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Biomedical subjects

Z Tamura

Publications and source records attributed to Z Tamura.

At least 19 recordsLinked to original sources

Primary malignant lymphoma of the urinary bladder. A case report.

A patient with primary malignant lymphoma of the urinary bladder is presented. Grossly, the bladder showed multiple submucosal masses. Histologically and immunohistochemically, diffuse B-cell lymphoma of the medium-sized cell type was revealed. On the basis of clinicopathological features, the present case resembled previously recorded cases of bladder lymphoma. The pathogenesis of this primary bladder lymphoma was presumably associated with follicular or chronic cystitis. Primary lymphoma of the bladder is a condition that is very rarely included in series of extranodal lymphomas, and there is a curious sex difference in its occurrence rates between Japan and Western countries. Primary lymphoma of the bladder may be considered a lymphoma that originates fro mucosa-associated lymphoid tissue.

Antibodies, Monoclonal

Sex difference of the metabolic disposition of clioquinol in rats.

The order of plasma levels of clioquinol and its conjugates in male rats after intraduodenal administration of 32.7 mumol/kg dose of clioquinol was clioquinol sulfate (C-Sul) greater than glucuronide (C-Glu) much greater than clioquinol, whereas that in female rats was C-Glu greater than C-Sul much greater than clioquinol. Total (urine + bile) recovery was almost the same among male and female rats. The percentage of excretion amounts of C-Sul (urine + bile) to the total excretion amounts for 24 h in male rats after intravenous administration of clioquinol was about twice that in female rats, while the percentage of excretion amounts of C-Glu to the total excretion amounts in male rats was smaller than that in female rats. In intravenous administration of 16.4 mumol/kg dose of C-Glu, C-Sul and clioquinol other than C-Glu were found in bile and urine of male and female rats. The percentage of excretion amounts of C-Sul and C-Glu (urine + bile) to the total excretion amounts was similar among male and female rats, respectively. In intravenous administration of 16.4 mumol/kg dose of C-Sul, C-Glu and clioquinol other than C-Sul were found in bile and urine of male and female rats, and the percentage of excretion amounts of C-Sul (urine + bile) to the total excretion amounts in male rats was 1.3 fold that in female rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Changes in lipid peroxide concentrations in plasma and tissues by repeated administration of clioquinol to neonatal rats.

The changes in lipid peroxide concentrations in plasma and tissues after subcutaneous administration of clioquinol to clioquinol-sensitive (S-rats) and -resistant neonatal rats (R-rats) were investigated. When a fixed dose of 150 mg/kg/d of clioquinol was given to R-rats for 14 d after birth, no significant difference in lipid peroxide concentrations in plasma, liver, kidney, brain and spinal cord at 5, 10 and 15 d was observed between clioquinol-treated and untreated rats. However, with increasing doses of clioquinol to R-rats every 5 d (150----300----600 mg/kg/d), the lipid peroxide concentrations at 15 d were higher in plasma, brain and spinal cord of clioquinol-treated rats than in those of untreated rats. These results suggested that repeated administrations of large doses of clioquinol to rats increased the lipid peroxides in nerve tissues. With S-rats at 5 d after birth, the lipid peroxide concentrations in liver were approximately twice those in R-rats regardless of the clioquinol administration.

Animals

Analysis of chinoform binding to human serum albumin by an improved partition equilibrium method.

Previous methods such as equilibrium dialysis to measure chinoform binding to human serum albumin are flawed with problems due to the drug's poor solubility in neutral aqueous solutions and its strong adsorption onto the surfaces of dialysis membrane and other apparatus. Accordingly, we adopted a previously reported improved partition equilibrium method to keep off such difficulties, and developed additionally a rapid method using oil-wells. Both of these methods were used in this study. The equilibration of both partition and binding was attained after 6 h by the standard method and after 2 h by the rapid method. Two binding sites were found on the albumin molecule. One had an extremely large affinity constant of 10(8) M-1 and the other had a moderate one of 10(6) M-1. These values obtained with both methods agreed well and were sufficiently reproducible. The bound percentage of chinoform in serum was estimated at 99.999% under the condition where chinoform reveals its nervous toxicity. The binding constant had a maximum at pH 7.6, the physiological pH of serum. The pH profile suggested the participation of a histidine residue in the binding site. The inhibition experiment with palmitic acid revealed that the first binding site of chinoform was not identical with that of palmitic acid. The present method is applicable to analyses of protein binding by other drugs showing similar physicochemical properties as chinoform.

Clioquinol

Absorption, distribution and metabolism of clioquinol in clioquinol-sensitive and -resistant neonatal rats.

Three types of rats with respect to sensitivity to clioquinol have been identified, the highly sensitive (S-rat), the intermediately sensitive, and the resistant (R-rat). In a toxicity test that lasted for 20 d after birth, the difference in sensitivity to clioquinol between S- and R-rats was confirmed by repeated subcutaneous administration of a clioquinol suspension prepared with polysorbate 80 (clioquinol dose of 150 or 300 mg/kg/d). Plasma and tissue concentrations of clioquinol and the rate of metabolism of the drug in neonatal S- and R-rats were measured. Plasma concentration of clioquinol in 1-d-old S-rats after a single subcutaneous administration was higher than that in the same age R-rats and the area under the mean plasma concentration-time curve for the S-rats was approximately twice that for the R-rats. In addition, clioquinol concentrations in liver, kidney and brain of S-rats at 9 h after the administration were more than twice those of the R-rats. From the experiments on the formation of clioquinol glucuronide and sulfate with 9000 g supernatant fraction of liver, it was suggested that the difference in the plasma concentration after the administration may be responsible for the difference in the metabolizing rate of clioquinol.

Animals

Studies on microcapsules to replace erythrocytes in the passive agglutination reaction.

Two kinds of microcapsules were made from polyurethane and polyurea. Each capsule had a mean diameter of 6 microns, a specific gravity of 1.10, and was red in color. The capsules were coated with ovalbumin condensed with glutaraldehyde. The coated capsules were agglutinated with anti-ovalbumin antibody. The polyurethane capsule (positive charge) bound more ovalbumin and showed a higher sensitivity than did the polyurea capsule (negative charge) or erythrocytes.

Agglutination Tests

Biopharmaceutical evaluation of methylcellulose as an excipient for nitroglycerin tablets.

To examine the bioavailability of nitroglycerin in sublingual tablet, 5 healthy adult volunteers underwent simultaneous sublingual administration of a tablet prepared with methylcellulose and a tablet prepared with lactose containing 0.15 mg of nitroglycerin and 0.15 mg of nitroglycerin-15N3, respectively. In 4 of 5 volunteers, no difference in plasma concentration determined by gas chromatography-mass spectrometry (GC-MS) was observed between 2 tablets described above, so it was well accepted that nitroglycerin in tablets prepared with methylcellulose had a similar bioavailability to that in tablets prepared with lactose. The simultaneous administration of the 2 nitroglycerin tablets to a healthy volunteer, one of which containing the drug labeled with a stable isotope followed by GC-MS assay, seems to be the most suitable method for a precise comparison of bioavailability of the formulations.

Adult

Sensitive fluorimetry of adenine-containing compounds with high-performance liquid chromatography.

A definitive method to determine adenine compounds simultaneously was established by introducing a new fluorescent reagent into high-performance liquid chromatography. Bromoacetaldehyde was the best reagent among the haloacetaldehydes examined. A quantitative reaction was obtained even for unstable ADP and ATP. A high resolution of adenine nucleotides was obtained using a column of Hitachi gel No. 3012-N. The method was applied to the measurement of cyclic AMP in urine, and ADP and ATP in brain and blood. Further, the sensitivity of the method was increased by a new fluorescence spectrophotometer constructed for micro-HPLC. Femtomole amounts of the adenine nucleotides were clearly separated.

Acetaldehyde

Quantitative determination of furosemide in plasma, plasma water, urine and ascites fluid by high-performance liquid chromatography.

A high-performance liquid chromatographic method using spectrofluorometric detection is described for the determination of furosemide in plasma, plasma water, urine and ascites fluid. The extraction procedure decreases interference from endogenous substances. The detection limit of furosemide is 10 ng in 0.5 ml of biological sample. The method is sufficiently sensitive for pharmacokinetic study of furosemide with normal subjects and patients with liver cirrhosis and/or renal disease after oral administration of furosemide in a retard capsule, and for study of protein binding of furosemide in patients with various diseases.

Ascitic Fluid

Saltatory conduction of peripheral nerve impulse in clioquinol-treated rats.

By using a new method, unidimensional latency-topography, which shows the saltatory conduction pattern of an impulse along peripheral nerve fibers, the internodal length, internodal conduction time and conduction velocity were determined from the L5 ventral and/or dorsal root filaments of clioquinol-treated rats (CTR). The saltatory conduction pattern was preserved in most of the CTR fibers tested, but was not seen in some fibers. A positive correlation was seen between the conduction velocity and the internodal length in the nerve fibers of both the normal rats and CTR. Although there was no difference in the internodal length between normal rats and CTR, conduction velocities determined in CTR fibers were lower than those in normal rat fibers. Myelin length was calculated from the saltatory conduction pattern in the topography to represent the functional length of the saltatory conduction. The functional myelin length of the CTR fiber was shorter than that of normal rats. Shortening of the functional myelin length in CTR is due to the widening of the Ranvier node, which corresponds to the exposure of the Ranvier node, i.e. demyelination. It was concluded that the decrease in conduction velocity in CTR fibers was due to exposure which caused delayed excitation at the Ranvier nodes.

Animals

Determination of the partition coefficient and acid dissociation constants of iodochlorhydroxyquin by an improved partition method.

A simple and precise method for determining partition coefficients was developed utilizing a disposable injector. The method was used to determine the partition ratio of iodochlorhydroxyquin between n-decane and phosphate-buffered saline, pH 7.4. The partition ratio was found to be 1750 with a coefficient of variation of 3%. Moreover, it was found that iodochlorhydroxyquin did not associate in n-decane at a concentration less than 1 X 10(-3) M. The acid dissociation constants and the partition coefficient of the undissociated species were determined. These values corresponded well with the values obtained from spectrophotometric methods.

Chemical Phenomena

Enterohepatic circulation of clioquinol in the rat.

The existence of the enterohepatic circulation (EHC) of clioquinol was confirmed by using paired rats, donor and recipient, which were connected to each other with a bile duct-to-duodenum cannula. The concentrations of clioquinol and its metabolites appearing in the plasma of the recipient following intraduodenal 10 mg/kg dose of clioquinol to the donor were fairly low. However, within 24 h after the administration ca. 12% of the dose was reexcreted in the bile of the recipient as clioquinol glucuronide and ca. 2% in the urine as clioquinol sulfate. From these results and the data of biliary excretion in our previous paper, the glucuronide was found to play a role on the EHC. Further, both in vitro and in situ results suggested that clioquinol glucuronide excreted in the bile may be absorbed partially after return to the parent drug in the intestinal tract and partially as such without deconjugation.

Animals

Determination of catecholamine sulfoconjugate isomers in normal human urine by use of high-performance liquid chromatography with a photochemical detector.

A method for the determination of catecholamine sulfoconjugate isomers (CA-S) in urine was developed. The photo-induced fluorogenic reaction of CA-S with ethylenediamine reported previously was applied to the postcolumn labeling of HPLC for sensitive and selective detection. Special equipment for the reaction was made with a uv-irradiation lamp and a reaction coil of Teflon tubing inside a temperature-controlled reaction box. Lower determination limits of this system were 1 to 2 pmol. Urine samples pretreated with small ion-exchange resin columns were subjected to HPLC. Peaks corresponding to CA-S were identified quantitatively by two different separation methods. Thus, all six CA-S were first detected in the urine of normal individuals. The excretion rates of dopamine 3-sulfate, dopamine 4-sulfate, norepinephrine 3-sulfate, norepinephrine 4-sulfate, epinephrine 3-sulfate, and epinephrine 4-sulfate were 420 +/- 240, 98 +/- 55, 86 +/- 95, 15 +/- 14, 18 +/- 7, and 3 +/- 1 ng/min (+/- SD), respectively (n = 5).

Catecholamines

O-methylation of dopamine-o-sulfates with catechol-0-methyltransferase.

[2H2]-dopamine-3-0-sulfate (DM-3-0-S) and [2H2]-dopamine-4-0-sulfate (DM-4-0-S) were synthesized to investigate the possibility of their being substrates for catechol-0-methyltransferase (COMT). [2H5]-3-0-methyldopamine (3-0-Me-DM) and [2H5]-4-0-methyldopamine (4-0-Me-DM) were also synthesized as internal standards for the determination of enzymatic products by gas chromatography-mass spectrometry (GC-MS). [2H2]-DM-3-0-S or [2H2]-DM-4-0-S was incubated at 37 degrees for 60 min in the presence of S-adenosyl-L-methionine with a crude enzyme preparation obtained from rat liver homogenate. The incubation mixture was treated with 0.5N HCl at 100 degrees C for 1h to hydrolyze the remaining sulfate moiety. The reaction products were extracted with an Amberlite XAD-4, derivatized with pentafluoropropionic anhydride and determined by GC-MS. When [2H2]-DM-3-0-S was used as a substrate, [2H2]-3-0-Me-DM was found to be a major product accompanied by [2H2]-4-0-Me-DM as a minor product. The ratio of [2H2]-3-0-Me-DM to [2H2]-4-0-Me-DM was found to be 26:1, while the ratio was 5.4:1 when [2H2]-dopamine was used as a substrate. When [2H2]-DM-4-0-S served as a substrate, [2H2]-3-0-Me-DM was preferentially produced without detectable formation of [2H2]-4-0-Me-DM.

Animals