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Biomedical subjects

N Hosokawa

Publications and source records attributed to N Hosokawa.

At least 19 recordsLinked to original sources
PubMed1992

Quercetin, a bioflavonoid, inhibits the increase of human multidrug resistance gene (MDR1) expression caused by arsenite.

Expression of the MDR1 gene, which encodes P-glycoprotein, is increased under some stress conditions. We have reported that quercetin, a bioflavonoid, inhibits the expression of heat-shock proteins. We have identified the effects of quercetin on the MDR1 gene expression in the human hepatocarcinoma cells line, HepG2. The increase of P-glycoprotein synthesis and MDR1 mRNA accumulation caused by exposure to arsenite were inhibited by quercetin. The CAT assay suggested that quercetin suppressed the transcriptional activation of the MDR1 gene after exposure to arsenite. Although many drugs that prevent the P-glycoprotein function have been reported, this is the first report to describe the inhibition of MDR1 expression by a reagent.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Quercetin, an inhibitor of heat shock protein synthesis, inhibits the acquisition of thermotolerance in a human colon carcinoma cell line.

Here, we describe the effects of quercetin on the induction of thermotolerance as examined by colony forming assay in a cell line derived from human colon carcinoma (COLO320 DM). Cells became resistant to heat treatment at 45 degrees C when they were preheated at 42 degrees C for 1.5 h or at 45 degrees C for 10 min. This induction of thermotolerance was almost completely inhibited by continuous treatment with 100 microM quercetin during the first and second heating sessions, and the interval between. This effect of quercetin was demonstrated to be dose-dependent over a concentration range of 50-200 microM. Quercetin did not increase the thermosensitivity of non-tolerant cells. The presence of quercetin during the first conditioning heating was more effective in inhibiting thermotolerance than its presence during the second heating. Quercetin was also found to inhibit the acquisition of thermotolerance induced by sodium arsenite. Cycloheximide, a nonspecific inhibitor of protein synthesis, did not affect the acquisition of thermotolerance by the same cell line. Quercetin specifically inhibits the synthesis of all heat shock proteins so far reported previously, and this leads to inhibition of the induction of thermotolerance. Such inhibition of thermotolerance by quercetin may improve the efficacy of clinical fractionated hyperthermia.

Arsenic↗
PubMed1992

Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids.

Transcriptional activation of human heat shock protein (HSP) genes by heat shock or other stresses is regulated by the activation of a heat shock factor (HSF). Activated HSF posttranslationally acquires DNA-binding ability. We previously reported that quercetin and some other flavonoids inhibited the induction of HSPs in HeLa and COLO 320DM cells, derived from a human colon cancer, at the level of mRNA accumulation. In this study, we examined the effects of quercetin on the induction of HSP70 promoter-regulated chloramphenicol acetyltransferase (CAT) activity and on the binding of HSF to the heat shock element (HSE) by a gel mobility shift assay with extracts of COLO 320DM cells. Quercetin inhibited heat-induced CAT activity in COS-7 and COLO 320DM cells which were transfected with plasmids bearing the CAT gene under the control of the promoter region of the human HSP70 gene. Treatment with quercetin inhibited the binding of HSF to the HSE in whole-cell extracts activated in vivo by heat shock and in cytoplasmic extracts activated in vitro by elevated temperature or by urea. The binding of HSF activated in vitro by Nonidet P-40 was not suppressed by the addition of quercetin. The formation of the HSF-HSE complex was not inhibited when quercetin was added only during the binding reaction of HSF to the HSE after in vitro heat activation. Quercetin thus interacts with HSF and inhibits the induction of HSPs after heat shock through inhibition of HSF activation.

Animals↗
PubMed1990

Isolation of polyamine transport-deficient mutants of Escherichia coli and cloning of the genes for polyamine transport proteins.

Escherichia coli KK313, which was deficient in spermidine transport, was isolated by treatment of E. coli MA261 with N-methyl-N'-nitro-N-nitrosoguanidine. E. coli NH1596, which was deficient in spermidine transport and has a 90% decreased putrescine transport activity, was obtained by a second treatment of E. coli KK313 with the same mutagen. Genes for polyamine transport systems were isolated by transforming E. coli NH1596 through DNA fragments from E. coli DR112 using pACYC184 as a vector. One clone for the gene of protein(s) catalyzing both putrescine and spermidine uptake (pPT104) was isolated. Two clones for the genes of protein(s) catalyzing only putrescine uptake (pPT79 and pPT71) were obtained. The genes encoded by pPT104, pPT79, and pPT71 were mapped at 15, 19, and 16 min of E. coli chromosome, respectively. Spermidine uptake by NH1596 carrying pPT104, and by MA261, was not inhibited by putrescine and several polyamine analogues, and the Kt values of these two systems were both approximately 0.1 microM. Putrescine transport by NH1596 carrying pPT104 was inhibited completely by spermidine, N,N-dimethyl-4,4'-bipyridylium (paraquat), and N1-acetyl-spermidine, and the Kt value was 1.4 microM. Putrescine uptake by NH1596 carrying pPT79 or pPT71 was not inhibited by spermidine and several polyamine analogues, and the Kt values were 0.5 and 1.8 microM, respectively. In MA261, the putrescine uptake was inhibited by 25-35% by paraquat and N1-acetyl-polyamines and showed two Kt values, 0.5 and 1.5 microM. Based on these findings, the polyamine transport systems of E. coli are discussed.

Bacterial Proteins↗
PubMed1990

N-myc suppression and cell cycle arrest at G1 phase by prostaglandins.

Effects of cyclopentenone prostaglandins, delta 12-prostaglandin (PG) J2 and PGA2 on the expression of N-myc in relation to the effects on cell cycle progression were investigated using human neuroblastoma cell line GOTO. Both PGs suppressed N-myc expression within several hours prior to inducing G1 arrest. The N-myc suppression with delta 12-PGJ2 was continued but with PGA2 it was gradually released, followed by the release of G1 arrest. These results suggest that delta 12-PGJ2 and PGA2 inhibit cell cycle progression in strong association with N-myc suppression and delta 12-PGJ2 is more potent and has a longer effect than PGA2.

Cell Cycle↗
PubMed1990

Inhibitory effect of quercetin on the synthesis of a possibly cell-cycle-related 17-kDa protein, in human colon cancer cells.

Quercetin inhibits growth of COLO320 DM cells, derived from a human colon cancer. The inhibitory effect is partially reversible when quercetin is removed from the culture medium. Flow cytometric analysis has revealed that quercetin causes perturbation of the cell cycle, inducing a frozen cell-cycle pattern and a block at the G1/S boundary. The synthesis of a 17-kDa protein was specifically inhibited by the addition of quercetin, and recovered when the cells at the G1/S boundary progressed into S-phase after the removal of quercetin from the culture medium. Furthermore, using synchronized cells obtained by centrifugal elutriation, we have shown that the rate of synthesis of a 17-kDa protein was low in G1, and high in S-phase of the cell cycle. Thus, this protein appears to be cell-cycle-related.

Cell Cycle↗
PubMed1990

The effect of quercetin on cell cycle progression and growth of human gastric cancer cells.

Quercetin, a flavonoid, is found in many plants, including edible fruits and vegetables. We examined the effects on cell growth of human malignant cells derived from the gastrointestinal tract and on cell cycle progression. Quercetin markedly inhibited the growth of human gastric cancer cells and the IC50 value was 32-55 microM. DNA synthesis was suppressed to 14% of the control level by the treatment with 70 microM quercetin for 2 days. Furthermore, quercetin blocked cell progression from the G1 to the S phase.

Antineoplastic Agents↗
PubMed1990

Flavonoids inhibit the expression of heat shock proteins.

Cells exposed to several forms of stress, such as heat shock, transiently synthesize a group of proteins called heat shock proteins (hsps). Although many stressors other than heat shock are known to induce hsps, inhibitors of hsp expression have never been reported. Here we show that quercetin and several other flavonoids inhibit the synthesis of hsps induced by heat shock in two human cell lines, Hela cells and COLO320 DM cells. Quercetin inhibited the induction of hsp70 at the level of mRNA accumulation. This is the first report to describe the inhibition of hsp expression by reagents.

Colonic Neoplasms↗
PubMed1990

[Perfusion study of the pulmonary hilar region by SPECT--normal cases].

Alveoli in the hilar region comprise the peripheral area containing daughter branches from subsegmental or one more divisional peripheral bronchi. Pulmonary perfusion in hilar region was examined by SPECT (single photon emission CT) in ten normal volunteers. ROI (region of interest) in the axial images were set in the hilar region, the upper, middle and lower lung fields with 10.8 mm thickness. Counts/one pixel (C/P) were calculated in these ROI. There was a tendency of C/P increase from upper to lower lung field. And there were no significant differences in C/P increase between hilar region and other axial fields. In the chronic obstructive pulmonary diseases, however, ventilation studies in the previous reports using Xe dynamic CT or PET (positron emission tomography) showed differences between outer region and hilar region. This method will be expected to evaluate the pulmonary perfusion not only in the whole lung but in different lung areas, including the hilar region in the chronic obstructive pulmonary diseases.

Adult↗
PubMed1990

Screening of antibiotics preferentially active against ras oncogene-expressed cells.

During the course of in vitro screening of agents which are preferentially active against ras oncogene-expressed cells, a new anthracycline (identified as 2-demethylsteffimycin D) and a heptaene (possibly a new member of partricins) were isolated from microbial fermentation broths. Among known compounds tested, 5-fluorouracil, 5-fluorodeoxyuridine and oxanosine showed high selectivity towards ras oncogene-expressed cells.

Animals↗
PubMed1989

A kinetic study on secretion and elimination of endogenous thyrotropin in the thyrotropin-releasing hormone test.

Serum thyrotropin (TSH) concentrations in normal young men were measured by a high-sensitivity immunoradiometric assay before and after intravenous administration of 500 micrograms of TSH-releasing hormone (TRH). A kinetic model was applied to evaluate the secretion rate both before (V0) and after (V0 + V* at maximum rate) the administration of TRH, the elimination constant (K), the latent time (L) between TRH administration and start of the stimulated secretion, and the total amount of TSH (T) released in response to TRH. V0, V* and T varied widely from individual to individual, but correlated well with TSH before TRH administration (r = 0.93, 0.80 and 0.87, respectively). A few minutes (1.89 +/- 1.30 min) after the administration of TRH, the secretion of TSH (0.025 +/- 0.016 microU/min ml) was stimulated, and the total release over about 1 h was 12.5 +/- 5.6 microU/ml. Serum TSH was maximum at 31.5 +/- 5.7 min. The half-time of disappearance of TSH was 42 +/- 9 min. These data confirm that the stimulated secretion continues for more than 30 min, and that the pituitary releases 43.2 +/- 22.9 mU of TSH (assuming the distribution volume of TSH is 5.8% of body weight) in response to TRH, an amount which correlates closely (r = 0.91) with TSH before TRH administration.

Adult↗
PubMed1989

[Scintigraphic estimation of dearterialization after transcatheter hepatic arterial embolization therapy].

Radionuclide angiography was performed by bolus injection of 99mTc-phytate in 10 patients with liver neoplasms before and after the transcatheter hepatic arterial embolization therapy. The ratio of the slopes of the upstrokes for the hepatic arterial and abdominal aortic first transit curves constitutes the regional hepatic arterial to aortic blood flow ratio (RHA/A ratio), which represents quantitatively the arterial blood flow of hepatic region of interest as a fraction of aortic blood flow. The degree of embolic dearterialization was estimated by the change of this ratio derives from the same region of interest for each patient before and after the embolization. The values and post-embolic reduction of the ratio correlated well individually with the angiographic features and other patients' data. The arterial blood supply to the tumor could not be reducted using Lipiodol alone as the embolic material in only 1 case. The finding that the splenic arterial to aortic blood flow ratio (S/A ratio), calculated in the same way, was practically unchanged after the hepatic arterial embolization indicates the good reproducibility of these measurements. This noninvasive method may be helpful to evaluate the therapeutic effect of hepatic arterial embolization.

Aged↗
PubMed1988

[The clinical evaluation of the serum SCC antigen levels with "SCC RIABEAD" by immunoradiometric assay].

The clinical significance of serum SCC antigen level was evaluated by the monoclonal antibody method (SCC.RIABEAD Dinabot Co. Ltd). Patients with squamous cell carcinoma showed a high positive SCC antigen level and positive rate elevated with the advance of the clinical stage. The serum SCC antigen level was decreased by treatment, and it increased again before obvious clinical recurrence was recognized. The results suggest that measurement of serum SCC antigen level is useful as a follow up of cancer treatment.

Antibodies, Monoclonal↗
PubMed1987

[Evaluation of pN factors in patients with primary lung cancer by using perfusion, inhalation and ventilation studies].

The interpretation of scintigraphic patterns and the role of pathophysiological mechanisms in patients with primary lung cancer were investigated. To determine the relative roles of perfusion, inhalation and ventilation scintigraphy, the relationship between the count ratio of the affected side to the healthy side and the post-surgical histological lymph nodes factors were observed in this study. These scintigraphic count ratio's in patients with primary lung cancer did not reflect the pN factors except in the perfusion study in patients with hilar primary lung cancer.

Humans↗