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Biomedical subjects

H Ohshima

Publications and source records attributed to H Ohshima.

At least 253 records · Page 14Linked to original sources

Formation of direct-acting genotoxic substances in nitrosated smoked fish and meat products: identification of simple phenolic precursors and phenyldiazonium ions as reactive products.

Epidemiological studies have associated the consumption of smoked fish and meat products with an increased risk of stomach cancer. Therefore, the reaction of such smoked foods with nitrite under acidic conditions was investigated and was shown to produce potent direct-acting genotoxic substances as detected by the SOS Chromotest. Similar genotoxic activity was observed in nitrosated samples of wood-smoke condensates. Simple phenolic compounds such as phenol, 3-methoxycatechol, catechol and vanillin were identified as the precursors of the genotoxic substances. These phenolic compounds also exhibited direct-acting genotoxicity after nitrosation. The major genotoxic substances formed after nitrosation of phenol were isolated and identified as 4- and 2-hydroxyphenyldiazonium ions. Nitrosation of various wood-smoke condensates was found to generate the same type of diazonium compounds, which in part account for the genotoxicity of nitrosated smoked foods.

Animals↗

Identification in rats of N-nitrosonipecotic acid as a major urinary metabolite of the areca-nut alkaloid-derived nitrosamines, N-nitrosoguvacoline and N-nitrosoguvacine.

N-Nitrosamines derived from areca-nut alkaloids have been implicated in cancer of the oral cavity and esophagus caused by betel quid chewing in India and other Asian countries. A major urinary metabolite of N-nitrosoguvacoline and N-nitrosoguvacine, both present in saliva of betel quid chewers of ppb levels, was isolated from rat urine and identified as N-nitrosonipecotic acid by comparison with the authentic compound. When a dose of 50 or 500 micrograms/rat of either compound was administered orally to BDIV rats, 66-85% of the dose was excreted in the urine as N-nitrosonipecotic acid and 2-8% as N-nitrosoguvacine. These N-nitrosamino acids could be analysed in the urine of betel quid chewers as a marker of exposure to areca-nut specific nitrosamines.

Animals↗

Lymphoepithelial cystic lesion related to adenocarcinoma in the mediastinum.

The authors report here a case of lymphoepithelial cystic lesion (LECL) of unknown origin in the mediastinum, which is closely related to a signet-ring cell adenocarcinoma. A 73-year-old man presented with a mass as revealed on a chest x-ray. During surgical operation, a solid, well-circumscribed and encapsulated 9 X 9 X 8 cm tumor was isolated from the right anterior mediastinum. This tumor had neither undergone metastasis nor invaded into the surrounding tissue and lymph nodes. Light microscopy revealed the tumor to be a signet-ring cell adenocarcinoma. Clinically, the neoplasm was coupled with an elevation in serum CEA level, which promptly returned to normal values following surgical removal. Immunohistochemistry pointed out that the majority of neoplastic cells stained positive for CEA. In addition, LECL of unknown origin was distinguished at the periphery of the tumor. LECL was characterized by microcysts which were lined by columnar epithelial and surrounded by lymphoid tissue with germinal centers. Transition between the neoplastic cells and benign epithelial cells of LECL was evident, showing that the previously mentioned mediastinal adenocarcinoma may be derived from the epithelial elements of LECL. This paper discusses the histogenesis of LECL.

Adenocarcinoma, Mucinous↗

Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer.

Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N-nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances.

Cotinine↗

Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc during compression load.

The behavior of water in the intervertebral disc of pig tail and its physiologic and biomechanical properties were investigated in relation to compression load. The water content, chemical composition, and swelling pressure in the intervertebral disc were measured, and the mechanism of the generation of the swelling pressure in relation to compression load stress was studied. The swelling pressure, through regulation of the water content of the disc and the resistance of the external load, differs with the region of the intervertebral disc. In the nucleus pulposus and the inner layer of the anulus fibrosus, the swelling pressure rises in proportion to the load, but few changes occur in the outer layer of the anulus fibrosus, and the constant pressure environment is thus maintained. The tritiated water (3H2O) uptake of the disc under various loads was measured. The molar partition coefficient of tritiated water is almost equal to 1 even under a compression load, which suggests that water is freely exchangeable. The diffusion of 3H2O in the intervertebral disc was traced using two pathway models: the perianular route and the end-plate route. The diffusion of water in the unloaded disc for both uptake and washout was about 2 to 3 times larger in the perianular route than in the end-plate route. Under load, the water diffusion was inhibited in both pathways. The relation between the load and displacement revealed viscoelastic properties indicating creep and stress relaxation. Young's modulus and the stiffness increased with a rise in load speed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vascularization of the enamel organ in developing molar teeth of rats--scanning electron microscope study of corrosion casts.

Vascularization of the enamel organ was demonstrated in the developing upper first molar teeth of rats from the 19-day embryo to 5 days after birth employing the vascular casting/scanning electron microscope method. Capillaries were first observed in the enamel organ at the 21-day embryo. By that time, with the beginning of differentiation of the inner enamel epithelium into ameloblasts, mesenchymal cells situated in close proximity to the inner enamel epithelium had begun to differentiate into odontoblasts, but deposition of organic substances had not commenced. The occurrence of blood capillaries before the nutritional supply through the dental papilla was interrupted by the deposition of dentin and enamel, may possibly be due to the high nutritional requirements of the ameloblasts following differentiation from the inner enamel epithelium. With the advance of dentin and enamel formation, many capillaries entered the enamel organ and finally formed a flattened vascular network next to the stratum intermedium. These findings suggest that the capillaries in the enamel organ should be regarded as a change which affords a rapid and sufficient supply of metabolic substances necessary for amelogenesis. The newly developed capillaries in the enamel organ grew first by sprouting and later by loop formation.

Animals↗

[The relationship between mitral regurgitation and asynergy of the left ventricle in old myocardial infarction].

To elucidate the mechanism of mitral regurgitation (MR) in patients with old myocardial infarction, two-dimensional (2D) and 2D Doppler echocardiographic examinations were performed in 92 patients. According to the sites of asynergy in the short-axis view of the left ventricle at the papillary muscle level, the patients were classified in three groups; i.e., anteroseptal (AS) group (49 cases), inferoposterior (IP) group (29 cases), and the AS + IP group (14 cases). The existence and severity of MR were evaluated by 2D Doppler echocardiography and the presence of mitral valve prolapse (MPV), by 2D echocardiography. The mitral valve ring diameter was also measured. The incidence of MR was significantly higher in the IP group (41%) and AS + IP group (43%) than in the AS group (20%) (p less than 0.05, respectively). In the IP group, 21 patients had left ventricular asynergy at the base of the posterior papillary muscle; eight did not. In the former 21 patients with asynergy, MR was detected in 12 (57%) and MVP in nine (43%), whereas neither MR nor MVP was detected in the eight patients without asynergy. The grade of MR assessed by 2-D Doppler echocardiography was significantly more severe in patients with MVP than in those without MVP (MR distance: 23 +/- 6 mm with MVP vs 11 +/- 1 mm without MVP; p less than 0.05, MR area; 312 +/- 217 mm2 with MVP vs 64 +/- 29 mm2 without MVP; p less than 0.05). MR appeared at the mitral orifice between its middle portion and the posteromedial commissure, which coincided with the site of MVP in the majority of cases. In the AS and AS + IP groups, however, such close relationships between MR and MVP were absent. In these groups, mitral valve ring diameters were significantly larger in patients with MR than in those without MR (AS group: 32 +/- 3 mm with MR vs 24 +/- 2 mm without MR; p less than 0.01, IP group: 26 +/- 2 mm with MR vs 25 +/- 2 mm without MR; NS, AS + IP group: 30 +/- 3 mm with MR vs 24 +/- 1 mm without MR; p less than 0.05). Mitral valve ring diameters in the IP group with MR (26 +/- 2 mm) were smaller than in those in the AS and AS + IP groups with MR, and did not differ from those in the IP group without MR (25 +/- 2 mm). In conclusion, posterior papillary muscle dysfunction was mainly responsible for MR in the inferoposterior infarction and the dilatation of the mitral valve ring in the infarction involving the anteroseptal wall.

Aged↗

Human exposure to endogenous N-nitroso compounds: quantitative estimates in subjects at high risk for cancer of the oral cavity, oesophagus, stomach and urinary bladder.

A sensitive procedure to quantitate human exposure to endogenous N-nitroso compounds (NOC) has been developed. It is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosamino acids in the urine, which are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, oesophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. The results point to an aetiological role of NOC in these human cancers and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.

China↗

A self-induced translation model of myosin head motion in contracting muscle. I. Force-velocity relation and energy liberation.

In our previous model, it was assumed that the two heads of myosin act co-operatively in producing force for the sliding of actin filaments relative to myosin filaments. We eliminate the assumption of co-operativity in the present model, following the conclusion by Harada and co-workers that a co-operative interaction between the two heads of myosin is not essential in producing actin filament movement. We assume that (1) a myosin head activated by ATP hydrolysis binds to the thin filament at a definite angle and does not do the power stroke, i.e. does not change its orientation during attachment, (2) a potential of force acting on the myosin head is induced around the thin filament when an ATP-activated myosin head binds to an actin molecule in the thin filament, and (3) the potential remains for a while after detachment of the myosin head and statistically controls the direction of thermal motion of the myosin head, so that the myosin head translates toward the Z-line as a statistical average. We did calculations on these assumptions with a mean tension approximation and got the following results. (a) The calculated force-velocity relation in muscle contraction is in fairly good agreement with experimental observation, including the give phenomenon that lengthening velocity becomes very large for a force about twice the isometric tension. (b) The calculated rate of energy liberation during muscle contraction as a function of load on muscle is in good agreement with experimental results. (c) The calculated distance over which a myosin molecule moves along the thin filament during one ATP hydrolysis can be more than 60 nm under unloaded conditions.

Energy Metabolism↗

Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention.

Although the proof that N-nitroso compounds (NOC), a versatile class of carcinogens in animals, are also carcinogenic in man is lacking, humans are exposed through ingestion or inhalation to preformed NOC in the environment and through the endogenous nitrosation of amino precursors in the body. Activated macrophages can synthesize nitrate, nitrite and nitrosating agents that can form NOC. A number of bacterial strains isolated from human infections can produce NOC enzymatically from precursors at neutral pH. As a consequence endogenous nitrosation may occur at various sites of the body such as the oral cavity, stomach, urinary bladder, lungs, and at other sites of infection or inflammation. Since the demonstration by Mirvish et al. (1972) showing that ascorbate can reduce tumor formation in animals following feeding of nitrite plus amine, numerous substances to which humans are exposed have been identified and shown to inhibit formation of NOC in vitro, in animal models and in humans. Such inhibitors of nitrosation include vitamins C and E, phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts. Nitrosation inhibitors normally destroy the nitrosating agents and thus act as competitors for the amino compound that serves as substrate for the nitrosating species. Independently, epidemiological studies have already established that fresh fruits and vegetables that are sources of vitamin C, other vitamins and polyphenols have a protective effect against cancers at various sites and in particular gastric cancer. Although the evidence that endogenously formed NOC are involved in human cancers is far from conclusive, it is suggestive and justifies preventive measures for reducing exposure to NOC. This article briefly reviews (i) the chemistry of NOC formation and inhibition, (ii) the studies in experimental animals which showed that inhibition of endogenous NOC synthesis leads to a reduction of toxic, mutagenic and carcinogenic effects, (iii) recent studies in humans where the degree of inhibition of endogenous NOC synthesis was directly quantified and lastly (iv) the contribution of nitrosation inhibitors to human cancer prevention.

Animals↗

Membrane transport of electrolyte ions and time-dependent membrane potential.

Equations are derived for the transport of a symmetrical electrolyte, consisting of cations and anions of equal valency, through a neutral membrane that separates two solutions of finite volume under quasi-steady-state conditions. The time-dependent membrane potential produced by the flow of ions is taken into account. Deviation of the time course of the solute concentrations from that of neutral solutes is found to be determined by the permeability ratio of cations and anions (when this ratio equals unity, the derived membrane transport equations reduce to those for neutral substances). Simple approximate expressions for the solute concentrations and of the membrane potential as functions of time are proposed, which are in excellent agreement with the exact numerical results.

Electrolytes↗

Membrane potential and Donnan potential.

The Nernst-Planck-Poisson equations for the potential profile across a membrane are exactly solved without recourse to the assumption of constant field within the membrane. It is assumed that the membrane core of thickness dc is covered by a surface layer of thickness ds in which the membrane-fixed charges are distributed at a uniform density N. The membrane boundary potentials as well as the diffusion potentials contribute to the membrane potential. It is shown that for ds greater or similar 1/k, k being the Debye-Hückel parameter, the potential in the membrane surface layer except in the region very near the membrane/solution boundary is effectively equal to the Donnan potential and that its contribution to the membrane potential becomes dominant as N increases. For low N, on the other hand, the membrane potential arises mostly from the diffusion potential.

Journal Article↗

pH dependence of electrostatic interaction between ion-penetrable membranes.

A theory on the electrostatic repulsion between ion-penetrable membranes proposed previously by us is extended by taking into account the degree of dissociation of the membrane-fixed ionizable groups. A system of equations which determines the pH dependence of the membrane interaction is presented. The density of membrane-fixed charges is consistently determined as a function of the electric potential so that both the membrane-fixed charge density and the potential are not constant but functions of the membrane separation. The pH at the surface of interacting membranes is also calculated as a function of the membrane separation.

Hydrogen-Ion Concentration↗

Epstein-Barr virus activation in Raji cells by extracts of preserved food from high risk areas for nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) activation of latent infection and traditional life styles, especially food habits, have been strongly associated with an increased risk of nasopharyngeal carcinoma (NPC) in humans. On the basis of anthropological studies in Tunisia, southern China and Greenland, extracts of representative preserved food items consumed frequently by the high-risk populations for NPC were assayed for the presence of EBV activators in Raji cells. A strong EBV activation activity was observed in aqueous extracts of some Cantonese salted dried fish from China, harissa (a spice mixture) and to a lesser extent qaddid (dry mutton preserved in olive oil) from Tunisia. These new data may support epidemiological evidence for the importance of Cantonese salted and dried fish and other food items in the etiology of NPC.

China↗

Analysis of rabbit intervertebral disc physiology based on water metabolism. I. Factors influencing metabolism of the normal intervertebral discs.

Basic factors influencing the metabolism of intervertebral discs of rabbits were quantitatively analyzed based on the water metabolism. The blood flow surrounding the intervertebral disc was calculated using pharmacokinetic concepts from the data obtained by time-related tritiated water distribution analyses. The blood flow was estimated as 0.056 (mg/min/mg tissue) in the anterior annulus, 0.106 in the posterior annulus, 0.120 in the lateral annulus, and 0.084 in the nucleus pulposus, respectively (Experiment 1). Water content and fixed charge density in the intervertebral disc fractions also were measured (Experiment 2). The cations and uncharged small solutes transported into the disc tissue ranged in descending order from nucleus pulposus, lateral annulus, posterior annulus, to anterior annulus. The authors also calculated theoretically the swelling pressure of the proteoglycan in the intervertebral disc fractions from the results of Experiment 2. It was concluded that swelling pressure was highest in the nucleus pulposus, and lowest in the anterior annulus. The water in the posterior annulus is less exchangeable than in the other disc tissue fractions.

Animals↗

Analysis of rabbit intervertebral disc physiology based on water metabolism. II. Changes in normal intervertebral discs under axial vibratory load.

Metabolic changes induced by axial vibratory load to the spine were investigated based on water metabolism in normal intervertebral discs of rabbits with or without pentobarbital anesthesia. Tritiated water concentration in the intervertebral discs of unanesthetized rabbits was reduced remarkably by axial vibration for 30 minutes using the vibration machine developed for this study. Repeated vibratory load for 18 and 42 hours duration showed the recovery of 3H2O concentration of the intervertebral disc without anesthesia. Computer simulation suggested a reduction of blood flow surrounding the intervertebral disc following the vibration stress. However, no reduction of the 3H2O concentration in the intervertebral disc was noted under anesthesia. Emotional stress cannot be excluded as a factor in water metabolism in the intervertebral disc.

Animals↗