of progressive motor and sensory neuropathy showed a marked increase of natural killer (NK) cells in the blood, and was diagnosed as having CNKL. Nerve conduction studies (NCS) revealed a mixed axonal and demyelinating neuropathy. A sural nerve biopsy revealed infiltration of NK cells into the nerve fascicles, and demyelinating changes with axonal degeneration. The infiltrating NK cells were adjacent to myelinated fibers, showing damage of Schwann cell membrane. Treatment with oral prednisolone resulted in rapid improvement of the sensory disturbance and weakness with a significant decrease of NK cells in the blood and disappearance of the conduction blocks in NCS. This is the first case of CNKL associated neuropathy in which infiltration of NK cells was demonstrated in the nerve fascicles. Our observations suggest that the infiltrating NK cells may directly damage myelin and Schwann cells, thus causing demyelination.

Action Potentials↗