Monoclonal antibody-conjugated immunotherapy of cancer.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Imai.
Explore the source record for details and available documents.
The hydroxyl radical (.OH)-scavenging activity of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a novel nonsteroidal anti-inflammatory drug (NSAID), and that of several other NSAIDs were investigated by the hyaluronic acid (HA) degradation method and the electron spin resonance (ESR) spin-trapping technique. The superoxide anion (.O2-)-scavenging activity of M-5011 was also measured by the ESR technique. (1) M-5011 and the other NSAIDs examined inhibited the degradation of HA induced by the Fenton reaction system in a dose-dependent manner. (2) M-5011 and the other NSAIDs scavenged .OH directly in a dose-dependent manner. (3) M-5011 was the most potent drug among the NSAIDs tested regarding the scavenging activity of .OH as follows; M-5011 > indomethacin > ketoprofen = suprofen > aspirin. The .OH-scavenging activity of M-5011 was potent in comparison with that of oxidized glutathione (GSSG), an endogenous .OH scavenger. (4) M-5011 did not scavenge .O2-; nor did GSSG. These results suggest that M-5011 acts as a scavenger of .OH at sites with inflammatory lesions.
The benign osteoblastoma is rarely seen as a tumor of the facial bone in infancy or early childhood. Only five cases with nasal involvement have been reported in the literature. The authors present a case of osteoblastoma of the nasal cavity, the nasal bone, the ethmoid sinus, and the anterior cranial base. This 3-year-old girl presented with a tumor surrounding the left medial canthus. Imaging studies, including x-ray films, computerized tomography scans, magnetic resonance images, a (99m)Tc-scintigram, and angiograms, confirmed the location of the tumor. A biopsy specimen of tumor was obtained intranasally and the pathological diagnosis was an osteoblastic tumor suggestive of osteoblastoma. Although the tumor margin was well defined on the radiological images, it was difficult to determine the exact margin during the operation. Therefore, it is important to show how to excise the tumor completely under direct view. With the use of a "dismasking flap," it was possible to resect the benign osteoblastoma completely from the nasal cavity, even though it extended into the orbit, the maxilla, and the anterior cranial base.
PURPOSE: The authors examine the effect of retinal branch vein occlusion (BVO), a common retinal vascular disorder, on protein tyrosine phosphorylation, production of angiogenic growth factors, and activation of signal proteins in the tyrosine kinase pathways in the retina. METHODS: Retinal branch vein occlusion was induced in cat retina by coagulation of retinal veins with diathermy. At 2 days, 1, 3, and 6 weeks after induction of BVO, the retina was divided into three parts: a part within the distribution of the occluded vein (BVO[IN]) or a part outside the distribution of the occluded vein (BVO[OUT]). Each part of the retina was prepared for Western blot analysis of tyrosine-phosphorylated proteins, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and four signal proteins in the tyrosine kinase pathways, which were phospholipase C gamma (PLC gamma), C-Src, SH2-containing protein (SHC), and mitogen-activated protein kinase (MAPK). RESULTS: Overall, tyrosine-phosphorylated proteins were increased after BVO, especially in BVO(IN) at 2 days and 1 week. The VEGF and bFGF also were increased in BVO(IN) at 1 week and 2 days, respectively. The PLC gamma and MAPK were activated at these time points. The C-Src and SHC were not activated in the retina after BVO. CONCLUSIONS: The BVO increased overall protein tyrosine phosphorylation in the cat retina in association with increase of angiogenic growth factors (VEGF and bFGF) and activation of two signal proteins (PLC gamma and MAPK) in the tyrosine kinase pathways. These results suggest that the protein tyrosine phosphorylation may in part play an important role in mitogenesis of vascular endothelial cells and other retinal responses after BVO.
PURPOSE: A new technique of transurethral resection of bladder tumors is described. MATERIALS AND METHODS: A 2.5 cm. papillary, sessile bladder tumor was treated via a rotational resection technique with a new arched electrode to replace longitudinal resection using a conventional loop electrode. RESULTS: This method was easy to perform and allowed for en bloc resection of bladder tumor. CONCLUSIONS: This rotational resection technique is useful for evaluation of pathological depth of tumors in resected specimens.
Hepatic stellate cells (vitamin A-storing cells, lipocytes, fat-storing cells, Ito cells) exist in the perisinusoidal space of the hepatic lobule, and store 80% of retinoids in the whole body as retinyl palmitate in lipid droplets in the cytoplasm. In physiological conditions, these cells play pivotal roles in the regulation of retinoid homeostasis; they express specific receptors for retinol-binding protein (RBP), a binding protein specific for retinol, on their cell surface, and take up the complex of retinol and RBP by receptor-mediated endocytosis. By contrast, in pathological conditions such as liver fibrosis, these cells lose retinoids, and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan and adhesive glycoproteins. The morphology of these cells also changes from the star-shaped stellate cells to that of fibroblasts or myofibroblasts. It is concluded that three-dimensional structure of the ECM components reversibly regulates the morphology, proliferation, and functions of the hepatic stellate cells.
Explore the source record for details and available documents.
Matrix metalloproteinases (MMPs) are expressed in osteoarthritic (OA) cartilage and are thought to be involved in the degradation of cartilage extracellular matrix (ECM). Among these proteinases, MMP-2 (gelatinase A) demonstrates a wide range of substrate specificity against the ECM present in cartilage. Although MMP-2 expression increases in OA cartilage, the activation mechanism of the corresponding zymogen (pro-MMP-2) in cartilage is unknown. In this study, we examined the expression pattern of membrane-type 1 MMP (MT1-MMP) in human OA articular cartilage and its correlation with the activation of pro-MMP-2. Immunohistochemical studies demonstrate that MT1-MMP localizes to the chondrocytes in the superficial and transitional zones in all of the samples examined directly correlating with cartilage degradation. Reverse transcription polymerase chain reaction confirmed the predominant expression of MT1-MMP mRNA in the OA cartilage. In situ hybridization revealed the site of expression of MT1-MMP in OA cartilage to be the chondrocytes. Through gelatin zymography and a sandwich enzyme immunoassay it was demonstrated that OA cartilage explants secrete significantly higher levels of pro-MMP-2 than normal samples. Pro-MMP-2 activation was enhanced in the OA cartilage samples and correlated with MT1-MMP expression in the cartilage. Plasma membranes prepared from cultured chondrocytes with MT1-MMP expression and those directly isolated from OA cartilage could activate pro-MMP-2. MT1-MMP gene expression in cultured chondrocytes was induced by treatment with interleukin-1 alpha and/or tumor necrosis factor-alpha. These data suggest that cytokine-induced MT1-MMP in the chondrocytes may play a key role in the activation of pro-MMP-2 in the OA articular cartilage, leading to cartilage destruction through ECM degradation.
It is known that the expression levels of intercellular adhesion molecule-1 (ICAM-1) in adult T cell leukemia(ATL) cells are high, whereas those in T-lymphoid cells are not. In order to investigate the factors that influence the induction of ICAM-1 molecules, Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 (HTLV-1) provirus were done. The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells. However, ILT-mat cells and ATL16T(-) cells, although they were ATL cells, showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression. Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells, respectively, whereas > 10 bands were detected in other ATL cells. These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell, especially the number of integration sites, is one of the factors for induction of ICAM-1 molecules.
Explore the source record for details and available documents.
OBJECTIVE: To assess the anterior mediastinal mass in recurrent testicular cancer, with relation to thymic hyperplasia after treatment. METHODS: The anterior mediastinal regions were fully evaluated by chest computed tomography (CT) at the initial staging and after treatment in 24 of 44 patients with testicular cancer. RESULTS: One patient with stage IIB tumor had thymic hyperplasia before treatment, and one with stage III had benign thymic hyperplasia after chemotherapy with salvage surgery. Three of 4 patients who had recurrence had an anterior mediastinal mass. One had benign thymic hyperplasia confirmed by histology and 2 had metastatic tumor confirmed by histology and clinical course, in which the mass became so enlarged that it obstructed major vessels. CONCLUSION: Although the relationship of the CT finding to the response to treatment in the anterior mediastinal mass and other metastatic lesions provide some clues helpful in differentiating benign from malignant masses, surgical exploration is recommended for the patient with an indication for salvage surgery.
A 79-year-old man developed nodular skin eruption in his trunk in March 1995. He was diagnosed as CTCL and hospitalized to the department of dermatology and low dose VP-16 therapy was started. 6 months later, he was referred to our department because of severe melena. On admission, marked monocytosis was observed both in the bone marrow (43.6%) and peripheral blood (monocyte > 1,000/microliter). Skin biopsy showed infiltration of large mononuclear cells in the dermis and subcutaneous tissue. Thus a diagnosis of CMML with skin infiltration was made. Skin eruption developed over his entire skin and peripheral monocytes increased over 5,000/microliter. Chemotherapy was started and skin infiltration was slightly improved, but the disease developed into acute phase and he died 3 months after admission.
Explore the source record for details and available documents.
Sustained left ventricular systolic dysfunction after transient myocardial ischemia is well known as "myocardial stunning", but little is known about the recovery in left ventricular diastolic function. Changes in left ventricular systolic and diastolic performance following dobutamine-induced ischemia were investigated in 13 patients with chest pain syndrome and normal coronary arteries (control) and 34 patients with coronary artery disease. Two-dimensional echocardiography and pulsed wave Doppler transmitral flow velocity curves were recorded at baseline, after infusion of a peak dose of dobutamine and at 20 min and 2 hours after dobutamine infusion. In control subjects, left ventricular ejection fraction and the peak early diastolic filling velocity increased at the peak dose of dobutamine. At 20 min after the cessation of dobutamine infusion, these values were restored to the baseline levels. In patients with coronary artery disease, ejection fraction and peak velocity increased at the peak dose of dobutamine but decreased at 20 min after infusion compared with baseline values despite the restoration of heart rate and blood pressure. Although ejection fraction increased at 2 hours compared with 20 min after infusion, peak velocity did not increase. Left ventricular diastolic dysfunction may be sustained longer than systolic dysfunction after transient myocardial ischemia.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Since the obtained results from the pilot study indicated that dilazep which was a membrane stabilizer would be benefit to treatment and prevention of anemia and chronic leg ulcer in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients, the authors had continued the study in a second phase, ie a double blind placebo control trial. Twenty-seven beta-thal/HbE patients were recruited in the study. Eight patients who suffered from chronic leg ulcer were given dilazep. The rest of patients were given dilazep or placebo according to a randomized table. Hence, 16 patients received dilazep and 11 received placebo. When we compared the number of unit of blood transfusion, hemoglobin level, 2-3 DPG and P50 value between the dilazep and placebo groups using unpaired t-test, we found that there were no statistical differences in any of the parameters. However, when we compared the data within the group using paired t-test, there was statistical decrease in blood requirement after treatment in the dilazep group (p < 0.05). Concerning with the treatment of chronic leg ulcer, 3 in 8 patients were completely healed within 3 months, 4 in 8 patients were improved and 1 in 8 patients was not improved. There were complaints of skin itching and mild epigastric pain in placebo group but the liver function tests, kidney function tests and cardiac enzyme did not significantly change during the medication.
Reports on the distribution, metabolism and origins of free D-amino acids in vertebrate tissues and body fluids are reviewed. The transient emergence of D-aspartic acid during the development of brain and peripheral organs or early stages of life is reported. D-Serine in brain is postulated to be a potentiator for the N-methyl-D-aspartate (NMDA) receptor. Some D-amino acid concentrations in human serum, such as D-Ser and D-Ala, are suggested to correlate with damage to renal function.