Biomedical subjects

Takashi Horie

Publications and source records attributed to Takashi Horie.

52 records · Page 3Linked to original sources

PubMed2002

Purging in autologous hematopoietic stem cell transplantation using adenosine triphosphate (ATP) and 4-hydroperoxycyclophosphamide (4-HC).

In this study, we show potent in vitro purging induced by adenosine triphosphate (ATP) for leukemic cells. The treatment of murine L1210 leukemic cells with 2mM of ATP in vitro for 3h was able to reduce the number of leukemic clonogenic cells by about one order of magnitude presumably by changing the permeability of the leukemic cell membrane. Furthermore, the incubation of L1210 cells with ATP (2mM) and low dose 4-hydroperoxycyclophosphamide (4-HC, 2 microg/ml) for 3h resulted in at least a four-log reduction of clonogenic L1210 cells. Only a slight degree of toxicity to pluripotent hematopoietic stem cells (CFU-S) was observed in both treatment protocols. To determine the efficacy of pharmacological purging by ATP, we designed a murine system to mimic the conditions expected in the clinical setting of autologous transplantation using simulated partial remission marrow (SPRM) which was prepared by mixing normal marrow cells and L1210 cells at a ratio of 9:1. After the SPRM cells were incubated in vitro at a concentration of 1 x 10(6)/ml with both ATP (2mM) and low dose 4-HC (2 microg/ml) for 3h, 5 x 10(4) of the cells were then injected into lethally irradiated 9 weeks male BDF1 mice. All the mice given untreated-SPRM died of leukemia by day 27, whereas none of the recipients transplanted treated-grafts had died by day 70, thus suggesting that the combination use of ATP and 4-HC may be a potentially effective way to purge leukemic cells in autologous stem cell transplantation. The mechanism of the selective killing of leukemic cells is assumed that 4-HC is effectively incorporated into leukemic cells by increasing the permeability of the cell membrane by ATP. Taken together, this simple and rapid procedure is able to purge leukemic cells from autologous bone marrow grafts.

Adenosine Triphosphate↗

PubMed2002

Different clones of t(1;12)/t(12;12) involving the ETV6 gene in a case of acute myeloid leukemia.

We describe here a case of a 77-year-old Japanese man who developed acute myeloid leukemia (AML-M2). Chromosome analysis of the bone marrow blast cells showed 46,XY,del(7q) at onset, and after relapse, two clones, 46,XY,t(1;12) and 46,XY,del(7q),t(12;12), were present. Fluorescence in situ hybridization analysis confirmed that each clone with the 12p abnormality involved the ETV6 gene. These findings suggest that the ETV6 gene rearrangements in this case were apparently independent of contribution to leukemogenesis, because this cytogenetic aberration appeared as a secondary change. To our knowledge, this is the first report of two different clones with ETV6 gene rearrangements in the same patient.

Aged↗

PubMed2002

p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase regulate interleukin-8 and RANTES production in hyperosmolarity stimulated human bronchial epithelial cells.

OBJECTIVE: We have previously shown that p38 mitogen-activated protein kinase (MAPK) regulates, at least in part, hyperosmolarity induced interleukin (IL)-8 expression in human bronchial epithelial cells (BEC). In the previous study, hyperosmolarity also activated c-Jun-NH2-terminal kinase (JNK); however, the role of the JNK signalling pathway has not been determined. In the present study, we examined the role of the JNK signalling pathway in hyperosmolarity induced IL-8 and RANTES production by BEC using the novel inhibitor of the JNK signalling pathway CEP 11004 in order to clarify these issues. METHODS: Bronchial epithelial cells that had been pre-incubated with SB 203580, CEP 11004 or a combination of these were exposed to a hyperosmolar medium and then the p38 MAPK and JNK phosphorylation activity in these cells and IL-8 and RANTES concentrations in the culture supernatants were determined. RESULTS: The results showed that: (i) hyperosmolarity induced the threonine and tyrosine phosphorylation of p38 MAPK and JNK; (ii) SB 203580, as the specific inhibitor of p38 MAPK activity, and CEP 11004 attenuated hyperosmolarity induced p38 MAPK and JNK activity, respectively; (iii) SB 203580 and CEP 11004, but not PD 98059, partially attenuated IL-8 and RANTES production; and (iv) a combination of SB 203580 and CEP 11004 attenuated IL-8 and RANTES production in an additive fashion. CONCLUSION: These results indicate that p38 MAPK and the JNK pathway regulate hyperosmolarity induced IL-8 and RANTES production by BEC.

Analysis of Variance↗

PubMed2002

Dose-intensified CHOP (double-CHOP) followed by consolidation with high-dose chemotherapy for high and high-intermediate risk aggressive non-Hodgkin's lymphomas.

Patients with aggressive non-Hodgkin's lymphoma (NHL) showing several risk factors have a poor prognosis. In such patients, conventional chemotherapy results in a low complete response rate and a high relapse rate. We performed a prospective trial of intensive induction chemotherapy followed by high-dose consolidation therapy to determine the feasibility of such an approach. We treated 39 patients with aggressive poor risk NHL with double-CHOP (D-CHOP) chemotherapy followed by high-dose therapy (HDT) with or without peripheral blood stem cell transfusion (PBSCT). The median age of the patients was 54 years (range 17-65). Twenty-seven were considered to be at high (H) and 12 were at high-intermediate (H-I) risk according to the age-adjusted International Prognostic Index. Thirty-four patients (87%) responded (complete response: 74%, partial response: 13%) to D-CHOP chemotherapy. Of the 34 responders, 24 received HDT followed by PBSCT, 7 received high-dose methotrexate, and 3 refused consolidation therapy. At a median follow-up period of 26 months, the estimated 3-year overall survival rate and event-free survival rate was 64 and 51%, respectively. Our data suggest that dose-intensified D-CHOP followed by consolidation HDT is safe and appears efficacious in aggressive NHL patients with H-I and H risk.

Adolescent↗

PubMed2002

Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea syndrome.

STUDY OBJECTIVE: To identify the determinants of chronic hypercapnia (ie, PaCO(2), > or = 45 mm Hg) in men with obstructive sleep apnea syndrome (OSAS) without airflow obstruction. DESIGN: An analysis was conducted of 143 male patients with OSAS, which had been diagnosed by polysomnography (PSG), who had been referred to a university hospital. Patients were classified as hypercapnic (ie, PaCO(2), > or = 45 mm Hg) and normocapnic (ie, PaCO(2), < 45 mm Hg), and obese (ie, body mass index [BMI], > or = 30 kg/m(2)) or nonobese (ie, BMI, < 30 kg/m(2)). Patients with airflow obstruction (ie, FEV(1)/FVC ratio, < 70%) were excluded from the study. Baseline clinical characteristics, pulmonary function, PSG data, and blood gas data were compared between hypercapnic and normocapnic patients. Correlations between PaCO(2) and several anthropometric, respiratory, and polysomnographic variables were determined by stepwise multiple regression analysis. RESULTS: Fifty-five patients (38%) were hypercapnic. Hypercapnic patients were younger and heavier, and had more abnormalities on pulmonary and PSG testing. Stepwise multiple regression analysis revealed that the PaCO(2) level was influenced significantly by the mean level of arterial oxygen saturation (SaO(2)) during sleep and by the percent of vital capacity (%VC) (R(2) = 0.430; p < 0.0001), indicating that 43% of the total variance in the PaCO(2) could be explained by the mean SaO(2) and %VC in hypercapnic patients. In contrast, only 13% of the total variance in the PaCO(2) was accounted for by the mean SaO(2) and BMI in normocapnic patients (R(2) = 0.134; p = 0.0034). The mean SaO(2), %VC, and PaO(2) were selected as independent variables for predicting the PaCO(2) in obese patients. These variables explained 41% of the total variance in the PaCO(2) (R(2) = 0.407; p < 0.0001), whereas the mean SaO(2) only accounted for 13% of the total variance in PaCO(2) levels in nonobese patients (R(2) = 0.134; p = 0.0064). CONCLUSION: Nocturnal desaturation and restrictive pulmonary impairment play major roles in determining the PaCO(2) in hypercapnic and obese OSAS patients without airflow obstruction.

Adult↗

PubMed2002

Relationship between quality of life and mood or depression in patients with severe obstructive sleep apnea syndrome.

STUDY OBJECTIVES: To assess the quality of life (QOL) in patients with severe obstructive sleep apnea (OSAS), and the relationship between the QOL and severity of OSAS, excessive daytime sleepiness (EDS), and mood. METHODS: Sixty patients with OSAS and 34 normal control subjects were assessed for QOL using the Medical Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36), for EDS using the Epworth sleepiness scale (ESS), and for mood using the Zung self-rated depression scale (SDS). The associations between each domain and the total score on the SF-36 and the baseline characteristics, polysomnographic parameters, ESS score, and SDS score were examined by simple regression analysis and stepwise multiple regression analysis. RESULTS: Six of eight domains and the total score on the SF-36 were significantly lower than those in the control subjects. The ESS and SDS scores were also more impaired in the patients than in the control subjects. There was no relationship between each domain on the SF-36 and the severity of OSAS and ESS score. Five of eight domains and the total score on the SF-36 were significantly correlated with the SDS score. Stepwise multiple regression analysis selected three variables, the SDS score (partial R(2) = 0.505), the lowest arterial oxygen saturation during sleep (partial R(2) = 0.064), and ESS score (partial R(2) = 0.053), as independent factors for predicting the total score on the SF-36. These three variables accounted for 62.2% of the total variance in the total score on SF-36 (R(2) = 0.622, p < 0.0001) CONCLUSIONS: The QOL of patients with severe OSAS was decreased compared with normal control subjects. The QOL of patients was strongly correlated with the depression scale on simple regression analysis. However, EDS score and oxygen desaturation during sleep also affected the QOL, although the magnitude of its effect was small.

Adult↗

PubMed2002

[Anti-neutrophil cytoplasmic autoantibody-associated rapid progressive glomerulonephritis complicated with both limited and diffuse scleroderma].

We report two patients with scleroderma, 73-year-old female and 67-year-old female, who developed anti neutrophil cytoplasmic autoantibody (ANCA) associated rapid progressive glomerulonephritis (RPGN). Both patients have had a long history of scleroderma (23 and 14 years, respectively) when ANCA-associated glomerulonephritis occurred. In the first patient, scleroderma was localized in both fingers. She has been followed-up as CREST syndrome rather than systemic sclerosis. The complaints on admission were leg edema and left chest pain in the first patient, and a pyrexia and dyspnea in the second patient. Both patients showed pulmonary manifestation (pleural effusion in the first patient, interstitial pneumonia and alveolar hemorrhage in the second patient, respectively) and rapid progressive glomerulonephritis. Both patients died in spite of corticosteroid therapy. Autopsy findings in the second patient demonstrated crescentic glomerulonephritis and alveolar hemorrhage. Our cases demonstrated that MPO-ANCA associated glomerulonephritis could be associated with limited scleroderma as well as systemic scleroderma. In these condition, the prognosis will be poor if scleroderma seemed to be stable.

Aged↗

PubMed2002

[A case report of intralobar pulmonary sequestration with an anomalous artery originating from the celiac artery].

A 43-year-old female was admitted to our hospital because of an abnormality detected in chest radiography. Chest radiographs showed a nodular shadow behind the heart. Chest CT revealed a nodule connected to the descending aorta with increased blood flow in left lower lobe, suggesting the presence of a pulmonary sequestration. Bronchography showed an intralobar sequestrated lung in the left lower lobe. Aortography demonstrated that the sequestrated lung was fed by an anomalous artery 20 mm in diameter, originating from the celiac artery. From those findings, Pryce type IIintralobar pulmonary sequestration was diagnosed, and the left lower lobe was removed. Histological findings from the excised tissues showed mild dilatation of the bronchioles and hypervascularity.

Adult↗

PubMed2002

[Thymoma complicated with miliary tuberculosis].

We report a case of thymoma complicated with miliary tuberculosis. A 69-year-old woman was admitted to a hospital because of body weight loss, general fatigue, and dyspnea. Chest X-ray showed a small, diffuse granular shadows in both lungs. Biopsied-specimens from bone marrow and left pharynx revealed granuloma with both giant cells and caseous necrosis. The diagnosis of miliary tuberculosis was made. The patient was then transferred to our hospital. Both chest X-ray and computed tomography conducted on admission revealed a mass in the mediastinum as well as diffuse granular shadows in both lungs. We suspected a presence of thymoma. Anti-tuberculosis therapy was started, and extended thymectomy was performed. The diagnosis of thymoma was confirmed pathologically. Immunological analysis of peripheral blood lymphocytes was done before and after the operation. Negative conversion of PPD reaction was observed after thymectomy. Although the response of peripheral lymphocytes to phytohaemoagglutinin (PHA) and concanavalin A recovered after thymectomy, a marked decrease of the number of CD 4 T cells, a decrease of T helper 1 cells, a slight increase in the number of B cells and cells expressing natural killer cell-related surface markers were observed throughout the course of illness.

Aged↗

PubMed2002

[Human herpesvirus-8 negative primary effusion lymphoma with complete clinical remission after removal of ascites].

A 58-year-old HIV-negative woman was admitted to our hospital with abdominal distension. She had a 5-year history of hypothyroidism and a 4-year history of diabetes mellitus. Physical examination revealed ascites. There was no lymphadenopathy or splenomegaly. Laboratory examination showed elevated levels of serum LDH and Al-p, polyclonal hypergammaglobulinemia, and was positive for anti-nuclear antibody, several autoantibodies and HCV-RNA. A computed tomographic scan of the abdomen and chest showed massive ascites, but there was no evidence of tumor masses or lymph node enlargement. Cytologic examination of the ascitic fluid revealed numerous abnormal lymphocytes which by flow cytometry demonstrated expression of CD5, CD19, CD20, and CD4. Cytogenetical analysis demonstrated a hyperdiploid karyotype, with numerical abnormalities. Southern blot analysis demonstrated rearranged monoclonal bands in JH and c-mycgenes. Polymerase chain reaction (PCR) analysis failed to detect the genomes of EBV and HHV-8 in the abnormal lymphocytes. A diagnosis of primary effusion lymphoma of B cell lineage was made. Following abdominal paracentesis, the patient remained in complete clinical remission for 7 months and died of an unrelated cause (cerebral bleeding). The present case demonstrated an HIV-, HHV-8-, and EBV-negative, and HCV-positive primary effusion lymphoma of B cell lineage, with a unique clinical course.

Ascites↗

PubMed2002

[Heerfordt syndrome].

The Heerfordt syndrome is characterized by fever, uveitis, swelling of parotid gland and facial nerve palsy, and 53 cases have been reported in Japan until 2000. In the present review, we mainly focused on those clinical cases reported. Most patients were between 20 and 40 years of age, and females appeared to have greater risk than males. The definite diagnosis of this syndrome is established histologically according to sarcoidosis. In addition 67 gallium scan is helpful for diagnosis, and it shows increased uptake of Ga to the ophthal lesion, parotid glands and hilar lesions. Therapeutic trial with prednisolone is sometimes required especially for facial palsy.

Adolescent↗

PubMed2002

[Risk factors in development of sleep apnea syndrome--a large population study using a simple monitoring system].

We studied the risk factors in the development of sleep apnea syndrome (SAS) in 779 patients (705 males and 74 females) using Apnomonitor R. The apnea index (AI) significantly correlated with the body mass index (BMI), and was higher in obese patients (BMI > or = 25 kg/m2) than in non-obese patients. The prevalence of SAS increased with patient age. Obesity was less common in older than in younger patients. The AI was significantly higher in smokers than in non-smokers, as was the prevalence of SAS. The AI and the prevalence of SAS were higher in smokers than in non-smokers in both obese and non-obese patients. The AI was significantly higher in males than in females, and so was the prevalence of SAS. The AI and the prevalence of SAS were always higher in male obese patients, non-obese patients, smokers, and non-smokers than in female patients in the same categories. These results suggest that obesity, age, smoking, and gender were independent risk factors in the development of SAS.

Adult↗

PubMed2002

[CD25 positive chronic eosinophilic leukemia with myelofibrosis].

A 70-year-old man was referred to our hospital in March 2001 for the purpose of evaluation for anemia and thrombocytopenia. Physical examination revealed hepatosplenomegaly, normal skin, and normal neurologic findings. Blood examination showed a white blood cell count of 10,900/microliter, with a differential count of 58.5% eosinophils and 3.5% blast cells. Flow cytometric analysis of eosinophils revealed that they were positive for CD33, CD13, CD25, and HLA-DR. Bone marrow aspiration could not be performed due to dry tap, and bone marrow core biopsy specimen revealed severe myelofibrosis with blastoid cells proliferation. Cytogenetic analysis of bone marrow cells showed isochromosome 17. FISH analysis using a RAR alpha probe (17q21.1) demonstrated 62% of peripheral blood nucleated cells having three signals. BCR/ABL gene rearrangement by FISH analysis was not observed. Allergic disease, infectious disease, parasitic disease, collagen vascular diseases, pulmonary disease, and neoplastic disorders were excluded. Therefore, a diagnosis of chronic eosinophilic leukemia was made. The patient had no symptoms of hypereosinophilia. However, eosinophils with sparse granulation, positivity for CD25, elevated serum levels of soluble IL-2 receptor, and elevated serum levels of eosinophil cationic protein suggested activation of eosinophils. Further analysis is needed regarding the activation of eosinophils in chronic eosinophilic leukemia.

Aged↗

PubMed2002

[Successful treatment with fludarabine of chronic lymphocytic leukemia associated with nephrotic syndrome].

We successfully treated a patient with chronic lymphocytic leukemia (CLL) associated with a nephrotic syndrome. An 82-year-old man had been diagnosed as having CLL and been under observation for a year without treatment. In January, 2001, he developed hypoprotenemia, proteinurea, and edema in the extremities and face. With the exacerbation of the symptoms, he was admitted to our hospital in March of the same year. Under the diagnosis of nephrotic syndrome with CLL, the patient underwent induction therapy for CLL with fludarabine (13 mg/m2/day for 4 days), which brought about a complete remission of CLL and the disappearance of the edema. To our knowledge, this was the first case in Japan where fludarabine was dramatically effective in treating both CLL and the nephrotic syndrome. This result indicated that fludarabine is beneficial for not only CLL but also complications like nephrotic syndrome.

Aged↗

PubMed2002

[Airway hyperreactivity in patients undergoing hematopoietic stem cell transplantation].

Airway hyperreactivity (AHR) was studied with an astograph for 34 sequential hematopoietic stem cell transplantation (HSCT) patients before and after HSCT. The percentage of Dmin positive patients was 25.0% before HSCT and 25.0-57.1% after HSCT, while all normal subjects were negative for Dmin. The mean Dmin of post HSCT patients was 22.7 u in days 501-1000 and 19.3 u after 1001 days, which was significantly lower than the 45.2 u of normal controls. The patients were divided into two groups according to the treatment before HSCT, strongly treated (S, acute leukemia and non-Hodgikin lymphoma) and weakly treated (W, chronic myelogenous leukemia and aplastic anemia) patients. The ratio of Dmin positive patients and mean Dmin in the W group after HSCT (38.9%, 27.8 u), and the S group before and after HSCT (55.6%, 20.5 u and 45.5%, 23.8 u, respectively), were significantly impaired compared with the findings in the normal controls (0%, 45.2 u). The mean sGrs/Grs count was higher in the W group before HSCT than in the other groups (W before and after HSCT, 0.58 and 0.19, respectively; S before and after HSCT, 0.21 and 0.22, respectively). Taken together, AHR was observed in HSCT patients, particularly for patients in the S group. These data indicate that high dose chemo-radiotherapy including conditioning regimen causes AHR. The mechanisms leading to AHR may be infection, inflammation, and remodeling of the airway.

Adolescent↗

PubMed2002

[Clinical usefulness of a cardiopulmonary sleep study in patients with sleep apnea syndrome].

Although polysomnography is indispensable in the diagnosis of sleep apnea syndrome (SAS), a common disease in Japan, it is a time-consuming procedure. We therefore assessed the clinical usefulness of a cardiopulmonary sleep study (CPSS), which monitors indices of respiratory and circulatory kinetics during sleep. Of ninety male patients (50 +/- 11 years old, BMI: 27 +/- 4), those with apnea indices (AI) > 5, as determined using an apnomonitor, underwent CPSS with a Night Watch System. Sixty-nine patients with indications for nasal CPAP (NCPAP) therapy underwent overnight CPSS and the optimum pressure was determined. AI was 31 +/- 17, whereas CPSS showed an apnea-hypopnea index of 49 +/- 24, a mean SaO2 of 93 +/- 3%, and a minimum SaO2 of 71 +/- 11%, indicating severe OSAS. The mean optimum pressure was 10 +/- 2 cm H2O, and the compliance was 86%, which was comparatively good. As CPSS can be performed on many patients in a short time, it may be useful for the early diagnosis and initial treatment of SAS.

Adult↗