[A study of reversed occlusion associated with posterior crossbite especially in relation to rapid maxillary expansion (author's transl)].
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Dental Arch↗
Biomedical subjects
N Motohashi
Publications and source records attributed to N Motohashi.
Electronic interaction of carcinogenic and noncarcinogenic benz(c)acridines and DNA.
Electronic interaction of DNA with nine benzacridine derivatives was studied. The interaction system of these benzacridines and DNA was found to show a marked hypochromism in the ultraviolet region. The orderly double helical structure of DNA was found to play an essential role in this spectroscopic change. A high concentration of the interactant, low environmental ionic strength, low pH, and low temperature were beneficial in this interaction. The degree of hypochromism expressed by the integrated and pKa of the benzacridines were found to be in parallel. The hypochromism of the interaction system, in which the carcinogenic benz[c]acridine derivatives took part, was larger than that of the system in which the noncarcinogenic derivatives were involved.
Acridines↗
The metabolic conversion of L-glutamate to pyrrolidone carboxylate in rat tissues.
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Acids↗
Monitoring of MRP-like activity in human erythrocytes: inhibitory effect of isoflavones.
A method to fluorometrically monitor efflux of 2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes was developed. Genistein, daidzein, sophoraisoflavone A, and licoisoflavone A induced 50% inhibition (IC(50)) of BCPCF efflux at 15-70 microM. The IC(50) value of the most efficient isoflavone, licoisoflavone A (15-25 microM), was comparable to that of indomethacin (approximately 10 microM) and markedly lower than for probenecid (100-200 microM), both known MRP1 inhibitors. Our results indicate that the human erythrocyte is a useful cell model in screening potential MRP inhibitors, that BCPCF is a good substrate for MRP, and that some isoflavones at low concentrations inhibit MRP-mediated efflux.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Relationship between radical intensity and biological activity of cacao husk extracts.
The relationship between radical intensity and biological activity of cacao husk extracts was investigated. Electron spin resonance (ESR) spectroscopy demonstrated that the radical intensity of hexane, acetone, methanol and 70% methanol extracts increased with water-solubility. Several fractions of these husk extracts, separated by different column chromatographies, significantly inhibited the cytopathic effect of human immunodeficiency virus (HIV) infection in parallel with their radical intensity. However, their cytotoxic activity against human leukemic and carcinoma cell lines is not always correlated with their radical intensity. Water-soluble and lipophilic compounds might induce cytotoxic activity by different mechanisms.
Anti-HIV Agents↗
Trichloroethylene. I. Carcinogenicity of trichloroethylene.
Trichloroethylene (TCE) as an industrial pollutant may damage human health and can be considered as carcinogen. TCE has been detected in the environment and in various human organs, e.g., liver, kidney and brain etc. There are histological alterations such as depletion of glycogen and hydropic degeneration in the liver, however, other signs of TCE effects can be found in various organs as well. TCE and its metabolites, e.g., trichlorethanol, trichloro-acetic acid and epoxides were recently identified as strong mutagens in Ames mutagenicity test inducing frameshift and base-substitution mutations. TCE induced predominantly hepatocellular carcinoma after long term administration in mice. In these animals, kidneys and liver were supposed to be primary target organs with low epoxy-hydrolase activity. A high level of mitotic gene conversion (or gene rearrangement) was indicated by the metabolism of TCE after repeated administration. Purified TCE by was a weak mutagen in the presence of S9 microsomal fraction of rats and as a consequence, the carcinogenic activity was low in the kidney of rats. However, a dose related increase of Leydig cell tumors was found in male rats.
Animals↗
Trichloroethylene. II. Mechanism of carcinogenicity of trichloroethylene.
The cancer inducing effect of trichloroethylene (TCE) was studied by various methods. DNA complexing activity and apoptosis inhibition were found to be the key elements of the carcinogenicity of TCE and its metabolites. The ability of TCE to interact with DNA was low, but its incorporation into the RNA and DNA of the brain, testis, pancreas, kidney, liver, lung and spleen, cannot be excluded. Exposure to TCE and its metabolites provides a selective growth advantage to spontaneously occurring mutations in some K- and H-ras oncogenes (as non specific results of secondary DNA or RNA damage). The amount of DNA-TCE adducts was higher in mouse hepatocytes than in rat hepatocytes. These differences may explain the species difference in carcinogenicity of TCE, which was dose dependent (due to metabolism) in mice but independent in rats. The blood level kinetics of TCE confirmed the faster metabolic rate in mice, including peroxisome proliferation and induction in hepatocytes. Dichloroacetic- and trichloroacetic acid were found to be hepatic carcinogens in mice, and the specificity depends on peroxisome proliferation induction. Possibly, TCE and related compounds down regulated apoptosis in mouse liver, and the reduced ability to remove initiated cells by apoptosis could be responsible for liver cancer induction by TCE.
Animals↗
Trichloroethylene. III. Prediction of carcinogenicity of investigated compounds including trichloroethylene.
The mutagenicity and carcinogenic properties of trichloroethylene (TCE) derivatives, and their correlation with its molecular properties were analyzed. The observed cancer incidence was compared to the predicted, calculated incidence. The predictions were based on the rodent bioassay results and were consistent with human data. The electrophilic data of molecules of the Ke system provided evidence for 205 rodent carcinogens, where Ke correlated with energy of the lowest unoccupied molecular orbital. The majority of carcinogenic compounds were found to be electron acceptors with decreased lowest unoccupied molecular orbital (LUMO) energy, indicating the particular DNA-reactivity leading to mutations and abnormal cell division. Based on the mutagenic activity in Ames test, the affinity of target organs for mutagens and non mutagens were compared in 351 rodent carcinogens. Nearly 80% of carcinogens (mutagenic and non mutagenic ones) were positive in the mouse and rat, in at least one of the most frequent target organs, i.e. liver, lung, mammary gland, stomach, kidney, hematopoietic system, urinary bladder and vascular system. Several predictive methods have been developed over the last 5 years based on structure-activity relationship studies known as US National Toxicology Program. One of these programs, called "PROGOL" is widely used for the prediction of carcinogenesis for a wide variety of compounds, e.g., nitro aromatics and suramin analogs. This program provides a simple model for predictive carcinogenesis, despite of the fact that the very first steps of carcinogenesis are not fully understood yet.
Animals↗
Antitumor activity of benzo[a]phenothiazines.
We have previously reported on the diverse biological activities of benzo[a]phenothiazines, such as the induction of antitumor and antimutagenic activity in vivo, and differentiation and apoptosis in vitro. The relationship of radical generation and pi-spin density or dipole moment was investigated, using quantum-chemical calculation with UHF/PM3. These data suggest that the origin of radical generation by active benzo[a]phenothiazines, which affect such biological activities might be N-atom at position 12.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Chemical structure and tumor type specificity of "half-mustard type" phenothiazines.
The antiproliferative activity of six "half-mustard type" phenothiazines against a total of 54 tumor cell lines: 4 leukemia, 9 non-small-cell lung, 7 colon-, 5 CNS-, 8 melanoma, 6 ovarian-, 8 renal-, 1 prostate and 6 breast cancer was determined by NCI-Information Intensive-Approach. The C-2 position of phenothiazines were substituted with H, Cl and CF3 groups. The half-mustard and ring system was linked either by a propylene or a butylene bridge. Colon-cancer cell showed the highest sensitivity against "half-mustard type" phenothiazines, followed by leukemia, melanoma, prostate-, CNS-, breast-, lung-, renal and ovarian cancer cells. These data suggest the "cancer-type-specific" antitumor action of "half-mustard type" phenothiazines.
Antineoplastic Agents, Alkylating↗
Electronic structure and cytotoxic activity of "half-mustard type" phenothiazines by MM3 and PM3 methods.
Among 54 cancer cell lines, colon-cancer cells were the most sensitive to six "half-mustard type" phenothiazines [7-12], followed by leukemia, melanoma, prostate-, CNS-, breast-, lung-, renal and ovarian cancer cells. The distribution of electrostatic potential (ESP) of "half-mustard type" phenothiazines [7-12] suggests that the ESP surface of urea site is important for the interaction between "half-mustard type" phenothiazines [7-12] and target cancer cell structures (or DNA base sequence). Actually, the urea site of "half-mustard type" phenothiazines displayed extensive variability in the energy of lone pair orbital and net atomic charges of N1, 0 and N3 atoms.
Algorithms↗
Relationship between cytotoxic activity and dipole moment for phthalimido- and chloroethyl-phenothiazines.
Among twelve phenothiazine-related compounds, the cytotoxic activity of six "half-mustard type" phenothiazines [7-12] was significantly higher than that of six phthalimido compounds [1-6]. 1-(2-Chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)propylurea [9], 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)butylurea+ ++ [10] and 1-(2-chloroethyl)-3-(2-trifluoromethyl-10H-phenothiazin-10-yl)b utylurea [12] showed the highest cytotoxic activity, in parallel with high delta mu (difference between two dipole moments, mu g and mu e). There was also positive relationship between cytotoxic activity and molecular orbital energy such as pi-LUMO, pi-HOMO, and lone pair orbitals originated from O, N1, and N3 atoms. The present study demonstrated that cytotoxic activity of "half-mustard type" phenothiazines can be predicted by their dipole moments and molecular orbital energies.
Cell Division↗
Plasmid elimination and immunomodulation by 3-benzazepines in vitro.
For studying the mechanisms of biological activity on 3-benzazepines, antimicrobial effect, F'lac plasmid elimination activity (a plasmid curing effect on F'lac plasmid) and antibody-dependent cellular cytotoxicity (ADCC) test were performed. A weak antiplasmid effect was found at sub-inhibitory concentrations. A combination of [KF4] with verapamil [2] did not alter the ineffectivity, however, [KF4] could inhibit the antiplasmid effect of promethazine, as compared to the control (promethazine alone) plasmid curing effect. A competition between promethazine and [KF4] might exist in plasmid elimination effect. ADCC activity of human leukocytes was enhanced by KF1, KF2, KF3, DA and NE at 1.0 microgram/mL concentrations. The majority of 3-benzazepines [KS02, KM57, KN50, KE04, KI10, KP80] was ineffective for plasmid curing, however, inhibited the ADCC reaction, but they did not show a real dose-dependent effect.
Adjuvants, Immunologic↗
3,5-diacetyl-1,4-dihydropyridines: synthesis and MDR reversal in tumor cells.
Eleven 4-phenyl-3,5-diacetyl-1,4-dihydropyridines (AcDHPs) [G1-11] substituted at the phenyl ring were synthesized and compared for their cytotoxic activity and multidrug resistance (MDR)-reversing activity in in vitro assay systems. Among them, compound [G7] showed the highest cytotoxic activity against human promyelocytic leukemia HL-60 and human squamous cell carcinoma HSC-2 cells. However, no compounds tested produced radicals at pH 7.4-12.5. The activity of P-glycoprotein (Pgp) responsible for MDR in tumor cells was reduced by compounds [G2, 3, 6, 5, 8, 1, 11], verapamil [VP] and nifedipine [NP]. However, compounds [G4, 7, 10] were hardly active while G9 did not show a MDR reversing effect at 2.0-20.0 micrograms/mL. These data show a relationship between chemical structures and MDR-reversing effect on tumor cells.
Antineoplastic Agents↗
Selective cytotoxic activity of grape peel and seed extracts against oral tumor cell lines.
Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate at higher concentrations. On the other hand, lower concentration of these extracts slightly reduced the radical intensity of sodium ascorbate, and scavenged superoxide anion, generated by hypoxanthine and xanthine oxidase reaction. These properties of grape seed extracts suggest their possible application for cancer prevention.
Anticarcinogenic Agents↗
Biological activity of feijoa peel extracts.
Fractionated extracts of Feijoa peels were studied for cytotoxic activity, anti-human immunodeficiency virus (HIV) activity and antibacterial activity. Two most cytotoxic fractions A3 of acetone extract and M2 of methanol extract had potent inhibitory activity against Gram-positive and Gram-negative bacteria as well as fungi tested. Fraction A4 of acetone extract showed multidrug resistance (MDR)-reversal activity comparable with that of verapamil (positive control). These results indicate the therapeutic value of Feijoa peel extracts as potential antimicrobial and MDR-modulating agents.
Anti-Bacterial Agents↗
Enhanced antibacterial effect of erythromycin in the presence of 3,5-dibenzoyl-1,4-dihydropyridines.
Fifteen 3,5-dibenzoyl-1,4-dihydropyridines (BzDHP, GB1-GB15) (nifedipine (NP) analogs) were tested on three different E. coli strains. The compounds had relatively high MIC values on these strains. In combination with erythromycin (Er), compounds (G1,3,4,6,7,10,12) reduced MIC values of Er. When the BzDHPs were tested on E. coli Gy-1/Apsen.Erres strain isolated from a clinical specimen, the reduction of MIC values were similar to the previous strains, but not identical. In the polyresistant clinically isolated E. coli Gy-2/Apres.Erres strain, the MIC values of Er were slightly reduced in the presence of GB1-GB7. Compound GB12 was the most effective in enhancing the activity of Er, and was selected for plasmid elimination studies. However, GB12 itself had no antiplasmid effect and did not alter the promethazine induced plasmid elimination.
Anti-Bacterial Agents↗
In vitro biological activity of prenylflavanones.
The biological activity of ten prenylflavanones purified from Sophora tomentosa L., and Sophora moorcroftiana Benth. ex Baker (Leguminosae) was investigated. The flavanones with prenyl-, lavandulyl- or geranyl groups on A ring, and two bioactive flavonostilbenes on ring B and stilbene (resveratrol) showed tumor-specific cytotoxic activity, antimicrobial activity, and anti-HIV activity, radical generation, and O2- scavenging activity. There was a positive relationship between radical generation and O2- scavenging activity in these prenylflavanones. These data suggest the medicinal significance of prenylflavanones.
Anti-HIV Agents↗