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T Nishimura

Publications and source records attributed to T Nishimura.

At least 1,135 records · Page 63Linked to original sources
PubMed1987

Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1.

Nuclear oncogene products have the potential to induce alterations in gene regulation leading to the genesis of cancer. The biochemical mechanisms by which nuclear oncoproteins act remain unknown. Recently, an oncogene, v-jun, was found to share homology with the DNA binding domain of a yeast transcription factor, GCN4. Furthermore, GCN4 and the phorbol ester-inducible enhancer binding protein, AP-1, recognize very similar DNA sequences. The human proto-oncogene c-jun has now been isolated, and the deduced amino acid sequence indicates more than 80 percent identity with v-jun. Expression of cloned c-jun in bacteria produced a protein with sequence-specific DNA binding properties identical to AP-1. Antibodies raised against two distinct peptides derived from v-jun reacted specifically with human AP-1. In addition, partial amino acid sequence of purified AP-1 revealed tryptic peptides in common with the c-jun protein. The structural and functional similarities between the c-jun product and the enhancer binding protein suggest that AP-1 may be encoded by c-jun. These findings demonstrate that the proto-oncogene product of c-jun interacts directly with specific target DNA sequences to regulate gene expression, and therefore it may now be possible to identify genes under the control of c-jun that affect cell growth and neoplasia.

Amino Acid Sequence↗
PubMed1987

Protein kinase C required for cytotoxic T lymphocyte triggering.

The role of protein kinase C (PK-C) in triggering the lytic response of cytotoxic T lymphocytes (CTL) has been examined. Both target cell lysis and the release of CTL-associated serine esterase (SE), a marker for cytotoxic granules, were used as indicators of the CTL lytic response. We found triggering of the CTL lytic response occurred when both a PK-C activator, phorbol 12-myristate 13-acetate (PMA), and a calcium ionophore, ionomycin, were added to CTL. The previously described inactivation of the CTL lytic response by long term treatment (24 hr) with PMA was also investigated. CTL cultured with PMA for 24 hr were unable to mediate target cell lysis or release SE; this inability to respond correlated with an absence of PK-C activity. Incubation of the PMA-treated CTL in the absence of PMA for an additional 24 hr resulted in recovery of PK-C activity, SE release, and the lytic response. These experiments strongly suggest that PK-C is involved with the transmembrane signaling required for SE release which is a necessary event in CTL-mediated target cell lysis.

Animals↗
PubMed1987

Combination tumor-immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice.

Recombinant human tumor necrosis factor (r-TNF) inhibits growth of various mouse tumor cell lines both in vitro and in vivo. Treatment of established tumor nodules with intratumoral (i.t.) injection of r-TNF caused hemorrhagic necrosis of tumor and temporary disappearance of tumor mass. However, a small number of tumor cells remained and later formed fresh nodules. In striking contrast, combination therapy with r-TNF and recombinant human interleukin-2 (r-IL-2) resulted in a marked inhibition of regrowth of tumor cells. More than 60% of MBL-2-bearing mice were completely cured of tumor by treatment with r-TNF and r-IL-2. Cured mice could also reject rechallenged MBL-2 lymphoma cells, indicating the generation of anti-tumor effector cells in vivo. However, lymphocytes obtained from mice cured of MBL-2 showed no significant in vitro cytotoxic activity against MBL-2 lymphoma cells. In contrast, in vitro sensitization of spleen cells from cured mice with mitomycin-C-treated MBL-2 lymphoma cells resulted in the generation of cytotoxic cells against MBL-2 lymphoma cells. Moreover, spleen cells from mice cured of MBL-2 by treatment with r-TNF and r-IL-2 revealed a strong anti-tumor activity upon in vivo neutralization tests. These results strongly suggest that tumor-bearing mice can acquire systemic immunological memory after combination therapy with r-TNF and r-IL-2.

Animals↗
PubMed1987

Up and down regulation of serine esterase release from mouse cytotoxic T lymphocytes by tumor-promoting phorbol ester.

Activation of mouse cytotoxic T lymphocytes (CTL) with target cells expressing antigen resulted in the release of serine esterase (SE) into the culture supernatant. Short term treatment (3 hr) of CTL with phorbol-12-myristate-13-acetate (PMA) plus ionophore also caused stimulation of SE release from CTL, while neither PMA alone or ionophore alone could induce SE release. In contrast to this, long term treatment (24 hrs) of CTL with PMA resulted in the inability of CTL to release SE in respond to antigen or PMA plus ionophore. It was also demonstrated that protein kinase C activity of CTL disappeared during induction of desensitization of CTL by PMA.

Animals↗
PubMed1987

Candidacidal activity of monocyte-derived human macrophages: relationship between Candida killing and oxygen radical generation by human macrophages.

Freshly isolated human monocytes ingested and killed Candida albicans, and generated O2- H2O2 and .OH efficiently. When monocytes were cultured in vitro, these cells transformed into macrophages. Cultured monocytes retained their ingestive activity but lost their candidacidal activity almost completely after day 3. The release of O2- by monocytes decreased slightly with culture and that of .OH was markedly decreased on day 3 of culture. The activity of myeloperoxidase in the monocytes decreased with culture. These results suggested that the loss of candidacidal activity is due to the decrease of .OH generation and myeloperoxidase activity in cultured monocytes.

Blood Physiological Phenomena↗
PubMed1987

Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin.

It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of 111In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. 111In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. The uptake of 111In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.

Animals↗
PubMed1987

Quantitative assessment of thallium myocardial washout rate: importance of peak heart rate and lung thallium uptake in defining normal values.

Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors influencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate was closely related to peak heart rate (r = 0.72) and inversely related to lung thallium uptake (r = -0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P less than 0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy.

Adult↗
PubMed1987

Clinical significance of 201Tl reverse redistribution in patients with aorto-coronary bypass surgery.

Detection of myocardial ischemia by the stress thallium scan has traditionally been performed using transient defect analysis on exercise, followed by redistribution studies. Worsening of the 201Tl myocardial image from exercise to redistribution is referred to as reverse redistribution. In this study, we found reverse redistribution in 10 (21%) of 48 angina pectoris patients who had undergone aortocoronary bypass surgery. The clinical significance of this phenomenon in these patients was investigated in relation to angiographic and surgical findings. Reverse redistribution was found to occur in regions which were supplied by bypass grafts. These areas showed increased coronary blood flow and rapid thallium washout. Our results indicate that a perfusion defect in the bypass region of the redistribution image might be caused by relatively rapid washout in the bypass graft region compared to the adjacent normal myocardium. These results should be considered in the clinical interpretation of stress thallium scans.

Adult↗
PubMed1987

Magnetic resonance imaging of human cerebral infarction: enhancement with Gd-DTPA.

Five patients (1 female and 4 males) with cerebral infarction of 4 h to 27 months duration were studied 9 times with magnetic resonance (MR) using Gd-DTPA. Spin-echo (SE) MR images (MRI) were obtained before and after the administration of Gd-DTPA, and correlative CT scans were performed on the same day. In 2 cases, 4 h and 27 months after the ictus, there was no enhancement with Gd-DTPA. There was faint enhancement in 2 cases with cerebral infarction of about 24 h duration and obvious enhancement in all cases in the subacute stage. Compared with enhanced CT, MR using Gd-DTPA demonstrated more obvious enhancement of infarcted areas. MR enhancement using Gd-DTPA showed a gradual increase and the accumulated Gd-DTPA in infarcted areas slowly diffused to the periphery. MR enhancement with Gd-DTPA is similar to that of enhanced CT, but may be more sensitive in the detection of blood brain barrier breakdown.

Adult↗
PubMed1987

Cor pulmonale due to embolization of metastatic chondrosarcoma.

A 25-year-old woman with acute dyspnea was found to have nodular shadows in a chest X-ray film. Multiple defects in a perfusion scan indicated pulmonary embolization. The cause of acute cor pulmonale was extensive metastatic embolization from chondrosarcoma of the calf. Embolization by metastasis as a rare occurrence resulting in acute cor pulmonale should be considered in patients with a malignant tumor.

Adult↗
PubMed1987

Identification of cardiac rejection with magnetic resonance imaging in heterotopic heart transplantation model.

It is important to evaluate the severity and extent of cardiac rejection in heart transplantations. Eight heterotopic heart transplantations using mongrel dogs were performed, and grated magnetic resonance imaging (MRI) of the donor hearts was carried out. High signal intensity was obtained in the rejected myocardium at the time of cardiac rejection, especially from the right ventricular wall to the intraventricular septal wall compared with the left ventricular posterolateral wall. In addition, MRI was performed in the excised heart. High signal intensity was also observed in the same region of the excised donor hearts. The histopathological rejection scores were well in agreement with prolonged T1 and T2 relaxation times; severe and mild rejection of the myocardium were distinguished by the T1 and T2 relaxation times. Our results suggest that MRI is able to visualize the transplanted myocardium undergoing rejection and that the right ventricular wall is more sensitive to cardiac rejection than the left. MRI may allow noninvasive evaluation of the severity and extent of cardiac rejection.

Animals↗
PubMed1987

Cardiac transplantation in dogs: evaluation with gated MRI and Gd-DTPA contrast enhancement.

It is important to evaluate the severity and extent of cardiac rejection in heart transplantation. Six heterotopic heart transplantation models in the peritoneal cavity were prepared with 12 adult mongrel dogs and in vivo imaging of the donor heart was performed using gated magnetic resonance imaging, (MRI) and Gd-DTPA contrast enhancement. In cardiac rejection, high signal intensity was obtained in the rejected myocardium, especially from the right ventricular wall to the intraventricular septal wall. The rejected myocardium was clearly visualized after administration of Gd-DTPA (0.5 mmol/kg body weight) via the femoral vein in all donor hearts. The mean ratios of signal intensity calculated from the rejected and normal myocardium were also increased from 25% to 42% after administration of Gd-DTPA. On the other hand, in the cases with no rejection, whole myocardium was visualized homogeneously before and after Gd-DTPA and there was no high signal intensity. Thus, our method has the potential of assessing the extent and severity of cardiac rejection using gated MRI and Gd-DTPA contrast enhancement.

Animals↗
PubMed1987

Scintigraphic assessment of double-chambered right ventricle.

A double-chambered right ventricle is often clinically misdiagnosed and may be missed even during cardiac catheterization. We encountered a 56-year-old male who had abnormal right ventricular thallium-201 uptake and a photon deficient area in the right ventricle by radionuclide cardioangiography. These findings strongly suggested the existence of anomalous muscle band in the right ventricle. It was demonstrated by contrast angiography that the right ventricle was divided into two chambers by a hypertrophic muscular band; the pressure gradient in the right ventricle was 98 mmHg.

Heart Ventricles↗
PubMed1987

The role of lymphokine-activated cell-associated antigen. II. Distribution and correlation with cell cycle.

It has previously been shown that killer-blocking monoclonal antibody (KBA MAb) recognizes lymphokine-activated cell-associated antigen (LAA) involved in broad-reactive killer. (BRK) cell-mediated cytotoxicity. We now report that LAA is expressed on all lymphoid cells, though the amount of LAA on unstimulated lymphocytes is low. In contrast, lymphocytes activated in vitro with either concanavalin A, alloantigens, lipopolysaccharide, or recombinant interleukin 2 express high levels of LAA. In addition, in vivo activated lymphocytes, such as OK-432-activated lymphocytes and tumor-infiltrating lymphocytes express higher levels of LAA than unstimulated lymphocytes. We also demonstrate that the expression of LAA is restricted in T-cell lymphomas and a M phi cell line, while myelomas, fibrosarcomas, and carcinomas do not express LAA. Cell cycle analysis using propidium iodide and KBA MAb showed that LAA expression was closely correlated with the transition of cells from G1a to G1b phase.

Animals↗
PubMed1987

The role of lymphokine-activated cell-associated antigen. III. Inhibition of T-cell activation by monoclonal killer-blocking antibody.

The addition of monoclonal killer blocking antibodies (KBA MAb) to cultured T cells resulted in significant inhibition of T-cell responses to concanavalin A (Con A), class I antigen and class II antigen, whereas T-cell responses to phytohemagglutinin are insensitive to KBA MAb. The inhibitory effect of KBA MAb is observed only when KBA MAb is added to the culture at an early time. This indicates that the lymphokine-activated cell-associated antigen (LAA) defined by KBA MAb plays an important role in the early stages of T-cell activation. Con A-induced interleukin 2 (IL-2) receptor acquisition and IL-2 production, both of which are required for the early steps of T-cell activation, were greatly inhibited by KBA MAb. However, KBA MAb did not inhibit the action of IL-2, which is required for later stages of T-cell activation.

Animals↗