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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 433 records · Page 24Linked to original sources

[Assessment by flow cytometric method of IgE-binding state of basophils in allergic disorders].

Basophils, as well as mast cells, express Fc epsilon RI on the surface. It is known that activation of basophils and mast cells leads to induction of chronic allergic inflammation. In this study, levels of IgE bound to the surface of peripheral blood basophils were measured using a flowcytometry, and their clinical relevance was evaluated. Peripheral whole blood samples were stained with FITC-conjugated anti-IgE. The fluorescence intensity of the FITC-positive cells within mononuclear cell region was determined. Basophil-bound IgE levels increased along with age and reached invariably high levels of adults. The levels of basophil-bound IgE were higher among allergics than normal controls, in early infancy. In addition, many of the infants with repeated wheezing episodes also exhibited high levels of it. These findings suggest that early exposure of predisposed infants to antigens leads to early sensitization of circulating basophils. Basophil-bound IgE levels correlated well with serum IgE concentration, but they remained constant when IgE concentrations exceeded 300 ng/ml, suggesting that IgE-binding capacity of basophils become saturated at this IgE level. In conclusion, it is shown that flowcytometric measurement of basophil-bound IgE provides a useful method of analyzing this rare cell population within the peripheral circulation, and it serves as a critical parameter to evaluate the allergic inflammation in vivo.

Adolescent↗

Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP-1).

We investigated the pathophysiological role of a potent macrophage (M(phi)) chemotactic cytokine (chemokine), monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), in an animal model of crescentic glomerulonephritis. Administration of a small dose of nephrotoxic sera induced severe proliferative and necrotizing glomerulonephritis, with crescentic formation in the early phase and glomerulosclerosis in the later phase, in Wistar-Kyoto rats. MCAF/MCP-1 protein was detected immunohistochemically in glomeruli, vascular endothelial cells, and tubular epithelial cells in the early phase of injured kidney tissues but not in normal ones. Anti-MCAF/MCP-1 antibodies decreased the number of M(phi) in glomeruli, and prevented crescentic formation and the fusion of epithelial cell foot process in nephritic rats, thereby decreasing the excreted amounts of protein to normal levels on days 3 and 6. Furthermore, anti-MCAF/MCP-1 antibodies remarkably reduced glomerulosclerosis and improved renal dysfunction as well as proteinuria in the later phase (56 days). These results indicate that MCAF/MCP-1 essentially participates in the impairment of renal functions associated with crescentic glomerulonephritis by recruiting and activating M(phi).

Animals↗

[Trial of home infusion therapy for near-terminal stage patients with lung cancer].

To improve the quality of life in patients with malignant diseases at the near-terminal stage, we established a system for home infusion therapy (HIT) in Osaka Prefectural Habikino Hospital in 1994. Thirty-three patients were taken care of at home using the HIT system from January, 1995 to May, 1996. Their average age was 70 years old. The duration of HIT varied from 1 to 105 days (mean:25.5 days). Twenty-four cases received parenteral nutrition. The others received agents for brain edema (4 cases), morphine hydrochloride (2 cases), and anti-fungal agents (3 case). Additionally, 63% of these patients required home oxygen therapy (HOT) with HIT. Questionnaires to their families revealed that they were afraid of the progress of the disease in patients and their physical burden became heavier after the start of HIT. However, they were quite satisfied with the results of HIT.

Adolescent↗

Construction of a cDNA library for a specific region of a chromosome using a novel cDNA selection method utilizing latex particles.

A novel method is described for the rapid concentration of particular cDNAs and their mapping to specific regions of a genome. The strategy for 'cDNA scanning' is based on the hybridization of an entire library of cDNAs to a large fragment of genomic DNA that is covalently bound to latex particles. The hybridized cDNAs are eluted, amplified by PCR and cloned into a lambda vector. Selected cDNAs that hybridized to the genomic DNA are cloned, with subsequent sequence analysis. Region-specific DNA fragments prepared from a yeast artificial chromosome (YAC) clone, EG10D9, which maps to chromosome 5 of the small cruciferous plant Arabidopsis thaliana (At), were used to prepare a model system and were covalently bound to latex particles. cDNAs that hybridized to EG10D9 were concentrated by hybridization to the immobilized DNA. The hybridized cDNAs were recovered and amplified by PCR. The resultant sub-library of cDNAs of 0.5-2 kb in length was enriched about 1000-fold. The partial sequences of the cDNAs provided information about genes that are located on the EG10D9 region of the At genome. The cDNA scanning strategy provides an efficient method for the mapping of expressed genes which could be used as expressed sequence tags (EST) within a genome.

Arabidopsis↗

Characterization of the truncated thrombopoietin variants.

Thrombopoietin (Tpo) is a specific cytokine which regulates megakaryocyte differentiation and maturation. We isolated a truncated mouse Tpo cDNA, the product of which turned out to function neither as an active Tpo variant nor as an antagonist. To define the functional domains of the Tpo molecule further, various truncated and point-mutated Tpo molecules were prepared and their biological activity was assayed. It was found that deletion of the amino terminal side of a potential proteolytic cleavage site, Arg-Arg motif, caused complete loss of Tpo's activity, and that point-mutants lacking one of four conserved cysteine residues lost Tpo activity. We also noticed that Tpo activity was inhibited by the reducing agent. Thus, it was concluded that the amino terminal half of the Tpo is sufficient for Tpo activity, and that the cysteine residues, especially the last cysteine residue located two amino acids away from the Arg-Arg motif, are critical for this activity.

Amino Acid Sequence↗

Reduction in risk of mortality from colorectal cancer by fecal occult blood screening with immunochemical hemagglutination test. A case-control study.

Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case-control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17-0.92], 0.41 (95% CI 0.20-0.82), and 0.48 (95% CI 0.25-0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.

Adult↗

CAF versus CAF plus Medroxyprogesterone Acetate for Treatment of Liver Metastases of Breast Cancer.

A controlled randomized trial was conducted to compare the effectiveness of a CAF therapy including cyclophosphamide (CPA), adriamycin (ADR) and 5-fluorouracil (5FU) with that of CAF plus medroxyprogesterone acetate (MPA) therapy including CPA, ADR and 5FU plus MPA for the treatment of liver metastases from breast cancer. A total of 34 patients with unresectable liver metastases from breast cancer were divided into two treatment groups(CAF and CAF + MPA)with stratification for estrogen receptor status. The response rate was 13%(2PR in 16 patients)for CAF therapy and 22% (1 CR and 3 PR in 18 patients) for CAF plus MPA therapy. There was no significant difference in response rates, median survival periods and survival rates between the two treatment groups. However, CAF therapy had significantly more toxicity than did CAF plus MPA therapy. The findings of this study suggested that CAF plus MPA therapy is a well-tolerated and effective treatment for patients with liver metastases of breast cancer.

Journal Article↗

Characteristics of specific 125I-omega-conotoxin GVIA binding and 125I-omega-conotoxin GVIA labeling using bifunctional crosslinkers in crude membranes from chick whole brain.

Characteristics of specific 125I-omega-conotoxin GVIA (125I-omega-CgTX) binding and 125I-omega-CgTX labeling using bifunctional crosslinkers were systematically investigated in crude membranes from chick whole brain. Aminoglycosides and dynorphine A (1-13) inhibited the specific binding of 125I-omega-CgTX, but not that of the L-type calcium ion channel antagonist [3H](+)PN200-110. It seems likely that the inhibitory effect of dynorphine A (1-13) does not involve kappa-opiate receptors, based on results with the opiate receptor antagonist naloxone and the kappa-opiate receptor agonist U50488H. Spider venom, Cd2+ and La3+ inhibited the specific binding of 125I-omega-CgTX, as well as that of [3H](+)PN200-110. Various L-type Ca2+ channel antagonists did not affect the specific binding of 125I-omega-CgTX. 125I-omega-CgTX specifically labeled 135 kDa and 215 kDa bands in crude membranes under reduced and non-reduced conditions, respectively. The crosslinker disuccinimidyl suberate (DSS) yielded better 125I-omega-CgTX labeling than the other two crosslinkers tested. We investigated the effect of various Ca2+ channel antagonists on 125I-omega-CgTX labeling with DSS in detail, and found that there is a strong correlation between the effects of Ca2+ channel antagonists on 125I-omega-CgTX labeling of the 135 kDa band and specific 125I-omega-CgTX binding. These results suggest that aminoglycosides and dynorphine A (1-13) are specific inhibitors of specific 125I-omega-CgTX binding, and that labeling of the 135 kDa band with 125I-omega-CgTX using DSS involves the specific binding sites of 125I-omega-CgTX, perhaps including one of the neuronal N-type Ca2+ channel subunits in the crude membranes.

Affinity Labels↗

Characteristics of [125I]omega-conotoxin labeling using bifunctional cross linker DSP in crude membranes from chick brain.

Characteristic of [125I]omega-conotoxin (omega-CgTX) labeling using bifunctional cross linker (dithio bis[succinimidyl propionate]:DSP) was systematically investigated in crude membranes from chick whole brain. [125I]omega-CgTX specifically labeled 216 kDa as a main and 236 kDa as a minor bands in the crude membranes under non-reduced condition, but not labeled under reduced condition. We investigated the effect of various Ca channel antagonists on [125I]omega-CgTX labeling with DSP in detail, and found that there is a strong correlation between the effects of Ca channel antagonists on [125I]omega-CgTX labeling of the 216 kDa band and specific [125I]omega-CgTX binding. These results suggest that labeling of the 216 kDa band under non-reduced condition with [125I]omega-CgTX using DSP involves the specific binding sites of [125I]omega-CgTX, perhaps including one of the neuronal N-type Ca channel subunits in the crude membranes.

Animals↗

Indium-111 antimyosin monoclonal antibody Fab imaging in patients with cardiomyopathy.

Six patients with cardiomyopathy were imaged following intravenous injection of an indium-111 labeled monoclonal antibody directed against the heavy chain of cardiac myosin. Two patients had hypertrophic non-obstructive cardiomyopathy (HNCM), two patients had dilated cardiomyopathy (DCM), and two patients had specific heart muscle disease. One of 2 patients with HNCM and one of 2 patients with DCM had a positive antimyosin scan. The 2 patients with specific heart muscle disease manifested persistent blood pool activity of the antibody, thereby precluding interpretation of the images. The present report demonstrates that antimyosin antibody imaging may provide evidence of myocardial injury, or necrosis in some patients with cardiomyopathy.

Adolescent↗

Differentiation and proliferative activity in benign and malignant cartilage tumors of bone.

To assess the histological grade in benign and malignant cartilage tumors of bone by more objective methods, we examined the differentiation and proliferative activity of tumor cells in six enchondromas, five chondroblastomas, and 13 chondrosarcomas immunohistochemically. A variable number of cells in all tumors showed S-100 protein and vimentin immunoreactivity. In fully differentiated cartilage of enchondromas and low grade chondrosarcomas, tenascin, which is an extracellular matrix glycoprotein, was present in small amounts or absent but was increased at the periphery of tumor lobules and even in the matrix throughout the high grade chondrosarcomas. Higher rate and intensity of proliferating cell nuclear antigen (PCNA) reactivity were found in chondrosarcomas, especially in spindle-shaped cells of high grade tumors, than in enchondromas. The distribution of PCNA-positive cells almost corresponded to the regions with tenascin reactivity. One tumor of high grade chondrosarcoma showed p53 protein immunoreactivity. Aberrant expression of cytokeratin was observed in four chondroblastomas. The expression of desmin was identified in relatively large proportions of enchondromas and chondrosarcomas, regardless of their benign or malignant nature and histological grade. Smooth muscle or muscle-specific actins also were present in a smaller number of tumors. Based on these findings, it is concluded that unusual staining characteristics were present, in addition to those of a chondroblastic nature, in the cartilage tumors of bone. Tenascin and PCNA positivity of various degrees in all chondroblastomas may suggest that they are chondrogenic tumors having a relatively high proliferative activity, albeit their benign clinical course. Proliferative activity of tumor cells in enchondromas and chondrosarcomas correlated well with their histological grade. Tenascin may play a role in promoting tumor cell proliferation of cartilagenous neoplasms and, on the other hand, the alterations of extracellular matrix involving tenascin synthesis seem to be a result of tumor development.

Adolescent↗

Mucosal condition of the oral cavity and sites of origin of squamous cell carcinoma.

PURPOSE: This study investigated the clinical appearance of the affected mucosa in patients with squamous cell carcinoma (SCC) in the oral and oropharyngeal region. PATIENTS AND METHODS: The mucosal conditions of 396 patients was classified into two types. Type A, showing ulcer formation and/or tumor formation, and type B, showing only mucosal enlargement without any other abnormality. RESULTS: Type A was detected in the oral cavity and oropharynx, and type B was observed only in the upper and lower alveolus and gingiva. Of 14 type B patients histologically evaluated for the relationship between the tumor cells and surface oral epithelium, 10 showed a disconnection between the epithelium and the tumor cells, whereas in two the tumor cells extended into the epithelium. CONCLUSION: It was concluded that SCC of type B is not of oral epithelial origin, but is of maxillary sinus epithelium or odontogenic cell origin. In the mandible, type B SCC originates from odontogenic epithelium (odontogenic carcinoma).

Carcinoma, Squamous Cell↗

Sarcolemmal indentation in cardiomyopathy with mental retardation and vacuolar myopathy.

Muscle biopsies from three patients with cardiomyopathy, mental retardation and increased serum creatine kinase levels revealed scattered fibers with tiny intracytoplasmic vacuoles containing basophilic and acid phosphatase-positive material and slightly increased amounts of PAS-positive granules. These findings are consistent with those seen in the so-called lysosomal glycogen storage disease with normal acid maltase. In addition to the vacuoles, there were occasional folds or indentations in the sarcolemma which were connected to the membrane enclosing the vacuoles. These membranes were well demonstrated histochemically by the nonspecific esterase and acetylcholinesterase stains. On electron microscopy, most of the vacuoles were bounded by membranes with basal lamina. The vacuolar membrane stained positively with antibodies raised to dystrophin, dystrophin-associated glycoproteins, laminin and type 4 collagen, and it was identical to the sarcolemma and its basal lamina. Therefore, the membrane abnormality which causes sarcolemmal folding is probably critical to understanding the pathomechanism of this disease.

Adolescent↗