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Biomedical subjects

Tomonobu Koizumi

Publications and source records attributed to Tomonobu Koizumi.

At least 19 recordsLinked to original sources
PubMed2006

IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement.

A 71-year-old man was admitted with malaise, mild fever, anorexia, body weight loss, lower back pain, thirst, and polydipsia. He showed bilateral swelling of the submandibular glands. Examinations showed panhypopituitarism and a high serum IgG4 concentration. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed uptake in the pituitary gland, bilateral submandibular gland, bilateral hilar and mediastinal lymph nodes, and a mass consistent with retroperitoneal fibrosis, but not in the pancreas. Biopsy specimens from the submandibular gland and retroperitoneal mass indicated sialadenitis and retroperitoneal fibrosis respectively, and showed severe fibrosis and inflammation with marked lymphoplasmacytic infiltration and IgG4-positive plasma cell infiltration. Hormone replacement therapy with hydrocortisone resulted in marked clinical improvement. Systemic involvement found in this patient possibly corresponded to the new concept of IgG4-associated multifocal systemic fibrosis.

Aged↗
PubMed2006

Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110alpha inhibitors.

3-{1-[(4-Fluorophenyl)sulfonyl]-1H-pyrazol-3-yl}-2-methylimidazo[1,2-a]pyridine, 2a, was discovered in our chemical library as a novel p110alpha inhibitor with an IC(50) of 0.67microM, through screening in a scintillation proximity assay. Optimization of the substituents of 2a increased the p110alpha inhibitory activity by more than 300-fold (2g: IC(50)=0.0018microM). Further structural modification of 2g afforded thiazole derivative 12, which has potent p110alpha inhibitory activity (IC(50) of 0.0028microM) and is highly selective for p110alpha over other PI3K isoforms. Compound 12 also inhibited serum-induced cell proliferation of A375 and HeLa cells in vitro with IC(50) values of 0.14microM and 0.21microM, respectively, and suppressed tumor growth by 37% in a mouse HeLa xenograft model when dosed intraperitoneally at 25mg/kg. These results suggest that selective p110alpha inhibitors may have potential as cancer therapeutic agents.

Animals↗
PubMed2006

Angiosarcoma with sacral origin metastasizing to the lung.

A 73-year-old man with fever, lumbago and hemosputum showed ground-glass opacity around multiple lung nodules on chest computed tomography. Examination of the man revealed anemia. Specimens obtained by video-assisted thoracic surgery revealed angiosarcoma, but the primary site of angiosarcoma could not be detected before autopsy. Angiosarcoma is a rare malignant neoplasm with rapid proliferation and they can arise at any region of the body. It can originate in the skin, soft tissue, liver or heart. Their multicentric and local recurrence easily leads us to misdiagnosis, and we have struggled to reach diagnosis and its origin. Angiosarcoma should be included in the different diagnosis of diffuse pulmonary hemorrhage with multiple lung nodules.

Aged↗
PubMed2006

Characteristics of asthma resistant to moderate dose inhaled corticosteroid treatment on bronchial hyperresponsiveness.

OBJECT: This study was performed to determine the clinical characteristics of asthmatics with bronchial hyperresponsiveness (BHR) that could not be normalized by 6 months of treatment with a moderate dose of an inhaled corticosteroid (ICS). METHODS: Thirty-four symptomatic patients with mild to moderate asthma, who had never received any ICS, were treated with 200 mug of inhaled fluticasone propionate twice a day for 6 months. Spirometry, BHR to methacholine, exhaled nitric oxide (NO) and eosinophils in induced sputum were examined before and 2 and 6 months after beginning treatment. RESULTS: FEV1 was increased and bronchial responsiveness, exhaled NO and sputum eosinophilia were significantly decreased 2 and 6 months after starting ICS treatment. Bronchial responsiveness was further decreased at 6 months together with a further increase in FEV1. In 13 patients, BHR was not normalized despite the 6 months of treatment. This group showed a higher prevalence of males, those with a smoking history and airflow limitation, a higher eosinophil count in the sputum following 6 months of treatment and a longer history of asthma. Multiple, stepwise, linear regression analysis showed that sputum eosinophilia and lower FEV1/FVC following 6 months of treatment and a longer history of asthma were significant independent determinants for BHR after 6 months of ICS treatment. CONCLUSIONS: These findings suggest that the resistance to a moderate dose of ICS for BHR in asthmatics may be significantly associated with remained airflow limitation, eosinophilic airway inflammation resistive to moderate dose of ICS, and delayed introduction of ICS therapy.

Administration, Inhalation↗
PubMed2006

Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110alpha inhibitors.

A series of 4-morpholino-2-phenylquinazolines and related derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. In this series, the thieno[3,2-d]pyrimidine derivative 15e showed the strongest inhibitory activity against p110alpha, with an IC(50) value of 2.0 nM, and inhibited proliferation of A375 melanoma cells with an IC(50) value of 0.58 microM. Moreover, 15e was found to be selective for p110alpha over other PI3K isoforms and protein kinases, making it the first example of a selective PI3K p110alpha inhibitor.

Animals↗
PubMed2006

Hypersensitivity pneumonitis induced by spores of Penicillium citrinum in a worker cultivating Enoki mushroom.

A 47-year-old Japanese woman was admitted to our hospital with a 2-week history of dry cough and shortness of breath. She had been engaged in Enoki mushroom production for 22 years. Chest X-ray and chest computed tomography (CT) scan showed bilateral fine-nodular shadows and ground glass opacity. Bronchoalveolar lavage fluid demonstrated an increase of total cell counts with predominant lymphocytosis. Pathological specimens obtained by video-assisted thoracoscopic surgery revealed alveolitis and noncaseating granuloma with giant cells. Lymphocyte stimulation test showed positive responses with Enoki mushroom, culture medium, and Penicillium citrinum. On double immunodiffusion test, a precipitation line was observed between patient's serum and Penicillium citrinum antigen. She was found to have hypersensitivity pneumonitis caused by Penicillium citrinum. This is the first report of mushroom worker's lung caused by Penicillium citrinum.

Agaricales↗
PubMed2006

Usefulness of preoperative endobronchial ultrasound for airway invasion around the trachea: esophageal cancer and thyroid cancer.

BACKGROUND: It is important to confirm preoperative tracheobronchial invasion to enable the selection of the most appropriate treatment. OBJECTIVE: This study was performed to compare the usefulness of computed tomography (CT), magnetic resonance image (MRI) and bronchoscopy by endobronchial ultrasonography (EBUS) for the assessment of invasion of thyroid or esophageal cancer in cases with suspected tracheobronchial invasion. METHODS: In cases with suspected contact between the tumor and tracheobronchial wall, CT, MRI and EBUS indicated deformity of the tracheobronchial wall due to the adjacent mass. The final diagnosis was based on surgical and histological results, and/or clinical follow-up. RESULTS: Fifty-four patients were included in this study. Based on the findings of CT, MRI and EBUS, invasion was suspected in 29, 28 and 25 patients, respectively. Seventeen patients did not undergo surgery based on the results of CT, MRI and bronchoscopy with EBUS. Final diagnosis was intact trachea or bronchial adventitia in 26 patients and invasion in 28 patients. The sensitivity and specificity of CT, MRI and EBUS for invasion were 59 and 56, 75 and 73, and 92 and 83%, respectively. The accuracy of EBUS was significantly greater than that of CT in the present study (p = 0.0011). The accuracy of EBUS was significantly different from that of CT and MRI in the surgically treated patients (p = 0.005 and p = 0.032, respectively). CONCLUSION: EBUS is the most useful technique for determining the depth and extent of tumor invasion into the airway wall. The combination of MRI and EBUS will contribute to surgical planning in patients with esophageal and thyroid cancer.

Adult↗
PubMed2006

Polymyxin B immobilized column is effective for hydrochloric acid-induced lung injury in rats.

The purpose of this study was to examine whether hemoperfusion using polymyxin B (PMX) immobilized column improves hydrochloric acid (HCl)-induced lung injury. Rats weighing 350 g underwent hemoperfusion for 30 min at a flow rate of 120 ml/h after the intratracheal instillation of hydrochloric acid or water. Rats were divided into those that underwent hemoperfusion, with or without polymyxin B column, 30 min after HCl instillation ("HCl+PMX" and "HCl"), and hemoperfusion with or without polymyxin B column 30 min after water instillation ("Aqua+PMX" and "Aqua"). Systolic blood pressure, arterial blood gas analysis and white blood cell count and neutrophils were measured before, 1 and 3h after hemoperfusion. Plasma and bronchoalveolar lavage fluid concentrations of growth-related oncogene/cytokine-induced neutrophils chemoattractant-1 (GRO/CINC-1) were measured at 1 and 3h after hemoperfusion. Arterial oxygen concentrations were higher in the "HCl+PMX" group than in the "HCl" group. The total numbers of cells and neutrophils in the bronchoalveolar lavage fluid were significantly higher in the "HCl" group than in the others. The GRO/CINC-1 concentrations in the plasma and bronchoalveolar lavage fluid and the albumin ratio in the "HCl+PMX" group were significantly lower than in the "HCl" group. Direct hemoperfusion using polymyxin B immobilized column treatment affects the recruitment of circulating neutrophils to the lungs due to the decrease in mediators for non-endotoxic lung injury.

Animals↗
PubMed2006

Clinical differences in the Global Initiative for Chronic Obstructive Lung Disease Stage 0.

This study was to examine the clinical differences between Stage 0 and normal subjects, using low-dose chest computed tomography (CT) and pulmonary function tests. Enrolled subjects performed as a health check for lung cancer screening including low-dose CT and pulmonary function tests. Subjects were divided into Stage 0, chronic obstructive pulmonary disease according to pulmonary function tests, and normal subjects. The severity of emphysema (visual score) was calculated on three low-dose CT slices. Low-dose CT and pulmonary function tests were performed in 1359 men and 888 women. The numbers and percentages of men and women smokers were 1076 (79.2%), and 107 (12.0%), respectively. A total of 722 individuals had one or more respiratory symptoms, such as cough (69.8%), sputum (75.8%), or shortness of breathing (0.83%). Of the 722 subjects, 71 (9.8%) individuals satisfied the criteria of chronic respiratory symptoms. Among the normal subjects, smoking caused differences in airflow limitation as a result of pulmonary function tests. The proportion of smokers and the visual score were significantly higher in Stage 0 than those in the normal subjects. The percentages of the maximal mid-expiratory flow (%MMF) and of the peak expiratory flow rate were significantly lower in Stage 0 than in the normal subjects. %MMF and the proportion of visual score were significantly lower in the smoking Stage 0 than in the nonsmoking Stage 0 subjects. Smoking would indicate early signs of emphysematous change between Stage 0 and normal subjects in comparison of pulmonary function tests and visual score of low-dose CT.

Female↗
PubMed2006

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji).

BACKGROUND: Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. METHODS: Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. RESULTS: Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. CONCLUSIONS: Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

Agaricales↗
PubMed2006

[A case of multiple lung abscesses successfully treated with computed tomography guided percutaneous thoracic drainage].

A 48-year-old woman who had abused alcohol admitted to our hospital because of fever and chest pain. Laboratory data presented inflammation and liver dysfunction. Chest X-ray films revealed multiple mass lesions with air fluid levels. We diagnosed multiple lung abscesses and started treatment with antibiotics. However, her fever did not improve and mass lesions increased. On day 6 of hospitalization, three drainage tubes were inserted percutaneously into the mass lesions under computed tomography (CT) guidance, and alpha-hemolytic streptococcus, peptostreptococcus sp. and neutrophils were isolated from the drainage fluid. Abcesses and inflammation were improved by administration of the antibiotics selected according to the result of fluid culture. Because all multiple abcesses were located near the pleura, we successfully treated them with simultaneous percutaneus thoracic drainage.

Drainage↗
PubMed2006

[A case of hyponatremia associated with combination therapy of systemic chemotherapy and paroxetine].

A 65-year-old woman with relapsed non small cell lung cancer, who had no prior chemotherapy, was admitted to our hospital. She was initially treated with paroxetine, a selective serotonin-reuptake inhibitor antidepressant, and received cisplatin-based chemotherapy three days after the initiation of the paroxetine. She developed hyponatremia on day 5 after the start of chemotherapy. Based on the laboratory examinations, the syndrome of inappropriate secretion of antiduretic hormone was suggested. Her plasma sodium concentration returned to normal after paroxetine withdrawal and appropriate fluid restriction. Cisplatin-based chemotherapies were subsequently continued without paroxetine and there were no further episodes of electrolyte disturbance. Paroxetine has been used widely for treatment of depressed patients with malignancies. However, careful monitoring of plasma sodium is needed following cisplatin-based chemotherapy in patients taking paroxetine.

Aged↗
PubMed2006

[Successful treatment of intrapericardial administration of carboplatin following systemic chemotherapy in a case of advanced thymic cancer with cardiac tamponade].

A 72-year-old woman developed cardiac tamponade due to direct invasion of thymic cancer. Carboplatin was administered into the pericardial cavity two times with a total dose of 600 mg. Pericardial effusion disappeared without any toxicities. Following four cycles of systemic chemotherapy by carboplatin, doxorubicin, vincristine, cyclophosphamide (ADOC), partial response was obtained. She is alive 10 month after being given a diagnosis of cardiac tamponade. Intrapericardial administration of carboplatin is a useful therapy for control of pericardial effusion and chemosensitive cases should de identified among patients with thymic cancer.

Aged↗
PubMed2005

Reduced lung uptake of iodine-123 metaiodobenzylguanidine in patients with myeloperoxidase antineutrophil cytoplasmic antibodies-positive vasculitis.

BACKGROUND: Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) lung uptake in the early phase has been proposed as a potential marker of endothelial function because MIBG behaves qualitatively similarly to norepinephrine in pulmonary circulation. OBJECTIVES: The purpose of the present study was to examine the lung uptake of (123)I-MIBG in patients diagnosed with myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis without clinical or radiological abnormalities of the thorax. METHODS: Six patients with MPO-ANCA-associated vasculitis were enrolled. They had severe renal damage (mean creatinine: 5.1 mg/dl, mean blood urea nitrogen: 54.6 mg/dl), but no respiratory symptoms clinically or radiographic findings on chest computed tomography. The total lung to upper mediastinum ratio of (123)I-MIBG uptake (L/M) 15 min after the injection was measured. The result was compared with those for 6 patients with renal damage due to other diseases (mean creatinine: 6.2 mg/dl, blood urea nitrogen: 51.7 mg/dl) and for 8 healthy subjects. RESULTS: The mean value of L/M in patients with MPO-ANCA-positive vasculitis was 1.21 +/- 0.04, which was significantly less than that of other groups (1.41 +/- 0.06 for patients with renal failure and 1.45 +/- 0.03 for normal volunteers). There were no significant differences in MIBG accumulation in the heart among the groups. CONCLUSIONS: The reduction in kinetic behavior of MIBG in the lung reflects the presence of pulmonary endothelial impairment in patients with MPO-ANCA-associated vasculitis, even though there are no clinical manifestations in the lungs.

3-Iodobenzylguanidine↗
PubMed2005

Hypersensitivity pneumonitis due to Bunashimeji mushrooms in the mushroom industry.

BACKGROUND: Detection of hypersensitivity pneumonitis (HP) in employees involved in the Bunashimeji mushroom industry is difficult. The level of precipitating antibody is not related with the prediction of progression and resolution of HP. The aims of this study were to examine the actual prevalence of HP in the Bunashimeji industry and the clinical differences among selected employees. METHODS: One hundred and fourteen employees worked in Bunashimeji enterprises. These subjects were divided into the following subgroups: office workers, pickers/packers with mask and pickers/packers without mask. We measured serum Krebs von der Lungen-6 (KL-6), surfactant protein (SP)-A and SP-D, and examined the stimulation index (SI) due to Bunashimeji spores. Chest high-resolution computed tomography (HRCT), pulmonary function tests and bronchoalveolar lavage (BAL) were performed for select employees who showed positive SI values (>200%) to examine the clinical differences. RESULTS: The proportion of respiratory symptoms was significantly higher in the pickers/packers than that in the office workers. The picker/packer group had high serum KL-6 concentrations and SI compared with the office worker group. Thirty select employees were divided into the following three subgroups: HP, select employees without HP, and SI <400% and KL-6 <500 U/ml , using high SI levels (>400%) and positive serum KL-6 concentration (>500 U/ml). Four exhibited ground glass opacities with centrilobular fine nodules on HRCT, and 8 had high numbers of lymphocytes in the BAL fluid. The BAL findings and serum KL-6 concentrations showed significant differences among the three groups. CONCLUSIONS: Four employees were evaluated as having HP. Serum KL-6 and SP-D may be related to the resolution of HP in addition to SI and chest HRCT.

Agaricales↗
PubMed2005

Comparison of cardiopulmonary response to endogenous nitric oxide inhibition in pigs inhabited at three levels of altitude.

Nitric oxide (NO) plays an important role for the pulmonary circulation in normal and chronic hypoxia. We examined effects of endogenous nitric oxide synthase (NOS) inhibition on pulmonary and systemic vascular resistance in unanesthetized pigs living at three levels of altitude to evaluate the role of NO in adaptation to a hypoxic environment. Unanesthetized male adult pigs in three areas [Matsumoto, Japan (680 m above sea level, n = 5); Xing, China (2,300 m, n = 5); and Maxin, China (3,750 m, n = 5)] were prepared for vascular monitoring. Pulmonary (P(pa)), and systemic artery pressure (P(sa)) were monitored, and pulmonary artery wedge pressure (P(cwp)) and cardiac output (CO) were measured before and after treatment with a non-selective NOS inhibitor, N(w)-nitro-L-argine (NLA; 20 mg/kg). Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were (P(pa)-P(cwp))/CO and P(sa)/CO, respectively. Related to altitude baseline P(pa) was elevated. After NLA administration, P(pa) and P(sa) increased and CO decreased in all animals, resulting in increases in PVR and SVR. However, there were no significant differences in the increase in PVR and SVR in the three groups of pigs. Thus, endogenous NO production contributes to regulate the basal pulmonary vascular tone, but the development of hypoxic pulmonary hypertension appears to be independent of the NO pathway in adult pigs.

Acclimatization↗
PubMed2005

Effects of nitric oxide synthase inhibitor on acid aspiration-induced lung injury in rats.

The current study was designed to determine the effects of nitric oxide synthase (NOS) in the development of acid aspiration-induced lung injury in rats. Hydrochloric acid (HCl, 0.1 N; 2 ml/kg) or normal saline (NS, 2 ml/kg) was instilled into the lung of anesthetized, ventilated Sprague-Dawley rats. NG-monomethyl-L-arginine (L-NMMA, 20 mg kg(-1)) and a selective inducible nitric oxide synthase (iNOS) inhibitor, ONO-1714 (0.1 and 0.3 mg kg(-1)), were used to block NOS. Bronchoalveolar lavage fluid (BALF) and wet and dry measurements of lung (W/D) were obtained 5h after HCl or NS instillation. Unlike the control group, rats instilled with HCl showed significant increases in total nuclear cell counts (NCC), neutrophil counts, concentrations of albumin, tumor necrosis factor-alpha (TNF-alpha), interleukine-6 (IL-6) and nitrites/nitrates (NO(x)) in BALF. These parameters were associated with the significantly increased W/D in the HCl group compared with the NS group. ONO-1714 (0.1 mg kg(-1)) significantly prevented the increases in all these parameters. Its inhibitory effects were superior to those of L-NMMA and 0.3 mg kg(-1) of ONO-1714. NOS plays an important role in the pathogenesis of acid aspiration-induced lung injury. Furthermore, selective iNOS inhibition at the optimal dose was most effective in improving lung injury induced by acid aspiration in rats.

Amidines↗