PubMed Health⌕ Search

Biomedical subjects

A Okamoto

Publications and source records attributed to A Okamoto.

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

Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group.

A series of A-ring pyrrole derivatives of duocarmycin bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. New Seg-B analogues bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group containing double bond as spacer had lower peripheral blood toxicity than the derivatives bearing 5',6',7'-trimethoxyindole-2'-carboxyl group in Seg-B of the natural type. Moreover, most of them exhibited potent antitumor activity against in vivo murine tumor models.

Animals↗
PubMed2000

Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups.

A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substituted A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs from KW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-2189.

Animals↗
PubMed2000

Development of novel lipophilic derivatives of DADLE (leucine enkephalin analogue): intestinal permeability characateristics of DADLE derivatives in rats.

PURPOSE: The objective of this study is to examine the intestinal permeability of novel lipophilic derivatives of DADLE (Tyr-D-Ala-Gly-Phe-D-Leu), an enkephalin analogue, using isolated rat intestinal membranes. METHODS: The novel lipophilic derivatives of DADLE were synthesized by chemical modification with various fatty acids at the C terminus. The pharmacological activities of these DADLE derivatives were assessed by a hot plate test. The intestinal permeability of these derivatives was estimated by the in vitro Ussing chamber method. RESULTS: We obtained four different DADLE derivatives including acetyl-DADLE (DADLE-C2), butyryl-DADLE (DADLE-C4), caproyl-DADLE (DADLE-C6), and caprylyl-DADLE (DADLE-C8). All the derivatives of DADLE had at least 75% of the activity of native DADLE, suggesting that chemical modification of DADLE at the C terminus did not markedly affect its pharmacological activity. These DADLE derivatives were more stable than native DADLE in jejunal and colonic homogenates. A "bell-shaped" profile was observed between the apparent permeability coefficients (Papp) of DADLE derivatives and lipophilicity. In particular, DADLE-C4 had the greatest permeability characteristics across the intestinal membrane of the acyl derivatives studied in this experiment. The permeability of DADLE-C4 across the jejunal membrane was further improved in the presence of puromycin, amastatin, and sodium glycocholate (NaGC), all at a concentration of 0.5 mM. CONCLUSIONS: We suggest that the combination of chemical modification with butyric acid and the application of a protease inhibitor are effective for improving the absorption of DADLE across the intestinal membrane.

Animals↗
PubMed2000

Expression of T-cell-associated antigens in B-cell non-Hodgkin's lymphoma.

We performed the immunophenotyping of 101 patients with B-cell non-Hodgkin's lymphoma (B-NHL) using two-colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of T-cell-associated antigen (T-Ag; CD2, CD5, CD7) in 25 patients (24. 8%). Among these three T-Ags, CD5 was the most frequently expressed, in 21 patients (20.8%), followed by CD7, expressed in five patients (5.0%), and CD2, which was expressed in two patients (2.0%). Two kinds of T-Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T-Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T-Ag-positive B-NHL (T-Ag(+) B-NHL) who were analysed. When comparing the clinical features between T-Ag(+) B-NHL and T-Ag-negative B-NHL (T-Ag(-) B-NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0.0119 and P = 0. 0302 respectively).

Adolescent↗
PubMed2000

Difference in tracks between habitual open and close mandibular movements at the condyle in children.

Although previous studies have paid much attention to the condylar movement in adults with permanent dentition, little attention has been paid to such movement in children. In this study, we therefore clarified the difference in habitual open and close movements at the condyle in children. Three groups of subjects were used; primary (10 children), early mixed (10 children), and permanent dentition (10 adults). The habitual open and close mandibular movement of each subject was measured using a TRIMET, which can three-dimensionally analyse the simultaneous movements of multiple points on the mandible of a subject. The measurements were then compared among the three groups. The three-dimensional analysis detected significant difference in all directions between children with primary dentition and adults with permanent dentition: primary dentition had the smallest anterior-posterior and superior-inferior directions, and the largest left-right direction. Coincidence of the open and close tracks occurred in the adults (adult group) but not in the children (primary and early-mixed dentition groups). The early-mixed dentition group showed tracks that were between those for the primary dentition group and the adult group. These results suggest that the regularity of the condylar track might be well established with dental development.

Adult↗
PubMed2000

Changes in the mechanical properties and surface texture of compomer immersed in various media.

STATEMENT OF PROBLEM: Limited information is available about the mechanical behavior of compomer under intraoral conditions. PURPOSE: This in vitro study evaluated changes in the mechanical properties and surface texture of compomer and other materials, used in similar clinical circumstances, when immersed in various media. MATERIAL AND METHODS: Hardness measurement for 5 tested materials and 4 immersion media was obtained with a Vickers hardness testing machine. Compressive strength was measured using an Autograph at a crosshead speed of 0.75 mm/min. All readings were taken for up to a 60-day period. An electron probe microanalyzer was used to give an SEM image. RESULTS: The average compressive strength and Vickers surface hardness showed a significant difference between materials. Results showed an overall increase in the solubility of specimens immersed in low pH soft drinks. CONCLUSION: There was a difference in the mechanical properties and surface texture of the materials tested in this study when they were immersed in various media.

Alcoholic Beverages↗
PubMed2000

Fistulation method: simple and safe pancreaticojejunostomy after pancreatoduodenectomy.

BACKGROUND: A pancreatic leak from the pancreaticojejunostomy after pancreatoduodenectomy has a potential risk of serious complications. We devised a simplified fistulation method for pancreaticojejunostomy. METHODS: The fistulation method, which uses a pancreatic drainage tube as a stent without pancreatic duct-to-jejunal mucosa anastomosis, was applied to 162 consecutive patients. They were divided into 3 groups according to the state of the pancreatic remnant: group 1, soft and normal parenchyma (n = 71); group 2, firm and thickened parenchyma (n = 40); group 3, hard and atrophic parenchyma (n = 51). The consistency in relation to the incidence of pancreatic leak and mortality were analyzed. Morphologic changes of the pancreatic remnant in long-term survivors of group 1 were assessed with computed tomography. RESULTS: A pancreatic leak occurred in 3 patients from group 1, in 2 patients from group 2, and in no patients from group 3 (leak rate, 3%). No operative mortality and 5 hospital deaths (3%) unrelated to a pancreatic leak were observed. The parenchyma of the pancreatic remnant was well preserved in 52% of the long-term survivors and the pancreatic duct was not dilated in 63%. CONCLUSIONS: The fistulation method can be performed safely and easily regardless of the state of the pancreatic remnant, and it provides every surgeon with a low incidence of pancreatic leak among patients.

Chi-Square Distribution↗
PubMed2000

Control of electron transfer in DNA by peptide nucleic acids (PNA).

The one-electron oxidation of PNA-DNA hybrid containing G-triplet sequence was examined. In DNA duplex G-triplet was selectively cleaved by oxidation, whereas in PNA-DNA hybrid cleavage efficiency was extremely lowered. These result suggested that cleavage efficiency of PNA-DNA hybrid was different from that of B-form DNA duplex.

Base Sequence↗
PubMed2000

Cocrystallization of a mutant aspartate aminotransferase with a C5-dicarboxylic substrate analog: structural comparison with the enzyme-C4-dicarboxylic analog complex.

A mutant Escherichia coil aspartate aminotransferase with 17 amino acid substitutions (ATB17), previously created by directed evolution, shows increased activity for beta-branched amino acids and decreased activity for the native substrates, aspartate and glutamate. A new mutant (ATBSN) was generated by changing two of the 17 mutated residues back to the original ones. ATBSN recovered the activities for aspartate and glutamate to the level of the wild-type enzyme while maintaining the enhanced activity of ATB17 for the other amino acid substrates. The absorption spectrum of the bound coenzyme, pyridoxal 5'-phosphate, also returned to the original state. ATBSN shows significantly increased affinity for substrate analogs including succinate and glutarate, analogs of aspartate and glutamate, respectively. Hence, we could cocrystallize ATBSN with succinate or glutarate, and the structures show how the enzyme can bind two kinds of dicarboxylic substrates with different chain lengths. The present results may also provide an insight into the long-standing controversies regarding the mode of binding of glutamate to the wild-type enzyme.

Aspartate Aminotransferases↗
PubMed2000

Effect of alcoholic and low-pH soft drinks on fluoride release from compomer.

PURPOSE: The purpose of this study was to evaluate the amount of fluoride released from compomer restorative materials after immersion in various media. MATERIALS AND METHODS: In this test, four materials were used: three compomers (Dyract, Dentsply, Konstanz, Germany; Compoglass, Vivadent, Schaan, Principality of Liechtenstein; and Xeno, Sankins, Tochigi, Japan) and one resin-modified glass ionomer cement (Fuji II LC, GC, Tokyo, Japan). There were four test solutions: one alcoholic (whiskey), two low-pH drinks (Coca-Cola, orange juice), and one deionized water. Over a period of 60 days, the tested specimens were immersed in the test solution for 3 hours every day, then kept in deionized water. The fluoride released was detected by using a fluoride ion selective electrode connected to a microprocessor ion analyzer. The fluoride ion concentration (ppm) of the test solutions and deionized water was recorded after 1, 2, 3, 4, 7, 30, and 60 days. Electron probe microanalysis was used for surface analysis of the fluoride released. RESULTS: When immersed in low-pH soft drinks, compomer showed a significantly higher fluoride release than when immersed in deionized water (p < .0001). For specimens immersed in Coca-Cola, the fluoride release levels (microgram/cm2, mean +/- SD) at 1, 7, and 60 days for Dyract (91.6 +/- 1.8, 39.3 +/- 3.1, 10.5 +/- 0.9), Compoglass (129.5 +/- 0.9, 66.5 +/- 2.7, 19.0 +/- 0.3), Fuji II LC (147.0 +/- 4.2, 50.8 +/- 3.1, 27.6 +/- 3.0), and Xeno (73.6 +/- 3.2, 27.3 +/- 2.1, 6.6 +/- 0.6) demonstrated the trend of significantly lower releases with time in water solution. Over a 60-day period, materials immersed in 100% orange juice released the highest amount of fluoride, which could be attributable to the erosive effect of the medium. Materials immersed in deionized water released the least amount of fluoride. Among the tested compomers, Compoglass released the most fluoride.

Alcoholic Beverages↗
PubMed2000

Color stability of compomer after immersion in various media.

PURPOSE: The purpose of this study was to evaluate the effect of various media on the color stability of compomer and to compare these results to those of other materials that could be used in similar clinical circumstances. MATERIALS AND METHODS: In this test, six materials (shade A2) were used: four compomers (Dyract, Compoglass F, Xeno, F2000), one composite resin (Clearfil AP-X), and one resin-modified glass ionomer cement (Fuji II LC). There were four test solutions: one alcoholic (whiskey), two low pH soft drinks (Coca Cola, orange juice), and deionized water as a control. A plastic ring mold (9-mm diameter x 1-mm height) was used to prepare 120 disk specimens. For 60 days, the test specimens were immersed in the various media daily for 3 hours then transferred to the deionized water. Color was measured by CIE L* a* b* relative to CIE source against a white background, using a colorimeter. Color change (delta E*) was calculated as delta E* = [(delta L*)2 + (delta a*)2 + (delta b*)2]1/2. Color changes (delta E*) were recorded after 1, 7, 30, and 60 days. RESULTS: The results indicated that compomer and resin-modified glass ionomer were susceptible to discoloration in various solutions over an extended period of time. Composite resin showed minimal perceptible color change. Specimens immersed in whiskey showed a significantly high perceptible color change (p < .0001). Water caused no perceptible color changes.

Analysis of Variance↗
PubMed2000

Low incidence of persistent tardive dyskinesia in elderly patients with dementia treated with risperidone.

OBJECTIVE: The authors studied the incidence of tardive dyskinesia in elderly institutionalized patients with dementia being treated with risperidone. METHOD: After participating in a 12-week multicenter double-blind study during which they received placebo or one of three doses of risperidone, 330 patients (mean age=82.5 years) with Alzheimer's, vascular, or mixed dementia were enrolled in a 1-year open-label study during which they received flexible doses of risperidone. Persistent emergent tardive dyskinesia was defined according to scores on the dyskinesia subscale of the Extrapyramidal Symptom Rating Scale. RESULTS: The mean modal risperidone dose was 0.96 mg/day (SD=0.53), and the median length of risperidone use was 273 days. The 1-year cumulative incidence of persistent emergent tardive dyskinesia among the 255 patients without dyskinesia at baseline was 2.6%. Patients with dyskinetic symptoms at baseline experienced significant reductions in the severity of dyskinesia. Patients who received 0.75-1.5 mg/day of risperidone showed a significant improvement in psychopathologic symptoms over the 1-year period. CONCLUSIONS: Although there was no control group, the observed incidence of persistent tardive dyskinesia with risperidone seemed to be much lower than that seen in elderly patients treated with conventional neuroleptics. The average optimal dose of risperidone in elderly dementia patients was found to be 0.75-1.5 mg/day.

Aged↗
PubMed2000

Occlusal contacts during lateral excursions in children with primary dentition.

The presence of non-working occlusal contacts in adults is considered abnormal and may initiate parafunctional activity. Few studies have looked for non-working occlusal contacts in children with primary dentition. The purposes of this study were (1) to prove the existence of non-working-side occlusal contacts, and (2) to quantify their area during lateral excursion in children with primary dentition. To achieve this purpose, we developed a measurement system that combined a tracking system for mandibular movements with a three-dimensional digitizer for tooth shape. Ten children were selected for this study. Estimated occlusal contact area of the primary second molar on the non-working side was 0.8 mm2, in contrast to 2.0 mm2 on the working side, at 3.0 mm of movement of the lower incisor. All children examined had some occlusal contacts on the non-working side during the first part of lateral excursion.

Child↗
PubMed2000

Physicians' conflicts of interest in Japan and the United States: lessons for the United States.

Japanese health policy shows that even with physician ownership and the absence of for-profit, investor-owned health care, physicians' conflicts of interest thrive. Physician dispensing of drugs and ownership of hospitals and clinics were justified in Japan as ways to avoid commercialization of medicine. Instead, they create physicians' conflicts and fuel patient overuse of services. Japan's Ministry of Health and Welfare (MHW) has responded by introducing per-diem payment, thereby creating incentives to decrease services in ways similar to those of American managed care organizations, but with none of their benefits, such as coordination of care, oversight of physicians practices, and quality assurance. Although the United States and Japanese health care systems are organized and financed differently there is convergence in the source of their physicians' conflicts and the way they are addressed. The United States is starting to integrate institutional and physician payment and align their incentives, in a traditional Japanese way. In so doing, the United States creates new physicians' conflicts and reduces the role of countervailing incentives and power, an advantage of previous policy. Japan, in turn, has combined incentives to increase and decrease services, thus moving closer to the U.S. policy.

Codes of Ethics↗
PubMed2000

Mithramycin represses MDR1 gene expression in vitro, modulating multidrug resistance.

The effect of an aureolic acid, mithramycin (MTM) on multidrug resistance (MDR) was investigated. At a concentration of 0.02--0.1 mg/ml (about 20--90 microM), MTM repressed MDR1 gene transcription of SBC-3/ADM, a MDR-phenotype subline derived from human small cell lung tumor. Under the same conditions, another aureolic acid, chromomycin A3, showed potent cytotoxicity. FACS analysis revealed that 5 microm MTM depleted the P-glycoprotein (Pgp) and lowered the efflux activity of SBC-3/ADM cells. Furthermore, MTM sensitized the cells against adriamycin. These results suggest that MTM would be a useful modulator of MDR induced by Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Two novel C-glycosides of aureolic acid repress transcription of the MDR1 gene.

In the search for compounds which repress MDR1 gene expression, two novel aryl C-glycosides were isolated from a broth of Streptomyces sp. They had the characteristic structure of a dideoxy-carbohydrate (oliose or olivose) linked directly to chromomycinone, an aglycone of aureolic acids. Further investigation revealed that they were artifacts yielded from an aureolic acid, mithramycin. Acid and methanol were necessary to yield the C-glycosides. This reaction would contribute to the design of useful aryl C-glycosides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗