[Two cases of parrotfish poisoning with rhabdomyolysis].
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Acrylamides↗
Biomedical subjects
S Okada
Publications and source records attributed to S Okada.
Nicotinic receptors involved in gastric noradrenaline release evoked by electrical stimulation of the splanchnic nerve in rats.
In the present experiment, we tried to compare the functional nicotinic receptors activated by electrical stimulation of the greater splanchnic nerve (containing preganglionic sympathetic nerves) to those activated by (-)-nicotine, using the isolated rat stomach. The stomach was perfused with Krebs-Ringer solution and endogenous noradrenaline released into the perfusate was electrochemically measured using high-performance liquid chromatography. The release of noradrenaline evoked by repeated application of 30 mM (-)-nicotine rapidly declined. However, the release of noradrenaline evoked by electrical stimulation of the splanchnic nerve at 2.5 Hz was not disturbed by the appearance of tachyphylaxis for (-)-nicotine. The (-)-nicotine-induced release of noradrenaline was abolished by diltiazem, but this reagent had no effect on the electrically evoked release of noradrenaline. The electrically evoked release of noradrenaline was not influenced by atropine, but was reduced to approximately 50% by hexamethonium. This electrically evoked release of noradrenaline was not influenced by alpha-bungarotoxin, alpha-conotoxin ImI (blockers of alpha 7 nicotinic receptors) or dihydro-beta-erythroidine (a blocker of alpha 4 beta 2 nicotinic receptors), but was reduced to about 50% by mecamylamine (a blocker of alpha 3 beta 4 nicotinic receptors). The (-)-nicotine-induced release of noradrenaline has already been shown to be partially blocked by dihydro-beta-erythroidine and to be abolished by mecamylamine as shown by Yokotani et al. [Eur. J. Pharmacol. 402 (2000) 223.]. These results suggest that the gastric release of noradrenaline in response to electrical stimulation of the greater splanchnic nerve is mediated by cholinergic (probably ganglionic alpha 3 beta 4 nicotinic receptor-mediated) and non-cholinergic mechanisms in rats. However, the functional nicotinic receptor activated by electrical stimulation of the splanchnic nerve seems to be different in character from that activated by (-)-nicotine.
Animals↗
A distinct pathway of cell-mediated apoptosis initiated by granulysin.
Granulysin is an antimicrobial and tumoricidal molecule expressed in granules of CTL and NK cells. In this study, we show that granulysin damages cell membranes based upon negative charge, disrupts the transmembrane potential (Deltapsi) in mitochondria, and causes release of cytochrome c. Granulysin-induced apoptosis is blocked in cells overexpressing Bcl-2. Despite the release of cytochrome c, procaspase 9 is not processed. Nevertheless, activation of caspase 3 is observed in granulysin-treated cells, suggesting that granulysin activates a novel pathway of CTL- and NK cell-mediated death distinct from granzyme- and death receptor-induced apoptosis.
Antigens, Differentiation, T-Lymphocyte↗
Ontogenesis of neurons immunoreactive for nitric oxide synthase in rat forebrain and midbrain.
We studied the immunohistochemical localization of neuronal nitric oxide synthase (nNOS) in the developing rat brain on embryonic days 13 (E13), 15 (E15), 17 (E17) and 19 (E19) and postnatal days 0 (P0), 7 (P7) and 14 (P14). A few neurons positive for nNOS were first detected at E15 in the hypothalamus and pons. At E17, many positive cells became detectable in the thalamus. At E19, the positive cells in these three regions were rapidly increased in number, and a few positive neurons were also observed in such regions as the cerebral cortex and striatum. Positive cells in the hypothalamus tended to locate ventrolaterally. Positive neurons, stained very intensely as in adult rats, were seen in the pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus and parafascicular nucleus. Two weeks after birth, positive neurons of larger somata with many processes were distributed widely in the cerebral cortex and hippocampus. The present study indicates that, in the forebrain and midbrain, the distribution pattern of nNOS-containing neurons is fundamentally completed by E19.
Animals↗
Binding of BAZF and Bc16 to STAT6-binding DNA sequences.
BAZF, a family member of Bcl6, can function as a sequence-specific transcriptional repressor. We determined BAZF-binding DNA sequence. The consensus binding sequence (CBS) of BAZF is almost the same as those of Bcl6 previously described. Three nucleotides of T, G and A at position 6, 8, and 9 in the CBS (5'-ATTCCTAGAAAG-3') are important nucleotides for binding of both BAZF and Bcl6. Since a part (5'-TTC-CTA-GAA-3') of the CBS resembled the sequence motif (5'-TTC-(N3-4)-GAA-3') bound by STAT factors, BAZF and Bcl6 can bind to the CD23b-STAT6-binding sequence (5'-TTTC-TTA-GAAAT-3'), the immunoglobulin germline epsilon-STAT6-binding sequence (5'-CTTC-CCAA-GAAC-3'), and the IL4-STAT6-binding sequence (5'-TTTC-CCA-GAAAA-3') with weak affinity. However, a mutation of C nucleotide to T nucleotide in the IL4-STAT6-binding sequence (5'-TTTC-CTA-GAAAA-3') strongly increased the binding activity of BAZF and Bcl6. These results suggest that BAZF and Bcl6 can repress some of STAT-induced transcription by binding to DNA sequences recognized by STAT factors.
Animals↗
Role of brain arachidonic acid cascade on central CRF1 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.
The present experiments were designed to characterize the mechanisms involved in the corticotropin releasing factor (CRF)-induced activation of central sympatho-adrenomedullary outflow in rats. Intracerebroventricularly (i.c.v.) administered CRF and urocortin (0.5, 1.5 and 3.0 nmol/animal) effectively and dose-dependently elevated plasma levels of adrenaline and noradrenaline, and the effect of urocortin was almost the same as that of CRF. The elevation of catecholamines induced by CRF and urocortin (1.5 nmol/animal) was reduced by CP-154,526(butyl-ethyl-(2,5-dimethyl-7-(2,4,6trimethylphenyl)-7H-pyrrolo [2,3-d] pyrimidin-4-yl]amine), a selective CRF1 receptor antagonist, in a dose dependent manner (1.2 and/or 2.4 micromol/animal, i.c.v.), and abolished by indomethacin (1.2 micromol/animal, i.c.v.), an inhibitor of cyclooxygenase. Furegrelate (1.8 micromol/animal, i.c.v.), an inhibitor of thromboxane A2 synthase, abolished the CRF-induced elevation of adrenaline, but had no effect on the evoked release of noradrenaline. These results suggest that activation of brain CRF1 receptor facilitates the central sympathetic and adrenomedullary outflow in distinct central pathways in rats; brain thromboxane A2 is involved in the central adrenomedullary outflow; an active metabolite of arachidonic acid other than thromboxane A2 (probably prostaglandin E2) may be involved in the central sympathetic outflow.
Analysis of Variance↗
Energetics and electronic structures of encapsulated C60 in a carbon nanotube.
We report total-energy electronic structure calculations that provide energetics of encapsulation of C60 in the carbon nanotube and electronic structures of the resulting carbon peapods. We find that the encapsulating process is exothermic for the (10,10) nanotube, whereas the processes are endothermic for the (8,8) and (9,9) nanotubes, indicative that the minimum radius of the nanotube for the encapsulation is 6.4 A. We also find that the C(60)@(10,10) is a metal with multicarriers each of which distributes either along the nanotube or on the C60 chain. This unusual feature is due to the nearly free electron state that is inherent to hierarchical solids with sufficient space inside.
Journal Article↗
Monochloramine inhibits etoposide-induced apoptosis with an increase in DNA aberration.
Monochloramine (NH(2)Cl) is a physiological oxidant produced by activated neutrophils, and it affects apoptosis signaling. We studied the effects of NH(2)Cl on the cell death induced by etoposide, a widely used anticancer agent that is directed to DNA topoisomerase II. Jurkat T cells, a human acute T cell leukemia cell line, were pretreated with 70 microM of NH(2)Cl for 10 min. After 24 h, 5-30 microM of etoposide was added to the NH(2)Cl pretreated and control cells, and their apoptosis, caspase activity, cell morphology, and cellular DNA contents were measured. NH(2)Cl pretreatment significantly inhibited apoptosis and caspase activation induced by etoposide or camptothecin, a DNA topoisomerase I poison, but not by staurosporine or Fas stimulation. The apoptosis inhibition actually resulted in the proliferation of the survived cells and, notably, the survived cells showed more aberrant morphology, such as variation in nuclear size, nuclear fragments, and multinucleated cells. DNA content analysis of the survived cells showed an increase in aneuploid nuclei. Cell cycle analysis after 24 h of NH(2)Cl treatment showed a significant decrease in S phase cells with a concurrent increase in G(0)/G(1) phase cells, which suggested that NH(2)Cl induced G(1) arrest. Using synchronized Jurkat cells, etoposide and camptothecin were found to be particularly cytotoxic to S phase cells, whereas staurosporine and Fas stimulation were not. Thus NH(2)Cl-induced G(1) arrest was a likely cause of the observed resistance to etoposide. These observations suggested that inflammation-derived oxidants may make the tumor cells more resistant to etoposide and increase the risk of tumor progression and the development of secondary tumors by increasing the survival of DNA damage-bearing cells.
Aneuploidy↗
Lack of effectiveness of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma.
BACKGROUND: Cisplatin has been reported to enhance the cell-killing effect of radiation. The current study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma. METHODS: Forty-one patients with pancreatic carcinoma that was unresectable but confined to the pancreatic region were treated with external beam radiation (50.4 grays [Gy] in 28 fractions over 5.5 weeks) and daily cisplatin (5 mg/m(2)/day as a 30-minute infusion just before each radiation fraction). Maintenance 5-fluorouracil (5-FU) (500 mg/m(2)) given once weekly was initiated 1 week after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. RESULTS: Of the 41 patients, 31 (76%) completed the scheduled course of chemoradiotherapy. The median survival time was 7.7 months, and the 1-year survival rate was 36%. The median progression free survival time was 5.8 months. The first site of failure was distant metastases in 25 patients, locoregional recurrence in 6 patients, and both sites in 1 patient. The major toxicity was leukocytopenia and nausea/emesis. CONCLUSIONS: Radiotherapy with daily cisplatin appears to be inferior to conventional chemoradiotherapy using 5-FU in patients with locally advanced pancreatic carcinoma.
Adenocarcinoma↗
A low-pH culture condition enhances the radiosensitizing effect of wortmannin.
PURPOSE: The radiosensitizing effect of wortmannin on human tumor cells in a low-pH microenvironment was compared with that in a neutral-pH environment. METHODS AND MATERIALS: A172 human glioblastoma cells, A549 human lung adenocarcinoma cells, and HMV-1 human melanoma cells were treated with 20 microM wortmannin 2 h before irradiation, and cell survival was examined. A low-pH microenvironment was simulated by exposing cells to low-pH culture medium for 24 h before wortmannin treatment. The effects of wortmannin on the repair of DNA double-strand breaks (dsbs) after 50-Gy irradiation in both low- and neutral-pH conditions were measured by pulsed-field gel electrophoresis. Expression of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in low-pH conditions was also compared with that in neutral-pH conditions by Western blot analysis. RESULTS: The radiosensitizing effect of wortmannin was greater in low-pH cultures than in neutral-pH cultures for all cell lines. The fast-rejoining component of DNA dsb repair was inhibited more strongly in low-pH than in neutral-pH conditions, although there was little difference in DNA-PKcs expression between groups. CONCLUSIONS: The low-pH culture condition, which was designed to mimic the microenvironment of the central tumor mass in actively proliferating solid tumors, enhanced the radiosensitizing effect of wortmannin by inhibiting the fast-rejoining component of DNA dsb repair and by prolonging the retention of nonrejoined DNA dsbs.
Adenocarcinoma↗
Expression of aldose reductase and sorbitol dehydrogenase genes in Schwann cells isolated from rat: effects of high glucose and osmotic stress.
To investigate the polyol pathway activity in Schwann cells, we determined the mRNA levels of aldose reductase (AR) and sorbitol dehydrogenase (SDH) in cultured cells under hyperglycemic or hyperosmotic conditions using competitive RT-PCR technique. The expressions of AR and SDH mRNAs in Schwann cells were unaltered by high (30 mM) glucose content in the medium. On the other hand, osmotic stress elicited significant increases in AR mRNA without any effect on SDH mRNA expression. The levels of AR mRNA determined by this RT-PCR system were significantly correlated with AR activity, as well as the levels of sorbitol accumulated in Schwann cells cultured under hyperosmotic conditions. These findings suggest that in contrast to the induction of AR expression by osmotic stress, high glucose per se does not up-regulate expression of the enzymes constituting the polyol pathway in Schwann cells. The RT-PCR system developed in this study may be a useful tool in ascertaining the relative contributions of AR and SDH to the metabolic derangements leading to diabetic complications.
Aldehyde Reductase↗
Inhibitory effect of theophylline on recombinant GABA(A) receptor.
Convulsions due to systemic toxicity are a major and frequently fatal side effect of theophylline. The cause of theophylline-induced convulsions is not clear, but antagonism of the inhibitory nervous system may be implicated, so we examined the effects of theophylline on GABA-induced currents using recombinant GABA(A) receptor (GABA(A)-R). Theophylline dose-dependently inhibited GABA-induced currents: the IC50 value was 1841+/-63 microM and Hill coefficient 1.09+/-0.03. The inhibitory action of theophylline on GABA-induced currents was competitive and voltage dependent. The inhibition of GABA-induced currents by theophylline may be a primary mechanism underlying theophylline-induced convulsions.
Animals↗
Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy.
BACKGROUND: The combination of radiation therapy and chemotherapy (chemoradiotherapy [CRT]) has been accepted as standard therapy for patients with locally advanced pancreatic carcinoma (PC). This study investigated prognostic factors in patients with locally advanced PC receiving CRT. METHODS: Fifty-five consecutive patients with locally advanced PC, who received concurrent radiotherapy (50.4 grays) and chemotherapy using 5-fluorouracil or cisplatin, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 301 days, 35.1% and 2.4%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0-1 (P < 0.01), absence of regional lymph node swelling (P < 0.01), and serum CA 19-9 level of less than 1000 (P = 0.02) were independent favorable prognostic factors. A prognostic index based on the coefficients of those prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 410, 239, and 143 days, respectively (P < 0.01). CONCLUSIONS: The results may be helpful in predicting life expectancy, determining treatment strategies, and designing future clinical trials.
Adult↗
SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick disease type C.
The molecular prenatal diagnosis of Niemann-Pick disease type C (NPC) is presented. The proband with a late infantile type of NPC was a compound heterozygote of a paternal missense mutation, T529G, and a maternal 2 bp deletion at nt 350 of the NPC1 gene. These mutations were detected by single-strand conformation polymorphism (SSCP) analysis of RT-PCR products. When the proband was aged 4 years 3 months, prenatal diagnosis for the second child was performed using both biochemical and molecular methods. SSCP analysis for the parental mutations using cDNA from cultured amniotic fluid cells revealed the absence of both mutations and the fetus was diagnosed as being unaffected. This diagnosis was supported by a normal level of cholesterol esterification using cultured amniotic fluid cells. After the child's birth, when he was 21 months old, the diagnosis was confirmed by SSCP analysis of genomic DNAs of his family. This analysis also revealed a unique variation of intron 13, IVS13+753-758 del TTTTTT, that was shared only by the proband and the father, and was suspected as being linked to the T529G missense mutation. A combination of both biochemical and molecular analyses is very useful and reliable for prenatal diagnosis of Niemann-Pick disease type C.
Adult↗
Adjuvant interferon for hepatocellular carcinoma.
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Antineoplastic Agents↗
Examination of intra-gastrointestinal tract signal elimination in MRCP: combined use of T(1)-shortening positive contrast agent and single-shot fast inversion recovery.
To examine the effects of removing the gastrointestinal signal in MR cholangiopancreatography (MRCP), investigations were carried out on the combined use of T(1)-shortening intestine-positive contrast medium, FerriSeltz with ferric ammonium citrate as the main component, and high-speed imaging using single-shot fast inversion recovery (SSFIR). The contrast effect was significantly elevated to 10.2 +/- 1.6 after administration, compared with 5.9 +/- 2.4 before administration (P < 0.001). The enhancement effect was also significantly elevated to 13.2 +/- 3.0 after administration, compared with 4.9 +/- 3.1 before administration (P < 0.001). These results were obtained because the null point of FerriSeltz aqueous solution (5.97 mmol/L) was in the range of approximately 180 msec. With the present method, adequate suppression of the signal intensity of the digestive tract was obtained relatively easily with MRCP, and the technique was found to be effective. J. Magn. Reson. Imaging 2001;13:738-743.
Adult↗
Mitotic index and ki-67 nuclear antigen labeling index as predictors of chemotherapy response in uterine cervical carcinoma.
OBJECTIVE: The aim of this study was to determine if the mitotic index (MI) and the Ki-67 nuclear antigen labeling index (Ki67LI) obtained from biopsy specimens could be used as predictors of chemotherapy response in uterine cervical carcinomas. METHODS: Six patients with squamous cell carcinoma who received neoadjuvant chemotherapy before radical surgery were entered into the study. The MI and the Ki67LI were evaluated using hematoxylin and eosin (H&E)-stained and immunostained slides before and after chemotherapy. Tumor size was measured three-dimensionally by magnetic resonance imaging. We compared the values of MI and Ki67LI with changes in tumor size. RESULTS: The cases were classified according to the percentage reduction in tumor mass: one case showed a marked response (98%), four showed a moderate response (53-78%), and one showed a slight response (approximately 0%). In the case with a marked response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 15, 2, and 0, respectively. The corresponding Ki67LI values were 51, 16, and 0, respectively. In the moderate response cases, the corresponding MI values before and 3 and 7 days after chemotherapy were 3.9-13.6, 0.8-1.6, and 1.6-4.0, respectively. The Ki67LI was 21.8-44.2 before chemotherapy, with two cases increasing and two decreasing at 7 days after chemotherapy. In the case showing a slight response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 0.5, 0.8, and 1.0, respectively. The Ki67LI was 4.0 before chemotherapy and increased slightly to 6.0 at 7 days after chemotherapy. CONCLUSIONS: In six cases examined, high MI and Ki67LI values before chemotherapy and a marked decrease in MI shortly after chemotherapy appeared to be predictors of good neoadjuvant chemotherapy response in uterine cervical carcinomas.
Adult↗
Distinctive multidrug sensitivity and outcome of acute erythroblastic and megakaryoblastic leukemia in children with Down syndrome.
We assessed the in vitro chemosensitivity of acute erythroblastic and megakaryoblastic leukemia cells from children with Down syndrome (DS) compared to non-DS children. We conducted in vitro tests using the MTT assay of bone marrow samples from 12 children with DS and 16 children without DS. Patients were newly diagnosed based on the morphology and expression of platelet-specific antigens. Induction failure occurred more frequently in the non-DS group (n = 4) than in the DS group (n = 0, P = .053). Children with DS had a superior event-free survival (EFS) probability of 0.750 at 4 years, compared to an EFS probability of 0.375 for non-DS children (P = .049). Blast cells from DS patients were significantly more sensitive to daunorubicin, melphalan, mitoxantrone, 4-hydroperoxy-cyclophosphamide, vincristine, etoposide, bleomycin, and pirarubicin than those from non-DS patients. Four of the 16 non-DS patients were found to have acquired an extra chromosome 21 in their leukemia cells: blasts from these patients also tended to have greater chemosensitivity than those from patients without an extra chromosome 21. Blast cells from DS patients are markedly sensitive to various drugs. These results suggest that the fragility of blast cells derived from DS patients may be related to an increased susceptibility to apoptosis.
Antineoplastic Combined Chemotherapy Protocols↗