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Biomedical subjects

J Tamura

Publications and source records attributed to J Tamura.

At least 199 records · Page 11Linked to original sources

[Absorption of 5-FU orally administered in a patient with postoperative gastric cancer under artificial dialysis].

A patient under artificial dialysis due to chronic renal failure suffered from gastric cancer concurrently. This patient underwent subtotal gastrectomy followed by consecutive oral administration of 5-FU (tablets) as a postoperative adjuvant chemotherapy. The 5-FU level in the peripheral blood on oral administration at 50 mg remained at 0.007-0.01 microgram/ml over 2 hours. This feature of 5-FU blood level is not seen in gastric cancer patients with normal renal functions on administration of 5-FU tablets, and it seems to approximate the features of a 5-FU prodrug level in the blood upon oral administration. Neither the influence of dialysis on the absorption of orally administered 5-FU nor side effects caused by 5-FU were observed. The above findings suggest that it may be possible to maintain a certain blood level of 5-FU and to perform adjuvant chemotherapy even in cancer patients under artificial dialysis, as long as the dose is controlled carefully.

Administration, Oral↗

Assessment of the in vitro growth of Plasmodium falciparum using fluorometry.

The growth of Plasmodium falciparum in vitro was quantitatively assessed by applying fluorometry using ethidium bromide. The fluorescence intensity of parasites stained with this dye was found to parallel the uptake of 3H-hypoxanthine into nucleic acids during one growth cycle of development. The assay system can be used as a substitute of morphological and radiometric methods in drug-sensitivity tests and for the screening of antimalarials.

Animals↗

A new technique for drug susceptibility tests for Plasmodium falciparum by ethidium bromide fluoroassay.

When Plasmodium falciparum parasites were stained with the fluorescent dye ethidium bromide, the fluorescence intensity of the solubilized parasites was correlated with the amount of nucleic acid present. It was possible to monitor development of the parasites from ring form to schizont by the fluoroassay. The assay system was applied to in vitro drug susceptibility tests on malaria parasites.

Chloroquine↗

Characteristics of taurine transport in rat hepatocytes in primary culture.

Characteristics of taurine transport in rat hepatocytes maintained in primary culture for 24 h (cultured hepatocytes) have been investigated. The uptake of [3H] taurine by cultured hepatocytes at 2 degrees C was unsaturable, whereas that at 37 degrees C consisted of unsaturable and saturable processes. The saturable transport system was sodium-dependent and consisted of two processes with low and with high affinities. The latter process (Km, 76.9 microM; Vmax, 0.256 nmole/mg protein/min; activation energy (EA), 37.8 kcal mol-1) was competitively inhibited by 2,4-dinitrophenol and ouabain, as well as by taurine analogues such as hypotaurine and guanidinoethyl sulphonate. The Vmax and EA values found in cultured hepatocytes at 37 degrees C were 6.0 and 6.8 times higher than those found in freshly isolated hepatocytes. These results indicate that taurine transport in hepatocytes in primary culture consisted of unsaturable, and saturable, sodium and energy-dependent carrier-mediated transport processes, respectively. The facilitation of the latter transport system by primary culture of hepatocytes is also suggested.

Animals↗

Cysteine uptake and taurine biosynthesis in freshly isolated and primary cultured rat hepatocytes.

Analysis of the uptake and metabolism of [14C]cysteine in rat liver was undertaken using freshly isolated hepatocytes and hepatocytes maintained in primary culture. The uptake of [14C]cysteine by freshly isolated hepatocytes was by means of both saturable and non-saturable transport systems and the former system was thought to involve facilitated diffusion. The uptake of [14C]cysteine by hepatocytes maintained in primary culture for 24 h also consisted of non-saturated and saturated transport mechanisms. The magnitude of the saturable transport system in cultured hepatocytes was, however, much greater than that found in freshly isolated hepatocytes, and was considered to be operated by active transport. Both freshly isolated and primary cultured hepatocytes had cysteine sulphinic acid decarboxylase activity, but this enzyme activity in the latter cells was noticeably reduced in comparison with that found in freshly isolated hepatocytes. Hepatocytes maintained in primary culture produced not only radiolabelled taurine, but also radiolabelled cysteine sulphinic acid, hypotaurine and alanine when incubated with [14C]cysteine. The present results indicate that cultured hepatocytes actively transport cysteine as well as metabolizing cysteine to taurine via cysteine sulphinic acid and hypotaurine.

Animals↗

Roles of endogenous and exogenous taurine and glycine in the formation of conjugated bile acids: analyses using freshly isolated and primary cultured rat hepatocytes.

The regulatory roles of intracellular taurine and glycine, transported and biosynthesized in hepatocytes, on the formation of conjugated bile acids were studied using freshly isolated hepatocytes (fresh hepatocytes) and hepatocytes in primary culture (cultured hepatocytes). Transported taurine significantly increased the rate of taurocholic acid formation both in fresh hepatocytes and cultured hepatocytes. Similarly, the addition of cysteine and hypotaurine, which were metabolically converted to taurine in hepatocytes, facilitated the formation of taurocholic acid in these cells. On the other hand, exogenous glycine into the incubation medium had no effect on the formation of glycocholic acid both in fresh and cultured hepatocytes. In contrast, the addition of serine and threonine, which are metabolically converted to glycine in hepatocytes, significantly increased the formation of glycocholic acid in fresh hepatocytes, although little effect of the additions of serine and threonine on the formation of glycocholic acid was noted in the case of cultured hepatocytes. The present results indicate that the formation of taurine-conjugated bile acids in hepatocytes is maintained by both transported and intracellularly formed taurine in hepatocytes, while that of glycine-conjugated bile acids is regulated by glycine formed within hepatocytes, but not by transported glycine.

Animals↗

[Clinical trials of plasma exchange therapy in patients with recurrent colon cancer].

Plasma exchange was performed in patients with recurrent colon cancer with evaluable liver metastasis or abdominal tumor with dissemination. This therapy was undertaken a total of 19 times in 11 cases. The cases were divided into effective and ineffective cases according in terms of the clinical effects, and changes in blood parameters and prognosis were examined in each case. Subjective symptoms, such as increase in appetite and disappearance of general fatigue or pain, were remarkably improved in 6 cases, and these patients were allowed to be discharged from the hospital. Marked regression of hepatomegalia was observed in 2 cases out of these 6 cases, but no remarkable effect was noted in patients with abdominal dissemination. In the effective cases the following parameters were significantly improved; beta- and gamma-globulin of serum protein fractions, IgG, IgA and IgM of immunoglobulin, alpha 2-macroglobulin, ceruloplasmin, and transferrin. However, since these effects are temporal and short-lived, one must consider applying plasma exchange therapy in conjunction with anticancer drugs, and the like. Plasma exchange seems applicable to cases of colon cancer with metastasis in the liver, because this therapy showed improvement in clinical symptoms, decreased hepatomegaly and prolonged survival.

Abdominal Neoplasms↗

Alteration of acetaldehyde metabolism in carbon tetrachloride-intoxicated rat liver: analysis using liver perfusion system.

The heptic metabolism of acetaldehyde in carbon tetrachloride (CCl4)-intoxicated rats was studied using a non-recirculating haemoglobin-free liver-perfusion system. Acetaldehyde uptake by the liver from acutely CCl4-treated animals (4.16 mmol/kg,i.p.) at 24 hr after the treatment was not significantly altered, whereas that by the liver from chronically CCl4-treated animals (2.08 mmol/kg,i.p., twice a week, for 8-12 weeks) was decreased by approximately 50% when it was determined in the presence of 0.01-5 mM acetaldehyde. In liver from rats chronically intoxicated with CCl4, the following important biochemical changes were observed: (1) The activity of low Km aldehyde dehydrogenase (ALDH) in hepatic mitochondria was decreased by approximately 75%. (2) The basal levels of the lactate/pyruvate (cytosolic [NADH]/[NAD+]) ratio as well as the beta-hydroxybutyrate/acetoacetate (mitochondrial [NADH]/[NAD+]) ratio were elevated by more than 2-fold. (3) Mitochondrial NADH oxidation was also reduced by approximately 35% of the control level. (4) The basal level of hepatic oxygen uptake was attenuated by approximately 50%, and the infusion of acetaldehyde (0.01-5.0 mM) caused a further decrease in the uptake. (5) The rate of ethanol production from acetaldehyde by the catalytic action of alcohol dehydrogenase was found to be unaltered when low concentrations of acetaldehyde (0.01-0.2 mM) were used, whereas a significant suppression of the rate of ethanol production was detected in the presence of high concentrations of acetaldehyde (0.6-5 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

Histopathological study on N-ethyl-N'-nitro-N-nitrosoguanidine-induced colon cancer in dogs.

We prepared a suppository containing 50 mg of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), and successfully produced experimental colon cancer with good reproducibility by continuous intrarectal insertion of one or two suppositories per day in dogs. The tumors were very similar to human colon cancers, macroscopically and histologically. In one of three dogs subjected to histopathological study, metastases to the lymph nodes, lung, liver and kidney were observed. This animal model produced by a simple procedure will be helpful in investigating treatment of rectal cancer.

Adenocarcinoma↗

Characteristics of cholic acid uptake in primary cultured hepatocytes.

The characteristics of cholic acid uptake by primary cultured hepatocytes was studied. The cholic acid uptake below 10 degrees C was unsaturable, while that determined at 20 degrees and 37 degrees C showed a biphasic type, which suggested the presence of a saturable process. This saturable process was a temperature-dependent and carrier-mediated transport process with an activation energy of 36.1 Kcal/mol. The apparent Km and Vmax values at 37 degrees C were 57.1 microM and 0.566 nmoles/mg protein/min, respectively. The saturable process was inhibited by 2,4-dinitrophenol and ouabain, and reduced significantly in the absence of sodium, suggesting that this process is energy- and sodium-dependent. The cholic acid uptake mediated by the saturable process in the absence of sodium was, however, significantly larger than that mediated by the unsaturable process. These results suggest that the transport of cholic acid in primary cultured hepatocytes may consist of three different types: unsaturable, sodium and energy-dependent carrier-mediated, and sodium-independent and energy-dependent processes, respectively. The presence of a common transport carrier for cholic acid and its conjugates with taurine and glycine in primary cultured hepatocytes was also suggested.

Animals↗

[Acute toxicity of ranitidine and its metabolite in mice, rats and rabbits, and subacute oral toxicity of ranitidine in rats].

Acute and subacute toxicities of ranitidine hydrochloride, a new histamine H2-receptor antagonist, and acute toxicity of ranitidine N-oxide, a metabolite of ranitidine hydrochloride, were investigated. The results are summarized as follows: (1) Oral, intravenous, subcutaneous, intraperitoneal and intramuscular LD50 values of ranitidine hydrochloride in 5- and 12-weeks old mice and rats and 12-weeks old rabbits were ranged from ca. 60 mg/kg (12-weeks old male mice, i.v.) to 6610 mg/kg (12-weeks old male rats, p.o.). In comparison of the LD50 values, it was revealed that female rats were more sensitive to the drug than males in the case of oral administration. (2) A single intravenous injection with ranitidine N-oxide at a dose of 1000 mg/kg, induced no lethal cases in mice, indicating that the N-oxide has very low toxicity in a comparison with that of ranitidine hydrochloride. (3) In the subacute toxicity test, male and female rats were orally administered with ranitidine hydrochloride for 35 days. Dose dependent changes such as increase in liver weight and water consumption, decrease in spontaneous movement and others were induced at doses of more than 500 mg/kg/day in females and 1000 mg/kg/day in males. These results indicate that the no effects were observed at levels of 250 mg/kg/day in females and 500 mg/kg/day in males. In the recovery test, however, no marked changes were observed in the rats which had been administered at 1000 and 2000 mg/kg/day for 35 days.

Administration, Oral↗

[Teratological study on ranitidine hydrochloride in rabbits].

Ranitidine hydrochloride, a histamine H2-receptor antagonist, was orally given to pregnant rabbits of Japanese White strain from day 6 to 18 of gestation at doses of 25, 100 and 400 mg/kg/day, as ranitidine base, and teratogenicity of the drug was studied. The results were as follows: (1) At dose of 400 mg/kg/day, ranitidine hydrochloride showed no effects on dams, excepting slight suppression in body weight gain in early period of administration. (2) In fetuses, no effects of ranitidine hydrochloride on fetal growth, sex ratio, viability and degree of ossification were observed. (3) External and visceral abnormalities were observed 5, 3, 3 and 4 fetuses in control, 25, 100 and 400 mg/kg/day groups, respectively, but there was no significant difference of the incidence ratio in the treated groups from control, and was no increase in the same type of abnormality. Ranitidine hydrochloride induced no increase in incidence of visceral and skeletal variations. Therefore it was concluded that ranitidine hydrochloride had no teratogenic effect on rabbits at dose of 400 mg/kg/day or lower than that.

Administration, Oral↗