Direct observation of deuterium migration in crystalline-state reaction by single-crystal neutron diffraction. III. Photoracemization of 1-cyanoethyl cobaloxime complexes.

The H atoms bonded to the chiral C atoms (stereogenic center) of the 1-cyanoethyl groups in two cobalt complexes, [(R)-1-cyanoethyl]bis(dimethylglyoximato)(pyridine)cobalt(III) (2) and [(R,S)-1-cyanoethyl]bis(dimethylglyoximato)(piperidine)cobalt(III) (3), were replaced with D atoms, such as Co--C*D(CH(3))CN. The crystals of the two cobalt complexes were irradiated with a xenon lamp for 72 h and 27 d, respectively. The unit-cell dimensions were gradually changed with retention of the single-crystal form. The crystal structures after irradiation were determined by neutron diffraction. In each crystal the chiral 1-cyanoethyl group of one of the two crystallographically independent molecules was partly inverted to the opposite configuration, whereas that of the other molecule kept the original configuration. The C*--D bond in the inverted group was completely conserved in the process of the inversion of the chiral alkyl group. This suggests that the inversion of the chiral 1-cyanoethyl group proceeds with the rotation of the cyanoethyl radical after the Co--C bond cleavage by photo-irradiation so that the opposite side of the radical faces the Co atom. This is followed by recombination of the Co--C bond to form the inverted 1-cyanoethyl group.

Direct observation of deuterium migration in crystalline-state reaction by single-crystal neutron diffraction. II. 3-1 photoisomerization of a cobal-oxime complex

Single crystal neutron diffraction analysis of photo-exposed (3-cyanopropyl-d2(alpha,alpha))-[(R)-1-phenylethylamine-d11]bis(dimethylglyoximato-d14)cobalt(III) was carried out in order to clarify the mechanism of the crystalline-state photoisomerization of the 3-cyanopropyl group bonded to the Co atom in some cobaloxime complexes. Before irradiation the two H atoms bonded to the C1 atom of the 3-cyanopropyl group were exchanged with the D atoms such as --CH2CH2CD2CN. On exposure to a xenon lamp, the cell dimensions of the crystal were gradually changed. After 7 d exposure the change became insignificantly small. The structure was analyzed by neutron diffraction. The 3-cyanopropyl group was transformed to the 1-cyanopropyl group such as --CD(CN)C(H1/2,D1/2)2CH3 with retention of the single-crystal form. This indicates that one of the D atoms bonded to C1 migrates to either position bonded to C2. The other atoms of the complex remained unchanged. These results indicate that photoisomerization proceeded in two steps: the 3-cyanopropyl group was isomerized to the 2-cyanopropyl group in the first place and then the 2-cyanopropyl group was transformed to the 1-cyanopropyl group. Moreover, it was made clear that the second-step isomerization was irreversible, since one of the D atoms was retained. The disordered structure at C2 is estimated to be caused by the interconversion between the 1-cyanopropyl group produced and its dehydrogenated olefin after the photoisomerization.

Patient access to medical records: problems and strategies for inpatient charts.

Fasing the impending introduction of patient access to medical charts, we have attempted to include a more substantial description of medical activity in specific areas. Using the guidelines published jointly by the Ministry of Health and Welfare and the Tokyo Metropolitan Office in October 1998, the staff of the medical records division examined and evaluated the layout and description of items on individual hospital charts, with excellent results. To encourage the continued improvement of medical chart recording in the future, incentives should be implemented to avoid insufficient descriptions, encourage regular chart inspections, and promote education regarding the need for a systematic approach to charts and chart recording.

Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans.

This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7-hydroxymethotrexate in animals and humans. When MTX 7-hydroxylase was assayed in six human liver cytosols, a 48-fold range of intersubject variation of the activity was observed. The variations were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate. Species differences of liver MTX 7-hydroxylase activity were also observed. The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetectable in dogs. Strain differences of MTX 7-hydroxylase activity based on aldehyde oxidase activity were also observed in rats and mice. The results suggest that aldehyde oxidase functions as MTX 7-hydroxylase in livers of animals and humans, and the observed differences of MTX 7-hydroxylase activity are due to variations in the amount of aldehyde oxidase present.

[Comparison of side effects caused by intra-arterial and intravenous infusion of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) for urothelial cancer].

We retrospectively studied the toxic effects in 14 patients with urothelial cancer who had undergone intra-arterial M-VAC chemotherapy (Group A) and 13 patients who had received intravenous M-VAC chemotherapy (Group V) between February 1991 and August 1995. No statistically significant differences were found in the white blood cell count nadir, liver function, renal function or appetite between the groups. While the platelet count nadir for intra-arterial infusion (14.0 x 10(4)/mm3) was larger than for intravenous infusion (9.0 x 10(4)), the median days to nadir for this count was shorter in the intra-arterial group (9.1 days) than in the intravenous group (13.5). In addition, the difference between the beginning hemoglobin level and the nadir level was larger in the intra-arterial infusion group (2.55 g/dl) than in the intravenous infusion group (1.95 g/dl). Additionally peculiar side effects were noted in the intra-arterial infusion group which included local erythema and nerve paralysis. Side effects should be managed for intra-arterial M-VAC as well as for intravenous infusion.

Effects of dietary vegetable oils on behavior and drug responses in mice.

Previously, we noted significant differences in the behavioral patterns of mice fed safflower oil with a very low alpha-linolenate/linoleate ratio and perilla oil with a high alpha-linolenate/linoleate ratio from mothers to offsprings. In this report, we compared the behavior and drug responses in mice fed diets containing six different vegetable oils-corn, rapeseed, soybean, safflower, perilla and a mixture of perilla and safflower oils- for a relatively short period: 8 months after weaning. Soybean oil is a component of most conventional diets and was used as a control. The alpha-linolenate/linoleate ratios of the oils appeared to affect the locomotor activities in a wheel cage: the activity decreased in the order of safflower, the mixture (1:1) and the perilla oil groups. However, the rapeseed oil group exhibited much higher locomotor activity than that expected from the alpha-linolenate/linoleate ratio. Additionally, the rapeseed oil group exhibited unusual behavior patterns, including higher ambulation and rearing activities, faster acquisition of the water maze task and slower habituation behavior as compared with the control group. Susceptibility to pentobarbital anesthesia tended to be higher in the rapeseed oil group. The differences in the alpha-linolenate/linoleate ratios of these oils alone do not account for the observed differences in the behavioral patterns among the six dietary groups. Although we cannot exclude the possibility that the observed behavioral anomaly is due to the unique fatty acid composition of rapeseed oil, we speculate that a factor(s) other than fatty acids in rapeseed oil affected nervous system functions.

Influences of aging and sex on renal pelvic carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice.

Influences of aging and sex on renal pelvic carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined in 6-, 15 -and 45-week-old male and female NON/Shi mice. Histopathological examination revealed an age-related shortening of induction time for renal pelvic carcinomas in males, although actual incidences did not increase. The histological patterns of carcinomas induced in both renal pelvis and urinary bladder demonstrated male mice to be more prone to develop transitional cell carcinomas, while squamous cell carcinomas were more likely to arise in females. Moreover, the sex factor appeared to influence the progression of both renal pelvic and urinary bladder carcinomas.

Effect of a high linoleate and a high alpha-linolenate diet on general behavior and drug sensitivity in mice.

Semi-purified diets supplemented with either a high linoleate (n-6) (safflower) oil or a high alpha-linolenate (n-3) (perilla) oil were fed to mouse mothers and their offspring through 6 weeks of age. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets while no difference was found in phospholipid compositions or cholesterol/phospholipid ratios. In the elevated plus maze task, the total number of entries into the open- and enclosed-arms was smaller and the time spent in the dark enclosed arms tended to be longer in the perilla group than the safflower group. The time required to reach a safe platform in Morris's water maze test was less in the perilla group, but no significant difference was observed in the entries into the arms darkened with a movable cover in Y-maze dark-preference task. The safflower group was more sensitive to pentobarbital; the anesthesia onset time was less and the anesthetic time was longer than in the perilla group. Increased locomotion induced by scopolamine injection was less in the safflower group as compared with the perilla group. These results indicate that in mice the dietary alpha-linolenate/linoleate balance affects the n-3/n-6 ratio of brain phospholipid acyl chains and that this is accompanied by general behavioral changes as well as changes in sensitivities to drugs known to affect behavior.

A case of mucosal prolapse syndrome.

A case of mucosal prolapse syndrome in the rectum is reported. A 61-year-old female presented complaining of bloody discharge and constipation for 2 months. Colonoscopy revealed an elevated lesion on the left anterior wall of the rectal canal. Biopsy showed glandular proliferation and fibromuscular obliteration of the lamina propria, findings characteristic of mucosal prolapse syndrome. It is a rare disorder affecting the rectum because the lesion looks macroscopically like a protruding adenoma.

No promotion of urinary bladder carcinogenesis by sodium L-ascorbate in male ODS/Shi-od/od rats lacking L-ascorbic acid-synthesizing ability.

The promoting effects of sodium L-ascorbate (Na-AsA) on two-stage urinary bladder carcinogenesis were investigated in male ODS/Shi-od/od rats. This strain genetically lacks L-ascorbic acid-synthesizing ability, which is controlled by a single autosomal recessive od gene; heterozygous ODS/Shi(-)+/od, normal ODS/Shi(-)+/+ or F344 rats are able to synthesize L-ascorbic acid. In experiment 1, ODS/Shi-od/od and F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 weeks and then basal CA-1 diet with or without 5% Na-AsA for 32 weeks. F344 rats were sensitive to the promoting effects of Na-AsA, whereas ODS/Shi-od/od rats were resistant. Administration of Na-AsA increased the urinary pH and the urinary concentrations of Na+ and total ascorbic acid in all strains. In experiment 2, DNA synthesis in the urinary bladder epithelium of F344 rats fed MF diet or CA-1 diet was increased by exposure to 5% Na-AsA for 8 weeks, but not in ODS/Shi-od/od rats fed CA-1 diet. In experiment 3, ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were given 0.05% BBN for 4 weeks and then CA-1 diet with or without 5% Na-AsA for 32 weeks. ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis. The urinary pH and the urinary concentrations of Na+ and total ascorbic acid in ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were increased by the administration of Na-AsA. These results indicate that ODS/Shi-od/od rats are resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis, and that the susceptibilities of ODS/Shi-od/od rats are regulated by genes different from the gene at the od locus.

Amitrole: strain differences in morphological response of the liver following subchronic administration to mice.

Strain differences in the induction of hepatocellular preneoplastic lesions by amitrole were examined in NOD, ICR and DS mice. Amitrole was administered to mice in drinking water at a dose of 1% for 6 months. After 3 months, hyperplastic nodules (HN) and severe fibrosis were prominent in NOD mice but not in other strains. On examination at 6 months, both number and size of HN were greatest in the NOD strain. Furthermore, a hepatocellular carcinoma was found in a NOD mouse, suggesting that this strain is more susceptible to amitrole-induced hepatocarcinogenesis than are ICR or DS mice.