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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 73 records · Page 4Linked to original sources

Augmentation by interleukin-18 of MHC-nonrestricted killer activity of human peripheral blood mononuclear cells in response to interleukin-12.

Interleukin (IL)-18 is a novel cytokine with pleiotropic functions. In the present study, we examined the induction of the killer activity of peripheral blood mononuclear cells (MNC) against lung cancer cell lines upon treatment with IL-18 in combination with IL-12. Cytotoxic activity was measured by standard (51)Cr release assay. IL-18 (100 ng/ml) was found to significantly augment IL-12-induced killer activity in a MHC-nonrestricted manner against allogeneic NK-resistant Daudi cells and lung cancer cell lines: SBC-3, RERF-LC-AI and A549. IL-18 could augment IL-12-induced killer activity both at the optimal as well as suboptimal doses of the latter. However, IL-18 was found to have little effect on the killer activity of MNC induced by optimal or suboptimal dose of IL-2 or IL-15. Treatment of MNC with IL-18 in combination with IL-12 for a period of more than 4 days was observed to optimally induce the killer activity. As for induction of IFN-gamma production by MNC, IL-18 augmented that induced by IL-2 and IL-15, as well as that induced by IL-12. These results show the potential of IL-18 in combination with IL-12 for clinical application in treatment of cancer.

Cytotoxicity, Immunologic↗

Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966.

serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells. Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype. These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological circumvention of multiple-organ metastases of refractory SCLC.

Animals↗

Effect of CT digital image compression on detection of coronary artery calcification.

PURPOSE: To test the effect of digital compression of CT images on the detection of small linear or spotted high attenuation lesions such as coronary artery calcification (CAC). MATERIAL AND METHODS: Fifty cases with and 50 without CAC were randomly selected from a population that had undergone spiral CT of the thorax for screening lung cancer. CT image data were compressed using JPEG (Joint Photographic Experts Group) or wavelet algorithms at ratios of 10:1, 20:1 or 40:1. Five radiologists reviewed the uncompressed and compressed images on a cathode-ray-tube. Observer performance was evaluated with receiver operating characteristic analysis. RESULTS: CT images compressed at a ratio as high as 20:1 were acceptable for primary diagnosis of CAC. There was no significant difference in the detection accuracy for CAC between JPEG and wavelet algorithms at the compression ratios up to 20:1. CT images were more vulnerable to image blurring on the wavelet compression at relatively lower ratios, and "blocking" artifacts occurred on the JPEG compression at relatively higher ratios. CONCLUSION: JPEG and wavelet algorithms allow compression of CT images without compromising their diagnostic value at ratios up to 20:1 in detecting small linear or spotted high attenuation lesions such as CAC, and there was no difference between the two algorithms in diagnostic accuracy.

Adult↗

Optimal tube current for lung cancer screening with low-dose spiral CT.

PURPOSE: To determine the optimal tube current for spiral CT for lung cancer screening. MATERIAL AND METHODS: Low-dose spiral CT images from 20 subjects were obtained with 50 mA, 25 mA, 10 mA and 5 mA tube currents. The accuracy in detecting 21 nodules measuring 3 to 14 mm in diameter was tested using receiver operating characteristics (ROC) to determine the diagnostic accuracy and statistical significance. RESULTS: Compared with 50 mA, 25 mA showed no statistical difference. A significant difference was seen between 50 mA and 5 mA images and between 25 mA and 10 mA images, in the detection of lung parenchymal nodular lesions. CONCLUSION: Approximately 25 mA is the optimal tube current for the detection of pulmonary nodules as it allows a reduction of the radiation dose without sacrificing diagnostic accuracy.

Adenocarcinoma↗

Differentiated thyroid carcinomas. Prediction of tumor invasion with MR imaging.

PURPOSE: To assess diagnostic accuracy for tumor invasion of surrounding organs by measurement of tumor circumferences on MR images in patients with differentiated thyroid carcinomas. MATERIAL AND METHODS: Surgical and MR imaging findings in 50 patients with differentiated thyroid carcinoma (43 primary, 7 recurrent lesions) were retrospectively reviewed. The degrees of circumference of tumor encroachment to the organs were measured, and the measurements and morphologic diagnosis of tumor invasion made by a head and neck radiologist were compared with surgical and pathologic findings using receiver operating characteristic curves. RESULTS: Diagnosis of tumor invasion by the radiologist was superior to the measurements of the carotid artery and cartilage, while the reverse was true for the trachea and esophagus. However, no statistical differences were noted between them for each structure. Optimal thresholds for tumor invasion were 90 degrees or more for the cartilage (94% accuracy) and esophagus (86% accuracy), 135 degrees or more for the trachea (86% accuracy), and 225 degrees or more for the carotid artery (90% accuracy). CONCLUSION: Tumor invasion was more accurately diagnosed by measurement of tumor circumferences of each organ on MR images.

Adenocarcinoma, Follicular↗

Primary thyroid lymphoma: diagnosis of immunoglobulin heavy chain gene rearrangement with polymerase chain reaction in ultrasound-guided fine-needle aspiration.

We present a case of primary thyroid lymphoma coexisting with Hashimoto's thyroiditis in a 75-year-old woman in whom B-cell lymphoma was substantiated based on the findings of immunophenotyping and polymerase chain reaction (PCR) gene rearrangement in specimens that had been obtained by ultrasound (US)-guided fine-needle aspiration biopsy (FNAB). The immunophenotyping technique showed A light chain restriction, and PCR-based assays showed a discrete narrow band, which was diagnostic for clonal B-cell proliferation. Analyses of PCR gene rearrangement in US-guided FNAB may be a useful ancillary technique to pathological findings for diagnosis of primary thyroid lymphoma, especially for differentiation between low-grade B-cell lymphomas and Hashimoto's thyroiditis.

Aged↗

Head and neck lesions: determination of an optimal MT technique for prediction of malignancies.

RATIONALE AND OBJECTIVES: To determine an optimal magnetization transfer (MT) technique for diagnosis of malignancies in the head and neck. METHODS: Lesion magnetization transfer ratios (MTRs) and lesion-to-muscle MTRs were prospectively measured in 52 head and neck lesions of 52 patients at frequency offsets of 0.3, 0.5, and 1 kHz from water resonance. The diagnostic capability for each MT pulse was calculated by using receiver operating characteristic (ROC) curves, and an optimal MT technique was determined for diagnosis of malignancies. RESULTS: The lesion MTRs and the lesion-to-muscle MTRs in malignant tumors were statistically significantly greater than those in benign lesions at both 0.5- and 1-kHz MT pulses, but no significant differences were noted between them at the 0.3-kHz MT pulse. Diagnosis with the lesion-to-muscle MTRs was better than that with the lesion MTRs at each MT pulse. Among all MTRs, lesion-to-muscle MTRs at the 1-kHz MT pulse showed the highest diagnostic capability for malignancies (area under the ROC curve = 0.82+/-0.06). With a lesion-to-muscle MTR at a 1-kHz MT pulse of 0.61 or greater, the highest accuracy of 85% was attained with 90% sensitivity and 77% specificity. CONCLUSIONS: Lesion-to-muscle MTRs at a 1-kHz MT pulse were optimal for diagnosis of malignancies in the head and neck.

False Positive Reactions↗

Solitary aneurysm of the innominate vein.

Two cases of isolated saccular aneurysms of the innominate vein are presented that appeared as mediastinal masses. Contrast-enhanced computed tomography (CT) allowed for accurate diagnosis in one patient, while the second patient had atypical CT findings that led to thoracotomy for proper diagnosis. A diagnosis of innominate vein aneurysm should be considered when a uniform attenuation mediastinal mass is seen on CT so that unnecessary biopsy and surgery can be avoided.

Adult↗

Spontaneous pneumomediastinum in 33 patients: yield of chest computed tomography for the diagnosis of the mild type.

BACKGROUND: Spontaneous pneumomediastinum (SPM) usually occurs in young people without an apparent precipitating factor or disease. Although there have been many studies focused on the clinical features and standard chest X-ray (CXR) findings of SPM, few have reviewed the chest computed-tomographic (CT) findings. OBJECTIVES: We assessed SPM using CXR and CT, and the relation between them. METHODS: We evaluated 33 patients (26 males) diagnosed with SPM on the basis of symptoms and chest radiological findings. RESULTS: Three patients showed normal CXR but a diagnostic CT scan. Seven showed mild pneumomediastinum on CXR. In these 10 patients, pneumomediastinum was easily detected by chest CT. Moderate and severe SPM were easily detected by both CXR and CT. CONCLUSIONS: These findings suggested that CXR alone poorly detected approximately 30% of SPM and that chest CT scan was needed to make the diagnosis in these cases. It seems likely that SPM is underdiagnosed by 30% or more in clinical practice.

Adolescent↗

CD13/aminopeptidase N, a novel chemoattractant for T lymphocytes in pulmonary sarcoidosis.

CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer membrane of a variety of cells. Because aminopeptidase expression was shown to be upregulated by a Th1-related cytokine, IFN-gamma, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in patients with sarcoidosis than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with lymphocyte percentages and the ratio of CD4+ to CD8+ T lymphocytes in the BALF, and was higher in patients with sarcoidosis with parenchymal involvement than in those without the involvement. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from patients with sarcoidosis at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentration range of 10(-)(5) to 10(-)(1) U/ml. The chemotactic activity was greater for CD4+ T lymphocytes than for CD8+ T lymphocytes. The enzymatic activity of CD13/aminopeptidase N was responsible for the chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from patients with sarcoidosis than in that from NV, and the activity was significantly decreased by treatment with bestatin. This study indicates that CD13/ aminopeptidase N expressed in AM may have a role in T-lymphocyte involvement in the sarcoid lung and the pathogenesis of alveolitis in this disorder.

Adult↗

Characteristics of small lung cancers invisible on conventional chest radiography and detected by population based screening using spiral CT.

Conventional chest radiography (CXR) is a poor diagnostic tool for detecting lung cancers at a surgically curable stage. To determine the visibility of peripheral small lung cancers on CXR, we retrospectively examined the usefulness of CXR using a consecutive series of 44 cases detected on CT screening and later confirmed by histopathology. All cases had been detected by low dose CT during a population based screening trial for lung cancer. The control group consisted of 48 chest radiographs of normal subjects. Tumour diameters ranged from 6 mm to 45 mm, with 95% (42/44) < or = 20 mm, and 5% (2/44) > 20 mm. CXR failed to detect 77% (34/44) of all cancers, including 79% (33/42) < or = 20 mm and 50% (1/2) > 20 mm. Of the 42 lung cancers < or = 20 mm, 74% (31/42) were located in the well penetrated lung zones and 71% (22/31) of these were missed on CXR. 26% (11/42) were concealed by hilar vessels, mediastinum, heart or diaphragm, and all (11/11) of these were missed on CXR. 93% (39/42) of the lung cancers < or = 20 mm were adenocarcinomas and 79% (31/39) of these were missed on CXR. 7% (3/42) were epidermoid carcinomas or small cell carcinomas and 66% (2/3) of these were missed on CXR. The overall accuracy of interpretation on CXR for lung cancers was 61%, sensitivity was 23% and specificity 96%. Although there was an association between presence of lung cancer and positive reading of CXR (chi 2 test of association, p < 0.05), the percentage of positive readings was only 23%. Thus, CXR was poor at visualizing CT detectable lung cancers of < or = 20 mm diameter, which are usually of very low density, and cannot be relied upon for detection of surgically curable small lung cancer.

Adenocarcinoma↗

Rapidly growing small peripheral lung cancers detected by screening CT: correlation between radiological appearance and pathological features.

12 peripheral small lung cancers (< 20 mm) of rapid growth (volume doubling time < 150 days), detected by repeated low dose CT screening, were evaluated to examine their CT features and to correlate such features with histopathological findings. Each patient's CT images, including follow-up and thin section CT images, were studied retrospectively to determine tumour growth rate and CT morphological features. Nine of the tumours exhibited a solid tumour growth pattern: seven of these showed a well defined, homogeneous, soft tissue density with spicular or lobulated margin. These seven tumours included small cell lung cancer (n = 3), moderately differentiated adenocarcinoma (n = 2), poorly differentiated adenocarcinoma (n = 1) and squamous cell carcinoma (n = 1). The other two tumours, a moderately differentiated adenocarcinoma and a well differentiated adenocarcinoma, appeared as irregular, soft tissue density nodules with poorly defined margins. The latter exhibited an air bronchogram pattern and a small cavity. The remaining three tumours exhibited a lepidic tumour growth pattern. They showed ground glass opacity or ground glass opacity with a higher density central zone on CT images and were well differentiated adenocarcinomas. In conclusion, most peripheral small lung cancers of rapid growth were adenocarcinomas. They also included small cell lung cancer and squamous cell carcinoma. The majority showed solid tumour growth pattern and lacked an air bronchogram and/or small air spaces in the nodule. Some well differentiated adenocarcinomas with lepidic tumour growth pattern also showed rapid growth.

Adenocarcinoma↗

Growth rate of small lung cancers detected on mass CT screening.

CT has recently been used in mass screening for lung cancer. Small cancers have been identified but the growth characteristics of these lesions are not fully understood. We identified 82 primary cancers in our 3-year mass CT screening programme, of which 61 were examined in the present study. The volume doubling time (VDT) was calculated based on the exponential model using successive annual CT images or follow-up CT images. All cases were also examined in the hospital by high resolution CT (HRCT). Lesions were divided into three types based on HRCT characteristics: type G (n = 19), ground glass opacity (GGO); type GS (n = 19), focal GGO with a solid central component; and type S (n = 23), solid nodule. 18 (95%) lesions of type G, 18 (95%) of type GS and 7 (30%) of type S were invisible on conventional chest radiographs. The mean size of the tumour was 10 mm, 11 mm and 16 mm for type G, type GS and type S, respectively. Most tumours (80%) were adenocarcinomas; 78% of these were GGO (type G and GS). Mean VDT values were 813 days, 457 days and 149 days for type G, type GS and type S, respectively; these are significantly different from each other (p < 0.05). Our results show that annual mass screening CT for 3 successive years resulted in the identification of a large number of slowly growing adenocarcinomas that were not visible on chest radiographs.

Adenocarcinoma↗

Human interferon-gamma enhances expression of ganglioside GM2 on human lung cancer cells and their susceptibility for antiganglioside GM2 monoclonal antibody-dependent cellular cytotoxicity.

Interferons are known to modulate several cellular functions by the induction of various proteins. In this study, we demonstrated that human interferon-gamma (HuIFN-gamma) enhanced the expression of ganglioside GM2 (GM2), which is a kind of tumor-associated antigen substantially expressed in human lung cancer and that human lung cancer cells expressing GM2 became more susceptible to anti-GM2 monoclonal antibody (mAb)-dependent tumor cell killing mediated by human effector cells after HuIFN-gamma treatment. GM2 expression on human lung cancer cells treated with or without HuIFN-gamma was measured by flow cytometry. The antibody-dependent cellular cytotoxicity (ADCC) activity was assessed by 4-h 51Cr release assay. HuIFN-gamma enhanced GM2 expression on human small-cell lung cancer (SCLC), SBC-3, and human non-small-cell lung cancer (NSCLC), A549 cells in a dose-dependent manner. The optimal concentration of HulIFN-gamma was 1,000 U/ml. The effect of HulFN-gamma reached maximum after 4 days of culture. HulFN-gamma did not have any effect to enhance the expression of other gangliosides in SBC-3 cells. No other cytokines used in this study modulated GM2 expression in SBC-3 cells. Anti-GM2 mAb-dependent ADCC activities induced by lymphocytes and monocytes were more potent against IFN-gamma-treated SBC-3 and A549 cells than nontreated cells. Taken together, HulFN-gamma combined with anti-GM2 mAb may be useful for immunotherapy against GM2-positive human lung cancer.

Antibodies, Monoclonal↗

Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer patients with bone metastases.

Animals↗

Synergistic effect of combining theophylline and drugs that potentially elevate serum creatine kinase.

An increase in the serum creatine kinase (CK) level is one of the side effects of theophylline; on rare occasions, the increase may be followed by rhabdomyolysis. Theophylline is often administered with drugs that potentially elevate the serum CK level (CK-elevating drugs) such as beta-agonists and steroids. However, the effects of the combined treatment of theophylline and CK-elevating drugs have not been reported. We, therefore, retrospectively investigated the effects of combined treatment on the serum CK level, in 391 asthmatic outpatients. In this study, the number and type of the CK-elevating drugs administered, and the serum levels of CK and theophylline, were investigated. The patients were divided into four groups: the theophylline-treated and CK-elevating drug-treated group, the theophylline-treated and non-CK-elevating drug-treated group, the non-theophylline-treated and CK-elevating drug-treated group, and the non-theophylline-treated and non-CK-elevating drug-treated group. The theophylline-treated and CK-elevating drug-treated group showed about 100% higher serum CK levels (225 IU/L) than any other group (102-124 IU/L), and no increase in the serum theophylline level. This result indicates that there is a synergistic effect of theophylline and CK-elevating drugs on the serum CK level. The combined treatment of theophylline and CK-elevating drugs induces a synergistic increase in the serum CK level, indicating not pharmacokinetic but pharmacodynamic interactions with these drugs.

Adolescent↗