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Biomedical subjects

H Ohshima

Publications and source records attributed to H Ohshima.

At least 325 records · Page 18Linked to original sources
PubMed1984

Monitoring endogenous nitrosamine formation in man.

Results from animal experiments and studies in human subjects indicated that the amount of nitrosoproline (NPRO) excreted in the 24-h urine, following ingestion of precursors, is an index for the rate of endogenous nitrosation; this method was found to be sensitive, reproducible and could be satisfactorily applied to human subjects in clinical and field studies. N-Nitrosothiazolidine 4-carboxylic acid (NTCA) and its 2-methyl derivative (NMTCA) were also identified in the urine of human subjects. As the respective amino precursors (thiazolidine 4-carboxylic acids) can be formed by reaction of formaldehyde or acetaldehyde with cysteine, measurement of NTCA and NMTCA in urine may provide a further index for endogenous nitrosation in the human body and may also allow monitoring of exposure of human subjects to aldehydes, nitrate and nitrite. The yield of nitroso compounds formed endogenously in the human body was shown to be linked to the intake of precursors, but several inhibitors and catalysts, either as pure substances or occurring in complex mixtures, were shown to modify the nitrosation reaction in vivo. In particular, ingestion of ascorbic acid after nitrate-rich meals was efficient in lowering human exposure to endogenously formed N-nitroso compounds. A dose-response relationship was established for the formation of NPRO in rats in vivo, after concurrent administration of various concentrations of the precursors, L-proline and sodium nitrite. The logarithm of the amount of NPRO formed was found to be proportional to the logarithm of the product of the proline dose and the square of the nitrite dose. On the basis of these results, a kinetic model was formulated allowing the estimation of the daily precursor dose quantity, ([amine][nitrite]2), required to give 50% tumour incidence in rats after two years of feeding. The potential application of this model, for the estimation of carcinogenic risk from endogenously formed N-nitrosamines in humans, is discussed. Our results demonstrate unequivocally the endogenous formation of N-nitroso compounds in the human body, the significance of which in human carcinogenesis remains to be established.

Animals↗
PubMed1983

Presence in human urine of a new N-nitroso compound, N-nitrosothiazolidine 4-carboxylic acid.

Urine samples collected in several countries from human subjects showed the presence of a number of N-nitroso compounds not previously identified. By several separative procedures and by comparison with authentic material, the major unknown N-nitroso compound was shown to be N-nitrosothiazolidine 4-carboxylic acid (NTCA). Although its origin in human urine is unknown, thiazolidine 4-carboxylic acid, the easily nitrosatable amine precursor, can be formed by reaction of formaldehyde with cysteine in vivo and in vitro. Thus measuring NTCA excreted in the urine may allow monitoring exposure of human subjects to precursors like formaldehyde and NO-3/NO-2.

Chromatography, Gas↗
PubMed1983

Carcinogenesis and aging. II. Modifying effect of aging on metabolism of methyl(acetoxymethyl)nitrosamine and its interaction with DNA of various tissues in rats.

Young (3 month-old) and old (14 month-old) female outbred rats received a single i.p. dose (13 mg/kg) of N-[14C]methyl-Nacetoxymethylnitrosamine [( 14C]DMN-OAc), which, under these conditions, selectively induces intestinal tumours. Complete DMN-OAc breakdown occurred within 30 min in both young and old rats but exhalation of 14CO2 continued for over 1 h in young rats and over 3 h in old rats. The highest level of methylation in both young and old rats was found in the DNA of epithelial cells of the colon and in other adjacent abdominal organs (liver and uterus). The initial capacity for excision of the O6-methylguanine from liver DNA was greater in young animals, but further this DNA adduct was repaired more efficiently by the liver of old rats. In the DNA of ileal and colonic enterocytes, O6-methylguanine excision was higher in young than in old animals. The DNA tertiary structure, measured by the sedimentation pattern of nucleoids in neutral sucrose gradient, was damaged in old rats, and, to a lesser extent, in young rats. The non-uniform pattern of DNA damage in young and old animals may be associated with differing carcinogenic effects of DMN-OAc in rats of different ages, a hypothesis which is currently under test.

Aging↗
PubMed1983

Inhibitory effect of betel nut extracts on endogenous nitrosation in humans.

Extracts of betel nut (Areca catechu) were tested for their capacity to inhibit the endogenous formation of nitrosamines by measurement of the amount of urinary N-nitroso-L-proline (NPRO) following ingestion of sodium nitrate (300 mg) and L-proline (300 mg) by 2 volunteers. A water extract of the dried nuts, an ether extract containing mainly (+)-catechin and (-)-epicatechin, and a caffeine-precipitated n-butyl alcohol extract containing primarily proanthocyanidins (tannins) strongly reduced the endogenous formation of NPRO. An average of 14.7 and 10.9 micrograms NPRO (8 expts per individual) was excreted in the urine of the 2 volunteers over a 24-hour period following the intake of sodium nitrate and L-proline. The water extract and the proanthocyanidin (tannin)-containing extract, both of which contain the dose equivalent of one-quarter of a nut, reduced the excreted NPRO to background levels, which varied from 0.5 to 3.6 micrograms and from 0.6 to 2.1 micrograms (6 expts) in 24-hour urine samples from the 2 volunteers. These results may exemplify the way in which naturally occurring phenolics, which are ingested daily in relatively large quantities, could affect the endogenous formation of carcinogenic nitrosamines.

Anthocyanins↗
PubMed1983

Dose-response study of N-nitrosoproline formation in rats and a deduced kinetic model for predicting carcinogenic effects caused by endogenous nitrosation.

A dose-response study on the endogenous formation of N-nitrosoproline in rats was carried out by feeding various doses of L-proline in the diet and sodium nitrite in the drinking water. N-Nitrosoproline excreted in the urine and feces of individual rats was monitored as an index for endogenous nitrosation of proline. The logarithm of the amount of N-nitrosoproline formed was found to be proportional to the logarithm of the product of the proline dose and the square of the nitrite dose, in agreement with in vitro studies. On the basis of these results, a kinetic model was formulated. Calculations were carried out with this model using published data on nitrosation and carcinogenic potency of selected N-nitrosamines. This allowed the estimation of the daily precursor dose quantity, [amine][nitrite]2, required to give 50% tumor incidence in rats after 2 years of feeding.

Animals↗
PubMed1983

[Change in the vaginal smear cycle following conventionalization and monocontamination of germ-free rats with Enterobacter cloacae].

The relationship between the microbial organism infection and the vaginal smear cycle was investigated using 12 germfree Wistar Imamichi rats at 50 days of age. Germfree rats exhibited continuous vaginal cornification which occasionally interrupted by the appearance of nucleated epithelial cells. However, leukocytes which are characteristic of the metestrus and diestrus stage in conventional rats were not observed in the vaginal smear of these animals. At 70 days of age, 8 animals were taken out from the germfree isolator and conventionalized. In other 4 animals, the vaginal lumen was contaminated with Enterobacter cloacae in the isolator. Within 3 days after the treatments, leukocytes appeared in the vaginal smear of all animals in both groups. Thereafter, these animals continued the regular 4 days vaginal cycle to 90 days of age, at which the observation was terminated. The above results suggested that the appearance of leukocytes in the vaginal smear in the rat is closely related to the bacterial colonization in the lumen, together with the action of the progesterone secreted from the ovary.

Age Factors↗
PubMed1982

Monitoring N-nitrosamino acids excreted in the urine and feces of rats as an index for endogenous nitrosation.

A simple and sensitive method for the quantitative estimation of endogenous N-nitrosation in rats has been developed. This approach is based on the findings that N-nitrosamino acids (e.g., nitrosoproline (NPRO), nitrosohydroxyproline (NHPRO) and nitrososarcosine (NSAR)) when administered orally to rats, are excreted unchanged almost quantitatively (88-96% of the dose) in the urine and feces. After sequential administration of a nitrosatable amino acid and sodium nitrite the nitrosamino acid excreted in the urine and feces was analyzed. The amount of NPRO excreted in the urine of rats was proportional to the dose of proline and to the square of the nitrite dose. Co-administration of ascorbic acid and alpha-tocopherol together with the precursors decreased the urinary NPRO whereas thiocyanate increased the yield. After feeding an amino acid precursor and nitrite, the yield of nitrosamino acids formed in vivo and excreted in the urine increased in the order: NPRO less than NSAR less than NHPRO. The same order was seen when the nitrosation rates of the amino acids in vitro were compared. Thus N-nitrosation in vivo in rats occurs via a similar mechanism as observed in vitro. Monitoring of N-nitrosamino acids excreted in the urine and feces thus appears to provide a valuable index for endogenous N-nitrosation.

Amino Acids↗
PubMed1982

Measurement of endogenous n-nitrosation in rats and humans by monitoring urinary and faecal excretion of N-nitrosamino acids.

N-Nitrosamino acids [N-nitrosoproline (NPRO), N-nitrosohydroxyproline and N-nitrososarcosine] given orally to rats were found to be excreted unchanged in the urine and faeces almost quantitatively. Fasted rats were gavaged with solutions of a nitrosatable amino acid, followed by nitrite or N-nitrosodiphenylamine (NDPhA). The N-nitrosamino acid excreted in the urine and faeces during 24 h was monitored as an index of endogenous N-nitrosation. The results obtained by applying this procedure to the study of endogenous N-nitrosation in rats were all in good agreement with those of in vitro experiments. Endogenous transnitrosation by NDPhA to proline was shown to occur in rats; thiocyanate catalysed this transnitrosation reaction in vivo. Formation of NPRO in a human was demonstrated by monitoring the excretion of NPRO in the urine of one male volunteer who had ingested vegetable juice, as a source of nitrate, and proline. The amounts of NPRO excreted in the 24-h urine appeared to be proportional to the proline dose and increased exponentially with the dose of nitrate ingested. The simultaneous intake of ascorbic acid or alpha-tocopherol inhibited NPRO formation in the human subject. Monitoring of urinary NPRO would appear to be useful for the estimation of the extent of endogenous N-nitrosation in high-risk populations or individuals, in which endogenously formed N-nitroso compounds have been associated with increased risk of cancers, such as those of the stomach and oesophagus.

Amino Acids↗
PubMed1981

Surface potential and surface charge density of the cerebral-cortex synaptic vesicle and stability of vesicle suspension.

Using a microelectrophoresis instrument employing the Lazer-Zee system, the electrophoretic mobility of synaptic vesicles isolated from Guinea-pig brain cortex was measured under conditions. The mobility was found to depend on both pH and ionic concentration of the solution. The surface of the synaptic vesicle was shown to be negatively charged under physiological conditions. The isoelectric point was observed at pH 4.0 in 0.01 M NaCl solution. Effects of divalent cations were examined and reversal of surface charge was observed in 0.1 M CaCl2 solution. Interaction of vesicles was also considered on the basis of the DLVO theory of colloid stability by using calculated values of surface charge density and surface potential of the synaptic vesicle.

Animals↗
PubMed1981

Pili mediated agglutination of Serratia marcescens in human urine.

Of 51 strains of Serratia marcescens isolated from patients with urinary or respiratory tract infections, 35 agglutinated in human urine. The agglutinating strains possessed numerous pili which were morphologically distinct from common pili or type I pili. The diameter of the pili was 3 nm and the average length was 0.3 micrometer. Electron microscopic examination showed that 80% or more of the cells of the agglutinating strains and 0 to 8% of the cells of the nonagglutinating strains were piliated. When an agglutinating strain was heated at 55 C for 10 min, it lost its agglutinating capacity and concomitantly its pili. These results suggest that the agglutination might occur because of interactions between the pili and some factors in human urine. The urinary slime appears to contain these agglutinating factors.

Agglutination↗
PubMed1981

Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in the urine.

Endogenous formation of N-nitrosoproline (NPRO) was demonstrated by monitoring its excretion in the urine of a male volunteer who had ingested vegetable juice, as a source of nitrate, and proline. The resulting NPRO was analyzed after derivatization by combined gas-liquid chromatography thermal energy analysis. The amount of total NPRO excreted in the urine was found to be proportional to the proline dose and increased exponentially with the nitrate dose ingested. Neither nitrate nor proline, when taken alone, led to a detectable increase in NPRO in urine. The amounts of NPRO formed (as estimated from the amounts excreted within 24 hr) after dosing 325 mg nitrate (NO3-) followed by 500 mg proline, ranged from 16.6 to 30.0 (mean, 23.3) micrograms per person. The simultaneous intake of ascorbic acid or alpha-tocopherol inhibited nitrosation of proline in vivo. Monitoring of NPRO or other N-nitroso compounds excreted in the urine thus appears to be a suitable procedure for estimating daily human exposure to endogenously formed N-nitroso compounds.

Ascorbic Acid↗