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Biomedical subjects

T Komai

Publications and source records attributed to T Komai.

At least 19 recordsLinked to original sources
PubMed1992

Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture.

The transport mechanism of pravastatin, a new cholesterol-lowering drug, was compared in vitro with rat hepatocyte primary culture and mouse skin fibroblasts (L-cells). The uptake of 14C-labeled pravastatin by cultured hepatocytes was temperature- and dose-dependent. The temperature-dependent uptake as a function of [14C]pravastatin concentration showed saturation kinetics with Km = 32.2 microM and a maximal uptake rate of 68 pmol/mg protein/min. The uptake of pravastatin was inhibited significantly by metabolic inhibitors such as rotenone, oligomycin A, antimycin A, 2,4-dinitrophenol and KCN. Unlabeled pravastatin as well as R-416 and R-195, structural analogues of pravastatin, effectively competed for the hepatic uptake of [14C]pravastatin at 37 degrees. These results indicate that pravastatin is taken up by the liver by an active transport. In contrast, the transport of pravastatin by L-cells was temperature-independent and non-saturable, suggesting that the uptake of pravastatin by L-cells is mediated by passive diffusion. The marked difference in the uptake mechanism of pravastatin between hepatocytes and L-cells may account for a unique feature of this drug in that the uptake and inhibition of cholesterol biosynthesis occur selectively in the liver.

Animals↗
PubMed1991

Studies on macrocyclic lactone antibiotics. XIII. Anti-tubulin activity and cytotoxicity of rhizoxin derivatives: synthesis of a photoaffinity derivative.

Chemical modification of the side chain in rhizoxin, a potent antimitotic agent, was attempted in order to study structure-activity relationships and also to devise a probe for photoaffinity labeling of tubulin. An OsO4/NaIO4 oxidation gave a nor-rhizoxin 20-al (5) which was converted to 20-ol (6) by a NaBH3CN reduction. Starting from these two compounds as key intermediates, a series of Wittig reaction products 7-2, and of 20-O-acylates 13-21 were prepared and their anti-tubulin activity and cytotoxicity were determined. An aryl azide derivative 23 was synthesized as a photoaffinity analogue.

Animals↗
PubMed1990

Brachycephalic, serrated curettes for anterior cervical spinal microsurgery. Technical note.

Modified spinal fusion curettes with two unusual features on the tip are described for anterior cervical procedures. The features are: 1) an elliptical, long sidewise ("brachycephalic") scoop at the tip and 2) a serration equipped on the distal scoop edge. These designs allow reliable manipulation and significant removal of the intervertebral space contents in the deep operative field under the microscope.

Cervical Vertebrae↗
PubMed1990

[Clinical and histological study of pituitary fibrosarcoma following radiotherapy for pituitary adenoma. Case report].

A 49-year-old male was admitted with a history of radiotherapy for a pituitary adenoma 9 years earlier. Three weeks prior to admission, he noticed visual loss in the left eye. Computed tomography (CT) scan revealed a sellar tumor. The patient underwent craniotomy and the tumor was partially resected. The histological diagnosis was benign pituitary adenoma. Two months after surgery, he began to complain of headache and left hemiparesis. CT scan at that time showed a large parasellar tumor extending into the right temporal lobe. A second craniotomy was performed and a firm tumor was partially removed. Under light microscopy, the tumor was composed of anaplastic spindle cells showing a fascicular pattern. Ultrastructurally, the tumor cells were spindle-shaped with elongated nuclei. The cytoplasm contained numerous distended rough endoplasmic reticula and free ribosomes, Golgi apparatus as well as glycogen granules. Some desmosome-like intercellular adherent were observed. Collagen fibers were scattered in the extracellular space. There was no apparent formation of a basement membrane. These findings suggested a close morphological similarity between tumor cells and fibroblasts, conforming to ultrastructural diagnostic criteria for fibrosarcoma. In spite of intensive treatment, such as a second radiotherapy and subsequent craniotomy, the patient died 9 months after admission. The clinical course and pathological findings of the post-irradiation pituitary fibrosarcoma are discussed.

Adenoma↗
PubMed1988

Recovery from congenital complete atrioventricular block.

Congenital complete atrioventricular block without any other intracardiac anomaly reverted to sinus rhythm at the age of 7 years. The girl had had heart failure and Adams-Stokes attacks when aged 1 year, requiring pacemaker implantation. Electrocardiography confirmed sinus rhythm for the first time at the age of 7 years. At the same time, a treadmill test yielded a normal tracing without any arrhythmias.

Adams-Stokes Syndrome↗
PubMed1988

Induction of peroxisome proliferation in rat liver by dietary treatment with 2,2,4,4,6,8,8-heptamethylnonane.

1. Exposure of rats to 1% (w/w) of 2,2,4,4,6,8,8-heptamethylnonane in the diet for 2 weeks resulted in marked induction of liver peroxisome proliferation as judged from electron micrography, elevated activities of hepatic catalase (36%), cyanide-insensitive palmitoyl-CoA oxidase (10-fold), carnitine acetyl transferase (9.6-fold), lauric acid hydroxylase (12.4-fold), and the induction of the 80 K protein in SDS-polyacrylamide gel electrophoresis (4.1-fold). 2. 2,2,4,4,6,8,8-Heptamethylnonane dicarboxylic acid, a non-beta-oxidizable fatty acid, was detected as the major metabolite in the liver, an example of an unmetabolizable lipophilic anion as a peroxisome proliferator.

Alkanes↗
PubMed1987

Extrarenal metabolism of N-ethyl [2, 3-14C] maleimide-S-glutathione, a model compound of glutathione conjugate.

Radioactive N-ethyl [2, 3-14C]maleimide-S-glutathione (14C-NEM-S-G) was used as a model compound of glutathione conjugate. The metabolism of the conjugate in the extrarenal tissues was investigated in nephrectomized rats and perfused rat livers. When 14C-NEM-S-G was injected intravenously into nephrectomized rats, a significant amount of 14C-NEM-S-cysteine (14C-NEM-S-Cys) was detected in the blood, demonstrating that the conjugate could be metabolized to its cysteine form by extrarenal gamma-glutamyl transferase and dehydropeptidase-I. In the isolated liver perfusion with Krebs-Henseleit buffer containing 25 mM Hepes, both 14C-NEM-S-Cys and 14C-NEM-S-cysteinylglycine (14C-NEM-S-Cys-Gly) were formed from 14C-NEM-S-G. Furthermore, 14C-NEM-S-Cys-Gly was converted to 14C-NEM-S-Cys in the plasma, although 14C-NEM-S-G was not metabolized by the plasma itself. These results demonstrate that the liver and plasma contribute to the metabolism of glutathione conjugates in vivo.

Animals↗
PubMed1987

Intestinal absorption of choline in rats.

The intestinal absorption of choline, an endogenous quaternary ammonium, from the rat jejunum has been investigated with an in situ ligated loop method and an in vitro everted sac method. Choline was absorbed rapidly from the ligated jejunum and structural analogs inhibited choline absorption competitively. In in vitro experiments, choline was transported from the mucosal fluid to the intracellular fluid against a concentration gradient and the rate of tissue uptake was highly affected by incubation temperature, aerobic condition and the presence of a metabolic inhibitor, 2,4-dinitrophenol. The tissue accumulation of choline was saturable at concentrations below 100 microM and, above this concentration the uptake ratio of choline (medium to tissue) was almost constant. One mM hemicholinium-3, which is well known to inhibit choline uptake by neurons through the choline specific carrier, also significantly inhibited choline uptake, especially at concentrations of choline below 100 microM. The fact that the choline uptake is linear in the presence of hemicholinium-3 shows that choline is partially absorbed by passive diffusion. The difference between the total tissue accumulation and choline uptake by the passive diffusional pathway followed Michaelis-Menten kinetics and the apparent Kt of 47 microM and Vmax of 4.1 nmol/ml intracellular fluid/min were determined by an in vitro everted sac method. These findings suggested that, a lower concentrations, choline was absorbed from the rat intestine mainly by an active transport system.

Animals↗
PubMed1987

Mineralization and biodegradation of CSF shunting systems.

The mineralization and biodegradation of cerebrospinal fluid shunting systems were studied using material from 25 shunts that had been implanted for between 6 days and 10 years. New unused materials were also examined for comparison. Surface changes in six systems could be observed under an operating microscope. Substantial quantities of a white deposit had adhered to the tubing in four of the shunts. These changes were most advanced in the galeal penetrative portion of the shunts and are believed to have been caused by mechanical stress. Scanning electron microscopic analysis revealed surface wrinkles, microscopic holes, and tiny particles, suggesting deterioration of the material itself. An energy-dispersive analysis using x-rays demonstrated that the surface deposits were due to mineralization of calcium phosphate and that the tiny particle growth was aluminum. These changes may be a consequence of the degradation of silicone rubber. A discriminant analysis of the mineralization was carried out; thus, the age of the host and the duration of system implantation could be correlated with the incidence of mineralization (p less than 0.1). A measurement of the physical properties showed progressive change with a remarkable deterioration in systems implanted for more than 5 years.

Adult↗
PubMed1987

Role of dehydropeptidase-I in the metabolism of glutathione and its conjugates in the rat kidney.

14C-N-Ethylmaleimide-S-cysteinylglycine was used to investigate the role of dehydropeptidase-I in the metabolism of glutathione conjugates. The dipeptide was rapidly hydrolyzed to 14C-N-ethylmaleimide-S-cysteine in isolated rat renal cells, and subsequently acetylated to 14C-N-ethylmaleimide-S-N-acetylcysteine. Cilastatin, a specific inhibitor of dehydropeptidase-I, strongly inhibited the hydrolysis of the dipeptide by the isolated cells. In rat kidney homogenates, the marked inhibitory effect of cilastatin was also observed on the hydrolysis of cystinyl-bis-glycine and leukotriene D4, which are dipeptide intermediates in the biotransformation of oxidized glutathione and endogenous glutathione conjugate, respectively. In contrast, the inhibitory effect of bestatin, a potent inhibitor of aminopeptidase-M, was much smaller than that of cilastatin on the hydrolysis of these dipeptides by the renal cells and homogenates. These results suggest that dehydropeptidase-I plays a more important role in the metabolism of glutathione and its conjugates than aminopeptidase-M does.

Animals↗
PubMed1986

The relation between structure and distribution of quaternary ammonium ions in mice and rats. Simple tetraalkylammonium and a series of m-substituted trimethylphenylammonium ions.

In order to determine the relationship between structure and distribution in mono-quaternary ammonium ions, the distribution of a series of 14C-labeled tetraalkylammonium and substituted trimethylanilinium ions in mice were comparatively studied by means of whole-body autoradiography and radioassay. The partition coefficient in n-octanol/water were also determined. With tetraalkylammonium, the concentration in blood and tissues decreased in the order of tetramethyl, tetraethyl and tetrapropylammonium, which was opposite to expectation based on their partition coefficient values, but was in the order of increasing steric hindrance at the cationic head. With substituted trimethylanilinium, the concentrations in the blood, skeletal and cardiac muscles, diaphragm and salivary gland after i.v. injection to mice increased in the order: m-NO2 less than Cl less than OCH3 less than H less than CH3. This did not coincide with the order of increasing the partition coefficients, but coincided with the decrease of the Hammett sigma-constants of the substituent. These results were interpreted on the basis of the assumption that the ion-pair formation of the cationic head with an anionic site of the tissue macromolecules played an important role in determining distribution. It was pointed out that although the lipophilic character of the molecule has been often cited as the most important factor determining the distribution of the drugs, the ionic character of the molecule or of the functional group can participate as a more important factor in determining tissue distribution.

Animals↗
PubMed1986

Intestinal absorption of tetramethylammonium and its derivatives in rats.

The intestinal absorption of tetramethylammonium (TMA) and its derivatives from rat jejunum has been investigated with an in situ loop method and an in vitro everted sac method. At a low concentration, TMA was absorbed rapidly from the in situ intestinal lumen without being metabolized in the tissue and the rate of absorption was dependent upon the concentration used. The profile of TMA absorption included two processes, i.e. saturable and non-saturable. The absorption of TMA was inhibited competitively by analogs that have a N-trimethyl group in their structure. Among them, choline showed the strongest inhibition to TMA absorption. The inhibitory potency of these analogs was related to their chemical structure. Although TMA was not transported into the intracellular fluid of the everted intestine against a concentration gradient, the tissue accumulation of TMA was inhibited by 2,4-dinitrophenol (2,4-DNP), a metabolic inhibitor, and was highly dependent upon the incubation temperature. These findings demonstrate that TMA is absorbed through the rat small intestine by a carrier mediated transport system. An apparent Kt of 0.73 mM and a maximum V of 11.5 nmol/g tissue wet wt/min were determined by an in situ loop method. It was also suggested that the endogenous quaternary ammonium compound, choline, might be absorbed by the same carrier system.

2,4-Dinitrophenol↗