Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 271 records · Page 15Linked to original sources

PubMed2000

Anti-tumor-promoting effects of isoflavonoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

As a part of screening studies for anti-tumor promoters, fifteen isoflavonoids isolated from plants of the genus Millettia (Leguminosae) were evaluated by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the compounds tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Auriculasin (11) and millepurone (13), which is an oxidized isoflavone analogue, both having one or more prenyl side-chains and a 3',4'-dihydroxyphenyl group in the molecule, showed more potent activity than any of the other compounds tested. Furthermore, millepurone (13) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that some of these isoflavonoids might be valuable anti-tumor promoters.

Animals↗

PubMed2000

Resuscitation of viable but nonculturable cells of Vibrio parahaemolyticus induced at low temperature under starvation.

Vibrio parahaemolyticus is known to exist in a viable but nonculturable state when incubated at low temperature under starvation. It has long been debated whether the culturable cells which appear after temperature upshift are the result of true resuscitation or regrowth of a few residual culturable cells. Starved V. parahaemolyticus cells at 4 degrees C reached the nonculturable stage in about 12 days. The true resuscitation of nonculturable cells of V. parahaemolyticus occurred after spreading them onto an agar medium supplemented with H(2)O(2)-degrading compounds such as catalase or sodium pyruvate. The proposed method may be applicable to detecting the enteropathogen from environmental samples.

Catalase↗

PubMed2000

Eel WT1 sequence and expression in spontaneous nephroblastomas in Japanese eel.

Nephroblastomas spontaneously developing in Japanese eel reared at farms for 5 to 9months after collection from the wild [Masahito et al., Cancer Res., 52 (1992) 2575-2579] were investigated to cast light on the role of Wilms' tumor 1 gene (WT1) in eel kidney tumorigenesis. Cloning of the WT1 counterpart, EWT1, revealed that conservation of an alternative splice II site, located between the third and fourth zinc fingers, was conserved. The zinc finger domain was highly conserved. The transregulator region, sequences corresponding to exons 4 and 5 in WT1, were lacking in EWT1 cDNA. EWT1 was found to be expressed in kidney, testis and spleen and in situ hybridization revealed dark-stained immature cells in elver kidney to be positive. Although no EWT1 gene mutations were found in 38 eel nephroblastomas, 26 polymorphic nucleic acid changes were observed. Aberrant WT1 expression was noted in epithelial (12 out of 27; 44%) and nephroblastic cell histological types (three out of five; 60%) of eel nephroblastomas. On in situ hybridization the EWT1 expressive cells resembled human blastema cells, similar to those in human Wilms' tumor. These data demonstrated strong signals that the EWT1 protein may function in the development of eel kidney and play a role in genesis of nephroblastomas as in mammals.

Amino Acid Sequence↗

PubMed2000

Acquired loss of p53 induces blastic transformation in p210(bcr/abl)-expressing hematopoietic cells: a transgenic study for blast crisis of human CML.

Chronic myelogenous leukemia (CML) begins with an indolent chronic phase but inevitably progresses to a fatal blast crisis. Although the Philadelphia chromosome, which generates p210(bcr/abl), is a unique chromosomal abnormality in the chronic phase, additional chromosomal abnormalities are frequently detected in the blast crisis, suggesting that superimposed genetic events are responsible for disease progression. To investigate whether loss of p53 plays a role in the evolution of CML, we crossmated p210(bcr/abl)-transgenic (BCR/ABL(tg/-)) mice with p53-heterozygous (p53(+/-)) mice and generated p210(bcr/abl)-transgenic, p53-heterozygous (BCR/ABL(tg/-)p53(+/-)) mice, in which a somatic alteration in the residual normal p53 allele directly abrogates p53 function. The BCR/ABL(tg/-)p53(+/-) mice died in a short period compared with their wild-type (BCR/ABL(-/-)p53(+/+)), p53 heterozygous (BCR/ABL(-/-)p53(+/-)), and p210(bcr/abl) transgenic (BCR/ABL(tg/-)p53(+/+)) litter mates. They had rapid proliferation of blast cells, which was preceded by subclinical or clinical signs of a myeloproliferative disorder resembling human CML. The blast cells were clonal in origin and expressed p210(bcr/abl) with an increased kinase activity. Interestingly, the residual normal p53 allele was frequently and preferentially lost in the tumor tissues, implying that a certain mechanism facilitating the loss of p53 allele exists in p210(bcr/abl)-expressing hematopoietic cells. Our study presents in vivo evidence that acquired loss of p53 contributes to the blastic transformation of p210(bcr/abl)-expressing hematopoietic cells and provides insights into the molecular mechanism for blast crisis of human CML. (Blood. 2000;95:1144-1150)

Animals↗

PubMed2000

Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor.

The contribution of the aryl hydrocarbon receptor (AhR) in induction of a battery of xenobiotic-metabolizing enzymes has been studied extensively. However, no direct proof has been obtained that it plays a role in modulating carcinogenesis. To address the question of whether AhR is required for tumor induction, we have investigated the response of AhR-deficient mice to benzo[a]pyrene (B[a]P), a widely distributed environmental carcinogen. B[a]P treatment induced expression of the cytochrome P450 gene Cyp1a1 in the skin and liver of AhR-positive mice bearing +/+ and +/- genotypes and did not induce expression of the cytochrome P450 gene Cyp1a1 in AhR-null mice in either skin or liver. In contrast, Cyp1a2 gene expression was positive in liver irrespective of the presence or absence of the AhR gene, or B[a]P treatment, although its inducibility was lost in the AhR(-/-) mouse. All AhR-positive male mice of both +/+ and +/- genotypes that received subcutaneous injection of B[a]P (2 mg) on the first and the eighth days had developed subcutaneous tumors at the site of injection at the end of the 18-week experiment. In contrast, no tumors were apparent in any of the AhR-deficient mice. Likewise, topical application of B[a]P (200 microg) at weekly intervals to the skin of female mice for 25 weeks produced skin tumors only in the AhR-positive mice. Thus the carcinogenic action of B[a]P may be determined primarily by AhR, a transcriptional regulator of the gene for CYP1A1. The results of the present study provide direct evidence that AhR is involved in carcinogenesis.

Animals↗

PubMed2000

Synergistic activation of NF-kappab and inducible isoform of nitric oxide synthase induction by interferon-gamma and tumor necrosis factor-alpha in INS-1 cells.

Interferon-gamma (IFN-gamma) is known to exert deleterious effects on pancreatic beta-cells and is implicated in the development of type 1 (autoimmune) diabetes mellitus. In this study, we investigated signaling mechanisms mediating the effects of IFN-gamma in pancreatic beta-cells using a differentiated rat insulin-secreting cell line, INS-1, with special reference to the activation of transcription factors STAT (signal transducers and activators of transcription)1 and NF-kappaB. Exposure of INS-1 cells to 100 IU/ml IFN-gamma for 24 h resulted in significant inhibition of nutrient-induced insulin secretion associated with impaired metabolism. In combination with tumor necrosis factor-alpha (TNF-alpha) (50 ng/ml), IFN-gamma elicited severe cytotoxicity and induced the expression of the inducible isoform of nitric oxide synthase (iNOS) mRNA. IFN-gamma promoted tyrosine phosphorylation and DNA-binding of STAT1 through Janus kinase (JAK)1 activation without apparent phosphorylation of JAK2. TNF-alpha did not affect STAT1 activation, but stimulated DNA-binding and transcriptional activity of NF-kappaB, both of which were further increased by IFN-gamma. These effects of IFN-gamma and TNF-alpha seem physiologically relevant, because either inhibition of STAT1 by the tyrosine kinase inhibitor herbimycin A or that of NF-kappaB by sulfasalazine resulted in the reduction of iNOS mRNA expression. In conclusion, IFN-gamma activates STAT1 and potentiates TNF-alpha-induced NF-kappaB activation in INS-1 cells, thereby inducing iNOS and cell destruction.

Animals↗

PubMed2000

Pituitary-adrenocortical responses to the first dyadic encounters in male rhesus monkeys: effect of dominance relationship.

Male rhesus monkeys unfamiliar with each other were paired in a cage, and blood samples were collected before and a few hours after pair formation. Adrenocorticotrophic hormone (ACTH) and cortisol levels in each blood sample were measured. Dominant-subordinate status was ascertained through two rank tests, the food competition test and the agonistic behavior test, which were performed immediately after pair formation. As a result, the dominance relationship was determined in seven pairs formed from five animals, and the differences in ACTH and cortisol values between the dominant and subordinate animal in these pairs were compared statistically. The day after the first encounter, a second encounter was conducted in randomly selected pairs of monkeys. In the first encounters, higher levels of both ACTH and cortisol were detected in dominant animals in comparison to subordinate animals. Changing the animal's partner altered the stress responses whenever the animal's dominant-subordinate status changed. The elevated levels of ACTH and cortisol in dominant animals disappeared on the day after the first encounter. In dominant animals, the pituitary-adrenocortical stress response reacts sharply to situational demands, whereas subordinate animals have a weaker response. This acute stress response is different from a chronic stress response. When the subordinate animal cannot escape, its hypothalamic-pituitary-adrenocortical axis appears to be suppressed.

Adrenocorticotropic Hormone↗

PubMed2000

Hydrogen peroxide decelerates recovery of action potential after high-frequency fatigue in skeletal muscle.

Effects of reactive oxygen species (ROS), especially hydrogen peroxide (H(2)O(2)), on recovery of action potential by resting for 30 min after high-frequency fatigue were studied using frog skeletal muscle fibers. After stimulation at a frequency of 50 HZ for 2 min, the action potential amplitude was decreased by 14.5 mV from controls, and resting membrane was depolarized by 15.4 mV. Action potential duration was also prolonged by high-frequency stimulation (1.5 ms in controls to 2.6 ms). The high-frequency stimulation used here caused no muscle damage. The action potential was partially improved after a 30-min rest. Addition of catalase at 500 units/ml or H(2)O(2) at 0.5 mM to sartorius muscle did not alter any of the parameters of the action potential after high-frequency stimulation. Treatment with catalase accelerated post-fatigue recovery of the action potential. Application of H(2)O(2) delayed post-fatigue recovery of resting and action potentials. When added to detubulated toe muscle fibers, catalase no longer improved the attenuation of action potential induced by high-frequency stimulation, even after a 30-min rest. These findings suggest that removal of H(2)O(2) from transverse tubules is effective for post-fatigue recovery of action potential in skeletal muscle.

Action Potentials↗

PubMed2000

Induction of MRP1 and gamma-glutamylcysteine synthetase gene expression by interleukin 1beta is mediated by nitric oxide-related signalings in human colorectal cancer cells.

Treatment of human colorectal cancer cells HT29 with interleukin 1beta (IL-1beta) induces expression of the multidrug resistance protein (MRP1) gene encoding the ATP-dependent glutathione S-conjugate export (GS-X) pump and the gamma-glutamylcysteine synthetase (gamma-GCSh) gene encoding heavy (catalytic) subunit of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the biosynthesis of glutathione (GSH). The induction can be suppressed by N(G)-methyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS). These results suggest that IL-1beta-mediated MRP1 and gamma-GCSh induction involve nitric oxide (NO) -related signaling. Further supports to the involvement of NO in the induction of MRP1 and gamma-GCSh expression are made by the following observations. (i) Expression of MRP1 and gamma-GCSh genes were induced by treating the cells with NO donors, i.e., S-nitro-N-acetyl-D,L-penicillamide (SNAP) and S-nitroso-L-glutathione, in a concentration-dependent manner. (ii) Ectopic expression of inducible NOS (iNOS) activity by transfecting expressible recombinant iNOS cDNA encoding functional iNOS but not the nonfunctional version resulted in elevated expression of MRP1 and gamma-GCSh. We also demonstrated that HT-29 cells treated with either 1L-1beta or SNAP induced ceramide production, and addition of C2 or C6 ceramides into cultured HT-29 cells resulted in induction of gamma-GCSh but not MRP1 expression. Collectively, our results demonstrate that induction of MRP1 and gamma-GCSh by IL-1beta is regulated, at least in part, by an NO-related signaling, and induction of gamma-GCSh is by NO-related ceramide signaling.

ATP-Binding Cassette Transporters↗

PubMed2000

Involvement of caspase 3 in apoptotic death of cortical neurons evoked by DNA damage.

Previous reports have shown that DNA-damage-evoked death of embryonic cortical neurons is delayed by general caspase inhibitors and is accompanied by an increase in DEVD-AFC cleavage activity. We show here that this cleavage activity is lacking in camptothecin-treated caspase 3-deficient neurons. Moreover, we report that death of camptothecin-treated caspase 3-deficient neurons cultured from E16 embryos is delayed and that no significant increase in survival is observed with cotreatment with the general caspase inhibitor BAF. These results indicate that caspase-dependent death of camptothecin-treated cortical neurons requires caspase 3 activity. The delay in death is accompanied by impairment of DNA fragmentation. However, Bax-dependent cytochrome c release still occurs in camptothecin-treated caspase 3-deficient cortical neurons. Accordingly, we hypothesize that the delayed death which occurs in the absence of caspase 3 activity may be due to mitochondrial dysfunction. Finally, we show that the delay in death observed with E16 caspase 3-deficient neurons does not occur in neurons cultured from E19 embryos. This suggests that the requirement for caspase 3 in death of neurons evoked by DNA damage may differ depending upon the developmental state of the cell.

Animals↗

PubMed2000

Acute changes in bladder volume produce minimal cardio-respiratory responses in lightly anesthetised humans.

PURPOSE: To examine whether changes in bladder volume elicit reflex cardiovascular and respiratory responses in humans under general anesthesia with sevoflurane and nitrous oxide. METHODS: Fourteen patients free of autonomic disorders were anesthetized with sevoflurane 0.5% and nitrous oxide 60% in oxygen that were approximately equivalent to 0.9 MAC. Warmed saline (6 ml x kg(-1), 37 degrees C) was instilled into the pre-emptied urinary bladder, and then the bladder was kept distended for five minutes. Following the distension, the instilled saline was drained to the pre-instilled volume of the bladder Arterial blood pressure, respiratory flow, and intra-vesicle pressure were continuously measured, and mean arterial pressure, pulse rate, respiratory rate, tidal volume, and minute ventilation were estimated offline from these signals. RESULTS: Bladder emptying produced small decreases in mean blood pressure (from 83.4+/-4.3 to 80.0+/-4.4 mm Hg, mean +/- SE, P = 0.017) and pulse rate (from 72.2+/-2.9 to 69.4+/-2.7 bpm, mean +/- SEM, P = 0.004). Only minimal respiratory reflexes were invoked by the bladder volume changes. CONCLUSION: In lightly anesthetized humans, the acute changes in bladder volume produce only mild cardiovascular and respiratory responses.

Adult↗

PubMed2000

Regression of left main coronary ostium stenosis after surgical revascularization and steroid therapy.

We describe a patient in whom stenosis of the left main coronary ostium completely regressed after steroid treatment following surgical revascularization. A 46-year-old woman with unstable angina underwent double coronary artery bypass grafting. Although she did not fulfill diagnostic criteria for Takayasu's disease, we began postoperative steroid therapy on postoperative day 14 based on clinical manifestations and histological findings. Coronary angiography 33 days after surgery showed the ostial stenosis of the left main coronary artery had disappeared. Steroid therapy for suspected Takayasu's disease should be considered even after surgical revascularization.

Coronary Artery Bypass↗

PubMed2000

Characterization of whole-cell currents elicited by mechanical stimulation of Xenopus oocytes.

Whole-cell mechanosensitive current (I(ms)) in Xenopus oocytes was studied using the two-electrode voltage-clamp technique. I(ms) was evoked by mechanically pressing the oocyte surface with a glass micropipette. The current was found to depend on the amplitude of the stimulus, showed a time-dependent decay, and turned off immediately after the stimulus was removed. The current-voltage relationship for the peak current exhibited inward and outward rectification at negative and positive potentials, respectively, while that for the sustained current exhibited only inward rectification. I(ms) was significantly suppressed by 30 microM Gd3+. One millimolar amiloride also significantly suppressed the inward I(ms) at negative potentials, but not the outward one at positive potentials. Replacing extracellular Na+ with K+ did not change the current-voltage relationship, whereas replacing extracellular Na+ with choline+ or tetraethylammonium+ significantly decreased the inward I(ms). The outward rectifier at positive potentials was abolished by replacing extracellular Cl- with gluconate-, by intracellular injection of 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), by extracellular application of anthracene-9-carboxylic acid, and by replacing extracellular Ca2+ with Mg2+. These results suggest that mechanical stimulation activates stretch-activated cation channels and Ca2+-activated Cl- channels, the latter being secondarily activated by an increase in intracellular Ca2+ concentration by Ca2+ influx through stretch-activated cation channels.

Animals↗

PubMed2000

The thoracoscopic approach for internal mammary nodes in breast cancer.

BACKGROUND: This pilot study was conducted to estimate the use of the thoracoscopic surgery as a new approach for the internal mammary nodes (IMN) in breast cancer. PATIENTS AND METHODS: For this study, 21 women with breast cancer who underwent the approach for nodes IMN were enrolled. All the women had suspicious IMN metastasis and no distant metastasis. RESULTS: Thoracoscopic IMN dissection was performed safely for 20 of the women, with an average operative time of 44 min. One woman was excluded from the procedure because of pleural adhesion. The patients were restricted from walking for 1.3 days because of chest drainage, but no patients had severe complication or chest wall deformity after the operation. Six patients had positive IMN outcomes. After surgery, 10 of the 20 patients had a lower tumor node metastases (TNM) staging. Two patients who tested positive for IMN and three who tested negative experienced a relapse, but none had pleural dissemination in a median follow-up period of 24 months. CONCLUSION: Thoracoscopic surgery may be useful in managing patients with IMN.

Adult↗

PubMed2000

Neovascularization (angiogenesis) after revascularization in moyamoya disease. Which technique is most useful for moyamoya disease?

The effects of direct and indirect revascularization for moyamoya disease were analyzed for each donor artery to determine which surgical procedure is most useful for the induction of neovascularization. In the past 12 years, 85 patients with moyamoya disease were surgically treated by combined surgery consisting of indirect revascularization via encephalo-duro-arterio-myo-synangiosis (EDAMS) and direct revascularization via the superficial temporal artery and the middle cerebral artery (STA-MCA) bypass. Among those patients, the post-operative changes in digital subtraction angiography were examined in 56 sides, including 34 sides in paediatric cases and 22 sides in adult cases. The neovascularization after indirect revascularization using the 1) superficial temporal artery (skin), 2) middle meningeal artery (dura mater), 3) deep temporal artery (temporal muscle) was analyzed. As results, in paediatric cases, the deep temporal artery and middle meningeal artery induced good neovascularization. However, the induction of neovascularization from the superficial temporal artery was not always good in most pediatric and adult cases. On the other hand, the direct bypass was useful in 90% of adult cases. In indirect revascularization surgery for moyamoya disease, the temporal muscle (the deep temporal artery) and the dura mater (the middle meningeal artery) are useful donors to the ischemic brain. The simple encephalo-arterio-synangiosis is not always effective. The direct bypass is a useful technique for adult moyamoya disease.

Adult↗

PubMed2000

Plasma concentration of brain natriuretic peptide as a biochemical marker for the evaluation of right ventricular overload and mortality in chronic respiratory disease.

The purpose of this study was to evaluate whether the plasma brain natriuretic peptide (BNP) concentration is a useful marker of right ventricular (RV) overload and whether it has prognostic value as a predictor of death in patients with chronic respiratory disease (CRD). We measured the plasma BNP and atrial natriuretic peptide (ANP) concentrations in 31 consecutive patients with CRD who underwent right-heart catheterization to evaluate pulmonary hypertension. All patients were followed for >12 months. The plasma BNP concentration closely correlated with the mean pulmonary artery pressure and pulmonary vascular resistance (r=0.62, P<0.0005 and r=0. 85, P<0.0001), and showed a weak linear correlation with cardiac output (r=-0.36, P<0.05). During the follow-up period, 5 (16%) end-stage CRD deaths (4 RV heart failure and 1 respiratory infection) and 2 non-end-stage CRD deaths occurred. In a stepwise multivariate Cox proportional-hazards regression analysis including age, sex, BNP, ANP, hemodynamic variables and the ratio of PaO(2) to fraction of inspired oxygen, only BNP (P<0.05) was an independent predictor of end-stage CRD death. The upward and leftward shift in the receiver operating characteristic curve between patients with end-stage CRD death and those without was greater for BNP than for ANP. Our findings suggest that the plasma BNP concentration may be an inexpensive, simple and useful marker of RV overload and end-stage CRD death in CRD patients. These preliminary results need to be confirmed in a large series of CRD patients.

Aged↗

PubMed2000

Cassane diterpenoid from Caesalpinia major.

A new cassane diterpenoid, 14-deoxy-epsilon-caesalpin was isolated from the seed kernels of Caesalpinia major and its structure was determined by spectroscopic data.

Diterpenes↗

PubMed2000

Prostaglandin A1 enhances c-fos expression and activating protein-1 activity.

Prostaglandin A1 (PGA1) increases heat shock element (HSE)-mediated transcription, thereby enhancing expression of HSE-bearing genes, including heat shock proteins. Because we recently found functional HSEs in the human and rodent c-fos promoters, we hypothesized that PGA1 might increase c-fos expression through the HSE. In this study, we revealed that PGA1 induces c-fos expression at least partly by increasing the binding between heat shock factor-1 and the HSE, and that PGA1 enhances activity of activating protein-1 (AP-1). Interestingly, so far as PGA, is present in the medium, AP-1-mediated transcription enhanced by PGA1 cannot be detected by the standard luciferase reporter gene assay. Instead, it can be detected by either checking luciferase mRNA levels in the presence of PGA1 or measuring luciferase activities just after removal of PGA1. These results showed that protein products of some stress-responsive genes can increase, not during the stressful condition, but immediately after recovery from stress.

Animals↗