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Biomedical subjects

T Aoki

Publications and source records attributed to T Aoki.

At least 505 records · Page 28Linked to original sources

Murine colon carcinoma cells engineered to produce human interleukin-2 induce tumor-specific anti-tumor response.

Murine colon carcinoma cells (colon 26) transduced by a retrovirus vector with the human interleukin-2 (IL-2) cDNA were studied for their tumorigenicity. Although cell growth in vitro was not affected by integration of the IL-2 gene, s.c. tumors of IL-2-producing colon 26 cells (H2) in syngeneic mice regressed spontaneously after producing small masses. Histological examination of the sites of tumor rejection revealed predominant infiltration of macrophages around the tumor necrotic mass. Subsequent challenge with parent colon 26 cells, but not with Meth A cells (fibrosarcoma of the same genetic background), did not result in tumor formation in mice which had been protected against H2 cells. Inoculation of H2 cells into syngeneic nude mice resulted in tumors with a retarded growth rate. Taken together, T cell-dependent, tumor-specific immunity is obtained by local IL-2 secretion around colon tumors, and this experimental animal model gives us a clue(s) for investigating host anti-tumor responses by cytokine production.

Animals↗

The ankyrin repeats but not the PEST-like sequences are required for signal-dependent degradation of IkappaBalpha.

The nuclear activity of Rel/NFkappaB transcription factors is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called IkappaBalpha. IkappaBalpha is rapidly phosphorylated and degraded in response to the stimulation through tumor necrosis factor alpha (TNFalpha) receptor, interleukin-1 receptor or CD40. To explore the molecular mechanisms of signal-induced depletion of IkappaBalpha, we have delineated the domain in IkappaBalpha that is required for TNFalpha-induced phosphorylation and rapid degradation of IkappaBalpha. In contrast to the previous reports, the PEST-like sequences, which are present in the carboxyl-terminal region of IkappaBalpha, are demonstrated here to be dispensable for TNFalpha-induced degradation but could be required for signal-independent degradation, as in the case of Cactus, Drosophila homologue of IkappaB. Furthermore, the ankyrin repeats, which are essential for forming a complex with Rel and RelA, are required for TNFalpha-induced degradation suggesting that the putative IkappaB protease could interact with IkappaBalpha in complex with RelA or could recognize the structure of ankyrin repeats. Our data also indicate that neither the ankyrin repeats nor the PEST-like sequences, are essential for TNFalpha-induced phosphorylation.

Amino Acid Sequence↗

Expression of heat shock proteins in the developing rat retina.

Expression of three heat shock proteins (HSPs), HSP70, HSP90, and immunoglobulin heavy chain binding protein (Bip) was examined in the developing rat retina using Northern blot analysis. The expression of the inducible form of HSP70 remained uniformly low throughout the perinatal period until P5 and increased rapidly at P7. On the other hand, the constitutive form of HSP70, HSP90, and Bip were expressed constitutively in the rat retina throughout the developmental stage except P3-P5, at which a transient decrease of the expression was observed. The increase of inducible HSP70 mRNA at P7 may correspond to the functional maturation of photoreception in the visual nervous system and may be one of the stress responses to photostimulation. The potential roles of each HSP during development of the rat visual system are discussed.

Animals↗

The anti-platelet and anti-thrombotic effects of FK633, a peptide-mimetic GPIIB/IIIA antagonist.

The anti-platelet and anti-thrombotic properties of FK633, a peptide mimetic GPIIb/IIIa antagonist were studied. In human platelet rich plasma, FK633 inhibited ADP-, collagen-, thrombin-, and PAF-induced platelet aggregation with IC50 values of 103, 87, 98, and 239 nM, respectively. RGDS acted similarly, but it's potency was about 1,000 times weaker than FK633, FK633 inhibited 125I-fibrinogen binding to human washed platelet with an IC50 of 88 nM. FK633 did not inhibit alphavbeta3, alpha5beta1, and alphavbeta1 integrin-mediated cellular adhesion up to 1.0mM, while RGDS inhibited all these interactions. In dogs, bolus injection of FK633 at 0.1 mg/kg significantly suppressed ex vivo ADP-induced platelet aggregation (>40% inhibition) and thrombus formation at stenosed and injured coronary artery, but did not prolong template bleeding time. However, FK633 inhibited >90% ADP-induced aggregation at 0.32 mg/kg, causing significant prolongation of the bleeding time. Thus, FK633 is a specific GPIIb/IIIa antagonist with potent anti-thrombotic effect in vivo, but careful dosing study might be necessary to avoid the bleeding complications in the clinic.

Animals↗

Rank-ordered regulation of motor units.

Myoelectric signals were detected from the tibialis anterior muscle of 5 subjects with a quadrifilar needle electrode while the subjects generated isometric forces that increased linearly with time (10% of maximal voluntary contraction/s) up to maximal voluntary level. Motor unit firing rates were studied as a function of force throughout the full range of muscle force output. The relationship between force and firing rate was found to contain three distinct regions. At recruitment and near maximal force levels, firing rates increased more rapidly with force than in the intermediate region. Furthermore, in the regions with rapid increases, the rate of change of firing rate was correlated to the recruitment threshold, with higher recruitment threshold motor units displaying greater rates of change. In the intermediate region, all motor units had similar rates of change of firing rate. A weak positive correlation was found between initial firing rate and recruitment threshold. Firing rates of motor units at any instant were found to be ordered according to the recruitment order: at any given time in the contraction motor units with lower recruitment thresholds had higher firing rates than units with higher recruitment thresholds. Firing rates of all motor units were observed to converge to the same value at maximal forces. Mechanisms underlying motor unit recruitment and firing rate modulation are discussed in the context of a conceptual model.

Action Potentials↗

Cloning and detection of the hemolysin gene of Vibrio anguillarum.

A 5 kb DNA fragment encoding a hemolysin was cloned from the fish pathogenic bacterium Vibrio anguillarum using the cosmid vector charomid9-36. An open reading frame of the hemolysin gene (VAH1) was 2253 bp and corresponded to a protein of 751 amino acid residues. The deduced amino acid sequence of the VAH1 gene and the previously reported Vibrio cholerae EI Tor hemolysin, V. vulnificus cytolysin-hemolysin, Aeromonas hydrophila AHH1 hemolysin, and A. salmonicida ASH4 hemolysin showed a significant degree of sequence homology, and the overall amino acid identities were 57.3%, 25.8%, 46.2%, and 43.7%, respectively. DNA hybridization analysis under high-stringent conditions using VAH1 as a probe, demonstrated that VAH1 hybridized with 25 out of 28 strains of V. anguillarum including serotypes A to I, but did not hybridize with other species of Vibrio, A. hydrophila or A. salmonicida. The targeted DNA fragment of VAH1 was successfully amplified from V. anguillarum-infected fish tissues by PCR.

Amino Acid Sequence↗

Mesenchymal chondrosarcoma of the rib: report of a case.

Mesenchymal chondrosarcoma is a rare malignant cartilaginous tumor arising within the bone or soft tissue. An 18-year-old woman presented with a tumor on her left fourth rib. We performed a wide resection of the tumor and administered three cycles of postoperative adjuvant chemotherapy. Three years after the operation, the patient is alive without any evidence of either local recurrence or distant metastases. The findings of this case may thus support the usefulness of a radical resection and adjuvant chemotherapy for mesenchymal chondrosarcoma.

Adolescent↗

MRI in the mild type of mucopolysaccharidosis II (Hunter's syndrome).

We report imaging findings in a 3-year-old boy with the typical mild type of Hunter's disease. MRI revealed multifocal large cyst- or spindle-like areas of increased and decreased signal in the white matter, including the corpus callosum on T1- and T2-weighted images. The white matter showed high signal on T2-weighted images, isointense with cerebrospinal fluid on all other pulse sequences. To our knowledge, these appearances have not been reported in this disorder. Deposition of mucopolysaccharide and/or glycolipid and increase in fluid content seem to be responsible.

Brain↗

Rapidly progressive hepatitis C in a patient with common variable immunodeficiency.

UNLABELLED: A 15-year-old girl with common variable immunodeficiency contracted hepatitis C, which progressed to liver cirrhosis and finally to hepatic failure 5 years later. Since she was agammaglobulinaemic, hepatitis C virus (HCV) infection was diagnosed on the basis of HCV-RNA detection. Quantification of her sera showed high levels of HCV-RNA (more than 10(7) copies of RNA/mL), which implied active viral replication. There were no other hepatotoxic factors except HCV infection. The initial liver biopsy at 16 years of age and the autopsy confirmed a rapid progression in liver histopathological change over 4 years. CONCLUSION: Contrary to the widely held view of a benign short-term prognosis in paediatric hepatitis C, progressive fatal liver disease can develop in some patients with HCV infection. Such a rapid progression of liver injury provides the rationale for antiviral therapy in at least certain high risk groups of these children. Hepatitis C may progress rapidly in an immune deficiency condition.

Adolescent↗

Effect of bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis.

Salicylazosulphapyridine and corticosteroids are the only remedies for inflammatory bowel disease currently in clinical use. They do not, however, necessarily bring about satisfactory therapeutic benefits, so that new agents are needed. In this study, we evaluated the effect of bucillamine, a new antirheumatic agent, in experimental rat colitis induced by trinitrobenzene sulfonic acid enema. Wistar rats were given vehicle alone (n = 16) or treated with 50 (n = 20) or 150 (n = 20) mg/kg of bucillamine daily for three weeks after induction of colitis. Conventional histological sections of the colon stained by haematoxylin and eosin were prepared and observed under a light microscope to determine colonic damage scores. The determinations were significantly lower in the group treated with 50 mg/kg of bucillamine and tended to be lower in the group treated with 150 mg/kg of bucillamine than in the untreated group, which implied that the experimentally induced colonic inflammatory changes and ulcerations were alleviated by bucillamine. Blood tests showed no abnormal values at the end of the treatment. The present observations suggest that bucillamine should be developed further as a possible therapy for inflammatory bowel disease.

Animals↗

Apoptosis induced by selenium in human glioma cell lines.

Several studies have shown that selenium can inhibit tumorigenesis in tissues. However, little is known about the mechanism and the effect of selenium on DNA, especially in brain tumor cells. In this study we examined the biological effect of selenium on human glioma cell lines (A172 and T98G). Selenium exhibited an antiproliferative effect on these cell lines (and induced the typical ladder pattern of DNA fragmentation commonly found in apoptosis), which were prevented by catalase. Few effects of selenium on NT14 fibroblasts were found. These findings demonstrate that selenium may induce, by apoptosis, cell death of human glioma cell lines, which are resulting from free radical oxygen forming.

Apoptosis↗

Giant degenerative perineurial cell tumor.

We report a case of giant perineurial cell tumor, probably benign, with extensive degenerative changes. The secondary changes were reminiscent of those in giant ancient neurilemomas. To our knowledge, there has been no documentation of the imaging features in perineurioma. The MR findings of the present tumor, especially on T2-weighted images, correlated well with the histologic appearance.

Aged↗

Secretory function of adrenal chromaffin cells cultured on polypyrrole films.

Polypyrrole (PPy) is a conducting polymer and is obtained electrochemically on an electrode such as indium-tin oxide (ITO). In this study, in order to develop a novel cell-culture system which makes it possible to communicate with cultured mammalian cells, bovine adrenal chromaffin cells were cultured on PPy-coated ITO plates for 7 days and the influence of PPy-coating on the cell functions was investigated. Since the chromaffin cells synthesize and secrete catecholamines such as adrenaline and noradrenaline, the amount of synthesized and released catecholamines from the chromaffin cells cultured on PPy-coating and ITO itself were measured. The cells on the PPy-coated ITO plate could be kept in culture, without any significant changes in morphology and in the secretory responsiveness to acetylcholine as compared with those of the cells cultured on collagen. On the contrary, the cells on the ITO plate lost the responsiveness, while the amount of catecholamines synthesized was affected little by both PPy and ITO surfaces. It is suggested that PPy supports the secretory function of the chromaffin cells when they are cultured on it. This paper describes that PPy films are applicable as a polymer-modified electrode which support the cell function without collagen.

Animals↗

Molecular and functional properties of cytochrome c from adult Ascaris suum muscle.

Mitochondrial cytochrome c was isolated at high purity from adult Ascaris suum muscle and its molecular properties were investigated. The molecular weight of A. suum cytochrome c was determined to be 13,119 by electrospray ionization mass spectrometry. The oxidation-reduction potential of nematode cytochrome c was measured to be +248 mV; this value is comparable to those for cytochrome c from mammalian sources. The A. suum cytochrome c, like bovine heart cytochrome c, showed biphasic kinetics against bovine heart cytochrome c oxidase. Comparative kinetic studies revealed species-specificity in the reaction between cytochrome c and cytochrome c oxidase from A. suum and bovine sources. The cytochrome c content in mitochondria was highest at the second larval stage, in which the respiratory chain is the most aerobic among various developmental stages of A. suum. These data clearly show that adult A. suum cytochrome c, as isolated, is a bona fide substrate for cytochrome c oxidase in the aerobic respiratory chain of second-stage larvae.

Age Factors↗

Two types of parenchymal cells in the lung fluke Paragonimus ohirai (Digenea: Troglotrematidae) characterized by the cytochemistry of their mitochondria.

Morphology and respiratory function were studied in situ and in the isolated mitochondria of Paragonimus ohirai. Two types of parenchymal cells (i.e., Pc1 and Pc2 cells), whose mitochondria differ in terms of morphology and staining for cytochrome c oxidase activity, were found in fluke tissues. Enzymatic and spectrophotometric analyses of the isolated mitochondria showed that fluke mitochondria possess both aerobic and anaerobic respiratory chains. These results suggest that there are two mitochondrial populations in fluke parenchymal cells, one possessing an aerobic respiratory chain and the other an anaerobic respiratory chain.

Animals↗

Studies on the site of ethanol action in inducing prolactin release in male rats.

Hypersecretion of prolactin (PRL) has been implicated as one of the factors that mediate ethanol-induced hypogonadism, but the site(s) in the central nervous system where ethanol acts to lead to the stimulation of PRL secretion is unknown. To clarify the site(s) of ethanol action, medial basal hypothalamic deafferentation (MBHD) or medial basal hypothalamic ablation (MBHA) were performed stereotaxically in male rats, and their PRL secretory capacity in response to acute ethanol administration was compared with that of intact or sham-operated controls. In intact control rats, plasma immunoreactive PRL concentration increased markedly (P < .001 v saline injection) following ethanol 400 to 500 mg/100 g body weight (BW) intraperitoneally (IP). The PRL response was dose-related and reached a maximum plateau level at 15 minutes. Plasma PRL returned to a near-basal level by 60 minutes. The response was blocked completely (P < .001) by pretreatment with dopamine (1 mg per rat), a specific inhibitor of adenohypophyseal PRL secretion. In sham-operated rats and in MBHD and MBHA rats, ethanol (500 mg/100 g BW IP) induced a significant (P < .001 to .05) elevation of PRL relative to the respective saline treatment. The basal level was significantly (P < .005) lower in the MBHD group (5.3 +/- 0.9 ng/mL) and significantly (P < .001) higher in the MBHA group (101.1 +/- 15.7 ng/mL) than in the sham group (17.2 +/- 5.9 ng/mL). These results suggest the following: (1) acute ethanol administration stimulates PRL secretion from the pituitary in a dose-related manner, (2) ethanol appears to have direct stimulatory effects on adenohypophyseal PRL secretion, and (3) extrahypothalamic brain areas exert a stimulatory influence and the hypothalamus an inhibitory influence on basal PRL secretion.

Animals↗

Identification of K1/K10 and K5/K14 keratin pairs in human melanoma cell lines.

Keratin expression in cultured malignant melanoma cells has been studied only rarely. Moreover, no studies have reported of universality of keratin expression in human malignant melanoma cells. In this study, therefore, we analyzed keratin expression in eight cell lines. Using a low-salt aqueous solution without high salt and Triton X-100, as a washing buffer for keratin extraction, followed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and immunological analysis, we demonstrated keratin expression in all eight human malignant melanoma cell lines. The keratin polypeptide expressions common to all melanoma cells were K1, K5, K10 and K14. In addition, K8, K13, K17 and K18, respectively, were detected in individual cells. A measure of keratin expression universality in malignant melanoma cells may have implications regarding their invasive and metastatic behaviors, co-expressed with vimentin.

Electrophoresis, Gel, Two-Dimensional↗