Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 19 recordsLinked to original sources

PubMed1992

Regulation of gene expression of proteasomes (multi-protease complexes) during growth and differentiation of human hematopoietic cells.

We have reported that proteasomes are expressed at abnormally high levels in various hematopoietic tumor cells (Kumatori, A., Tanaka, K., Inamura, N., Sone, S., Ogura, T., Matsumoto, T., Tachikawa, T., Shin, S., and Ichihara, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7071-7075). In the present study, we examined changes in the expressions of proteasomes during growth of peripheral T-lymphocytes from healthy adults and differentiation of human leukemic cell lines. Up-regulation of mRNAs encoding multiple proteasome subunits was observed during proliferation of resting T-cells induced by mitogens such as phytohemagglutinin and interleukin-2. In contrast, in vitro terminal differentiation into monocytic, granulocytic, and erythroid cells of various immature leukemic cell lines, such as HL-60 promyelocytic leukemia cells and K562 erythroleukemia cells, by various inducing agents caused rapid and marked down-regulation of proteasomes expression, independently of the cell type, direction of differentiation, or type of signal. The syntheses of proteasome subunits of 21-31 kDa and their associated components of 35-110 kDa, measured by [35S]methionine incorporation, were much higher in mitogen-activated T-cells and unstimulated HL-60 cells, which grow rapidly, than in resting and differentiated cells, indicating apparent correlations of the mRNA levels of proteasomes with their translational activities. However, immunochemically, no detectable difference in the cellular contents of proteasomes was found in these cells in induced and uninduced states for proliferation and differentiation, suggesting accelerated turnover of proteasomes in rapidly proliferating cells. Inhibition of proteasome expression by an antisense oligodeoxynucleotide for the largest proteasome subunit, C2, caused partial arrest of cell cycle progression of T-lymphocytes, suggesting that up-regulation of proteasomes is indispensable for proliferation of the cells. We also observed that the nuclear fraction of proteasomes increased in proliferating T-cells and that proteasomes moved rapidly between the nucleus and cytoplasm during differentiation of HL-60 cells.

Base Sequence↗

PubMed1992

IL-4 up-regulates IL-1 receptor antagonist gene expression and its production in human blood monocytes.

IL-4 down-regulates the productions of IL-1 and TNF-alpha in human monocytes. We examined whether the productions of IL-1 and a specific receptor antagonist of IL-1 (IL-1Ra) in human blood monocytes were regulated differently. Highly purified blood monocytes, isolated by centrifugal elutriation from healthy donors, were stimulated with LPS in the presence or absence of IL-4, and their productions of IL-1 and IL-1Ra were measured by Northern blot and immunoblot analyses. IL-1 and IL-1Ra were produced by monocytes stimulated with LPS, but not with IL-4 alone. Marked up-regulation by IL-4 of IL-1Ra production in LPS-stimulated monocytes was observed at both the mRNA and protein levels. Maximal expressions of IL-1 beta and IL-1Ra mRNA in LPS-stimulated monocytes were observed 2 h and 8 h, respectively, after stimulation. The enhancement of IL-1Ra production by IL-4 was concluded to be due to enhanced gene transcription, because there was no difference in the half-lives of IL-1Ra mRNA in monocytes cultured with and without IL-4. Up-regulation of IL-1Ra production by IL-4 was also observed in monocytes stimulated with adherent IgG at both the mRNA and protein levels. This unique property of IL-4 may be important in down-regulation of the IL-1-initiated immune and/or inflammatory response, not only directly through inhibition of IL-1 production, but also indirectly through up-regulation of IL-1Ra production.

Gene Expression↗

PubMed1992

[Radiation therapy of intracranial germinoma].

The appropriate radiation dose and field for the treatment of intracranial germinoma were investigated in 33 patients. Recurrences were observed in 4 cases treated with local field irradiation only, and all of them were recognized at the margin of the radiation field or under the dose (less than 25 Gy) area. This suggests that whole cranial irradiation (dose of 25 to 30 Gy) should be added even if the tumor is solitary. The effective dose for cerebrospinal dissemination appears to be 25-35 Gy, but prophylactic CNS irradiation seems unnecessary for patients who have not undergone surgical procedures. Changes in mental status were seen in 5 patients (26.3%). Doses of over 59 Gy may be related to this complication.

Adolescent↗

PubMed1992

Differential effects of interleukin-4 on superoxide anion production by human alveolar macrophages stimulated with lipopolysaccharide and interferon-gamma.

The effect of interleukin-4 (IL-4) on the activation state of human alveolar macrophages (AMs) and blood monocytes induced by lipopolysaccharide (LPS) or recombinant interferon-gamma (IFN-gamma) was investigated on the basis of their ability to produce superoxide anion (O2-). AMs were obtained from healthy donors by bronchoalveolar lavage, and O2- productions of these cells were assayed by a cytochrome c reduction method after incubation with stimulants for 24 h. AMs produced more O2- than autologous blood monocytes when stimulated with LPS. IL-4 alone had little effect on O2- production by unstimulated AMs but down-regulated O2- production by LPS-stimulated AMs in a dose-dependent manner. IL-4 also suppressed O2- production by AMs induced by the synergistic actions of muramyl dipeptide (norMDP) and IFN-gamma. Maximum suppression by IL-4 of O2- production by AMs was observed when IL-4 was added within 1 h after initiation of LPS stimulation. AMs also showed high O2- production when stimulated with IFN-gamma alone. In contrast to its suppression of O2- production by LPS-stimulated AMs, IL-4 enhanced O2- production by AMs stimulated with IFN-gamma. These data suggest that IL-4 is an important regulator of O2- production by macrophages through different pathways depending on the stimulus.

Adult↗

PubMed1992

Human blood monocyte activation by Nocardia rubra cell wall skeleton for productions of interleukin 1 and tumor necrosis factor-alpha.

Human blood monocytes were obtained from peripheral blood of healthy donors by counter-flow centrifugal elutriation. Functional integrity of monocytes for production of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to Nocardia rubra cell wall skeleton (N-CWS) was examined by bioassay and enzyme immunoassay. Monocytes treated with N-CWS at more than 0.5 microgram/ml produced IL-1 and TNF-alpha extracellularly. Extracellular TNF activity appeared within 4 h, and maximally, 16 h after N-CWS stimulation, whereas longer time was needed for IL-1 activity to appear, the peak production being at 24 h. The neutralizing experiment also showed that anti TNF-alpha antibody did not affect IL-1 production by the monocytes treated with N-CWS, suggesting independency of IL-1 production of TNF-alpha. These results suggest that the therapeutic antitumor effect of N-CWS is due, in part at least, to the augmented production of these monokines.

Bacterial Proteins↗

PubMed1992

Thin-rim enhancement in Gd-DTPA-enhanced magnetic resonance images of tuberculoma: a new finding of potential differential diagnostic importance.

The article describes rim enhancement seen on Gd-DTPA-enhanced magnetic resonance (MR) images of two patients with tuberculoma. Pathologic examination of the surgical specimens disclosed that the peripheral portion of the tuberculoma, which showed contrast enhancement, was composed mainly of a fibrous capsule and epithelioid granulomas and that the central zone, which showed no contrast enhancement, was composed of caseous necrotic material. In a retrospective study of MR images from 20 consecutive cases of surgically proven bronchogenic carcinoma, none showed a thin enhancing rim on postcontrast MR images. Although confirmation of these findings must await further experience, the postcontrast MR findings described here may prove to be of value in distinguishing tuberculoma and possibly other granulomatous lesions from bronchogenic carcinoma.

Adult↗

PubMed1992

Effector cell analysis of human multidrug-resistant cell killing by mouse-human chimeric antibody against P-glycoprotein.

A mouse-human chimeric monoclonal antibody (mAb), MH162, against P-glycoprotein was previously found to be more effective than an all-mouse mAb (MRK16) in lysis of multidrug-resistant (MDR) tumor cells by blood mononuclear cells. The present study was performed to identify the effector cells responsible for the chimeric mAb-dependent cell-mediated cytotoxicity (ADCC) against MDR cells. The ADCC reaction was assessed by a 6-h 51Cr release assay. Highly purified lymphocytes (greater than 99%), monocytes (greater than 99%) and neutrophils (greater than 96%) were obtained from peripheral blood of the same healthy donors. A comparison of these three effector cell populations showed no difference between MH162 and its all-murine counterpart MRK16 in MDR cell lysis by monocytes or neutrophils. But MH162 was more effective than MRK16 in lymphocyte-mediated lysis of the MDR cells. The lymphocytes responsible for this ADCC had CD16+ Fc receptors. Pretreatment of monocytes with colony-stimulating factors (IL-3, GM-CSF and M-CSF) caused significant increase in their MH162-mediated lysis of MDR cells. Another anti-P-glycoprotein chimeric mAb (MH171) was also more effective than its murine counterpart MRK17 in lymphocyte-mediated lysis of MDR cells. These findings suggest that mouse-human chimeric mAbs may be useful therapeutically for in vivo destruction of MDR cancer cells by the ADCC reaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Inhibition by fibrin coagulation of lung cancer cell destruction by human interleukin-2-activated killer cells.

We examined the effect of fibrin coagulation on tumor cytotoxicity mediated by human lymphokine (IL-2)-activated killer (LAK) cells. LAK cells were induced from peripheral blood mononuclear cells (MNC) by culture with recombinant IL-2 for 4 or 5 days, and LAK cell-mediated cytotoxicity against tumor cells was assessed by 51Cr release assay in the presence or absence of plasma from normal subjects and lung cancer patients. Plasma did not affect the phase of induction of LAK activity by IL-2, but dose-dependently inhibited the effector phase of LAK cell-mediated cytotoxicity against Daudi cells. Similar inhibition of LAK cell-mediated cytotoxicity was observed on pretreatment of Daudi cells and human lung cancer cell lines with human fibrinogen plus thrombin. A parallel relationship was found between the amount of fibrinogen in plasma of lung cancer patients and inhibition of LAK cytotoxicity. This inhibition was reduced by addition of anticoagulants (heparin or argatroban). These findings suggest that fibrin coagulation on tumor cells protects them from LAK cell-mediated tumor cytotoxicity in malignant lesions and that a combination of an anticoagulant drug and IL-2/LAK therapy may be effective for treatment of lung cancer patients.

Aged↗

PubMed1992

Enhancement by monocytes of perforin production and its gene expression by human CD8+ T cells stimulated with interleukin-2.

Pore-forming protein (PFP) is an important effector molecule for cytotoxicity mediated by cytotoxic T cells and NK cells. In the present study, the effect of monocytes on PFP production by interleukin-2 (IL-2)-stimulated T lymphocytes was examined. Highly purified lymphocytes (> 99%) and monocytes (> 90%) were isolated by centrifugal elutriation from peripheral blood of healthy donors, and, CD4+ and CD8+ cells were isolated from the purified lymphocytes by using antibody-bound magnetic beads. PFP production was quantitated with a universal microspectrophotometer in combination with immunostaining using anti-PFP antibody. Monocytes did not produce any PFP. High levels of PFP production were observed in CD8+ cells, but not CD4+ cells after incubation for 4 days with IL-2. Addition of monocytes to cultures of CD8+ cells resulted in significant augmentation of PFP production after 3 days' stimulation with IL-2. Monokines (TNF alpha and IL-6) caused a significant increase in PFP production by IL-2-stimulated CD8+ cells. Northern blot analysis revealed that the PFP mRNA levels was enhanced by stimulation with IL-2, and that addition of monocytes to cultures of CD8+ cells plus IL-2 augmented their PFP mRNA expression. These observations suggest that monocytes are important in in situ regulation of the CD8+ T cell-mediated cytotoxic response through production of PFP.

Adult↗

PubMed1992

IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2.

The levels and activities of endogenous IL-6 in malignant pleural effusions due to lung cancer before and during daily intrapleural instillations of recombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependent murine hybridoma cell line MH60.BSF2. Before therapy, malignant pleural effusions contained various levels of IL-6. Daily intrapleural instillation of recombinant IL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleural effusions. On fractionation of the pleural effusion by chromatography, one major peak of material with a mol. wt of 24 kD showed IL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-1 beta was detectable in pleural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 production.

Adenocarcinoma↗

PubMed1992

MR imaging of thymoma: radiologic-pathologic correlation.

MR images in 17 patients with surgically proved thymomas (12 malignant and five benign) were reviewed and compared with pathologic specimens. In nine cases, MR images of excised specimens also were made and evaluated. On T2-weighted images, 11 of 12 malignant thymomas had an inhomogeneous signal intensity, half with and half without a lobulated internal architecture. None of the five benign thymomas had a lobulated internal architecture, and they all had a moderately or slightly inhomogeneous signal. Cystic regions and/or hemorrhage were noted pathologically, and corresponded to areas of inhomogeneous high signal intensity seen on T2-weighted images. Examination of the excised specimens in malignant thymomas showed that the lobulated configuration seen in the tumors was caused by thick fibrous septa. Our experience suggests that, although calcification cannot be identified, MR is helpful in making a differential diagnosis of mediastinal tumors and in determining malignancy of thymoma.

Adult↗

PubMed1992

Intrathoracic neurogenic tumors: MR-pathologic correlation.

An MR-pathologic correlation of nine intrathoracic neurogenic tumors (three neurofibromas, four schwannomas, and two ganglioneuromas) was performed to characterize their MR appearances. The three types of intrathoracic neurogenic tumor were found to have characteristic appearances on MR images that should be helpful when establishing the differential diagnosis of posterior mediastinal tumors. The MR and histologic features of these tumors are illustrated and described in this essay.

Adolescent↗

PubMed1992

[Induction of tumor cell killing by human alveolar macrophages and its regulation by IL-4].

The present study was undertaken to examine the effects of IL-4 on induction of cytotoxic killer activity and on production of antitumor mediators by human monocytes and alveolar macrophages (AM). The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4. Addition of IL-4 to cultures of AM or monocytes with endotoxin resulted in dose-dependent suppression of their cytotoxic activity against A375 and its variant cells resistant to IL-1 and TNF-alpha. IL-4 inhibited the production of IL-1 and TNF-alpha by AM at the protein and mRNA levels. Oxygen radical production was also suppressed by treating AM with IL-4. IL-1 receptor antagonist (IL-1ra) was also produced by monocytes stimulated with LPS, but not with IL-4. Marked up-regulation by IL-4 of IL-1ra production in LPS-stimulated monocytes was observed at both the mRNA and protein levels. These findings suggest that IL-4 may be important in down-regulation of antitumor activation of human monocyte-macrophages, not only directly through inhibition of production of antitumor effector molecules, but also indirectly through up-regulation of production of IL-1ra.

Cells, Cultured↗

PubMed1992

[A new polar map to quantify reversible area by myocardial 201Tl single photon emission computed tomography and clinical application to patients before and after percutaneous transluminal coronary angioplasty].

In the studies of stress 201Tl single photon emission computed tomography, we have developed a computer method to discriminate reversible from irreversible defect, then quantify each area and display the area on the polar map. Initial percent uptake (%Ui) and delayed percent uptake (%Ud) were expressed as percent of the maximum uptake area and were defined as regional myocardial 201Tl uptake in initial and delayed image, respectively. The %Ud/%Ui ratio was defined as redistribution ratio (RD-ratio). The values of %Ui obtained from each pixel of short axis slices were plotted against the values of RD-ratio on XY co-ordinates. In this graphic display, normal area, ischemic viable area and non viable area were separated by the following four lines. A; The straight line (Y = 2.0-0.012X) indicating the relationship between %Ui and RD-ratio for the group with ischemic viable myocardium. B; The parallel line to A and shifted to -1.5 SD from A. C; The vertical line at 67.0% level (ischemic upper level). D; The vertical line at 27.6% level (viable lower level). Each area was discriminated by color display and calculated relative area values were displayed on the polar map. Criteria for discriminating each area were derived from the results of ischemic pre-transluminal coronary angioplasty (PTCA) lesions (n = 21) in which viability was confirmed by successful PTCA and previous results of 66 cases with single vessel disease and 16 cases of control group. This new computerized technique was applied for evaluation of another group with successful PTCA (n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Induction by local injections of IL-2 of antitumor effector cells and secondary production of cytokines in malignant pleural effusion].

The present study was undertaken to examine the effects of intrapleural administration of IL-2 on induction of cytotoxic killer cells and on secondary production of cytokines in malignant pleural effusions. During daily local administration of IL-2, significant in vivo induction of cytotoxic activity was observed after 3-7 days, followed by a decrease in this activity in pleural mononuclear cells (MNC) to almost zero by day 15. IL-4 suppressed induction of IL-2-inducible killer cells from MNC in blood and pleural effusion, but significantly augmented the killer induction from pleural effusion MNC obtained after local 7-day administration of IL-2. Before therapy, malignant pleural effusions contained various levels of IL-6 and M-CSF, but no IL-4 or IFN-gamma. Daily intrapleural instillation of IL-2 resulted in significant augmentation of the levels of IL-4, IL-6, IFN-gamma and M-CSF. Chromatographical fractionation of the pleural effusion showed only one major peak with a MW of 24 kD, which had IL-6 activity. The level of the latent form of TGF-beta also increased during local IL-2 therapy. In contrast, significant levels of TNF (alpha, beta), IL-1 beta or IFN-alpha were not detectable in pleural effusions before or during therapy. These data suggest that IL-2 is an important inducer of secondary production of various cytokines in vivo, responsible for up- or down-regulation of induction of IL-2-inducible killer activity.

Cytokines↗

PubMed1992

Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.

Adult↗

PubMed1991

[Noninvasive quantitative measurement of cerebral blood flow with 123I-IMP--a study concerning the input function].

For the noninvasive quantitative measurement of cerebral blood flow (CBF) using N-isopropyl-[123I]p-iodoamphetamine (IMP), we studied the usefulness of the lung clearance curve obtained by a single probe detector as the input function for brain as an alternative to arterial blood activity. In four patients, we compared the time-activity curve of the lung and serial arterial blood activity for approximately 20 minutes following an IV bolus injection of IMP. Significant positive correlations were observed between lung clearance and the integral of arterial blood activity of IMP. In addition, a study to identify the best region for monitoring lung activity with the probe detector was performed in six patients using a gamma camera and region of interest (ROI) management. The central region of the right lung was found to be the best position for monitoring lung radioactivity. This study suggests that the lung clearance curve of IMP can be used as the input function for brain in the quantitative assessment of CBF.

Amphetamines↗

PubMed1991

Down-regulation by interleukin 4 of activation of human alveolar macrophages to the tumoricidal state.

The effect of recombinant human interleukin 4 (IL-4) on the expression of antitumor activity of human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined. AM were incubated for 16 h in medium with various macrophage activators [lipopolysaccharide, des-methyl muramyldipeptide, Nocardia rubra cell wall skeleton, and heptanoyl-gamma-D-Glu-(L)-meso-alpha,epsilon-A2pm(L)-D-Al aOH] in the presence or absence of IL-4, and then their tumoricidal activity was assayed by measuring 125I-UdR release from human melanoma (A375) cells. The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4 in 3 of 7 donors. Addition of IL-4 to cultures of AM with the activators resulted in dose-dependent suppression of AM-mediated cytotoxicity against A375 cells. IL-4 also inhibited AM-mediated cytotoxicity against A375-R cells, which are resistant to interleukin 1 (IL-1) and tumor necrosis factor alpha, HT-29 colon cancer cells, and KB cells. IL-4 inhibited the early induction phase of AM activation. Pretreatment of AM with IL-4 also suppressed their expression of antitumor activity in response to lipopolysaccharide. IL-4 inhibited the production of monokines (IL-1 and tumor necrosis factor alpha) by AM at the protein and mRNA levels. These findings suggest that IL-4 may be important in vivo in the down-regulation of antitumor expression of AM in the lung by inhibiting the production of monokines and other killing mechanisms.

Down-Regulation↗