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Biomedical subjects

Yoshinosuke Fukuchi

Publications and source records attributed to Yoshinosuke Fukuchi.

At least 37 records · Page 2Linked to original sources

[Measurement of diffusing capacity by the intrabreath method].

The diffusing capacity of the lung for carbon monoxide (DLco) is usually measured by the single breath method with a 10-second breath hold. With the introduction of rapid gas analyzers, an alternative method for measurement of DLco, the intrabreath method, has been developed. The intrabreath method does not depend upon length of time or other conditions during either breath holding or expiration. The aim of this study was to compare the single breath method and intrabreath method of DLco measurement. DLco measured by the intrabreath method (DLco IB) was compared with DLco measured by the single breath method (DLco SB) in 32 normal subjects, 88 patients with obstructive impairment and 39 patients with restrictive impairment. DLco SB could not be measured in 2 patients with obstructive impairment and 7 patients with restrictive impairment, while in all except one patient with severe restrictive impairment, DLco IB was able to be measured. There was an excellent correlation between DLco IB and DLco SB in normal subjects (rho = 0.942, p < 0.0001). There was no difference in the mean value between DLco IB (21.0 +/- 5.4 ml/min/mmHg) and DLco SB (20.9 +/- 4.9 ml/min/mmHg). In the obstructive impairment group there was also an excellent correlation between DLco IB and DLco SB (rho = 0.922, p < 0.0001). In the mild or moderate obstructive impairment group (%FEV1 > 50%), no difference between DLco IB (11.8 +/- 5.80 ml/min/mmHg) and DLco SB (12.4 +/- 4.68 ml/min/mmHg) was found. In the severe obstructive impairment group (%FEV1 < 50%), the DLco IB (7.29 +/- 3.61 ml/min/mmHg) was lower than the DLco SB (8.58 +/- 3.24 ml/min/mmHg) (p < 0.0001). The relation between DLco SB and DLco IB was equally strong in patients with restrictive impairment (rho = 0.742, p < 0.0001). There was an excellent correlation between DLco IB and DLco SB in normal subjects, the obstructive impairment group and the restrictive impairment group. The intrabreath method therefore seems to be a useful and reliable alternative to the single breath method for clinical measurement of DLco.

Aged↗

[An elderly case of sarcoidosis with multiple pulmonary cysts].

We report an elderly case of sarcoidosis with multiple pulmonary cysts. An 80-year-old woman was admitted to our hospital for detailed examinations of multiple cysts in both lungs. Chest radiography and chest CT revealed multiple cystic lesions with thin walls which were clearly separated from normal lung. A transbronchial lung biopsy revealed epitheloid cell granuloma, indicating sarcoidosis. Although elderly cases of sarcoidosis with multiple pulmonary cysts are very rare, sarcoidosis should be considered in the differential diagnosis.

Aged↗

An early case of pulmonary lymphangioleiomyomatosis diagnosed by video-assisted thoracoscopic surgery.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare and progressive disease of young women that usually causes death from respiratory failure. Here we report an early case that was diagnosed by thoracoscopy. A 28-year-old woman presented to a local clinic with chest pain and her chest X-ray film showed left pneumothorax. After placement of a chest tube, the lung re-expanded fully. Following the recurrence of left pneumothorax, she was referred to our hospital and underwent video-assisted thoracoscopic surgery (VATS). However, left pneumothorax recurred again one month later. She underwent a second thoracoscopic operation, during which a bulla was recognized in the lingular segment of the left lung and was resected. On histological examination of the surgical specimen findings consistent with LAM were obtained. Taking the preoperative imaging findings and the thoracoscopic findings into consideration, a diagnosis of early lymphangioleiomyomatosis was made. Thoracoscopic management of pneumothorax in young women can facilitate the early diagnosis of this condition.

Adult↗

Osteopontin is strongly expressed by alveolar macrophages in the lungs of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by an intense inflammatory response in the lung parenchyma. Recent studies suggest that excessive nitric oxide (NO) production mediated by inducible NO synthase (iNOS) in macrophages is partially involved in mediating acute lung injury in ARDS. On the other hand, osteopontin (OPN) is a cytokine which is capable of inhibiting NO production by suppressing iNOS mRNA expression in macrophages. In this study, we investigated the expression of OPN in the lungs of 10 patients with ARDS. In most patients, OPN is strongly expressed on alveolar macrophages. In addition, we produced a murine model for ARDS by intratracheal administration of lipopolysaccharide and investigated the expression of endogenous OPN and iNOS in the lungs of ARDS mice. Immunostaining demonstrated that in vivo OPN protein was coinduced with iNOS protein predominantly in the accumulating alveolar macrophages. OPN mRNA expression was also coinduced with iNOS mRNA, but was induced more slowly than iNOS mRNA in the lungs of ARDS mice. These results suggested that OPN, which may reduce NO production of macrophages by inhibiting iNOS expression, is significantly induced and expressed on alveolar macrophages in the lungs of ARDS. It is possible that OPN is partially involved in playing a protective role against excessive production of NO in ARDS.

Adult↗

Hypoxia and hypercapnia affect contractile and histological properties of rat diaphragm and hind limb muscles.

The effects of hypoxia and hypercapnia on contractile and histological properties of the diaphragm and skeletal muscles of the hind limb were examined. Eight-week-old male Sprague-Dawley rats ( [Formula: see text] ) were kept in hypobaric hypoxic ( [Formula: see text] ) or hypercapnic ( [Formula: see text] ) chambers for 6 weeks, and compared with the control rats (room air, [Formula: see text] ). Contractile properties were evaluated with twitch kinetics, force-frequency curve and fatigue tolerance. After the experiments on contractile activities, muscles were fixed for histological examination with ATPase staining. It was demonstrated that peak twitch tension of diaphragm decreased with no significant histological changes under hypoxic conditions while significant contractile and histological changes were observed under hypercapnic conditions. Skeletal muscles of the hind limbs were affected also under hypoxic and hypercapnic conditions but the profiles of the changes in contraction and histology were different from those of the diaphragm. These results suggest that hypoxia and hypercapnia affect differently on contractile and histological properties of respiratory and hind limb muscles. Furthermore, when we consider the conditions involved in chronic obstructive respiratory disease (COPD; both hypoxia and hypercapnia are deeply involved), our results indicate that COPD should be regarded as a systemic disorder rather than a respiratory disease.

Journal Article↗

A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD.

A large-scale prospective study was conducted in 3810 Japanese elderly (> or =65 years old) patients with asthma or chronic obstructive pulmonary disease (COPD) who had been treated with sustained-release theophylline tablets (THEODUR) at a dose of 400 mg/day for 1-6 months, in principle. Among 3798 protocol-complying patients (mean age: 73.8 +/- 0.10 years, 1997 with COPD), 261 theophylline-related adverse events were observed in 179 (4.71%) patients. The 5 most frequently observed adverse events were "nausea" (40 episodes, 1.05%), "loss of appetite" (22 episodes, 0.56%), "hyperuricemia" (16 episodes, 0.42%), "palpitation" (15 episodes, 0.39%), and "increased alkaline phosphatase" (11 episodes, 0.28%). No convulsions were reported. Six patients had serious adverse events. The incidence of theophylline-related adverse events was higher in patients with hepatic disease (odds ratio: 1:1.81) and in patients with arrhythmia (odds ratio: 1:1.88). Blood drug concentration measurements in 736 patients indicated that the drug levels were < or =15 microg/ml in 641 patients (87.1%), and no correlation was noted between dose and theophylline-related adverse events. These results suggest that sustained-release theophylline can be used safely in elderly patients with asthma or COPD.

Aged↗

Lymphangiogenesis in lymphangioleiomyomatosis: its implication in the progression of lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the lungs, lymph nodes, and/or other organs. We examined lymphangiogenesis using immunohistochemistry for Flt-4 (VEGFR-3), a new specific marker for lymphatic endothelial cells, as well as the expression of vascular endothelial growth factor (VEGF)-C in LAM. Specimens were obtained from 6 autopsy cases, a single lung transplant case, and 8 surgical cases for analyses. We demonstrated that lymphatics were extremely abundant in both pulmonary and extrapulmonary LAM and that lymphatic endothelial cells not only proliferated encompassing LAM foci but also infiltrated the intra-LAM foci, and that in advanced LAM, lymphangiogenesis involved vascular walls and interstitium surrounding the area where LAM cells proliferate. In contrast, angiogenesis, confirmed with CD31 immunostaining, was observed less in the LAM foci. LAM cells demonstrated positive reactivity against anti-VEGF-C antibody at varying intensities. Significant correlation (P < 0.001) was noted between the degree of lymphangiogenesis in LAM or VEGF-C expression on LAM cells and lymphagioleiomyomatosis histologic score (LHS), which represents the histologic severity of pulmonary LAM and has been reported to have prognostic significance. Our study is likely to provide a novel point of view on the pathophysiologic significance of lymphangiogenesis in LAM.

Adult↗

Senescence marker protein-30 knockout mouse as a novel murine model of senile lung.

Senescence marker protein-30 (SMP30) was originally identified as a novel protein of which expression decreases in an androgen-independent manner with aging in the rat liver and functions to protect cells from apoptosis. By reverse transcription-polymerase chain reaction analysis, SMP30 mRNA transcripts were found in the mouse lung, liver, kidney, testis and cerebrum. We examined SMP30 expression in the mouse liver, kidney and lung during aging and a distinct temporal profile of SMP30 expression was found in each tissue; the SMP30 mRNA level peaked at 1-3 months of age and decreased thereafter in the liver (the highest at 1 month of age followed by a rapid decline and consistently low thereafter in the kidney), and peaked at 12 months of age in the lung. To investigate the physiological role of SMP30 in the lung, immunohistochemical studies of wild-type (SMP30Y/+) mice and histopathological examinations of SMP30 knockout (SMP30Y/-) mice were performed. Immunoreactivity against anti-SMP30 antibody was mainly detected in bronchial epithelial cells and strongly detected at 6-12 months of age. Morphometric analysis was performed to measure the mean linear intercept and destructive index, and found peripheral airspace enlargement without alveolar destruction in SMP30Y/- mice at 1, 3 and 6 months of age compared with the SMP30Y/+ mice. Our results strongly suggest that SMP30Y/- mice could be a novel model for a senile lung and further examinations of SMP30Y/- mice may offer clues to elucidate the mechanisms of the development of pulmonary diseases in the elderly.

Aging↗

Adult-onset familial pulmonary fibrosis in Japanese brothers.

Two Japanese brothers were diagnosed in their 20s with familial pulmonary fibrosis, the pathological findings of which were consistent with usual interstitial pneumonia (UIP). However, an atypical characteristic was observed in the lungs of these brothers; 2-mm areas of 'honeycomb' were identified throughout the lungs, which is smaller than the generally observed 5-10 mm honeycombing seen in UIP. Fibroblastic foci were demonstrated in the second eldest brother, but not in the eldest, which indicates that the lungs of the eldest brother was in a more advanced stage of fibrosis. Their youngest brother and parents have no clinical evidence of pulmonary fibrosis. All five family members had low values for the diffusion capacity of the lung for carbon monoxide (DLCO), suggesting the presence of an inheritable disease and the existence of different phenotypes. The genomic DNA of the affected brothers was sequenced for the reported surfactant protein C (SP-C) gene mutations in patients with familial pulmonary fibrosis, but none was documented. It is necessary to clarify the presence of novel gene mutations of SP-C or other genes to explain these particular pathological findings and the low DLCO observed in this family.

Adult↗

Inflammatory response and cathepsins in silica-exposed Hermansky-Pudlak syndrome model pale ear mice.

Hermansky-Pudlak syndrome (HPS) is a hereditary disorder involving the sorting processes of intracellular organelles such as lysosomes of reticuloendothelial cells. Pale ear (ep) mouse is known to have the HPS1 gene mutation, which is seen in patients with HPS and pulmonary fibrosis. As pulmonary fibrosis is not spontaneously observed in ep mice, we hypothesized that external stimuli are necessary for the genetic predisposition of its development. We used silica as the external stimulus to induce the alveolar macrophage-mediated inflammatory response and evaluated the pathological changes of the lung and biochemical analysis of collagenolytic lysosomal enzymes cathepsins L and B in ep mice. Treatment with silica induced the following: persistent accumulation of activated macrophages; delayed clearance of silica from alveolar spaces; and increased collagen fibers in alveolar tissues, which were shown with trichrome staining in ep mice. The comparison of bronchoalveolar lavage cells between the naïve ep and control mice revealed: decreased enzymatic activities but increased antigenic levels of cathepsins L and B, resulting in significantly lower ratios of activity to antigen; increased ceroid deposits and cathepsin L antigens in lysosomes; and no abnormal forms of cathepsins were detected. After silica instillation, activities of cathepsin L in the ep mice increased but ratios of activity to antigen were still significantly low. These phenomena induced by silica suggest that external stimuli bring forth fibrogenesis in the animal models or humans that have HPS1 gene mutation.

Animals↗

Pancoast's syndrome in a patient with B-cell lymphoma diagnosed and confirmed with immunoglobulin gene rearrangement.

Pancoast's syndrome due to malignant lymphoma is extremely rare. A case of diffuse large B-cell lymphoma presenting as Pancoast's syndrome is described. A 66-year-old man complained of pain and weakness of the right arm, and CXR revealed a right apical lung tumour. Histological findings were consistent with it being a diffuse large cell type lymphoma and Southern blot analysis revealed clonal rearrangement of the immunoglobulin heavy-chain JH. Thus, the tumour in this patient was diagnosed to be diffuse large B-cell lymphoma. Malignant lymphoma is an extremely rare cause of Pancoast's syndrome and only five cases have been described. This is the first reported case of Pancoast's syndrome caused by B-cell lymphoma, which was accurately diagnosed by analysis of gene rearrangement.

Aged↗

COPD in Japan: the Nippon COPD Epidemiology study.

OBJECTIVES: Despite high smoking rates, few prevalence studies of COPD have been performed in Asia. The Nippon COPD Epidemiology (NICE) Study used spirometry to measure prevalence of airflow limitation in Japanese adults. METHODOLOGY: Clinical, spirometric, and risk factor exposure data were collected on 2343 subjects aged > or = 40 years who were demographically similar to the Japanese population. Airflow limitation was defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC < 70%). RESULTS: Prevalence of airflow limitation was 10.9%. Based upon GOLD severity criteria, 56% of these cases were found to be mild, 38% moderate, 5% severe, and 1% very severe. Airflow limitation was significantly more prevalent in males than females (16.4% vs. 5.0%; P < 0.001), in male ever-smokers than female ever-smokers (17.1% vs. 7.5%; P < 0.001), and in older subjects (3.5% in 40-49 years olds vs. 24.4% in those > 70 years; P < 0.001). Of note, airflow limitation was also found in 5.8% of non-smokers and 4.6% of those younger than age 60 years. Only 9.4% of cases with airflow limitation reported a previous diagnosis of COPD. CONCLUSIONS: Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.

Adult↗

[A case of primary squamous cell carcinoma of the lung with a metastatic thyroid tumor improved following chemotherapy].

Metastatic thyroid tumor is rarely diagnosed clinically. We report here a case of a 59-year-old male of a primary squamous cell carcinoma of the lung with metastatic thyroid tumor diagnosed by an ultrasonography-guided aspiration cytology. A squamous cell carcinoma of the lung (c-T4N3M1 stage IV) was diagnosed in March 2001, and so chemotherapy using carboplatin and paclitaxel was tried initially. A partial response was obtained. Then, he was re-admitted to our hospital because his thyroid gland was swollen. Ultrasonography-guided aspiration cytology of the thyroid tumor was performed and revealed a metastatic squamous cell carcinoma from the lung cancer. The patient was given chemotherapy using gemcitabine and docetaxel as second line chemotherapy. This reduced the thyroid tumor size and improved the symptoms.

Antimetabolites, Antineoplastic↗

[A case of organizing pneumonia associated with myelodysplastic syndrome (MDS)].

A 53-year-old man was referred to our hospital because of atypical cells in the peripheral blood. Myelodysplastic syndrome (MDS) was diagnosed by bone marrow examination. Since he had a continuous dry cough, high fever, and air space consolidation in both lower lung fields, he was admitted to our hospital for further examination. Infectious disease, autoimmune disease, vasculitis and neoplasms were excluded. A transbronchial lung biopsy (TBLB) was performed at the right S(10), and histopathological examination of the specimen thus obtained suggested an organizing pneumonia (OP) associated with MDS. Oral prednisolone 30 mg was administered daily, and the symptoms and radiographic findings immediately improved. Accurate diagnosis of the pulmonary involvement associated with patients with MDS is sometimes difficult to make. However, either BOOP or OP should be considered as a differential diagnosis in case the patient presents with continuous coughing, high fever, and air space consolidation. Interventional examinations such as TBLB should be conducted to make a histological diagnosis if the patient's condition allows it.

Anti-Inflammatory Agents↗

[Case of malignant lymphoma arising from the posterior mediastinum, with pleural effusion].

We report a rare case of malignant lymphoma arising from the posterior mediastinum with bilateral pleural effusion. A 71-year-old man was admitted to our hospital for evaluation of a posterior mediastinal tumor and bilateral pleural effusion revealed on a chest CT scan. Because no tumor tissue could be obtained by fiberbronchoscopy, video-assisted thoracoscopic surgery was performed. The tumor sample was composed of large, atypical lymphocytes positive for CD20 on immunohistochemical analysis. A diagnosis of diffuse large B cell lymphoma was made from the typical histological features. The patient was treated with combination chemotherapy (CHOP) and rituximab and improved dramatically.

Aged↗

[A national survey of results of lung volume reduction surgery (LVRS) for pulmonary emphysema in Japan].

We made a national questionnaire survey of conditions and results of lung volume reduction surgery (LVRS) performed for pulmonary emphysema in 273 hospitals. The survey covered: number of hospitals, number of patients, indications, operative procedures, improvement of FEV1% and dyspnea score, mortality, cause of death, 5-year survival rate, characteristics of patients who died, and current conditions of LVRS. The response rate was 63%. A total of 619 patients at 41 hospitals underwent LVRS. The most common types of surgical procedure were bilateral LVRS through median sternotomy and unilateral LVRS with video-assisted thoracoscopic surgery (VATS), followed by bilateral LVRS with VATS. Postoperative improvement in FEV1% averaged 39%. Dyspnea improved in 80% of patients. Mortality rate was 1.9% (8 of 432 cases). Postoperative infectious diseases, namely pneumonia and sepsis, were common causes of death. The 5-year survival was 65 +/- 8%. The causes of death over 5 years were respiratory failure in 60%, malignant neoplasms in 17%, cardiovascular accidents in 13% and others in 10%. The number of operations and hospitals decreased in 2002, compared to 2001.

Aged↗

[Usefulness of low-dose single-slice CT (SSCT) for mass screening to detect various thoracic diseases including lung cancer].

This study assessed the usefulness of SSCT for mass screening retrospectively in 8885 subjects (6781 men, 2104 women) who had received mass screening to detect thoracic disease by using SSCT from 1999 to 2003. In the 8885, 119 (1.3%) lesions were detected as active thoracic disease. These 119 lesions comprised 39 neoplasms and 80 instances of non-neoplastic disease. Of those with neoplastic lesions, 25 had lung cancer (adenocarcinomas, 20; Squamous, 3; carcinoids, 2), 7 had mediastinal tumors and 7, others. Non-neoplastic cases comprised 39 of COPD (pulmonary emphysema), 17 of pulmonary tuberculosis, 8 of non-tuberculous mycobacteriosis and 16 others. Surgical treatment was performed in 46 cases: 25 of lung cancer, 14 of non-cancerous neoplasms, 3 of pulmonary sequestration and 4 others. In the lung cancer cases, the post-surgical staging was I or II (stage I, 20; stage II, 5). Low-attenuation areas (LAA) were seen on multiple CT slices in 2.2% of all subjects (195). These 195 cases had no respiratory symptoms such as exertional dyspnea, But 39 of them had an FEV1.0% (FEV1.0/FVC) of less than 70%. All 39 had a history of smoking, We suggested that SSCT screening is a useful method of mass screening to detect thoracic neoplastic lesions as well as non-neoplastic lesions.

Adult↗