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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 289 records · Page 16Linked to original sources

ATP-dependent reversible association of proteasomes with multiple protein components to form 26S complexes that degrade ubiquitinated proteins in human HL-60 cells.

The role of proteasomes in ubiquitin (Ub)-dependent protein degradation was studied by analyzing lysates of human promyelocytic leukemia HL-60 cells by glycerol density gradient centrifugation. High succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide hydrolyzing activity was found in the 26S fraction, whereas the 20S fraction containing proteaomes had no activity. Addition of 0.05% sodium dodecylsulfate to the latter fraction, however, induced marked activity. The 26S, but not the 20S fraction catalyzed ATP-dependent degradation of [125I]lysozyme-Ub conjugate. Depletion from the lysate of ATP caused complete shift of the active 26S complex to the latent 20S form, whereas in the lysate prepared from ATP-depleted cells, ATP converted 20S proteasomes to 26S complexes. The immunoprecipitated 26S complexes were found to consist of proteasomes and 13-15 other proteins ranging in size from 35 to 110 kDa. We conclude that in the lysate, latent proteasomes undergo reversible, ATP-dependent association with multiple protein components to form 26S complexes that catalyze ATP-dependent degradation of Ub-protein conjugates.

Adenosine Triphosphate↗

A novel differentiation antigen on human monocytes that is specifically induced by granulocyte-macrophage colony-stimulating factor or IL-3.

A mouse mAb (TOMS-1) was generated against human blood monocytes that had been cultured for 4 days in medium with recombinant human granulocyte-macrophage CSF (GM-CSF). TOMS-1 (IgG1) detected a unique cell surface Ag with a molecular mass of about 43 kDa under both reducing and nonreducing conditions. TOMS-1Ag was expressed on monocytes treated with GM-CSF, but not on fresh or untreated monocytes. This Ag was induced dose dependently during culture of monocytes with GM-CSF for more than 24 h, reaching a maximum level in 3 or 4 days. Treatment of monocytes with cycloheximide in the presence of GM-CSF blocked TOMS-1Ag induction completely, indicating that de novo protein synthesis was required for its expression. TOMS-1Ag was also induced by treatment of monocytes with IL-3, but not with other cytokines such as macrophage-CSF, IL-4, and IFN-gamma or stimulators including LPS, desmethyl muramyl dipeptide, and PMA. TOMS-1Ag expression induced by GM-CSF was up-regulated by IL-4, but down-regulated by IFN-gamma. TOMS-1Ag was not induced on lymphocytes, granulocytes, or AM by GM-CSF or appropriate stimuli. TOMS-1Ag was also not expressed on any cell lines of human leukemias or solid tumors examined. Thus, TOMS-1Ag is a monocyte-specific differentiation Ag induced by GM-CSF or IL-3. These results suggest that TOMS-1 should be useful for monitoring the process of monocyte differentiation by GM-CSF or IL-3.

Antigens, Differentiation↗

[MR evaluation of wallerian degeneration of the pyramidal tract].

This study is based on 135 magnetic resonance (MR) exams of 110 patients with wallerian degeneration of the pyramidal tract shown on MR images acquired on a mid field imaging scanner. The MR findings of wallerian degeneration were abnormal signal band along the course of the pyramidal tract and ipsilateral brain stem shrinkage. In all 110 cases an abnormal signal band was seen on T2-weighted spin-echo images, that is, a hypointense band in four exams between 30 days and 116 days after onset of symptoms, and hyperintense bands in 122 exams. The hyperintense signal on T2-weighted images was shown in most cases after 200 days from the onset. In one case a signal of the pyramidal tract showed a hyperintense band at 7 days, hypointense at 30 days, and hyperintense again at 123 days after onset. Sequential MR exams of another case showed gradual narrowing of the hyperintense signal band and progression of the ipsilateral brainstem shrinkage. The narrowing of the pyramidal tract and the ipsilateral brain stem shrinkage tended to be shown after 6 months from onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Liver abscess as the initial manifestation of colonic Crohn's disease: report of a case.

Liver abscess is a rare complication of Crohn's disease and in most of the reported cases, the diagnosis of Crohn's disease preceded that of liver abscess. We report herein a case in which a liver abscess was the initial clinical manifestation of Crohn's disease in a 36 year old man who presented with high fever and weakness. The diagnosis of liver abscess was established by abdominal ultrasonography, computed tomography and an arterial blood culture. The abscess was resolved with antibiotic therapy alone and during the drug therapy, a barium enema examination was performed which revealed a stricture at the transverse colon. Resection of the transverse colon was performed and macroscopic and microscopic examination of the resected specimen established the diagnosis of Crohn's disease. The liver abscess was thus speculated to be secondary to the inflamed bowel. Although rare, Crohn's disease should be included in the differential diagnosis of diseases causing liver abscess.

Adult↗

Interleukin-4 downregulates interleukin-6 production by human alveolar macrophages at protein and mRNA levels.

Effects of interleukin-4 (IL-4) on IL-6 production by human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined at the protein and gene levels. IL-6 production was quantitated by enzyme immunoassay (EIA) and bioassay using the IL-6 dependent murine hybridoma cell line MH60.BSF2. Results showed that when activated with LPS, AM released significantly more biologically active IL-6 than blood monocytes. Human rIL-4 significantly suppressed IL-6 production by AM and monocytes stimulated with LPS. Northern blot analysis revealed that IL-4 reduced the expression of IL-6 mRNA in LPS-stimulated AM and monocytes. The inhibitory effect was most pronounced when IL-4 was added with LPS or within the first 4 hr after LPS to AM or monocytes. The suppressive effect of IL-4 was completely neutralized by pretreatment with anti-IL-4 antibody. IL-4 also showed a suppressive effect on IL-6 production by macrophages generated in vitro by maturation of blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF). These observations suggest that IL-4 may play a critical role in in situ regulation of immune responses through suppression of IL-6 production.

Adult↗

Potential value of cetylmannoside-modified liposomes as carriers of macrophage activators to human blood monocytes.

The present study was undertaken to examine the potential value of cetylmannoside-modified multilamellar liposomes (Man-MLV) as carriers for transfer of macrophage activators to blood monocytes. Highly purified blood monocytes were isolated by centrifugal elutriation from healthy donors under endotoxin-free conditions. Freshly prepared monocytes phagocytosed Man-MLV to a lesser extent than monocyte-derived macrophages, but they took up Man-MLV much more effectively than control liposomes without cetylmannoside (control MLV). Phagocytosis of Man-MLV, but not control MLV by monocytes was inhibited by addition of D-mannose, but not of D-galactose. Desmethyl-muramyl dipeptide (norMDP) entrapped in Man-MLV was far more effective than norMDP entrapped in MLV in activating monocytes to the tumoricidal state. The effect of encapsulation of recombinant human macrophage colony-stimulating factor (M-CSF) in Man-MLV on prolongation of survival of monocytes was examined. Blood monocytes that had been incubated for up to 21 days with Man-MLV containing 5-20 U of M-CSF per ml were effective in prolonging monocyte survival, but monocytes that had been incubated in medium with less than 50 U/ml of M-CSF or with control MLV containing 5-10 U of M-CSF showed no increase of monocyte survival over that in medium alone. Addition of rabbit anti-M-CSF antiserum did not affect survival prolongation of monocytes by M-CSF encapsulated in Man-MLV. We conclude that liposomes modified with cetylmannoside are far more effective than unmodified liposomes as a carrier to deliver biological response modifiers to human blood monocytes.

Cell Survival↗

Interleukin-2-inducible killer activity and its regulation by blood monocytes from autologous lymphocytes of lung cancer patients.

The ability of blood lymphocytes of newly diagnosed lung cancer patients to respond to interleukin 2 (IL-2) to become IL-2-activated killer (LAK) cells and its regulation by autologous monocytes were examined. LAK activity was measured by 51Cr release assay. The abilities of lymphocytes among blood mononuclear cells (MNC) of subjects of different ages without malignancies to generate LAK activity against NK-cell resistant Daudi cells and lung adenocarcinoma (PC-9) cells were very similar. The LAK activity of blood MNC of lung cancer patients was also nearly the same as that of blood MNC of control subjects. There was no significant difference in IL-2-inducible LAK activity between MNC of patients with small cell lung cancer (SCLC) and those of patients with non-SCLC. Monocytes and lymphocytes were separated from blood MNC on a one-step Percoll gradient. Monocytes of lung cancer patients were found to augment in vitro induction of LAK activity by IL-2 of autologous blood lymphocytes. In contrast, endotoxin-stimulated monocytes suppressed LAK induction of autologous lymphocytes of cancer patients. These findings suggest that administration of IL-2 and LAK cells induced in vitro may be of benefit in the treatment of lung cancer.

Aged↗

Development of a high-resolution digital tomosynthesis system and its clinical application.

Conventional tomography has been criticized for its low contrast caused by scattered radiation and tomographic blur. The authors developed a digital tomosynthesis system as a substitute for conventional tomography. With the image processor in the system, two types of postprocessing can be performed to improve the quality of synthesized tomograms. One-dimensional spatial frequency filtering effectively reduces linear tomographic blur and enhances image information when an appropriate filter is used. Correction of structure mottle helps enhance the image clarity. The system allows reconstruction of tomograms at any desired depth and performance of tomosynthetic angiography and dual-energy subtraction. The system solves some of the problems associated with plain tomography and dual-energy subtraction and provides diagnostic clinical images.

Humans↗

Macrophage colony-stimulating factor activity in malignant pleural effusions. Its augmentation by intrapleural interleukin-2 infusions.

The activity of endogenous colony-stimulating factor (CSF) in malignant pleural effusions of lung cancer patients before and during daily intrapleural infusions of recombinant interleukin-2 (IL-2) was measured quantitatively by colony-forming bioassay and radioimmunoassay (RIA). Before therapy, malignant pleural effusions had various levels of CSF activities, and this CSF activity was neutralized almost completely by anti-M-CSF antibody. RIA also showed that the effusions contained various amounts of M-CSF. Daily intrapleural infusion of recombinant IL-2 caused significant increase in the CSF activities and M-CSF levels in pleural effusions. These results indicate that in vivo treatment with IL-2 induces production of endogenous M-CSF.

Adult↗

[A case of small cell lung cancer associated with pulmonary sarcoidosis].

A 63-year-old man with pulmonary sarcoidosis, diagnosed by mediastinal lymph node biopsy in 1977, was admitted in Feb. 1987 because of shortness of breath and cough. Chest X-ray showed bilateral hilar lymphadenopathy and a tumor shadow in the right lung field. Histological examination of specimens biopsied from the right lung revealed small cell carcinoma (S.C.C.). Bronchoalveolar lavage was performed to evaluate the disease activity of sarcoidosis, and the total number of cells and T-lymphocytes; the ratio of CD4+ cells to CD8+ cells was not increased. He was treated with combination chemotherapy, however, he died of respiratory failure after 7 months. An autopsy was performed, and the lesions were examined histologically. The sarcoid lesion in a lymph node obtained at autopsy was not active, in contrast to that obtained by mediastinal lymph node biopsy. Lung cancer and sarcoidosis are both common diseases, but their coexistence in the same patient is not common, and autopsied cases are rare. In this case, an autopsy was performed, and BAL had been performed prior to his death. The relationship between the BAL findings and the histology of sarcoidosis was examined. Based on the results of autopsy and BAL, the sarcoidosis was inactive prior to death, but had been histologically active 10 years previously. Therefore, this is a very interesting case, since we can examine the relationship between the two diseases, and the progression of each disease. This case also provides an interesting example of differentiation of sarcoidosis from S.C.C. Metastatic invasion of the hilar lymph nodes without bronchial stenosis and changes secondary to stenosis may often occur in patients with small cell lung cancer. Such metastatic invasion closely resembles the bilateral hilar lymphadenopathy of sarcoidosis; therefore, in some cases, it may be extremely difficult to differentiate the two diseases.

Bronchoalveolar Lavage Fluid↗

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.

Adult↗

Local adoptive immunotherapy using lymphokine-activated killer cells and interleukin-2 against malignant pleural mesothelioma: report of two cases.

Malignant pleural mesothelioma is refractory to conventional therapy. We tried local adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) to control malignant pleural effusion due to mesothelioma in two patients: Case 1 was that of a 69-year-old man, and Case 2 that of a 49-year-old woman with complicating chronic idiopathic thrombocytopenic purpura. A systemic survey revealed no sign of metastasis in either case. Intrapleural instillations of 6.7 x 10(9) autologous LAK cells in Case 1, or 11.3 x 10(9) allogeneic LAK cells in Case 2, with daily injections of IL-2 resulted in reductions of the pleural effusions in each case and in a decline in the level of hyaluronic acid in the effusion, in Case 1. The instillations of autologous and allogeneic LAK cells were well tolerated. The results suggest that local adoptive immunotherapy could be useful in the treatment of malignant effusion due to mesothelioma.

Aged↗

[A case of metastatic rib tumor from thyroid cancer confirmed by the presence of thyroglobulin].

A 63-year-old female, with a chief complaint of right chest pain was referred to our hospital because of an abnormal right chest wall shadow on chest X-ray. A rib tumor was suspected based on her chest CT scan. Percutaneous needle biopsy yielded a diagnosis of well-differentiated adenocarcinoma. As metastatic rib tumor was suspected, the primary tumor was sought for. A thyroid gland nodule was recognized by ultrasonography, and the cytological diagnosis was class V. Immunohistological demonstration of the thyroglobulin studies of the rib tumor tissue revealed papillary and trabecular patterns of cell arrangement and the presence of thyroglobulin existence. Definitive diagnosis of metastatic rib tumor from thyroid cancer was established. Immunohistological examination is useful to confirm the diagnosis of metastatic cancer of thyroid origin.

Adenocarcinoma↗

[Auditory brainstem response and extratympanic recorded electrocochleography in patients with multiple and severe handicaps].

Nine patients ranged between 5 months and 35 years (means 14 years) of age with multiple and severe disabilities were comparatively studied, on extra-tympanic recorded compound action potential (AP) of electrocochleography and auditory brainstem response (ABR). Both ABR and AP were obvious in 3 patients with clear auditory behavioral responses. The ABR was not recorded to high intensity click stimuli in six patients without visible auditory behavioral responses. Four of the 6 cases showed undetectable AP and the 2 rest of the 6 cases showed abnormal but discernible AP. In two cases with history of the anoxic encephalopathy, AP was recorded but ABR was not detected in one case, and in the other, neither AP nor ABR was recorded. At least two different levels of lesions could be differentiated in cases without detectable ABR by using extra-tympanic recorded electrocochleography in these kinds of severely handicapped patients.

Action Potentials↗

Digital image processing to remove blur from linear tomography of the lung.

We have studied digital image processing methods to reduce blur in linear tomography of the lung performed with the Fuji computed radiography (FCR) system. One-dimensional unsharp (blur) mask filtering in the direction of tomographic movement was found to be effective in reducing blur. The appearance of the processed tomograms varied depending largely on the properties of the unsharp mask filters applied. With regard to the spatial frequency response of the filter, a high mid-frequency response and a low low-frequency response of the tomographic image data was most effective in obtaining high image quality tomograms. When the standard 2-dimensional unsharp mask technique of the FCR system was additionally applied to the one-dimensional unsharp mask processed tomogram, the clarity of the tomogram was further enhanced. These observations may also be helpful when considering image processing to obtain diagnostically informative digital radiography.

Humans↗

[Colony-stimulating factor activity in malignant pleural effusions and its augmentation by local administration of interleukin 2].

The activity of endogenous colony stimulating factor (CSF) in pleural effusions of patients with lung cancer was measured quantitatively by colony-forming bioassay. Before treatment malignant effusions contained various levels of CSF activities. Anti-GM-CSF and anti-M-CSF antibodies neutralized approximately 60% and 70% of CSF activities in malignant effusions, respectively. Significant increase in the CSF activity in malignant effusion was seen during intrapleural injections of recombinant interleukin-2 (IL-2). Thus, in vivo treatment with IL-2 can induce production of endogenous CSF which may be responsible for proliferation and differentiation of mononuclear phagocytes.

Adult↗

Effects of experimental hyper- and hypothyroidism on natural defense activities against Lewis lung carcinoma and its spontaneous pulmonary metastases in C57BL/6 mice.

The effects of expermentally induced hyper- and hypothyroidism on the growth and development of spontaneous pulmonary metastases of Lewis lung carcinoma (3LL) cells were studied in a murine system. Progression of 3LL tumors growing in mice was associated with significant reduction in the serum levels of T3 and T4. Subcutaneous (s. c.) injections (3 times/week) of T3 resulted in a hyperthyroid state with elevated T3 and reduced T4, whereas treatment with T4 induced a hyperthyroid state with elevated T3 and T4 levels. On the other hand, treatment with methimazole induced hypothyroidism with reduced T3 and T4 levels. Under these experimental conditions, treatment with T3 significantly inhibited spontaneous pulmonary metastases, and prolonged survivals of the mice. Methimazole suppressed primary and metastatic tumor growth and prolonged survival. In contrast, treatment with T4 enhanced primary tumor growth and development of pulmonary metastases of 3LL cells. Alveolar macrophages showed enhanced cytotoxicity against 3LL tumor cells after injections of thyroid hormones (T3 and T4) for 4 weeks. The NK activities of spleen cells of mice treated with T4 or methimazole were much lower than those of control mice, and were not affected by treatment with T3. These results imply that changes in thyroid functions may have important influence on natural host defenses against primary and metastatic lung cancer in humans.

Animals↗

[Digital TV tomosynthesis--system development, digital image processing and clinical applications].

We have designed and developed two types of high-resolution digital X-ray TV tomosynthesis systems which incorporate an X-ray TV fluororadiographic unit with tomographic function and a digital image processor, which handles image data from the image intensifier-TV camera chain. We have studied methods of improving image quality of the tomosynthesis images and their clinical applicability. As a result of clinical application of this method, a number of advantages have already become apparent, as listed below: 1) Low patient radiation dose per examination, short examination time, and early display of the image on the CRT. 2) Reconstruction of the tomograms at any desired depth and oblique tomograms. 3) Spatial frequency filtering to improve the image quality, particularly one-dimensional spatial filtering process to reduce linear tomographic blur. 4) Digital angiotomosynthesis with and without subtraction. 5) Dual energy subtraction digital tomosynthesis. 6) Electronic storage and transmission of image data. Clinical effectiveness of this method was shown in such areas as imaging of the ear, spine and lung, angiography of the brain and abdominal organs, and arthrography.

Equipment Design↗