Biomedical subjects

Takayuki Honda

Publications and source records attributed to Takayuki Honda.

At least 19 recordsLinked to original sources

PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗

PubMed2007

Effects of bronchodilators on dynamic hyperinflation following hyperventilation in patients with COPD.

BACKGROUND AND OBJECTIVE: The present study was performed to examine the occurrence of dynamic hyperinflation following hyperventilation in COPD patients and former smokers without COPD, and the efficacy of short-acting anticholinergic agents (SAAC) and beta2-agonists (SABA) for lung hyperinflation following metronome-paced hyperventilation in COPD. METHODS: Fifty-nine patients with COPD, 20 ex-smokers without COPD and 20 healthy subjects who had never smoked were examined for dynamic hyperinflation by metronome-paced hyperventilation with respiratory rate increasing from 20 to 30 and 40 tidal breaths/min. Dynamic hyperinflation was evaluated as the decrease in inspiratory capacity (IC) following hyperventilation, and the effects of SAAC and SABA on dynamic hyperinflation were assessed. RESULTS: COPD patients showed a significant increase in end-expiratory lung volume and a decrease in IC following hyperventilation, and ex-smokers without COPD also showed mild but significant dynamic hyperinflation. Multiple stepwise linear regression analysis revealed that the carbon monoxide transfer coefficient (DLco/VA) and RV/TLC were significant and independent determinants of dynamic hyperinflation in COPD. Treatment with SAAC and SABA significantly increased IC at each respiratory rate, independently of the increases in FEV1. Furthermore, SABA significantly inhibited the decrease in IC due to hyperventilation. CONCLUSIONS: These findings suggest that lung hyperinflation following hyperventilation may be a useful method for detecting dynamic hyperinflation observed not only in patients with COPD but also in ex-smokers without COPD, and both SAAC and SABA are effective in reducing dynamic hyperinflation in COPD.

Administration, Inhalation↗

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

Mass and local topography measurements of Itokawa by Hayabusa.

The ranging instrument aboard the Hayabusa spacecraft measured the surface topography of asteroid 25143 Itokawa and its mass. A typical rough area is similar in roughness to debris located on the interior wall of a large crater on asteroid 433 Eros, which suggests a surface structure on Itokawa similar to crater ejecta on Eros. The mass of Itokawa was estimated as (3.58 +/- 0.18) x 10(10) kilograms, implying a bulk density of (1.95 +/- 0.14) grams per cubic centimeter for a volume of (1.84 +/- 0.09) x 10(7) cubic meters and a bulk porosity of approximately 40%, which is similar to that of angular sands, when assuming an LL (low iron chondritic) meteorite composition. Combined with surface observations, these data indicate that Itokawa is the first subkilometer-sized small asteroid showing a rubble-pile body rather than a solid monolithic asteroid.

Journal Article↗

PubMed2006

Characteristics of COPD phenotypes classified according to the findings of HRCT.

The present study was performed to clarify the clinical characteristics of chronic obstructive pulmonary disease (COPD) patients classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening evaluated by chest high-resolution computed tomography (HRCT). Eighty-five patients with stable COPD (FEV1 < or = 80%) were examined by chest HRCT. Emphysematous changes and bronchial wall thickening were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without bronchial wall thickening (A phenotype), emphysema without bronchial wall thickening (E phenotype), and emphysema with bronchial wall thickening phenotype (M phenotype). Clinical characteristics were compared among the three phenotypes. The A phenotype group showed a higher prevalence of subjects who had never smoked and patients with wheezing, higher values of body mass index (BMI) and DLco, milder lung hyperinflation, and greater reversibility of airflow limitation responsive to inhaled beta2-agonist as compared with the other phenotypes. The degree of emphysema was significantly associated with Brinkman index, lower BMI, decrease in DLco, lower FEV1/FVC. The presence of bronchial wall thickening in A- and M- phenotype was significantly associated with reversibility responsive to treatment with inhaled corticosteroid and sputum eosinophilia. These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to treatment with bronchodilators and inhaled corticosteroids.

Administration, Oral↗

PubMed2006

First isolation of Dysgonomonas mossii from intestinal juice of a patient with pancreatic cancer.

BACKGROUND: Dysgonomonas species were first designated in 2000. However, clinical infections due to this microorganism have rarely been described. Our aim was to present the first isolation of Dysgonomonas mossii from intestinal juice of a patient with pancreatic cancer. METHODS: Predominantly appearing grayish-white colonies grown on chocolate and sheep blood agar plates were characterized morphologically by Gram stain, biochemically by automated instrument using Vitek II ID-GNB card together with commercially available kit systems, ID-Test HN-20 and API rapid ID 32A32A, and genetically by sequencing the 16S rRNA gene of the organism using a Taq DyeDeoxy Terminator Cycle Sequencing and a model 3100 DNA sequencer instrument. The isolate was further characterized by antimicrobial susceptibility using MicroFast 4J Panels and additional biochemical and physiological properties. RESULTS: The isolate was finally identified as D. mossii from the findings of the morphological, cultural, and biochemical properties together with the comparative sequence of the 16S rRNA genes. The isolate was highly susceptible to many antibiotics but resistant to penicillins and cephems. CONCLUSIONS: As D. mossii was rarely encountered in the clinical microbiology laboratory, it may be misidentified as an X-factor-dependent Haemophilus species due to its negative result for the porphyrin test. Accumulation of the case reports with the isolation of this species is expected to elucidate the infections due to D. mossii. The presence of D. mossii caused no significant clinical infection despite repeated isolations, as the patient had no conspicuous abdominal complaints. However, our report is a noteworthy and useful piece of information.

Bacterial Infections↗

PubMed2006

Heterogeneous proliferation of type II pneumocytes in usual interstitial pneumonia.

AIMS: Heterogeneous alveolar fibrosis, the most specific pathological finding in idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), enables differentiation of UIP from other interstitial pneumonias. Heterogeneous and mild alveolar injury may occur, and this will be a clue to clarifying the pathogenesis of UIP. METHODS: We examined nine lung biopsy specimens obtained from patients with IPF and five control specimens. We semi-quantitatively examined alveolar injury by measuring the density of type II pneumocytes. Serial 3 microm sections were stained with anti-Thomsen-Friedenreich (TF) antibody. We divided each UIP lesion into three areas: area near fibrosis (fibrous area), area with an apparently normal alveolar structure (normal area), and area between the fibrous and normal areas (intervening area). RESULTS: Immunostaining with anti-TF antibody stained the apical surface of type II pneumocytes and enabled us to recognise and count type II pneumocytes. The density of type II pneumocytes was increased in the fibrous area, and gradually decreased away from the fibrous lesion. The densities of type II pneumocytes in the above three areas were, respectively: 13.9+/-2.0, 7.2+/-1.6, and 9.5+/-1.6/mm alveolar length. The densities in the fibrous and intervening areas were significantly greater than those in the normal area and in control specimens (6.6+/-0.7/mm). CONCLUSIONS: If the density of type II pneumocytes indicates their degree of regeneration after alveolar injury, it reflects the severity of the pre-existing injury. This study confirms that heterogeneous and mild alveolar injury occurs in UIP.

Adult↗

PubMed2006

Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using high-resolution computed tomography.

OBJECTIVE AND BACKGROUND: The present study was performed to clarify the clinical characteristics of patients with COPD classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening (BWT) evaluated by chest high-resolution CT. METHODS: A total of 172 patients with stable COPD (FEV1<80%) were examined by chest high-resolution CT. Emphysematous changes and BWT were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without BWT (A phenotype), emphysema without BWT (E phenotype) and emphysema with BWT phenotype (M phenotype). The clinical characteristics were compared among the three phenotypes. RESULTS: The A phenotype showed a higher prevalence of those who had never smoked and patients with wheezing both on exertion and at rest, higher values of BMI and diffusing capacity for carbon mononide (DLCO), milder lung hyperinflation, and greater reversibility of airflow limitation responsive to beta2-agonist as compared with the E phenotype. The M phenotype showed a higher prevalence of patients complaining of a large amount of sputum, productive cough and wheezing, higher rate of exacerbation or hospitalization and greater reversibility of airflow limitation responsive to beta2-agonist as compared with the E phenotype. CONCLUSIONS: These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to bronchodilators.

Adrenal Cortex Hormones↗

PubMed2006

Reduction of human T-cell leukemia virus type 1 (HTLV-1) proviral loads in rats orally infected with HTLV-1 by reimmunization with HTLV-1-infected cells.

Human T-cell leukemia virus type 1 (HTLV-1) persistently infects humans, and the proviral loads that persist in vivo vary widely among individuals. Elevation in the proviral load is associated with serious HTLV-1-mediated diseases, such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, it remains controversial whether HTLV-1-specific T-cell immunity can control HTLV-1 in vivo. We previously reported that orally HTLV-1-infected rats showed insufficient HTLV-1-specific T-cell immunity that coincided with elevated levels of the HTLV-1 proviral load. In the present study, we found that individual HTLV-1 proviral loads established in low-responding hosts could be reduced by the restoration of HTLV-1-specific T-cell responses. Despite the T-cell unresponsiveness for HTLV-1 in orally infected rats, an allogeneic mixed lymphocyte reaction in the splenocytes and a contact hypersensitivity response in the skin of these rats were comparable with those of naive rats. HTLV-1-specific T-cell response in orally HTLV-1-infected rats could be restored by subcutaneous reimmunization with mitomycin C (MMC)-treated syngeneic HTLV-1-transformed cells. The reimmunized rats exhibited lower proviral loads than untreated orally infected rats. We also confirmed that the proviral loads in orally infected rats decreased after reimmunization in the same hosts. Similar T-cell immune conversion could be reproduced in orally HTLV-1-infected rats by subcutaneous inoculation with MMC-treated primary T cells from syngeneic orally HTLV-1-infected rats. The present results indicate that, although HTLV-1-specific T-cell unresponsiveness is an underlying risk factor for the propagation of HTLV-1-infected cells in vivo, the risk may potentially be reduced by reimmunization, for which autologous HTLV-1-infected cells are a candidate immunogen.

Administration, Oral↗

PubMed2006

[Usefulness of a new sheet-like apparatus (SD-101) for screening of sleep apnea syndrome].

Polysomnography (PSG) is the gold standard for the diagnosis of sleep apnea syndrome (SAS). However, PSG is not suitable as a first-line examination for all people suspected as having SAS because PSG requires hospitalization. Therefore, it is hoped that a simple examination can be developed which is available for use in the home. The present study evaluated the usefulness of a new sheet-like apparatus (SD-101) which is equipped with 162 pressure sensors for SAS diagnosis. One hundred patients hospitalized for PSG were simultaneously examined using the SD-101, and 25 patients, who underwent both PSG and SAS screening with MORPHEUS R, were also studied. The SD-101 is inserted between a sheet and the bed, and detects pressure from many points on the patient's body as it presses against the bed. Continuous changes of these pressure points are converted to respiratory movement. A very close correlation was seen between the apnea hypopnea index of PSG and a respiratory disturbance index of SD-101 (r=0.90), although there was a significant but lower correlation between data obtained PSG and MORPHEUS R(r=0.84). The sensitivity and specificity of the examination using SD-101 were 98.2% and 55.8%, respectively. These findings suggested that a new apparatus, SD-101, may be useful for the screening of SAS.

Bedding and Linens↗

PubMed2005

Comparison of bronchoscopic diagnosis for peripheral pulmonary nodule under fluoroscopic guidance with CT guidance.

BACKGROUND: A new diagnostic procedure has been established for the selection of appropriate therapy for small lung lesions. We compared the sensitivity of real-time multi-slice computed tomography (MSCT) and X-ray television (TV) fluoroscopic guidance for performing bronchoscopy. METHODS: The first author performed and interpreted all bronchoscopies described in this study. The diagnosis of malignancy or benign was based on the results of histopathological examination, as well as clinical and imaging follow-up MSCT. We also compared the diagnostic yields of lesion size between MSCT and X-ray TV fluoroscopic guidance. RESULTS: Real-time MSCT and X-ray TV fluoroscopic guidance was conducted in 82 and 78 patients, respectively. The lesion size detected by real-time MSCT and X-ray TV fluoroscopic guidance was <10 mm (n=21, 14), 11-15 mm (n=24, 12), 16-20 mm (n=19,14), 21-25 mm (n=9, 12) and >26 mm (n=9, 26). The sensitivity of real-time MSCT- and X-ray TV fluoroscopic guidance was 62.2% and 52.6%, respectively. The sensitivity of real-time MSCT fluoroscopic guidance for histopathologic diagnosis of lesions less than 15 mm was higher than that of X-ray TV fluoroscopic guidance. While it was difficult to histopathologically diagnose small lung lesions less than 10mm in diameter, real-time MSCT fluoroscopic guidance offers a better chance of such diagnosis, irrespective of the size of the lesion, compared with X-ray TV fluoroscopic guidance. CONCLUSION: Real-time MSCT fluoroscopic guidance allows the bronchoscopist to accurately determine the location of the instruments in relation to the lesion in real time, thus helping to reduce the number of negative cases.

Adult↗

PubMed2005

The medial surface of the mandible as an alternative source of bone grafts in orthognathic surgery.

A technique of harvesting bone grafts from the medial surface of the angle of the mandible during a bilateral sagittal split osteotomy procedure is described. In 20 patients who underwent mandibular setback for the correction of class III dentofacial deformities, bone grafts were harvested from the medial mandibular angle and used for simultaneous augmentation of the midface or for interpositioning and stabilization of the maxilla after LeFort I maxillary anterior or inferior repositioning. The mean postoperative follow-up was 6 months (range, 3-12 months). No complications occurred, and postoperative morbidity was similar to that encountered by patients who undergo sagittal split osteotomy without bone harvest. The technique described shows that the medial mandibular angle is a suitable donor site for membranous bone grafts in patients who undergo sagittal split osteotomy.

Adolescent↗

PubMed2005

Distinct clinicopathological entity 'autoimmune pancreatitis-associated sclerosing cholangitis'.

Autoimmune pancreatitis (AIP) is a recently proposed disease entity, in which an elevated serum IgG4 is characteristic. This disease is sometimes associated with other inflammatory diseases: Sjögren's disease, or sclerosing cholangitis. The aim of the present paper was to examine the difference in pathophysiology between AIP-associated sclerosing cholangitis (AIP-SC) and primary sclerosing cholangitis (PSC). The clinicopathological findings and the immunohistochemical expressions of IgG subclasses (IgG1, IgG2, IgG3, and IgG4) were evaluated for the two aforementioned diseases (six patients with each disease). Radiologically, the extrahepatic bile duct was involved in AIP-SC, whereas both extrahepatic and intrahepatic bile ducts were involved in PSC. Clinically, bile duct lesions in the former responded well to steroid therapy. Histologically, various degrees of mononuclear cell infiltration and fibrosis around bile ducts and portal tracts were found in all patients. Immunohistochemically, the IgG4-positive plasma cell/mononuclear cell ratio was significantly higher in AIP-SC than in PSC (P < 0.05). The IgG4-positive plasma cell/mononuclear cell ratio is a useful index to help distinguish AIP-SC from PSC. A mechanism similar to that involved in AIP may be involved in AIP-SC. The latter is a distinct clinicopathological entity that should be distinguished from PSC because it responds well to steroid therapy.

Adult↗

PubMed2004

A three-dimensional analysis of blood vessels in bronchioloalveolar carcinoma.

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 microm thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08+/-1.10 microm, 3.95+/-1.02 microm, 5.04+/-1.56 microm, and 6.11+/-2.23 microm, the circumferences of those vessels seen as complete circles were 43.11+/-12.78 microm, 43.71+/-12.87 microm, 95.21+/-39.32 microm, and 126.77+/-54.65 microm; the lengths between vessel bifurcations were 13.28+/-3.08 microm, 13.47+/-4.58 microm, 24.91+/-9.66 microm, and 41.82+/-28.08 microm in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2004

Pulmonary lymphoepithelioma-like carcinoma: predominant infiltration of tumor-associated cytotoxic T lymphocytes might represent the enhanced tumor immunity.

Lymphoepithelioma-like carcinoma (LELC) of the lung is an undifferentiated carcinoma with prominent lymphoid stroma. We encountered a case of synchronous primary lung cancers of LELC and papillary adenocarcinoma in a 67-year-old Japanese woman. By in situ hybridization, Epstein-Barr virus (EBV) genome was detected in malignant epithelial cells of LELC but not in the papillary adenocarcinoma. Tumor-infiltrating lymphocytes in LELC were predominantly CD8+ and T cell intracytoplasmic antigen (TIA-1)+ cytotoxic T cells with closely associated with HLA-DR-positive LELC cells by double immunostaining. These data indicate that the exaggerated lymphoid infiltration in and around the EBV-infected carcinoma cells may represent the enhanced tumor immunity, suggesting a better prognostic indicator.

Adenocarcinoma, Papillary↗

PubMed2004

[A case of lung adenocarcinoma presenting a solitary, predominantly solid pulmonary nodule that showed slow growth over 7 years].

A small, solitary, predominantly solid pulmonary nodule (7 x 6 mm) was found in a 63-year-old woman during a CT screening for lung cancer. After 7 years, another chest CT examination revealed that the lesion had grown to a size of 15 x 10 mm. The patient then underwent surgery to remove the nodule, because primary lung cancer was strongly suspected. The resected specimen proved to be a poorly differentiated adenocarcinoma of type D according to the criteria of Noguchi et al. The tumor doubling time (TDT) in this case was estimated to be 661 days, which was longer than in other reported cases of Noguchi type D adenocarcinoma. High-resolution CT (HRCT) of the nodule revealed a predominantly solid lesion with a polygonal shape. No further changes were observed in a one-year follow-up CT, suggesting a benign tumor. We therefore suggest that the follow-up of small, solitary pulmonary nodules is of diagnostic value.

Adenocarcinoma↗

PubMed2004

[Cobalt].

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Biomarkers↗