Search PubMed⌕ Search

Biomedical subjects

H Ohshima

Publications and source records attributed to H Ohshima.

At least 217 records · Page 12Linked to original sources
PubMed1991

Further studies on membrane transport with time delay.

A theory of cell membrane transport with a time delay which predicts under certain conditions overshoot or oscillatory permeation (Ohshima and Kondo, Biophys. Chem. 33 (1989) 303), is extended with the introduction of a parameter expressing a fraction of solutes inside the cell interior that suffer time delay. It is found that criterion for oscillation depends strongly on this parameter. Results will also be presented for the case of an exponential-type distribution of the delay time.

Journal Article↗
PubMed1991

Growth prediction of young chicks: do equal deficiencies of different essential amino acids produce equal growth responses?

1. Prediction of the growth of young chicks was attempted by means of a computerised mathematical model, by fitting a 4 parameter kinetic equation (Mercer, 1982) to data obtained experimentally and from the literature. Amino acid antagonisms between arginine and lysine, and between branched-chain amino acids were taken into account. 2. In order to pool the data, dietary concentrations of essential amino acids were standardised by expressing as percentages of requirements according to Japanese Feeding Standard (1984), and growth responses were expressed relative to growth at or above this requirement. 3. The kinetic model gave an excellent fit (R2 = 0.92-0.99) to independent growth data obtained experimentally and from the literature, validating the use of the equation. 4. It was implied from predicted growth that the responses to alterations in dietary concentrations of different essential amino acids differed substantially, in a characteristic pattern, even when percentages of requirements were the same. 5. The validity of the model was tested against data that were not used in its construction. It was found that the simulation model could predict the growth of young chicks satisfactorily from dietary amino acid patterns.

Amino Acids, Essential↗
PubMed1991

Endogenous nitrosation of L-proline by dietary-derived nitrate.

Two studies were conducted to assess the availability of normal dietary sources of nitrate for endogenous nitrosation of an amino acid substrate, L-proline, and to investigate the potential for dietary ascorbic acid to inhibit such nitrosation. In the first study, 16 subjects consumed a salad meal (containing about 172 mg nitrate) with and without a loading dose of proline. A significant increase (10.8 compared with 2.7 micrograms/24 hrs, p less than 0.0001) in mean urinary N-nitrosoproline (NPRO) excretion following meal plus substrate ingestion was indicative of intragastric proline nitrosation by meal-derived nitrate. In the second study (19 different subjects), the mean urinary NPRO level was significantly decreased (15.8 micrograms compared with 28.4, p = 0.022) by inclusion of ascorbic acid sources in the meal. This demonstrated inhibition of proline nitrosation by dietary sources of the vitamin. Large interindividual variation in nitrosating ability was apparent that was associated with variation in meal nitrate to salivary nitrite conversion. Although meals containing fresh vegetables, as tested here, could provide sufficient nitrate to result in endogenous formation of N-nitroso compounds, there will be considerable inter- and intraindividual variation in the extent of this process.

Administration, Oral↗
PubMed1991

Bacterial formation of N-nitroso compounds from administered precursors in the rat stomach after omeprazole-induced achlorhydria.

The role of bacteria in catalysing intragastric formation of N-nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine was investigated in a rat model of omeprazole-induced achlorhydria. Omeprazole-treated rats gavaged with nitrosation-proficient bacteria were treated with nitrosamines and/or precursors and compared to control animals that received no omeprazole treatment/no bacteria. Rats given thiazolidine-4-carboxylic acid, nitrate and 10(11) cells of Escherichia coli, had a five times higher endogenous formation of N-nitrosothiazolidine-4-carboxylic acid as compared to controls. Endogenous formation of N-nitrosomorpholine was quantified by measuring its urinary metabolite N-nitroso-(2-hydroxyethyl)glycine; when rats were given morpholine and nitrite together with E. coli or Pseudomonas aeruginosa endogenous N-nitrosomorpholine formation was increased approximately 2.5-fold as compared to controls. In the same experiment, a higher excretion of unchanged N-nitrosomorpholine was also observed in omeprazole-treated rats receiving bacteria as compared to controls. Rats given morpholine, nitrate and E. coli or P. aeruginosa, excreted three times higher levels of N-nitrosomorpholine as compared to controls. These results conclusively demonstrate that nitrosation-proficient bacteria are capable of increasing intragastric formation of N-nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine. These N-nitrosamines are formed from nitrate (or nitrite) and the respective amino precursor via reduction of nitrate into nitrite and bacterial nitrosation catalysis.

Achlorhydria↗
PubMed1991

Unusually high levels of carcinogenic tobacco-specific nitrosamines in Sudan snuff (toombak).

The aim of these studies was to determine the levels of carcinogenic tobacco specific nitrosamines (TSNA) in Sudanese oral snuff (toombak) as recent retrospective epidemiological studies suggested an association between the use of toombak and subsequent development of oral cancer. We have analyzed the TSNA levels in 20 samples of Sudanese toombak, of four different quality levels, collected from five different vendors. Using GC coupled with thermal energy analysis, four TSNA were quantified in snuff extracts: N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unusually high levels of these TSNA (mean; range, mg/g snuff, dry wt) were detected; NNN (1.13; 0.50-3.08); NAT (0.08; 0.02-0.29); NAB (0.22; 0.02-2.37); and NNK (2.31; 0.62-7.87). Previously, the highest levels of NNN and NNK reported in any snuff were 0.154 and 0.014 mg/g dry wt respectively. In comparison, the levels in Sudanese toombak were up to 20 and 560 times higher respectively. As the public health implications of these findings are significant, attempts should be made to reduce exposure to TSNA in oral snuff users in Sudan.

Carcinogens↗
PubMed1991

L-arginine-dependent formation of N-nitrosamines by the cytosol of macrophages activated with lipopolysaccharide and interferon-gamma.

The cytosol fraction of J774-1 murine macrophages activated with lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) was found to nitrosate a wide range of secondary and tertiary amines. The reaction was dependent on L-arginine and NADPH. The optimal pH for nitrosation was 7.2-7.3. Nitrosation was inhibited by arginine derivatives such as NG-monomethyl-L-arginine and NG-nitro-L-arginine, well-known inhibitors of nitric oxide (NO) synthase. These results indicate that nitrosation is mediated by NO synthase, which catalyzes formation of NO and L-citrulline from L-arginine. Nitrosamine formation also required oxygen and was inversely correlated with the basicity of nitrosatable amines. The nitrosation was inhibited by oxyhemoglobin, an NO trapping agent, and enhanced by superoxide dismutase, which stabilizes NO. LPS + IFN-gamma induced approximately 500-600 times greater nitrosation activity than that of non-activated macrophages. Macrophages treated with LPS alone exhibited 3-4 times greater nitrosation activity than untreated macrophages, whereas macrophages treated with IFN-gamma alone did not show enhanced nitrosation activity. A combination of the cytosols from macrophages treated with LPS alone and IFN-gamma alone did not nitrosate morpholine as rapidly as the cytosol of macrophages treated with both compounds together. The activity for forming L-citrulline and nitrite/nitrate from L-arginine was markedly induced by treatment with either LPS alone or LPS + IFN-gamma but not with IFN-gamma. Those results suggest that some other factor(s) in addition to NO synthase is involved for efficient nitrosation by the macrophage cytosol. This factor(s) was not induced in macrophages by either LPS- or IFN-gamma alone, but was induced only in the presence of the two compounds.

Amino Acid Oxidoreductases↗
PubMed1991

Induction of aberrant crypt foci in the large intestine of F344 rats by oral administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to rat colon was investigated using the appearance of colonic aberrant crypt (AC), a preneoplastic lesion, as a marker. The number of AC foci per colon at experimental week 4 was 1.3 +/- 0.8; almost half the level of AC foci induced by 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), which is a known colon carcinogen. No ACs were observed in rats of the control group. A repeat experiment showed that induction of AC foci by PhIP administration was reproducible and a significant increase in the number of AC foci, 3.0 +/- 0.0, was observed after 12 weeks of PhIP administration. The majority of ACs induced by PhIP were localized in the distal part of the colon. The distribution was similar to those induced by Glu-P-1 and 1,2-dimethylhydrazine. Those data suggested that PhIP is possibly carcinogenic to rat colon.

1,2-Dimethylhydrazine↗
PubMed1991

Clinicopathological study of upper urinary tract tumors associated with bladder tumors.

Among 535 cases of urothelial tumors (upper urinary tract and bladder tumors) from 1970 to 1988, 40 had upper urinary tract tumor associated with bladder tumor. Of 40 cases, 18 (45%) were synchronous, 17 (43%) were metachronous with primary upper urinary tract tumor followed by subsequent bladder tumor 18.5 +/- 14.1 (means +/- SD) months later and 5 (12%) were metachronous with primary bladder tumor followed by subsequent upper urinary tract tumor 40.2 +/- 13.6 months later. The incidence (17/52 = 0.32) of bladder tumor occurrence subsequent to primary upper urinary tract tumor was much higher than that (5/465 = 0.01) of upper urinary tract tumor subsequent to primary bladder tumor. The histologic grades of upper urinary tract tumor and associated bladder tumor were consistent in 73%. Except in 1 case, multiple occurrence of upper urinary tract tumor was always observed unilaterally on the side involved. The current results not only support the theory of multicentricity but raise the possibility that tumor cell implantation may play some role at least in the development of bladder tumor subsequent to upper urinary tract tumor.

Carcinoma, Transitional Cell↗
PubMed1991

Effect of particle size on phagocytosis of latex particles by guinea-pig polymorphonuclear leucocytes.

The effect of the size of foreign particles on phagocytosis by guinea-pig polymorphonuclear leucocytes (PMNs) was investigated using latex particles having approximately the same surface potentials but different sizes. Two types of latexes with different negative surface potentials, those having amino groups (Ami-latexes) and those having carboxylic acid groups (Ca-latexes), were used in this experiment. Since Ca-latexes had different surface potentials for different particle sizes, the carboxylic acid groups were modified by the carbodiimide method to make the surface potentials almost equal. Phagocytosis was estimated by the rate of oxygen consumption. It was found that the phagocytosis reached its maximum when the latex particle size was about 0.5 microns. This finding was plausibly explained by considering the two probabilities that a latex particle comes into contact with a PMN surpassing a potential barrier and the contact takes place at certain receptor areas favourable to phagocytosis on the PMN surface.

Animals↗
PubMed1991

Adsorption of negatively charged microcapsules to a poly(2-hydroxyethylmethacrylate)/polyamine graft co-polymer surface.

The electrokinetic properties of artificial particles--microcapsules--were compared with those of the rat lymphocyte sub-populations, T and B cells, and similar results were obtained. The affinity of the microcapsules to the polyamine graft co-polymer, which was claimed to be capable of separating the cells efficiently, was measured and it revealed that not the magnitude of the surface negative charge and the kind of dissociable groups, but the balance of the anionic and cationic charges on the microcapsule surface played a key role in their adsorption to the co-polymer.

Adsorption↗
PubMed1991

[Histopathological findings of prostate carcinoma--nuclear anaplasia (NAN) and structural atypism (SAT)].

Most of the previous publications have focused mainly on structural atypism (SAT) or differentiation in the studies on histopathological findings of prostate carcinoma. We studied nuclear anaplasia (NAN) as well as SAT in prostate carcinoma, comparing with differentiation grade or Gleason's pattern, to find NAN's clinical implication. We also compared histopathological findings of prostate carcinoma in our cases with those in U.S.A. Analysis of NAN grade and SAT grade distribution in stages revealed a correlation between the grades and the stages, in which SAT1 or NAN1 decreased while SAT3 or NAN3 increased in their frequencies as stage progressed. A similar correlation was found between mean value of SAT + NAN grade and stage. While NAN grade and SAT grade agreed with each other in 70% of the patients with prostate carcinoma, that was not the case in the remaining patients. This suggested a complementary relationship between NAN grade and SAT grade in some patients. A similar relationship was found between NAN grade and Gleason's pattern. These results suggest that, in a non-negligible number of patients, the NAN grade does not agree with the SAT grade or Gleason's pattern which is defined by atypism in the glandular structure. Disease-specific survival in each SAT grade could be further defined by the NAN grade. For example, in both SAT2 and SAT3, NAN3 tended to have a poorer prognosis than NAN2. Thus, NAN grading system would furnish more accurate information to predict the patients' clinical course.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaplasia↗
PubMed1991

Epstein-Barr virus activators, mutagens and volatile nitrosamines in preserved food samples from high-risk areas for nasopharyngeal carcinoma.

Representative samples of preserved foods collected from high-risk areas for nasopharyngeal carcinoma were assayed for capacity to induce Epstein-Barr virus (EBV) by measuring induction of the DR promoter gene or of genes for early antigens in Raji cells. The two assays gave concordant results, but the DR induction assay detected EBV-inducing substances at lower concentrations and more reproducibly. Three of 17 preserved food items were active in both assays; they were also weakly mutagenic in the SOS chromotest and contained low or moderate levels of volatile N-nitrosamines. After in-vitro nitrosation, the levels of mutagens and nitrosamines increased, whereas EBV-inducing activity was unchanged or decreased. Thus, EBV inducers appear to be a different class of substances from mutagens and volatile N-nitrosamines but could act with them in the etiology of nasopharyngeal carcinoma.

Food Analysis↗
PubMed1991

Endogenous nitrosamines and liver fluke as risk factors for cholangiocarcinoma in Thailand.

Cholangiocarcinoma (CCA) is one of the most prevalent cancers in north-east Thailand and has been associated with infestation by the liver fluke Opisthorchis viverrini (OV). Two samples of 12-h overnight urine (after dosing with 500 mg proline and 200 mg ascorbic acid or 500 mg proline alone) were collected from about 100 inhabitants in five contrasting incidence areas for CCA and hepatocellular carcinoma. The incidences of CCA and hepatocellular carcinoma were not correlated with either the amount of NPRO or other nitrosamino acids, endogenous nitrosation potential (difference in NPRO levels between proline dose and proline and ascorbic acid dose), or nitrate level. However, when urinary levels of nitrosamino acids were compared in subjects living in high-risk areas, subjects who were positive for OV antibody excreted significantly more (p less than 0.01) NPRO (12.3 +/- 18.7 micrograms/12 h) after proline ingestion than those who were negative 3.5 +/- 3.2 micrograms/12 h). After ingestion of ascorbic acid, the NPRO levels in the positive subjects were significantly reduced (p less than 0.01) to 2.4 +/- 2.0 micrograms/12 h, suggesting that endogenous nitrosation of proline was inhibited. Thus, endogenous nitrosation potential estimated from the difference of NPRO and sum of nitrosamino acids excreted in the two urine samples was significantly higher in subjects positive for the OV antibody. In addition, of the representative food samples and beverages consumed frequently in high-risk areas for CCA, fermented fish and pork contained N-nitrosodimethylamine (0-26 micrograms/kg), N-nitrosopyrrolidine (0-117 micrograms/kg) and N-nitrosopiperidine (0-23 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct↗
PubMed1991

[Clinical studies on endocrine therapy for prostatic carcinoma (4): Initial response to endocrine therapy and prognosis].

We have already pointed out by the use of multivariate analysis that local response of the prostate is one of the important prognostic factors in patients receiving endocrine therapy. Herein, we investigated how the local response to endocrine therapy affects the survival rate or the survival period. We also studied the relationship between the local response and histopathological findings. The local response of prostate was not correlated with the stage progression. Sixty-seven percent of the patents in each stage had an initially favorable local response of the prostate, in which the primary tumor became flattened or reduced by endocrine therapy. By contrast, the local response of the prostate was well correlated with the prognosis in each stage. Patients with a flattened or reduced primary lesion following endocrine therapy showed a higher survival rate or a longer survival period than those with the unchanged lesion. This result has confirmed that the local response of prostate to endocrine therapy is useful in predicting clinical courses of patients. Grade of structural atypism (SAT), one of the pathological findings, had a correlation with local response of the prostate. With an elevation of the SAT grade, the proportion of patients with unchanged primary lesion was increased.

Humans↗
PubMed1991

[Clinical studies on endocrine therapy for prostatic carcinoma (5): Analyses of relapse from endocrine therapy].

Prostate carcinomas are well known to be initially responsive to endocrine therapy. However, a significant number of the patients experience a relapse from endocrine therapy during the follow-up period. We clinically analyzed various aspects of the relapse which indicate a limitation in the effectiveness of endocrine therapy for prostate carcinoma. In a total of 372 patients, 117 (31.5%) had some evidence of local relapse such as regrowth of the primary lesion, or a generalized relapse such as re-elevation of total acid phosphatase, reactivation of previously present metastasis or the new appearance of metastasis, during endocrine therapy. Of these, one-fourth had local relapse alone and the remainder showed generalized relapse. The interval from the start of the treatment to the time of relapse tended to become shorter; 45.9 months (mean) in stage B, 36.8 in stage C and 29.3 in stage D, according to the stage progression. As to the non-relapse rate of the primary lesion, no differences were found among the stage, with the rate being approximately 90% at the fifth year in each stage. However, the generalized relapse-rate tended to increase with the stage progression. In the generalized relapse, the patients of stage C or D showed a non-relapse rate of 71.7% or 67.4%, respectively. Most of the generalized relapse appeared within five years following start of endocrine therapy in these advanced stages. The interval from relapse to prostate carcinoma-related death in patients with the generalized relapse was 9 approximately 21 months, and those in stage D tended to show a a poorer prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Exposure to N-nitrosamines and other risk factors for gastric cancer in Costa Rican children.

The hypothesis that endogenous chemical nitrosation in the normal stomach in early life could play a crucial role in inducing chronic atrophic gastritis/intestinal metaplasia in later life was tested by applying the N-nitrosoproline (NPRO) test to 12-h urine samples from about 50 children (aged 8-14 years) living in high- and low-risk areas for stomach cancer. The median values of NPRO and the sum of four nitrosamino acids analysed were 0.28-0.84 micrograms/12 h and 0.75-1.75 micrograms/12 h, respectively. The NPRO level after proline intake was significantly higher in children from a high-risk area than in those from a low-risk area (p less than 0.04), and markedly reduced after ingestion of ascorbic acid and proline (p less than 0.05). Urinary nitrate level was lower than that of adults. NPRO levels on the day of proline intake, however, correlated well with nitrate levels (p less than 0.001), indicating that children in a high-risk area in Costa Rica have high endogenous nitrosation potential. Blood samples were also collected from about 300 children (aged 7-20 years) and analysed for antibodies against Campylobacter pylori, a suspected gastritis-causing bacteria. About 71% of children in both high- and low-risk areas for stomach cancer had antibodies. In addition, raw and cooked beans, which are consumed very frequently in Costa Rica, were collected from families in both areas and analysed for levels of nitrite/nitrate, total N-nitroso compounds and genotoxicity in the SOS chromotest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

N-nitroso compounds, genotoxins and their precursors in gastric juice from humans with and without precancerous lesions of the stomach.

We are investigating the interrelationships between levels of total N-nitroso compounds (NOC), genotoxic activity (both before and after nitrosation), degree of bacterial colonization in gastric juice and degree of severity or absence of precancerous lesions of the stomach. The mean level of constitutive total NOC in gastric juice was similar in the different groups of patients, but it was higher in acidic gastric juice (n = 30) than in gastric juice at pH greater than 4.5 (n = 12). Acid-catalysed nitrosation of gastric juice in vitro increased the concentration of total NOC by up to several thousand fold, to a maximum of 1330 mumol/l. Genotoxicity, expressed as SOS-inducing potency per 100 microliters of gastric juice was measurable in only 20% of gastric juice samples tested. After acid-catalysed nitrosation, however, all samples showed genotoxic activity, the mean SOS-inducing potency being four to seven times greater than the corresponding constitutive value. There was no association between the mean SOS-inducing potency of gastric juice and the severity of precancerous lesions. The mean SOS-inducing potency of neutral or basic gastric juice was slightly greater than that of acidic samples. In a kinetic study on N-nitrosation of gastric juice in vitro, a mixture of amino and amido substrates was nitrosated; both qualitative and quantitative individual differences in nitrosatable substrates in gastric juice were seen. Fractionation of acidic, neutral and basic nitrosated gastric juice samples revealed a preponderance of nonvolatile, unknown NOC with varying polarities. The results of our study suggest that only pH determines the nature and level of precursors of NOC and of nitrosation-dependent genotoxins in gastric juice.

Adult↗