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Biomedical subjects

A Iida

Publications and source records attributed to A Iida.

At least 55 records · Page 3Linked to original sources
PubMed2000

Podophyllotoxin aza-analogue, a novel DNA topoisomerase II inhibitor.

The pendant E-ring moiety of the podophyllotoxin aza-analogue 1 that is a potent inhibitor of microtubule assembly was modified in order to acquire inhibitory activity of DNA topoisomerase II. The monophenolic analogue 2 did not exhibit human topoisomerase II inhibition, while the ortho-quinone 3 that was obtained by oxidation of 2 inhibited its catalytic activity (decatenation) in a dose-dependent manner and stimulated double strand DNA breaks in supercoiled circular plasmid DNA, resulting in the production of linear DNA. These results showed that the topoisomerase II inhibition of the ortho-quinone 3 is due to stabilization of the topoisomerase II-DNA covalent binary complex. On the other hand, the ortho-quinone 3 did not inhibit the relaxation process of supercoiled DNA by topoisomerase I at concentrations up to 400 microM, nor was intercalation observed in unwinding measurements of 3. Therefore, the ortho-quinone 3 was shown to be a novel nonintercalative topoisomerase II specific inhibitor that stabilizes the cleavable complex. The present results suggest that the 4'-free hydroxyl group on the E-ring and the sugar moiety on the C-ring are not a prerequisite for topoisomerase II inhibition by podophyllotoxin derivatives.

DNA↗
PubMed2000

[5-FU concentration in the serum and the tumor tissue after administration of UFT 200 mg/day to patients over 80 years of age with oral cancer].

UFT was administered orally at a dosage of 200 mg/day, 2 times a day, to patients over 80 years of age with oral cancer. The concentration of 5-FU in the serum and tumor tissue, as well as the side effects, were investigated. The results were as follows: 1. The concentration of 5-FU in the serum peaked (0.017 to 0.066 microgram/ml) 1 or 2 hours after UFT administration. The concentration 8 hours after administration was relatively high (0.016 to 0.041 microgram/ml). 2. The 5-FU concentrations in the tumor tissues in 3 out of 5 cases were greater than 0.05 microgram/g, which is considered to be the effective level. The concentration tended to be higher with increased duration of administration. 3. A minor side effect, bone marrow dysfunction, was observed. No effect on the function of the liver or digestive system was observed.

Aged↗
PubMed1999

Peptidic immunosuppressants from the fungus Trichoderma polysporum.

Three new 10-residue lipopeptaibols, trichopolyns III-V have been isolated from the fungus Trichoderma polysporum together with the known trichopolyns I and II. Structure determination has been achieved on the basis of spectroscopic and chemical evidence. These peptides have been shown to suppress the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction.

Animals↗
PubMed1999

Physiological mechanism for enhancement of paracellular drug transport.

We examined the action mechanisms of enhancers that improve paracellular drug transport. For sodium caprate (C10), the increase in the intracellular calcium level was considered to induce the contraction of calmodulin-dependent actin filaments, followed by dilation of the paracellular pathway. Although decanoylcarnitine (DC) also increased the intracellular calcium level, the action was independent of calmodulin and thus, the action mechanism of acylcarnitines was considered to differ from that of C10. Other acylcarnitines, lauroylcarnitine (LC) and palmitoylcarnitine (PC) and organic acids, tartaric acid (TA) and citric acid (CA) decreased the intracellular ATP level and the intracellular pH. From these results, it was considered that one of the action mechanism of acylcarnitines and organic acids is that the intracellular acidosis increases the calcium level through the decrease in ATP levels, followed by opening the tight junction. Membrane dysfunction which was expected from the above mechanism was assessed by the transport function of electrolytes. Membrane conductance, which was increased by C10, LC and PC, returned to the control value during a 3- to 6-h recovery period. On the other hand, Cl(-) ion secretion, which was obtained from short-circuit current (I(sc)), was decreased by these enhancers, but was normalized by C10 but not by LC and PC. Accordingly, C10 can be considered a safer enhancer than acylcarnitines.

Acylation↗
PubMed1999

Laparoscopic common bile duct exploration: long-term outcome.

HYPOTHESIS: Transcystic laparoscopic common bile duct exploration (LCBDE) with biliary endoscopy results in excellent long-term clinical outcome and patient satisfaction. DESIGN: Prospective cohort study of unselected patients found to have common bile duct stones during laparoscopic cholecystectomy between October 1989 and April 1998. A mailed survey assessed symptoms, outcome, and satisfaction. SETTING: A large community teaching hospital. PATIENTS: Two hundred seventeen patients with common bile duct stones. INTERVENTION: Transcystic LCBDE with choledochoscopy. MAIN OUTCOME MEASURES: Success of LCBDE, morbidity, postoperative symptoms, and satisfaction. RESULTS: One hundred sixteen surveys (54%) were returned. Mean follow-up was 60 months. The LCBDE procedure failed in 6 patients and endoscopic retrograde cholangiopancreatography was performed in 4 patients (3%). One patient had unsuspected retained stones. No patient had late recognition of retained stones or a bile duct stricture. Abdominal pain was present in 90 patients (89%) preoperatively and in 29 patients (26%) postoperatively (P = .001). The LCBDE procedure reduced 3 specific pain profiles: epigastric, from 47% (n = 54) to 7% (n = 8); back, from 31% (n = 36) to 6% (n = 7); and shoulder, from 18% (n = 21) to 2% (n = 2). When pain persisted, it was different in character in 15%. All nonpain symptoms (such as nausea, bloating, indigestion, and gas) were reduced from 78% (n = 91) to 34% (n = 39) (P = .001) except diarrhea. Diarrhea was present in 24 patients (22%) preoperatively and postoperatively, though it was a new postoperative symptom in 11 patients (11%). One hundred two patients (95%) were satisfied or mostly satisfied with LCBDE. CONCLUSIONS: Pain and nonpain symptoms, while reduced significantly after LCBDE, may persist. The LCBDE procedure does not result in common bile duct strictures or a significant rate of retained stones. This relatively new treatment for common bile duct stones is safe and effective.

Cholecystectomy, Laparoscopic↗
PubMed1999

Localization of tumor suppressor gene associated with distant metastasis of urinary bladder cancer to a 1-Mb interval on 8p22.

To identify the location of one or more putative tumor suppressor genes that may be involved in urinary bladder cancer, we examined 82 such tumors for allelic losses at 19 microsatellite loci on 8p. Loss of heterozygosity was observed in 31 of the cases. Deletion mapping identified a commonly deleted region at 8p22, within the 1-Mb interval flanked by D8S1135 and AFM177XB10. Allelic loss at 8p22 was associated with higher tumor grade (17/31, 55%, vs. 12/51, 23%; P = 0.0013). Furthermore, no tumor that retained heterozygosity for markers at 8p22 had metastasized to distant organs, whereas a substantial portion of tumors that lost alleles in that region had done so (0/51, 0%, vs. 6/31, 20%; P = 0.001). These data imply that loss or inactivation of tumor-suppressing activity encoded on 8p contributes to malignancy and to the metastatic potential of bladder cancers.

Chromosome Deletion↗
PubMed1999

Transient expression of the beta-glucuronidase gene in tissues of Arabidopsis thaliana by bombardment-mediated transformation.

Particle bombardment has proved to be useful for the transformation of plants. We have previously reported successful transient expression of the beta-glucuronidase (GUS) gene in cultured plant cells and tissues and the stable transformation of various plants using a pneumatic particle gun. In this chapter, we describe transient expression of the GUS gene in Arabidopsis thaliana leaves and roots using the pneumatic particle gun.

Arabidopsis↗
PubMed1999

Responses of Xenopus laevis water nose to water-soluble and volatile odorants.

Using the whole-cell mode of the patch-clamp technique, we recorded action potentials, voltage-activated cationic currents, and inward currents in response to water-soluble and volatile odorants from receptor neurons in the lateral diverticulum (water nose) of the olfactory sensory epithelium of Xenopus laevis. The resting membrane potential was -46.5 +/- 1.2 mV (mean +/- SEM, n = 68), and a current injection of 1-3 pA induced overshooting action potentials. Under voltage-clamp conditions, a voltage-dependent Na+ inward current, a sustained outward K+ current, and a Ca2+-activated K+ current were identified. Application of an amino acid cocktail induced inward currents in 32 of 238 olfactory neurons in the lateral diverticulum under voltage-clamp conditions. Application of volatile odorant cocktails also induced current responses in 23 of 238 olfactory neurons. These results suggest that the olfactory neurons respond to both water-soluble and volatile odorants. The application of alanine or arginine induced inward currents in a dose-dependent manner. More than 50% of the single olfactory neurons responded to multiple types of amino acids, including acidic, neutral, and basic amino acids applied at 100 microM or 1 mM. These results suggest that olfactory neurons in the lateral diverticulum have receptors for amino acids and volatile odorants.

Action Potentials↗
PubMed1999

Two target regions of allelic loss on chromosome 9 in urinary-bladder cancer.

Allelic losses on chromosome 9 are common in a wide variety of human tumors; moreover, two predisposing loci for some inherited cancer syndromes, i.e., familial malignant melanoma and Gorlin syndrome, have been identified on this chromosome. To define the location of putative tumor suppressor genes involved in cancer of the urinary bladder, 85 bladder cancers were examined for allelic loss at 18 microsatellite loci on chromosome 9. Correlations were also sought between loss of heterozygosity on chromosome 9 and several clinicopathological parameters. Allelic loss was observed in 54 of the tumors (64%) and deletion mapping identified two target regions; one at an interval on 9p21 flanked by D9S736 and D9S165, and the other at an interval on 9q31-34 flanked by D9S58 and D9S61. No subtle mutation was detected in the PTCH gene which lies in the latter interval. Allelic loss on chromosome 9 was observed frequently in low grade and non-invasive tumors as well as in tumors of more advanced phenotype. Inactivation of tumor suppressor genes lying in either of two regions of common deletion identified on chromosome 9 might affect carcinogenic mechanisms at an early stage of tumor development in the urinary bladder.

Chromosome Mapping↗
PubMed1999

Intramyocardial vascular volume distribution studied by synchrotron radiation-excited X-ray fluorescence.

We evaluated the vascular volume distribution with fine resolution (0.1-1.3 mg myocardial tissue) in the sagittal plane of the left ventricle by using the microsphere filling method in 21 dogs. The coronary arterial volume density in the sagittal plane did not exhibit normal distribution and was characterized by variability among the outer-to-inner layers and within the layers (+2SD/-2SD > 80 times), and the median values in the layers ranged from 4.7 to 22. 9 nl/mg myocardial tissue. The fractal analysis of vascular volume revealed a self-similar nature with a fractal dimension (D value) similar to that of flow distribution (1.20 +/- 0.05 and 1.24 +/- 0. 09 for vascular volume and flow distribution, respectively) and had a more marked variability than the flow. The correlation of the regional vascular volume between adjacent regions decreased as the distance increased. However, the correlation coefficients in the endocardial-to-epicardial direction were significantly higher than those in the anterior-to-posterior direction (P < 0.05 by paired t-test). In conclusion, we determined intramyocardial vascular volume density in the sagittal plane, and the distribution revealed considerable variability, self-similarity, and asymmetry in the correlation among the adjacent regions. These observations could be related to the characteristics of the intramural coronary vascular network.

Animals↗
PubMed1999

Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis.

Thirty-two patients with advanced gastric cancer underwent continuous hyperthermic peritoneal perfusion (CHPP) combined with surgery: to prevent peritoneal recurrence in 15 patients without peritoneal metastasis (prophylactic CHPP) and to treat 17 patients with peritoneal metastases (therapeutic CHPP). The postoperative outcome was compared with that of control patients treated with surgery alone. Peritoneal recurrence was less frequent (26%) and the 5-year survival rate was significantly higher (39%) in the patients with prophylactic CHPP than in 40 control patients (42 and 17%, respectively). The patients with therapeutic CHPP showed significantly better median survival than did 20 control patients (11 vs. 6 months). Cox multivariate regression analysis revealed that CHPP was an independent prognostic factor in the prophylactic study (hazard ratio = 0.3965), and that the independent prognostic factor in the therapeutic study was not CHPP but complete resection of the peritoneal metastasis. Thus, CHPP has no marked benefit for established peritoneal metastasis. CHPP for the prevention of peritoneal recurrence may have a beneficial effect on long-term survival, but a prospective randomized trial is needed to clarify its prognostic value.

Adult↗
PubMed1999

Allelic loss at 1p34, 13q12, 17p13.3, and 17q21.1 correlates with poor postoperative prognosis in breast cancer.

Allelic losses of tumor suppressor genes (TSGs), or the chromosomal regions harboring them, in tumor DNA may become useful postoperative prognostic indicators. To examine whether specific allelic losses might correlate with postoperative survival in a 5-year prospective follow-up, we tested tumors from a cohort of 264 breast cancer patients for allelic losses of 18 microsatellite markers representing either a known TSG or a region where genetic alterations are frequent in breast tumors. Patients whose tumors had lost an allele at 1p34, 13q12, 17p13.3, or 17q21.1 had significantly higher risks of postoperative mortality than those whose tumors retained both alleles at those loci (at 1p34, a 5-year mortality rate of 29% among patients with losses vs. 7% with retentions, P = 0. 0008; at 13q12, 31% vs. 10%, P = 0.0062; at 17p13.3, 24% vs. 13%, P = 0.026; and at 17q21.1, 31% vs. 13%, P = 0.0047). Furthermore, combined losses at 13q12 and 17p13.3 increased the predicted postoperative mortality risks by a factor of 9.6 (5-year mortality rate of 42% vs. 5% with retentions, P = 0.0001), and combined losses at 1p34 and 17p13.3 raised the predicted postoperative mortality risks by a factor of 8.6 (27% vs. 3%, P = 0.0064). We conclude that allelic losses at these loci can serve as negative prognostic indicators to guide postoperative management of patients. Genes Chromosomes Cancer 26:134-141, 1999.

Adult↗
PubMed1999

Iatrogenic gallbladder perforation during laparoscopic cholecystectomy: etiology and sequelae.

Iatrogenic perforation of the gallbladder (PGB) during laparoscopic cholecystectomy (LC) leads to spillage of bile and gallstones into the peritoneal cavity, which can result in serious postoperative infection. The objective of this study is to prospectively evaluate with long-term follow-up the risk factors, mechanisms, and complications associated with PGB in patients undergoing LC. Data from 1412 patients undergoing LC were collected prospectively between 1989 and 1995. Patients with and without iatrogenic gallbladder perforation were compared. Long-term follow-up was obtained using mailed questionnaires and telephone interviews, when needed. Of the 1412 patients, 512 (36%) sustained a PGB. Male sex, weight, gallbladder inflammation, thickening of the gallbladder, presence of adhesions, and a difficult hilar dissection were all associated with an increased incidence of PGB. The most common mechanisms of PGB were laceration due to grasper traction (55%) and electrocautery dissection (40%). Both the operating time and length of hospital stay were significantly longer in the PGB group. No difference was observed in the rate of wound infections between PGB and non-PGB patients (1.6% versus 1.8%). Only one patient (with an inflamed and perforated gallbladder) developed an early postoperative intra-abdominal abscess. Long-term follow-up averaging 48 months was achieved with a response rate of 44 per cent. No late intra-abdominal abscesses or complications attributable to retained gallstones were discovered.

Cholecystectomy, Laparoscopic↗
PubMed1998

Purification and cDNA cloning of cytokinin-specific binding protein from mung bean (Vigna radiata).

Synthetic urea derivatives such as N-phenyl-N'-(4-pyridyl)urea (4PU) and N-(2-chloro-4-pyridyl)-N'-phenylurea (4PU30) have strong cytokinin activities. Using tritiated 4PU30 as a probe, we previously established the presence of a cytokinin-specific binding protein (CSBP) of high affinity (Ka for 4PU30 = 4x10(10) M(-1)) in the soluble fraction of etiolated mung bean seedlings [Nagata, R., Kawachi, E., Hashimoto, Y. & Shudo, K. (1993) Biochem. Biophys. Res. Commun. 191, 543-549]. In this report, we purified CSBP by the use of 4PU-Sepharose 4B, an affinity gel liganded with 4PU. We determined partial amino acid sequences of CSBP and isolated its cDNA by reverse-transcription (RT) PCR. The cDNA encoded a protein with a calculated molecular mass of 17 kDa. A data base homology search revealed that CSBP is a novel member of a major pollen allergen/pathogenesis-related protein family. Recombinant CSBP was expressed in Escherichia coli and was confirmed to bind specifically to cytokinins.

Amino Acid Sequence↗
PubMed1998

In vitro inhibitory effects of DNA topoisomerase II by fernane-type triterpenoids isolated from a Euphorbia genus.

Several kinds of naturally occurring fernane-type triterpenoids isolated from a Euphorbia genus were tested on the inhibitory effects of DNA Topoisomerases I (Topo I) and II (Topo II) activities. A-ring cleaved 3,4-seco-8 beta H-ferna-4(23),9(11)-dien-3-oic acid and its 3-hydroxyl derivative were found to be selective inhibitors of Topo II activity without the stabilization of a DNA/Topo II cleavable complex.

DNA↗
PubMed1998

Asymmetrical membrane fluidity of bovine adrenal chromaffin cells and granules and effect of trichosporin-B-VIa.

We examined membrane fluidity of bovine adrenal chromaffin cells and chromaffin granules using cationic trimethylammonium derivative of diphenylhexatriene (TMA-DPH) as a fluorescence probe. After adding TMA-DPH to the suspension of chromaffin cells and that of granules, it first bound to the outer layer of the plasma membrane of the cells and that of the granule membrane, then gradually penetrated the inner layer of each membrane and distributed to both leaflets of the respective membranes. Accompanying increases in the ratio of incorporated probe on the cytoplasmic side of the chromaffin cell membrane, its fluorescence anisotropy gradually decreased. However, in chromaffin granules, the fluorescence anisotropy gradually increased with increases in the ratio of incorporated probe. These findings suggest that the inner layer of the plasma membrane and outer layer of the granular membrane are more fluid than the corresponding side of each membrane, which is suitable for the fusion between both membranes. We also examined the effect of trichosporin-B-VIa, a fungal ion channel forming alpha-aminoisobutyric acid-containing peptide, on the fluidity of chromaffin cells using TMA-DPH. The peptide decreased the fluorescence anisotropy and increased the fluorescence intensity in the concentration range that induced Ca2+ dependent catecholamine secretion, suggesting that a change in lipid dynamics of the lipid bilayer of the plasma membrane was induced by this peptide.

Animals↗
PubMed1998

Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line.

We examined the effects of nicergoline on hydrogen peroxide (H2O2)-induced neurotoxicity in cultured rat neuronal cell line (B50). H2O2 induced death of B50 cells in a dose-dependent manner. The H2O2-induced neuronal cell death was significantly decreased in B50 cells maintained in the presence of nicergoline. We compared the levels of antioxidants (glutathione, catalase and superoxide dismutase) in nicergoline-treated and untreated B50 cells. Lipid peroxidation products (thiobarbituric acid reactive substances, TBARS) levels were also measured. Cultures treated with nicergoline had higher levels of catalase activity. TBARS level was significantly lower in nicergoline-treated cells than in untreated cells. Our results suggest that nicergoline may induce the up-regulation of intracellular antioxidant defences and protect the neuronal cells against oxidative stress.

Animals↗