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Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

At least 487 records · Page 27Linked to original sources

[Establishment and characterization of a human breast cancer cell line, OCUB-1].

We established new human breast cancer cell line, OCUB-1 derived from the pleural effusion of 53-year old female with recurrent breast cancer. Two sub-cell lines were also established with cloning technique from OCUB-1. Investigating the differences of characteristics between OCUB-1M and 1F, OCUB-1M shows a monolayered growing and OCUB-1F grows in floating. OCUB-1M and 1F revealed Modo 84 and 41 by chromosomal analysis and flow cytometric analysis showed OCUB-1M had twice amount of DNAs as -1F. OCUB-1M revealed higher expression of E-cadherin and laminin receptor against-1F, and activity of 92kDa type IV collagenase could be seen only in OCUB-1M. Estorogen and progesteron receptor were negative in either OCUB-1M and -1F, and no production of tumor markers in the spent media (CEA, CA19-9, CA15-3 and NCC-ST439) was detected in both cells. Both cells could be hetero-transplanted in nude mice, but they showed different histology.

Animals↗

Regional changes in alpha-tubulin and beta-actin mRNA accumulations after transient ischemia in spontaneously hypertensive rat brains.

Regional changes in the mRNA accumulations for cytoskeletal proteins alpha-tubulin and beta-actin were examined by in situ hybridization and Northern blot analysis in spontaneously hypertensive rat brains at chronic stages after 3 hours of transient ischemia. alpha-Tubulin mRNA accumulations showed no significant change at 2 weeks after transient ischemia except for a significant decrease in the frontal cortex (9.7%, p < 0.01) coinciding with ischemia induced histological changes. beta-Actin mRNA level was significantly increased in the parietal cortex (8.5%), septum (10.0%), amygdala (11.0%), CA4 area (5.8%) and the dentate gyrus (7.5%) of the hippocampus at 2 weeks after recirculation compared with a sham-operated control group (p < 0.01). The ischemic areas of hippocampal and frontocortical lesions receive afferent neurons from those regions where beta-actin mRNA was increased, suggesting that ischemia-induced increases in beta-actin mRNA may reflect actin synthesis in these neurons to compensate for lost synaptic connections. Two cytoskeletal mRNA concentrations reacted differently to cerebral ischemia, and did not parallel histological signs of ischemia either temporally or spatially.

Actins↗

Interleukin-1 beta-mediated metallothionein induction and cytoprotection against cadmium and cis-diamminedichloroplatinum.

Metallothioneins (MTs) are major intracellular protein thiols that have been associated with resistance to the cytotoxicity of heavy metals and some cytotoxic anticancer drugs. The accumulation and subcellular location of MT and its functionality were examined in a human hormone-independent prostatic tumor cell line (DU-145) exposed to cytokines that participate in autocrine growth and the acute phase response. Incubation of DU-145 cells with interleukin-1 beta (IL-1 beta) caused a concentration-dependent increase in MT protein reaching a 2- to 3-fold maximum increase 24 to 48 hr after treatment with 10 U of IL-1 beta/ml; smaller increases were seen with human recombinant IL-1 alpha and tumor necrosis factor alpha. DU-145 cells constitutively expressed only MT-IIa and MT-Ie mRNA and the IL-1 beta-mediated increase in MT protein was preceded by a marked elevation solely in MT-IIa mRNA. Basal MT was immunolocalized by confocal microscopy primarily to the nucleus of DU-145 cells with some granular deposits near the cell surface. IL-1 beta treatment increased nuclear MT. DU-145 cells pretreated with IL-1 beta were 2- to 3-fold resistant to the toxicity of CdCl2 and cis-diamminedichloroplatinum(II) (cisplatin). Both MT induction and cytoprotection against CdCl2 and cisplatin were blocked by concomitant incubation with a recombinant human IL-1 receptor antagonist protein. These results suggest the responsiveness of human prostatic tumor cells to cytotoxic electrophilic anticancer drugs can be diminished by direct exposure to the cytokine IL-1 beta, possibly by a mechanism involving MT.

Cadmium↗

[Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627) in children].

The results are summarized as follows: 1. A total of 10 patients were treated with biapenem (L-627). We received informed consent from all of their parents. Each dose was 6 mg/kg, and it was administered 3 times daily (40 mg/kg, 4 times daily in meningitis), in a 30-minute intravenous drip infusion for 5-17 days. The clinical efficacies of L-627 in 10 patients with bacterial infections (1 with purulent meningitis, 1 with sepsis, 5 with pneumonia, 2 with urinary tract infection and 1 with purulent tonsillitis) were evaluated as excellent in 8 patients, as good in 2 patients with an efficacy rate of 100%. Seven causative organisms found in 5 patients (Streptococcus pneumoniae in 2, Moraxella (Branhamella) catarrhalis in 2, Haemophilus influenzae in 2 and Pseudomonas aeruginosa in 1) were eradicated. No adverse reaction was observed in any of the 10 patients. 2. Pharmacokinetic studies Peak plasma concentrations of L-627 were 12.5-13.7 micrograms/ml at the dose of 6 mg/kg administered by 30-minute drip infusion. Plasma half-lives of L-627 in the beta-phase averaged 0.72 hour (0.63-0.80 hour). CSF concentration/plasma concentration ratios of L-627 were 1.12/8.16 micrograms/ml (Day 2, 1.17 hours after at dose of 20 mg/kg), 0.88/3.44 micrograms/ml (Day 3, 4.0 hours after at dose of 30 mg/kg) and 0.68/5.12 micrograms/ml (Day 13, 3.0 hours after at dose of 40 mg/kg) administered by 30-minute drip infusion in the child with purulent meningitis (case 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

[Assay of circulating thyroid stimulator determined by I- efflux].

The thyroid stimulating antibodies (TSAb) have been widely used as a clinical marker for diagnosis of hyperthyroidism due to Graves' disease. Immunoglobulins (IgG) of Graves' patients as well as TSH is known to stimulate cAMP production in FRTL-5 cells, a cell-line derived from normal rat thyroid. On the other hand, it has been shown that TSH-induced I- efflux in these cells is associated with production of inositolphosphate as well as intracellular Ca2+ increase. An attempt was made to determine whether Graves' IgG also can mimic such TSH action as a cause of Graves' disease. Polyethyleneglycol precipitated serum fraction of Graves' patients were prepared. The cells grown in the presence of TSH were incubated for 3 weeks in a Ham's 10 medium containing 1% calf serum, insulin and hydrocortisone for TSH depletion. After preincubation with 125I-iodide for 50 min to label intracellular iodide, the cells were challenged by serum samples for 1 min. The addition of normal pooled serum hardly affected the I- efflux. The Graves' immunoglobulin G fractions stimulated I- efflux dose-dependently. The mean potency of 12 patient's sera relative to the values of the pooled serum as 100% was 217 +/- 56.4%, which was significantly higher (p < 0.001) than that for 8 normal subjects (110 +/- 16.1%). The results obtained herein indicate that IgG of Graves' patients activate both adenylate aclase-cAMP system and a phospholipid-Ca2 system. I- efflux stimulating immunoglobulins (IESI) activity is a useful marker in making a diagnosis or determining a remission of hyperthyroidism due to Graves' disease.

Adenylyl Cyclases↗

The effect of endurance training on the relationships between sex hormone binding globulin, high density lipoprotein cholesterol, apoprotein A1 and physical fitness in pre-menopausal women with mild obesity.

The purpose of the present study was to investigate the relationships of change in high density lipoprotein cholesterol (HDL-C) with changes in sex hormone binding globulin (SHBG), physical fitness and spontaneous dietary intake before and after endurance training. Ten pre-menopausal obese women (32 to 49 years) who had never smoked or regularly drunk alcohol participated in this study. Physical training at an intensity of lactate threshold was performed for six months at a frequency of three times per week for 60 minutes using a cycle ergometer. Together with a reduction in body weight (-4.1 kg; P < 0.05) and with increases in maximal oxygen uptake (VO2max = +3.4 ml/kg/min or +0.09 l/min; P < 0.05), the training induced some changes in both plasma lipid and lipoprotein. Although the total cholesterol (total-C), triglyceride, HDL2-C and apoprotein A1 (Apo A1) levels did not change, significant increases in HDL-C and HDL3-C, and significant reductions in Apo B, total-C/HDL-C ratio and fasting insulin concentrations were found after training. SHBG levels tended to increase after endurance training, but the changes were not significant. No alteration was observed in spontaneous dietary intake after training. A significant correlation (r = 0.648) was observed between the change in VO2 max(l/min) and the change in SHBG. In addition, changes in both VO2 max(l/min) and SHBG were significantly associated with changes in HDL-C, HDL2-C and Apo A1. The changes in dietary intake did not correlate with the changes in SHBG, VO2max, HDL-C, HDL2-C and Apo A1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A single species of A1 adenosine receptor expressed in Chinese hamster ovary cells not only inhibits cAMP accumulation but also stimulates phospholipase C and arachidonate release.

Chinese hamster ovary cells were transfected with both A1 adenosine receptor and muscarinic type 3 acetylcholine receptor cDNAs. The muscarinic receptor agonist carbachol stimulated phospholipase C activity, resulting in Ca2+ mobilization and arachidonate release. N6-Cyclopentyladenosine (CPA), an A1 receptor agonist, did not activate Ca(2+)-related signal transduction systems by itself but instead inhibited cAMP accumulation. In the presence of carbachol, however, the A1 receptor agonist enhanced muscarinic receptor agonist-induced phospholipase C/Ca2+ responses. In addition, the arachidonate release caused by Ca2+ ionophores or thapsigargin was also amplified by CPA, without a change in phospholipase C activity. Thus, CPA augments Ca(2+)-mediated phospholipase A2 activation in addition to and separate from its ability to amplify phospholipase C-mediated Ca2+ mobilization. Because the permissive actions of CPA on phospholipase C and phospholipase A2 activation were each reversed by pertussis toxin treatment, in a manner similar to that of the CPA-induced inhibition of cAMP accumulation, we conclude that a single species of A1 receptor expressed in Chinese hamster ovary cells can couple to multiple signal transduction systems stemming from phospholipase C stimulation, phospholipase A2-mediated and Ca(2+)-dependent arachidonate release, and inhibition of cAMP accumulation. A pertussis toxin-sensitive G protein (or proteins) mediates the permissive actions of the A1 receptor in the stimulation of phospholipase C- and phospholipase A2-mediated arachidonate release.

Adenosine↗

Synthesis and aldose reductase inhibitory activity of 2-substituted-6-fluoro-2,3-dihydrospiro [4H-1-benzopyran-4, 4'-imidazolidine]-2',5'-diones.

Optically active and racemic 2-substituted-6-fluoro-2,3-dihydrospiro[4H-1-benzopyran-4, 4'-imidazolidine]-2',5'-diones were synthesized from (+)-, (-)-, and (+-)-6-fluoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid. These compounds were then evaluated for in vitro and in vivo aldose reductase inhibitory activity. The 2S,4S isomers were found to be more potent aldose reductase inhibitors than the other corresponding stereoisomers. Among these compounds, (2S,4S)-6-fluoro-2,3-dihydro-2',5'-dioxospiro[4H-1-benzopyran-4, 4'-imidazolidine]-2-carboxamide ((+)-1b, SNK-860, CAS 105300-43-4) showed the most potent in vitro and in vivo activity.

Aldehyde Reductase↗

Inhibitory effect of bisbenzylisoquinoline alkaloids on nitric oxide production in activated macrophages.

Bisbenzylisoquinoline (BBI) alkaloids are anti-inflammatory constituents of plants of the families Menispermaceae and Ranunculaceae, which have been used as folk remedies in Japan and China. Five BBI alkaloids (cepharanthine, chondocurine, cycleanine, isotetrandrine and tetrandrine) were tested for suppressive effect on in vitro nitric oxide (NO) production by lipopolysaccharide-stimulated peritoneal macrophages, which were induced with thioglycollate or bacillus Calmette-Guerin in mice. All these BBI alkaloids significantly suppressed NO production at 5 micrograms/mL. Cepharanthine, isotetrandrine and cycleanine were slightly more inhibitory than tetrandrine and chondocurine. The suppression persisted for at least 48 hr. As NO is one of the critical mediators in inflammation, these results may explain some aspects of the anti-inflammatory mechanisms of BBI compounds.

Alkaloids↗

Suppression of lipopolysaccharide-induced fulminant hepatitis and tumor necrosis factor production by bisbenzylisoquinoline alkaloids in bacillus Calmette-Guerin-treated mice.

The bisbenzylisoquinoline (BBI) alkaloids chondocurine, cycleanine, tetrandrine and berbamine were tested for their capacity to suppress hepatic injury and production of tumor necrosis factor (TNF) induced by lipopolysaccharide (LPS) in mice primed with bacillus Calmette-Guerin (BCG). When administered for three consecutive days before LPS injection, chondocurine, cycleanine and tetrandrine (10 mg/kg/day) strongly suppressed serum alanine aminotransferase (EC 2.6.1.1.) and aspartate aminotransferase (EC 2.6.1.2.); however, berbamine gave only slight protection. Chondocurine, cycleanine and tetrandrine but not berbamine significantly reduced the level of TNF which peaked 2 hr after LPS injection. This study shows that BBI alkaloids prevent BCG/LPS-induced hepatitis at least in part by suppressing TNF production.

Alkaloids↗

Lipoxygenase in soybean seedlings catalyzes the oxygenation of phospholipid and such activity changes after treatment with fungal elicitor.

Lipoxygenase (LOX) activities in the crude extracts of soybean cotyledons on phospholipid were measured by a chemiluminescence (CL) assay system. The activity of LOX on phospholipid increased at 6 h after treatment with fungal elicitor, whereas the activity in the control experiment without elicitor treatment declined with incubation. A rise of LOX activity at 6 h incubation is considered to be induced by the elicitor treatment. The LOX fraction obtained from soybean cotyledons at 6 h after elicitation by a DEAE column chromatography was reacted with 1-palmitoyl-2-linoleoyl-phosphatidylcholine substrate. The reaction product was analyzed by HPLC equipped in series with a UV (205 nm) and a CL detector. Most of the substrate was converted to a hydroperoxy compound. By the CL-HPLC analysis after transesterification of reaction product and by mass spectrum of the trimethylsilyl derivative after reduction of methyl ester confirmed that the linoleic moiety was subjected to oxygenation at 13-position. The steric analysis of menthoxyacetyl derivative prepared from hydroxy fatty acid methyl ester showed S configuration. These findings suggest that the oxygenation of membrane lipids in biological plant tissues might be initiated by the direct action of LOX.

Chromatography, High Pressure Liquid↗

Prevention of carcinogenicity of anticancer drugs by metallothionein induction.

We examined the efficacy of metallothionein induction in the prevention of the carcinogenic action of cis-platinum and melphalan administered repeatedly to mice over a relatively long period. The increased pulmonary metallothionein induced by bismuth or zinc compounds during the period of chemotherapy with cis-platinum or melphalan protected the mice from carcinogenesis of these drugs in the lung. These results suggested the efficacy of metallothionein inducers in suppression of carcinogenicity considered as a secondary effect of anticancer agents in cancer chemotherapy.

Animals↗

Intrahepatic cholangiocarcinoma with sarcomatous change. Clinicopathologic and immunohistochemical evaluation of seven cases.

BACKGROUND: Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure. METHODS: Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin-biotin-peroxidase complex method were performed on these cases. RESULTS: The tumor showed both mucin-producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease-free for 3 years after surgery. CONCLUSIONS: These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Adenocarcinoma, Mucinous↗

UTP activates phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor in PC12 cells.

Extracellular ATP (a purine nucleotide) and UTP (a pyrimidine nucleotide) both activated phospholipase C with a similar potency and efficacy; however, in contrast to ATP which induced a remarkable norepinephrine release, UTP-induced norepinephrine release was small in PC12 cells, a rat pheochromocytoma cell line. ATP, its derivatives (2-methylthioadenosine 5'-triphosphate (MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP)) and UTP increased intracellular Ca2+ in the presence of 2 mM extracellular Ca2+ with the potency order of ATP > MeSATP > BzATP = UTP. Under the low extracellular Ca2+ conditions, the Ca2+ response to purine nucleotides was markedly reduced, but the UTP response was not. The [32P]BzATP labeling of a 53-kDa putative ATP receptor coupled to a channel system (Majid, M.A., Okajima, F., and Kondo, Y. (1992) Biochim. Biophys. Acta 1136, 283-289) was markedly inhibited by ATP, but not by UTP. These results suggest that UTP activates the phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor.

Adenosine Triphosphate↗