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Biomedical subjects

H Ohshima

Publications and source records attributed to H Ohshima.

At least 289 records · Page 16Linked to original sources

N-nitrosamine formation by microorganisms isolated from human gastric juice and urine: biochemical studies on bacteria-catalysed nitrosation.

Twelve out of 14 bacterial strains isolated from patients with urinary infections and nine out of 30 microorganisms isolated from gastric juice from patients with gastric achlorhydria were shown to catalyse the formation of N-nitrosomorpholine (NMOR) from nitrite and morpholine at neutral pH. The effects of various metal ions and cofactors on the bacterial nitrosation reaction was investigated. The presence of nitrate in the culture medium was required to induce nitrosating activity in bacteria, but low nitrate concentrations inhibited the nitrosation reaction.

Escherichia coli↗

Roles of cysteine as both precursor of thiazolidine 4-carboxylic acids found in human urine and possible inhibitor of endogenous N-nitrosation.

In order to compare the utility and significance of 2-R-N-nitrosothiazolidine 4-carboxylic acids excreted in human urine as an index for exposure to N-nitroso compounds, the differences in formation of N-nitrosothiazolidine 4-carboxylic acid (NTCA; R = H) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA; R = CH3) were studied in vitro. It was determined that NMTCA has a 3:1 trans:cis stereoisomer ratio, while NTCA has a 1:1 trans:cis ratio; nitrosation acts on a pH-dependent equilibrium mixture of cysteine and aldehyde in equilibrium with thiazolidine 4-carboxylic acid, with cysteine blocking N-nitrosation. Previous reports on 2-R-N-nitrosothiazolidine 4-carboxylic acids in human urine show widespread involvement of cysteine, which has a dual role with nitrosating species. In view of this and the rapid blocking of N-nitrosation and slow trans-nitrosation by cysteine at acid pH, it is suggested that there may be a hitherto unrecognized protective role of thiol functions in dietary constituents.

Cysteine↗

N-nitrosamine formation in urinary-tract infections.

Urine samples from 31 patients with urinary-tract infections and from 31 controls were analysed for volatile nitrosamines, N-nitrosamino acids, total N-nitroso compounds as a group, and nitrite/nitrate. The concentration of N-nitrosodimethylamine was significantly elevated in urines infected with Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae. The levels of nitrite, N-nitrosoproline and total N-nitroso compounds, when expressed as the amount per mol creatinine, were also significantly increased in patients with bacteriuria. Several bacterial strains were capable of catalysing nitrosation of morpholine at neutral pH. These results suggest that N-nitroso compounds can be formed in vivo in the infected bladder, which could explain the association between urinary-tract infections and increased risk for bladder cancer.

Adolescent↗

Occurrence of volatile nitrosamines in food samples collected in three high-risk areas for nasopharyngeal carcinoma.

Fifty-four samples of foods consumed frequently in Tunisia, southern China and Greenland, all high-risk areas for nasopharyngeal carcinoma (NPC), were analysed for the presence of volatile nitrosamines by gas chromatography (GC) combined with a thermal energy analyser (TEA). Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) were found in Tunisian stewing base (touklia) and dried mutton preserved in olive oil (qaddid). In one Chinese salted and dried fish sample, a high level of NDMA (133 micrograms/kg) was detected, but for the 14 others the levels ranged from undetectable to 14 micrograms/kg, with a mean of 3 micrograms/kg. Similarly high levels of NDMA, were found in Eskimo dried, unsalted fish samples. NDMA, NPIP and NPYR at various levels were present in Chinese vegetables fermented in brine. The possible role of nitrosamines in the etiology of NPC is discussed.

China↗

Endogenous nitrosation in the oral cavity of chewers while chewing betel quid with or without tobacco.

In order to evaluate endogenous nitrosation in the oral cavity of chewers of betel quid with tobacco (BQT) or without tobacco (BQ), saliva samples were collected from healthy male volunteers after chewing sequentially (i) unmodified BQT or BQ, (ii) BQT or BQ to which proline has been added, and (iii) BQT or BQ to which proline and ascorbic acid had been added. Samples were collected over 20 min and analysed for N-nitrosoproline (NPRO), tobacco-specific nitrosamines (TSNA) and areca nut-specific nitrosamines using gas chromatography-thermal energy analysis, arecoline and nicotine using gas chromatography-nitrogen phosphorus-specific detector, and for nitrite and thiocyanate. When results were expressed as a ratio of NPRO (ng/ml) to nicotine (micrograms/ml), all BQT chewers had increased NPRO contents after chewing BQT with proline. For BQ chewers, when the results were expressed as a ratio of NPRO (ng/ml) to arecoline (micrograms/ml), a similar increase in NPRO content was observed. However, the presence of ascorbic acid inhibited the increased nitrosation in only four out of ten BQT chewers and in five out of ten BQ chewers; in the rest of the samples, its presence enhanced the levels of NPRO. N'-Nitrosoanatabine (NAT) and N-nitrosoguvacoline (NGCO) levels decreased significantly in saliva of chewers of BQT in the presence of ascorbic acid, suggesting inhibition of their formation. In-vitro nitrosation of BQT/BQ with proline and proline plus ascorbic acid showed a similar pattern of nitrosation at salivary pH. The study confirmed previous results that certain nitrosamines are formed during the chewing of BQT/BQ.

Areca↗

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants in high- and low-risk areas for stomach cancer in northern Japan.

Three samples of 24-h urine were collected from each of 104 inhabitants of high-risk (Akita) and low-risk (Iwate) areas for stomach cancer in northern Japan, according to the following protocols: (i) when they were undosed, (ii) after ingestion of proline three times a day and (iii) after ingestion of proline together with vitamin C three times a day. These samples were analysed for N-nitrosamino acids, nitrate and chloride ion as indices of the exposure. The median values of N-nitrosoproline (NPRO) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA) excreted in the urine of undosed subjects were not different between the two areas; however, that of N-nitrosothiazolidine 4-carboxylic acid (NTCA) was significantly higher in subjects of the high-risk area. Salt intake, estimated from the level of chloride ion in the urine, did not differ in two areas. After intake of proline, the NPRO level increased significantly only in subjects of the high-risk area, but not in those of the low-risk area; intake of vitamin C inhibited this increase of NPRO and lowered the levels of other nitrosamino acids only in the high-risk subjects. In contrast, the urinary level of nitrate was higher in subjects of the low-risk area than in those of the high-risk area; nitrate levels were found to correlate well with the amounts of vegetables consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid↗

A correlation study on urinary excretion of N-nitroso compounds and cancer mortality in China: interim results.

Samples of 12-h overnight urine were collected from approximately 40 male adults in each of the 26 counties of China. Two urine specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids, nitrite and nitrate were measured in urine samples and correlated with cancer mortality per 100,000 male subjects in the truncated age range 35-64 years. Preliminary results show no clear correlation between presence of stomach cancer or liver cancer and nitrosation potential [as measured by the urinary level of N-nitrosoproline (NPRO) after the proline load test or of nitrate]. There was a moderate, although not clearly significant, tendency for oesophageal cancer mortality rates to be associated positively with nitrosation potential and negatively with background ascorbate levels in plasma. This result was due chiefly to the inclusion of one county (Song Xian) in which there is a fairly high oesophageal mortality rate, an average nitrosation potential three times greater than that of any other county, and the lowest ascorbate index of any county. Further study of this county is planned.

Adult↗

Intragastric nitrosation and precancerous lesions of the gastrointestinal tract: testing of an etiological hypothesis.

The N-nitrosoproline (NPRO) test was used to study whether subjects with precancerous conditions of the stomach have an elevated potential for endogenous nitrosation. The highest yield of NPRO after ingestion of beetroot juice (as a source of nitrate) and proline was seen in subjects whose pH of fasting gastric juice was about 1.5-2. No increased level of NPRO was detected in subjects with more advanced lesions, compared to those with a normal stomach. Counts of total and nitrate-reducing bacteria were positively correlated with the pH of gastric juice but did not correlate with the urinary level of NPRO in the same individuals. Bacteria and intragastric nitrosation are discussed as possible etiological factors in human stomach cancer.

Adult↗

Effects of carbamazepine and valproic acid on brain immunoreactive somatostatin and gamma-aminobutyric acid in amygdaloid-kindled rats.

Somatostatin and gamma-aminobutyric acid (GABA) concentrations were evaluated in the brain of kindled rats treated chronically with carbamazepine and valproic acid. Kindled seizures were almost completely blocked by treatment with carbamazepine, whereas the effect of valproic acid was partial, suppressing only generalized seizures. The duration of after-discharge in amygdala was suppressed by carbamazepine not by valproic acid. Carbamazepine induced a decrease in immunoreactive somatostatin concentration and an increase in GABA concentration in the temporal cortex of kindled rats. Valproic acid induced only an increase in GABA concentration. The results suggest that somatostatin may be associated with the suppression of focal seizure in amygdala and GABA may have a role in the suppression of generalized seizures.

Amygdala↗

Urinary N-nitrosamino acids as indices of endogenous formation of N-nitroso compounds.

Exposure to their precursors (e.g., amines, nitrate/nitrite, NOx) can lead to formation in the human body of N-nitroso compounds (NOC), a class of potent animal carcinogens, which are also suspected of being carcinogenic in man. A non-invasive method, the 'N-nitrosoproline (NPRO) test', for estimating endogenous nitrosation in man was developed in our laboratory. This test, which monitors 24-hr-excretion of urinary N-nitrosamino acids, is now applied in clinical and field studies, with the aim of measuring nitrosamine exposure and of identifying dietary, life-style, and host factors, or disease states, that affect nitrosation in man. Results from such studies are used to identify populations/individuals at high risk for cancers of the stomach, oesophagus, and oral cavity possibly caused by endogenous nitrosamines, and to indicate preventive measures by which the body burden of endogenous nitroso carcinogens can be lowered efficiently.

Amino Acids↗

Identification, occurrence and mutagenicity in Salmonella typhimurium of two synthetic nitroarenes, musk ambrette and musk xylene, in Indian chewing tobacco and betel quid.

During N-nitrosamine analysis of extracts of betel quid with tobacco and of the saliva of chewers of betel quid with tobacco for N-nitrosamines using a Thermal Energy Analyzer, two unknown compounds were detected. They were identified as synthetic nitro musks, musk ambrette (5-tert-butyl-1,3-dinitro-4-methoxy-2-methylbenzene, CAS No. 83-66-9) and musk xylene, (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene, CAS No. 81-15-2), by gas chromatography-mass spectrometry and Fourier transform nuclear magnetic resonance spectroscopy. These compounds were detected in several samples of betel quid with tobacco and in perfumed tobacco used for chewing in India in amounts ranging from 0.45-23.5 mg/g wet weight. Musk ambrette was found to be mutagenic in Salmonella typhimurium TA100 requiring metabolic activation by rat-liver postmitochondrial supernatant but musk xylene lacked mutagenicity.

Animals↗

Circadian rhythm of REM sleep of chronic alcoholics during alcohol withdrawal.

Sleep structures were polygraphically investigated during the alcohol withdrawal periods of six male alcoholics. Polygraphic recordings were taken 10 days, 1 month and 3 months after hospitalization. Total sleep time was almost equal among the three recording nights for each patient. Stages 3 and 4 sleep were remarkably reduced on all the recording nights. REM sleep time was normal throughout the study. REM latency decreased in many patients on the 10th day, and gradually increased on the following nights. A very important change was observed in the distribution of REM sleep. Maximal duration was noted in the first REM episode on the 10th day in four of the six. On the second recording night the second REM episode was the longest in five of the six subjects. On the last recording night many patients exhibited a normal distribution of REM sleep. These findings which suggest that the acrophase of REM sleep is advanced by several hours for a few months after alcohol withdrawal have also been observed in patients with endogenous depression. Although our patients did not show any depressive symptoms during the study, one of them developed a severely depressive state after he began to drink alcohol thereafter.

Adult↗

[Combined laboratory/epidemiological studies on endogenous nitrosation and human cancer].

Endogenous formation of carcinogenic N-nitroso compounds has been suspected of being associated with an increased risk for cancer of the stomach, esophagus and bladder, but no convincing epidemiological evidence has been presented. For these reasons, a new, non-invasive method for quantitative estimation of endogenous nitrosation in humans has been developed on the basis of the findings that certain non-carcinogenic N-nitrosamino acids such as N-nitrosproline are excreted unchanged almost quantitatively in the urine. Some results from the application of this method to clinical and epidemiological studies to evaluate the role of endogenous nitrosation in human cancer are presented.

Animals↗

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C.

A total of 238 samples of 24-h urine were collected from inhabitants of high-risk (Lin-xian) and low-risk (Fan-xian) areas for esophageal cancer in northern China, according to three protocols: (a) from undosed subjects; (b) from subjects who had ingested 100 mg L-proline three times a day 1 h after each meal; and (c) from subjects in Lin-xian who had ingested 100 mg ascorbic acid together with 100 mg L-proline three times a day 1 h after each meal. As an index of individual exposure to N-nitroso compounds or their precursors, ingested in food and/or formed endogenously, the levels of four urinary N-nitrosamino acids and nitrate were determined. The amounts of N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, N-nitrososarcosine, and nitrate excreted in the 24-h urine of undosed subjects in Lin-xian were significantly higher than those in Fan-xian, indicating a higher exposure of the inhabitants in the high-risk area to N-nitroso compounds and their precursors. Ingestion of L-proline resulted in a marked increase in urinary N-nitrosoproline levels in inhabitants from both areas, suggesting that endogenous nitrosation may occur to a larger extent when appropriate amine precursors are ingested in foods. Intake of moderate doses of ascorbic acid by high-risk subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in the low-risk area. If N-nitroso compounds formed in vivo are among the causative factors for esophageal cancer in this area of northern China, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds, thus offering a rational basis for long-term intervention studies in this area.

Adult↗