Search PubMed⌕ Search

Biomedical subjects

H Ohshima

Publications and source records attributed to H Ohshima.

At least 235 records · Page 13Linked to original sources
PubMed1991

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

N-Nitrosamine formation by bacteria in the achlorhydric stomach has been proposed as an important factor in the development of gastric cancer. Thus, the effect of the presence of bacteria in the stomach on endogenous nitrosation was investigated in rats given omeprazole (an inhibitor of gastric H+, K((+)-ATPase) which reduces gastric secretion sufficiently to allow survival of a bacterial suspension of Escherichia coli or Pseudomonas. When rats were given both thiazolidine 4-carboxylic acid and nitrate, greater endogenous nitrosamine formation was observed in rats receiving omeprazole and an E. coli suspension than in control or omeprazole-treated rats. A similar result was obtained when rats were given morpholine and nitrate. Since the endogenous formation of N-nitrosomorpholine (NMOR) can be evaluated more precisely from the levels of its urinary metabolites, N-nitrosohydroxyethylglycine (NHEG), the metabolism of NMOR was studied in omeprazole-treated rats. In this preliminary study, we showed that 60% of an oral dose of NMOR was excreted as NHEG, while in rats with a higher gastric pH 20% was excreted as NHEG. The amount of endogenously formed NMOR was increased in omeprazole-treated rats given morpholine and nitrite together with bacteria, and greater excretion of unchanged urinary NMOR was observed. Thus, as shown in this in-vivo model, bacteria efficiently reduce nitrate to nitrite and catalyse nitrosation, resulting in increased endogenous formation of N-nitroso compounds in the achlorhydric stomach.

Achlorhydria↗
PubMed1991

Nitrotyrosine as a new marker for endogenous nitrosation and nitration.

A sensitive and selective method has been developed for analysing 3-nitrotyrosine (NTTYR), an exposure marker for exogenous and endogenous nitrosating or nitrating agents, in tissue and blood proteins by gas chromatography-thermal energy analysis. Using this method, a number of kinetic studies were carried out. Free and protein-bound tyrosine were reacted easily to yield NTTYR. The method was also applied to the study of NTTYR formation in vivo; a dose-dependent increase in NTTYR was seen in both plasma proteins and haemoglobin obtained from rats 24 h after intraperitoneal injection of various doses (0.5-2.5 mumol/rat) of tetranitromethane. Major urinary metabolites of NTTYR, given orally to rats, were isolated and identified as 3-nitro-4-hydroxyphenylacetic acid (NHPA) and 3-nitro-4-hydroxyphenyllactic acid. About 44% and 5% of the oral dose of NTTYR (100 micrograms/rat), respectively, was excreted as these metabolites. Some human urine samples were analysed for NHPA by gas chromatography-thermal energy analysis after ethyl acetate extraction and high-performance liquid chromatography purification; 2.8 +/- 2.3 (mean +/- SD; n = 11) micrograms/24 h, ranging from 0-7.9 micrograms/24 h, were detected (detection limit, 0.2 micrograms/l). In conclusion, NTTYR in proteins or its metabolites in urine could be readily analysed by gas chromatography-thermal energy analysis as a new, additional marker for endogenous nitrosation and nitration.

Animals↗
PubMed1991

[A case of right atrial myxoma--the availability of transesophageal echocardiography in the detection of right atrial myxoma].

A 72-year-old woman had experienced palpitation and fatigue during exertion for two months and was referred to our hospital from her nearby hospital. On physical examination, a systolic murmur was heard in the left fourth intercostal space. A chest X-ray film showed cardiac enlargement (CTR 64%). An ECG showed elevated P waves in leads II, III. Transthoracic echocardiography revealed a large oval heterogeneous mass in the right atrium. Transesophageal echocardiography (TEE) revealed the right atrial mass clearly, which was attached to the atrial septum with a short wide stalk. This mass prolapsed from the right atrium into the right ventricle in diastole. And there were some cysts in the homogeneous high-echoic lesion. The chest CT and MRI also showed the mass in the right atrium. However, these images were not clear. Surgical excision of the mass was undertaken. A solid mass measuring 75 x 50 x 45 mm was attached to the fossa ovalis with a wide short stalk. There were several cysts in the mass. Pathological examination showed myxomatous tissue. In this case, TEE was the most valuable means for evaluation of the right atrial mass.

Aged↗
PubMed1990

[Combination chemotherapy with methotrexate, vincristine, cis-platinum, cyclophosphamide, adriamycin, and bleomycin: MVP-CAB for disseminated urological cancer].

Twenty-eight evaluable patients with disseminated measurable malignancies of the genitourinary organs except testicular cancer were treated with MVP-CAB, between May 1985 and June 1988. Chemotherapy was given at 3 to 4 week intervals, as follows. On day 1, methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg/body were administered. On day 2, cis-platinum 50 mg/m2, on day 1 to 3, prednisolone 20 mg/body were also administered. The administration of bleomycin and adriamycin were limited to 90 mg/body and 400 mg/m2. The median age was 59 years. The median follow-up duration was 11 months. The primary lesions were urothelial tract cancer (19 patients), malignant lymphoma (1 patient), renal cell adenocarcinoma, penile cancer, prostatic adenocarcinoma, and leiomyosarcoma (2 patients each). CR was observed in 2 patients, and PR in 11 patients with urothelial tract cancer. The overall response rate was 68% (13/19). The response rates in primary and metastatic lesions were 56% (5/9) in primary, 73% (8/11) in lymph node, 71% (5/7) in lung, 67% (2/3) in liver, and 20% (1/5) in bone. The median duration of survival in the responders was 13.5 months, and in the non-responders was 5 months. The 1 year survival rate by Kaplan-Meier method was 70% in responders. On the other hand, the longest survival time in non-responders was 9 months. Marked improvement of survival time was noted in the responders. PR was observed in 1 patient with malignant lymphoma, prostatic adenocarcinoma, and leiomyosarcoma in each. The main toxic effect of MVP-CAB was bone marrow suppression. Leucopenia (WBC less than 4,000/mm3) was noted in 24 patients (86%), and 16 patients (57%) had a WBC count nadir below 2,000/mm3. Thrombocytopenia (plt less than 10 x 10(4)/mm3) was noted in 10 patients (36%). However, there were no deaths due to the bone marrow suppression.

Adult↗
PubMed1990

Structural basis of the genotoxicity of nitrosatable phenols and derivatives present in smoked food products.

The CASE methodology for studying structure-activity relationships has been applied to investigating the basis of the genotoxicity of phenols and derivatives following exposure to nitrous acid. The structural features identified include availability of positions para or ortho to the hydroxyl groups, that one meta position must remain unoccupied and one ortho or para position must be unsubstituted as well. The analyses revealed that genotoxicity is dependent upon the ease of formation of the active phenyldiazonium intermediate and is influenced only secondarily by the nature of the genotoxicant or its ease of entry into the cell. With this data base, CASE predicts the genotoxicity, following nitrosation, of a number of agents, including serotonin, acetaminophen, and of some naturally-occurring pesticides present in edible plants.

Food Analysis↗
PubMed1990

Exposure of humans to endogenous N-nitroso compounds: implications in cancer etiology.

Two sensitive procedures to quantitate human exposure to endogenous N-nitroso compounds (NOC) and/or methylating agents have been developed. One, the NPRO test, is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosoamino acids in the urine, that 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, esophagus, 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. In experimental animals 3-methyladenine (3-MeAde) is excreted in urine following exposure to methylating NOC. Humans normally excrete 3-MeAde, the origin of which remains unknown. Recently developed analytical methodology permits large numbers of human urine samples to be analyzed and a wide variation is observed. Preliminary results suggest a weak correlation between basal NPRO excretion and background 3-MeAde excretion. Taken together, the results point to an etiological role of endogenously formed NOC in certain human cancers, and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.

Adenine↗
PubMed1990

Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins.

3-Nitrotyrosine (NTYR) in tissue or blood proteins was evaluated as a possible exposure marker for exogenous and endogenous nitrosating or nitrating agents. A sensitive and selective method for analysing NTYR by gas chromatography with a thermal energy analyser (GC-TEA) was developed. Using this method, a number of kinetic studies were carried out. It was found that free and protein-bound tyrosine residues easily react with nitrating/nitrosating agents to yield NTYR. NTYR formation in vivo showed a dose-dependent increase in NTYR in both plasma proteins and haemoglobin obtained from rats 24 hr after ip injection of various doses (0.5-2.5 mumol/rat) of tetranitromethane. Major urinary metabolites of NTYR, given orally to rats, were isolated and identified as 3-nitro-4-hydroxyphenylacetic acid (NHPA) and 3-nitro-4-hydroxyphenyllactic acid (NHPL). About 44% and 5% of the oral dose of NTYR (100 micrograms/rat) was excreted as NHPA and NHPL, respectively. Eleven 24-hr human urine samples were analysed for NHPA by GC-TEA after ethyl acetate extraction and HPLC purification: quantities ranging from 0 to 7.9 micrograms/24 hr, mean +/- SD 2.8 +/- 2.3 (n = 11) were detected (detection limit 0.2 micrograms/litre). NTYR in proteins or its metabolites in urine can be readily analysed by GC-TEA as a new/additional marker for endogenous nitrosation and nitration.

Animals↗
PubMed1990

Relationship among the surface potential, Donnan potential and charge density of ion-penetrable membranes.

Calculation of the potential distribution across a uniformly charged ion-penetrable membrane that we developed previously is extended to derive a relationship among the surface potential, Donnan potential and charge density of an ion-penetrable membrane in a mixed solution of 2-1 and 1-1 electrolytes. We also present an approximate method for calculating the surface potential/Donnan potential/charge density relationship for membranes with an arbitrary distribution of membrane-fixed charges.

Journal Article↗
PubMed1990

Kinetic model for membrane transport. 1. Effects of membrane volume and partitioning kinetics.

Equations for the transport of solutes through a membrane are derived, taking into account both the membrane volume and the partitioning kinetics, and have been found to involve two rate constants for solute transport, namely, those corresponding to solute transport from the solution to the membrane (k1) and from the membrane to the solution (k2). The time course followed before partitioning equilibrium has been attained, which is usually ignored, is shown to depend strongly on the relative magnitudes of k1 and k2.

Biological Transport↗
PubMed1990

Kinetic model for membrane transport. 2. Time lag and overshoot.

A lag time during the period of variation in solute concentration in the receiver phase and overshoot in that in the membrane phase have been predicted to occur with a kinetic model for membrane transport which takes into account both the membrane volume and the partitioning kinetics (Makino et al., Biophys. Chem. 35 (1990) 85). The duration of the lag time becomes longest when the donor and receiver phases have the same volume. This maximum grows in length with increase in the partition coefficient, tending to be proportional to the volume fraction of the receiver phase. Moreover, it displays an increase in length with decreasing membrane volume fraction. Overshoot occurs only when the volume fraction of the receiver phase is greater than that of the donor. Overshoot is observed during the earlier stages of membrane transport when the partition coefficient is smaller or the volume fraction of the receiver phase is larger.

Biological Transport↗
PubMed1990

Blood vascular architecture of the rat lingual papillae with special reference to their relations to the connective tissue papillae and surface structures: a light and scanning electron microscope study.

Subepithelial blood vessels of the rat lingual papillae and their spatial relations to the connective tissue papillae and surface structures were demonstrated by light and scanning electron microscopy. In the rat, four types of papillae were distinguished on the dorsal surface of the tongue, i.e. the filiform, fungiform, foliate and circumvallate papillae. Vascular beds of various appearance were found in all four types of lingual papillae: a simple or twisted capillary loop in the filiform papilla; a basket- or petal-like network in the fungiform papilla; a ring-like network in the foliate papilla, and a conglomerated network surrounded by double heart-shaped capillary networks in the circumvallate papilla. These characteristic vascular beds corresponded to the shape of the connective tissue papillae and surface structures. The vascular bed beneath the gustatory epithelium in the fungiform, foliate and circumvallate papilla consisted of fine capillary networks next to the taste buds.

Animals↗
PubMed1990

Ultrastructural changes in odontoblasts and pulp capillaries following cavity preparation in rat molars.

Responses of odontoblasts and pulp capillaries to cavity preparation were investigated in the upper first molar teeth of rats, using light and transmission electron microscopy. At 100 days of age, the blood vessels of the pulp formed a subodontoblastic network consisting of continuous capillaries at a short distance from the odontoblast layer. Cavity preparation caused the displacement of some odontoblasts into the dentinal tubules, while others were separated from the predentin by rapid inflammatory exudation after drilling. The subodontoblastic capillary network under the injured dentin was shifted inwards together with the separated odontoblasts. The endothelium of the shifted capillaries showed a remarkable increase of pinocytotic vesicles, an event thought to be closely related to the formation of the exudative lesion. By one day after cavity preparation, most of the damaged odontoblasts had degenerated. Many cells with high nucleus/cytoplasm (N/C) ratios and prominent nucleoli accumulated around the subodontoblastic capillaries, some of which had many endothelial fenestrae facing these cells. These cells were suggestive of newly differentiating odontoblasts receiving nutritional supply from the capillaries. Three days after cavity preparation, newly differentiating odontoblasts took the place of the degenerated odontoblasts. They began to produce reparative dentin by five days after cavity preparation. Capillaries were located beneath the newly differentiating odontoblasts, but endothelial fenestrae gradually decreased in number. During the active reparative dentin formation, capillaries remained closely beneath the new odontoblast layer. Although the rate of reparative dentin deposition was not significantly lower than that in the primary dentin formation, one could not recognize an invasion of capillaries into the odontoblast layer nor a remarkable increase of endothelial fenestrae, both of which are common in active primary dentin formation. The results suggest that the function of capillaries differs between primary and reparative dentin formation.

Animals↗
PubMed1990

[Clinical studies on endocrine therapy of prostatic carcinoma (1): Multivariate analyses of prognostic factors in patients with prostatic carcinoma given endocrine therapy].

The general trend on the treatment for prostatic carcinoma has been changing from endocrine therapy alone to an alternative type according to stage. We evaluated clinically the favorable and unfavorable outcome of endocrine therapy in Japan, so that others will be appropriately evaluated. In a cooperative study made by members of five universities, 572 patients with clinically or histologically reconfirmed prostatic carcinoma were entered in this retrospective study. We studied the true influence of prognostic factors on the prognosis of 497 patients with prostatic carcinoma who had received endocrine therapy, employing multivariate analyses, such as quantification method II, multiple regression analysis and Cox's proportional hazard model. Twelve factors were considered in the study; "age", "stage", "histological findings (structural atypism = SAT, nuclear anaplasia = NAN, Gleason's primary and secondary pattern)", "pretreatment level of total acid (ACP) and of alkaline phosphatase (ALP)", "castration performed or not performed", "doses of estrogen", "type of response of local prostatic tumor and of ACP to endocrine therapy". Analysis of the "importance" of a prognostic factor by a partial correlation determined by quantification method II, revealed "stage" to have the greatest "importance" on prognosis throughout the entire period. "Response of local prostatic tumor", "response of ACP" and "Gleason's primary pattern" tended to be important factors for prognosis, in particular, in the first half period, and "age" and "Gleason's secondary pattern" were important in the latter half. Multiple regression analysis revealed the "stage", once again to be the most influential factor on the prognosis for the entire observation period. Also "response of local prostatic tumor", "SAT" and "Gleason's primary pattern" affected the patients' prognosis in the first half of the observation period. In the latter half, "age" became more of an influential factor than "histological findings". Analysis with Cox's proportional hazard model revealed that "response of ACP", "stage", "age", "Gleason's primary and secondary pattern", and "response of local prostatic tumor" were definitely the more influential prognostic factors, of which chi-square values (or t values) were statistically significant. Comparison of the significant factors in each multivariate analysis revealed that common influential prognostic factors, such as "age", "stage", "histological findings (mainly Gleason's primary and secondary pattern)", "response of local prostatic tumor" and "response of ACP" were coincident to the clinical impression. The clarification of these factors would be clinically beneficial when treating patients with endocrine therapy.

Estrogens↗
PubMed1990

[A case of right-sided infective endocarditis in a drug addict].

A 49-year-old man was admitted to Mitsui Memorial Hospital because of fever of unknown origin. Since one year ago, he had often used intravenous narcotic drugs. Ten months before his admission, he had his first experience of fever and a chill. Four months later, he was admitted to a hospital under the diagnosis of pneumonia and he was treated successfully. After his discharge, he began to use drugs again, which resulted in the repetition of fever and chills during four months prior to his admission to our hospital. On admission, physical findings concerning the patient were unremarkable, except for mild hepatomegaly. ECG and chest X-ray were normal. Laboratory data revealed marked inflammatory changes and severe liver injury. Blood culture disclosed Campylobacter fetus and two dimensional echocardiography showed a large vegetation on the anterior tricuspid valve. He was diagnosed as isolated tricuspid infective endocarditis accompanied with acute hepatitis due to drug abuse. Moreover pulmonary perfusion scintigraphy showed decreased perfusion in the right lower lung field, which suggested that pneumonia of six months ago was due to septic pulmonary emboli from the infected tricuspid valve. The combined antibiotics therapy was successful. By the follow-up echocardiographic studies, the size of vegetation was observed to decrease progressively.

Campylobacter Infections↗
PubMed1989

Volatile nitrosamine levels and genotoxicity of food samples from high-risk areas for nasopharyngeal carcinoma before and after nitrosation.

Traditional life-style, especially food habits, infection by Epstein-Barr virus (EBV) and genetic factors, have been associated with an increased risk of nasopharyngeal carcinoma (NPC). N-Nitroso compounds and other carcinogens either present in food or formed endogenously, as well as food constituents that activate EBV, have been suspected as etiological factors in NPC pathogenesis. For their characterization preserved food items, frequently consumed in NPC endemic areas in Tunisia, South China and Greenland, were sampled and screened for the presence of mutagens and volatile nitrosamines before and after nitrosation. Aqueous extracts as well as 2 organic extracts of the samples were assayed for genotoxicity in 2 Salmonella typhimurium strains and the SOS chromotest. The same extracts had previously been analyzed for volatile nitrosamines and for EBV-activating substances in Raji cells. In our study, 13 out of 16 food samples showed a weak, directly-acting genotoxicity in the SOS chromotest in at least one of the extracts, but only one sample from Greenland was found to be weakly mutagenic in Salmonella TA 98. Chemical nitrosation for 9 out of 15 samples of aqueous food extracts increased the genotoxic effect in the SOS chromotest. Levels of volatile nitrosamines were also elevated for 12 out of 15 samples; highest levels of N-nitrosodimethylamine were found in hard salted and dried fish from China (1,200 micrograms/kg) and highest N-nitrosopyrrolidine levels in a Tunisian spice (3,840 micrograms/kg). In non-nitrosated aqueous food extracts, the level of volatile nitrosamines and genotoxic activities were not correlated with the EBV-inducing activity of the same samples. After chemical nitrosation, EBV-inducing activity was decreased or showed no change and was not correlated with increases in either the genotoxicity or the nitrosamine levels. Our results suggest that EBV-activating compounds belong to a different class of substances. However, there was an association between the changes in genotoxicity and nitrosamine levels due to nitrosation.

Carcinoma↗
PubMed1989

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

Urine samples were collected from 96 inhabitants of a high-risk rural area and a low-risk urban area for stomach cancer in Poland, according to the following protocol: (1) when they were undosed; (2) after ingestion of proline 3 times a day; and (3) after ingestion of proline together with vitamin C 3 times a day. The samples were analyzed for N-nitrosamino acids and nitrates, as indices of exposure to preformed and endogenously formed N-nitrosamines. The median values of N-nitrosoproline (NPRO) and N-nitrosothiazolidine 4-carboxylic acid (NTCA) excreted in the urine of undosed subjects were not different between the two areas; but N-nitrososarcosine and 3-(N-nitroso-N-methylamino)propionic acid levels were 3- to 4-fold higher in subjects of the high-risk area. After intake of proline, the NPRO level increased (p less than 0.02) only in subjects in the high-risk area; intake of vitamin C tended to inhibit this increase in NPRO and lowered the levels of other nitrosamino acids. The urinary level of nitrates was 1.4-fold, but significantly higher among subjects in the high-risk area than among those in the low-risk area; nitrate levels were not correlated with the amounts of cured meat or types of vegetables consumed. Urinary nitrate levels and excretion of NPRO, NTCA and the sum of all nitrosamino acids analyzed showed positive, though modest, correlations. These results indicate a higher potential for endogenous nitrosamine formation, possibly by intragastric nitrosation among subjects in the high-risk rural area.

Adult↗
PubMed1989

Evidence of potential tumour-initiating and tumour-promoting activities of hickory smoke condensate when given alone or with nitrite to rats.

Epidemiological studies have indicated that the consumption of smoked fish and meat products is associated with an increased risk of stomach cancer. A commercial hickory smoke condensate (HSC) was evaluated for its tumour-initiating and promoting activities in the glandular stomach using short-term methods in vivo. HSC (1 ml of a 10-100% v/v solution/rat) was given orally, either with or without nitrite (25-100 mumols/rat) to male F344 rats. The potential of HSC to act as a glandular stomach carcinogen was revealed by the induction in the pyloric mucosa of the stomach of ornithine decarboxylase (ODC), replicative DNA synthesis (RDS) and DNA single-strand breaks. The administration of HSC with nitrite also induced unscheduled DNA synthesis in the pyloric mucosa, but led to decreased induction of ODC, RDS and DNA single-strand breaks in comparison with treatment with HSC alone. These results suggest that HSC contains substance(s) that have potential tumour-initiating and/or tumour-promoting activities and that reaction with nitrite generates new substance(s) that could act as potential tumour-initiators in the rat glandular stomach.

Animals↗