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Biomedical subjects

M Koike

Publications and source records attributed to M Koike.

At least 379 records · Page 21Linked to original sources
PubMed1986

Immunohistochemical localization of pancreatic secretory trypsin inhibitor in fetal and adult pancreatic and extrapancreatic tissues.

Pancreatic secretory trypsin inhibitor (PSTI) has been thought to be only a secretory trypsin inhibitor of human pancreas, but the serum content of immunoreactive PSTI is elevated without pancreatic disease. Using the peroxidase-antiperoxidase method, immunoreactive cells for PSTI were found in human pancreas, stomach, duodenum, appendix, colon and urinary tract of both fetus and adult, adult gall bladder, and fetal lung. PSTI-immunoreactive cells were identified in fetal pancreas at the tenth gestational week, and in extrapancreatic tissues at the sixteenth (gastrointestinal and urinary tract) and twentieth weeks (lung). PSTI-immunoreactive cells of fetal lung were present in neuroepithelial bodies. Strongly positive cells in fetal duodenum were argyrophilic and resembled endocrine cells. Immunohistochemical study was also performed on tissues associated with inflammatory diseases of gastrointestinal tract. The distribution pattern of immunoreactive cells in the stomach varied in accordance with chronic gastritis. Immunoreactive cells were also found in endocrine micro-nests and in a carcinoid tumor associated with fundic gastritis. These results suggest that PSTI may play some physiological role other than secretory trypsin inhibition of the pancreas.

Adult↗
PubMed1986

Glycoprotein hormone alpha-subunit in human stomach.

To demonstrate the immunoreactive alpha-subunit of human chorionic gonadotropin (hCG) or glycoprotein hormones in non-neoplastic gastric mucosa, and to clarify the nature and significance of alpha-subunit-immunoreactive cells, immunohistochemical studies were performed on gastric mucosa using polyclonal antibodies for hCG alpha and beta, hLH beta, hFSH beta, hTSH beta, and gastrin, and a monoclonal antibody for hCG alpha. Surgically resected stomachs were classified as follows: nearly normal (Group A); antral gastritis (Group B); fundic gastritis with pseudopyloric glands (Group C); and intestinal metaplasia (Group D). Cells immunoreactive for the alpha-subunit were present in the pyloric glands and to a lesser extent in the fundic glands (Groups A and B). Almost all alpha-subunit-immunoreactive cells were nonreactive for the beta-subunits of the four glycoprotein hormones. alpha-subunit-immunoreactive cells corresponded to gastrin-containing cells in the pyloric glands, but were unrelated to gastrin in the fundic glands. In fundic gastritis, alpha-subunit-immunoreactive cells appeared to increase (Group C), and many hyperplastic foci were observed in atrophic glands with hyperplasia of the argyrophilic cells (Groups C and D). Isolated hCG alpha or the alpha-subunit of glycoprotein hormones may be present in the endocrine cells of gastric mucosa, and alpha-subunit-immunoreactive cells in the fundic glands seem to proliferate in fundic gastritis.

Adult↗
PubMed1986

Intestinal activation of a new sleep inducer 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative, in rats.

5-[(2- Aminoacetamide)methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl]- N,N-dimethyl-1 H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S) is a newly synthesized sleep inducer, which itself has negligible affinities for benzodiazepine receptors. However, several active metabolites have been found in rat plasma. In this paper, the mechanisms and contribution of the activation of 450191-S in rat small intestine were investigated. When 450191-S was incubated with rat everted small intestine, desglycylated 450191-S (191 DG) was released in the medium and subsequently converted to 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-1). The results obtained using synthetic 191DG indicated that the conversion of 191DG to M-1 was spontaneous and very rapid, with a half-life of 9 min in pH 7.4 buffer. After incubation, the intestinal tissue contained a small amount of unchanged 450191-S but large amounts of 191DG and/or M-1. Next, metabolites in the mesenteric blood were determined following instillation of 14C-450191-S into a segment of rat ileum and it was found that almost all of the radioactivity in the blood was accounted for by 191DG and/or M-1. In conclusion, 450191-S is metabolized by intestinal aminopeptidases to 191DG, which is spontaneously converted to M-1, an active metabolite, and the activation is completed by a single passage through the intestinal wall.

Aminopeptidases↗
PubMed1986

Effect of food on absorption of 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative from rat small intestine.

5-[(2-Aminoacetamide)methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl]- N, N-dimethyl-1 H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S), a newly synthesized sleep inducer, is a masked compound which is converted to 1,4-benzodiazepine by intestinal aminopeptidases during absorption from the small intestine. This study was an investigation on the effects of food on 450191-S pharmacokinetics. When 14C-450191-S was administered to non-fasted rats, peak plasma levels of total radioactivity were markedly reduced and its excretion into the bile was more delayed than when it was administered to fasted rats. One of the causes for these phenomena was thought to be a delayed absorption caused by the direct interaction between 450191-S and food in the intestinal lumen as well as the delayed gastric emptying rate. To confirm this interaction, we examined the effect of food on 450191-S uptake by the small intestine using rat everted jejunal sac in vitro. Subsequently, we found that the desglycylation of 450191-S was inhibited by rat food and that the uptake of 450191-S was reduced. In conclusion, 450191-S absorption is delayed by food, which results in the decreased total plasma level of 450191-S metabolites.

Administration, Oral↗
PubMed1986

Uptake of 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative, in the everted sac of rat small intestine: role of intestinal aminopeptidases.

5-[(2-Aminoacetamido)methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl ]-N,N-dimethyl-1 H-1,2,4-triazole-3-carboxamide hydrochloride dihydrate (450191-S), a sleep inducer, is a ring-opened derivative of 1,4-benzodiazepine and has been reported to be activated by intestinal aminopeptidases in a step of absorption. In this study, we investigated the role of the intestinal aminopeptidases in the uptake of 450191-S by the intestine by using various aminopeptidase inhibitors in everted sacs of rat small intestine in vitro. Glycylglycine did not affect the desglycylation of 450191-S but glycyl-L-leucine or L-leucyl-L-leucine inhibited the reaction. This inhibition was accompanied by reduced concentration of 450191-S metabolites in the intestinal tissue. When the incubation was carried out at 0 degrees C or with puromycin, the desglycylation was also inhibited and the concentration was similarly reduced. Since the extent of inhibition of the desglycylation of 450191-S was negatively correlated with the total concentration of 450191-S metabolites in the intestinal tissue (r = 0.9660), the aminopeptidases must play an important role in the uptake of 450191-S by the intestine. To confirm this, we examined the uptake of the desglycylated product of 450191-S, 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo- [1,5-alpha] [1,4]-benzodiazepine-2-carboxamide (M-1) in the same manner. No effect of dipeptides, puromycin or reduced temperature was found on M-1 uptake by the intestine, leading to the conclusion that the aminopeptidases are important for enhancing the uptake of 450191-S in the intestine.

Aminopeptidases↗
PubMed1986

Biopharmaceutical characterization of 450191-S, a ring-opened derivative of 1,4-benzodiazepine. I. Active metabolite levels in rat plasma.

5-[(2-Aminoacetamido)methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl ]-N,N-dimethyl-1 H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S), a sleep inducer, is a ring-opened derivative of 1,4-benzodiazepine and has been reported to be activated by intestinal aminopeptidases. In order to determine the biopharmaceutical significance of 450191-S as the ring-opened derivative of 1,4-benzodiazepine, we examined plasma levels of active metabolites in rats following oral administration of 450191-S or its primary active metabolite, 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-1). By increasing the dose of 450191-S, the plasma level of the active metabolites increased dose-dependently, which appeared to be due to saturation of hepatic elimination. The areas under the plasma concentration-time curves of active metabolites at a dose of 30 mg/kg of 450191-S were 2- to 20-fold higher than those at the same dose of M-1 administration per se. These results appeared to be attributable to the presence of a labile precursor of M-1, desglycylated 450191-S, which could avoid extensive first-pass extraction by the liver. In conclusion, the results suggested that 450191-S is superior to M-1, since the former maintained higher plasma levels of the active metabolites.

Animals↗
PubMed1986

Identification of novel N-glucuronides in rat bile after administration of 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative.

5-[2-Aminoacetamido)methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl] -N,N-dimethyl-1H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S) is a ring-opened derivative of 1,4-benzodiazepine, which is activated by desglycylation and subsequent cyclization. After 450191-S administration, rat bile contained three novel conjugates which released active metabolites possessing the 1,4-benzodiazepine structure through beta-glucuronidase hydrolysis. Since the released metabolites have no functional groups to conjugate with glucuronic acid, we speculated that the aglycone might be the ring-opened form of 1,4-benzodiazepine which spontaneously cyclizes after the release of glucuronic acid. This possibility was tested by chemically reducing the ketone group of the ring-opened 1,4-benzodiazepine glucuronate conjugates, which would prevent the spontaneous ring closure reaction after the release of the glucuronic acid moiety. The NaBH4 reduction of the ketone of the benzophenone moiety of the conjugates and subsequent treatment with beta-glucuronidase allowed identification of the reduced aglycones with authentic samples using gas chromatography-mass spectrometry.

Animals↗
PubMed1986

Autoinduction of 450191-S, a new sleep inducer of 1H-1,2,4-triazolyl benzophenone derivative, in dogs.

Alterations of plasma metabolite profiles were studied following single or multiple oral administrations of 5-[(2-aminoacetamido) methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl]-N, N-dimethyl-1H-1, 2,4-triazole-3-carboxamide hydrochloride dihydrate (450191-S) in Beagle dogs. In plasma, unchanged 450191-S was not detected, but active metabolite, 8-chloro-6-(2-chlorophenyl)-2-(N, N-dimethylcarbamoyl)-4H-1,2, 4-triazolo [1, 5-a] [1, 4] benzodiazepine (M-1) appeared first, followed by four active metabolites that were hydroxylated or demethylated in the N, N-dimethylcarbamoyl side chain of M-1. At single doses of 5 to 50 mg/kg, the areas under the plasma concentration-time curves (AUCs) of the metabolites were linearly increased, showing that there was no saturable process in the steps of absorption, distribution, metabolism and excretion. After multiple administrations (50 mg/kg/d for 15 d), the same metabolites appeared in the plasma but the patterns of the plasma metabolite profiles were considerably different from those after single administrations. The peak plasma levels of M-1 and its hydroxylated metabolites in the carbamoyl side chain were attained more rapidly in the multiple administrations, demonstrating higher peak values compared to those in the single administrations, and the eliminations of these metabolites from plasma were also rapid. However, no difference in the values of the AUCs were observed between single and multiple administrations. With the other active metabolites, the peak plasma levels after multiple administrations were considerably lowered by rapid elimination, resulting in a marked increase in AUCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cerebral venous thrombosis due to high-altitude polycythemia. Case report.

A case of cerebral venous thrombosis due to polycythemia secondary to adaptation to a high altitude is reported. A 27-year-old previously healthy man developed severe neurological symptoms after climbing 8511 m. Computerized tomography and cerebral angiography suggested hemorrhagic infarction or intratumoral hemorrhage, and a craniotomy was performed. Pathological examination confirmed the diagnosis of hemorrhagic infarction secondary to cortical venous thrombosis. The etiology and incidence of cerebral venous thrombosis secondary to polycythemia are discussed.

Adult↗
PubMed1986

Rapid and simple isolation procedure for three component enzymes of pig heart 2-oxoglutarate dehydrogenase complex.

A novel procedure was developed for rapid separation of the three component enzymes of pig heart 2-oxoglutarate dehydrogenase complex by high performance liquid chromatography on a gel filtration column. The complex was dissociated and separated into two fractions of the first dihydrolipoamide succinyltransferase and a second yellow fraction within 1 h by chromatography on a preparative TSK-GEL G4000SW column equilibrated with 0.05 M potassium phosphate buffer (pH 7.0) containing 0.7 M guanidine hydrochloride, 0.05% Triton X-100 and 2 mM dithiothreitol at 10 degrees C. The dihydrolipoamide succinyltransferase fraction was further purified by incubation with 0.5% sodium deoxycholate and subsequent ammonium sulfate fractionation. The other two component enzymes, 2-oxoglutarate dehydrogenase and lipoamide dehydrogenase were separated from the second yellow fraction by chromatography on a calcium phosphate gel-cellulose column. The TSK-GEL column permitted very rapid dissociation and separation of the three component enzymes accompanied by good preservation of their activities and high overall yields.

Acyltransferases↗
PubMed1986

Human chorionic gonadotropin in lung and lung tumors. Immunohistochemical study on unbalanced distribution of subunits.

To demonstrate unbalanced distribution of subunits of human chorionic gonadotropin (hCG) in the lung and lung tumors and to clarify its significance in differentiation and carcinogenesis of the lung, immunohistochemistry was performed on human fetus, infant, and adult lungs, and endocrine and nonendocrine tumors of the lung. Tissues were immunostained for alpha-subunits and for beta-subunits of glycoprotein hormones (hCG, luteinizing hormone, follicle stimulating hormone, and thyroid stimulating hormone), serotonin, and gastrin-releasing peptide. Immunoreactive alpha-subunit was first identified in endocrine-like cells at the 39th gestational week, and was found in all infant lungs and two-thirds of adult lungs. The hCG beta-immunoreactive cells were extremely rare in an adult lung, and were not found in fetus or infant lungs. The alpha-subunit-containing cells were present in neuroepithelial bodies, tumorlets, carcinoid tumors, and small cell carcinomas of the lung (SCCL). There were occasionally alpha-subunit-containing cells in non-SCCL but one of the carcinomas also contained many serotonin-positive and gastrin-releasing peptide-positive cells in the same region. All alpha-subunit-immunoreactive cells lacked immunoreactivity for beta-subunits of glycoprotein hormones, except some for hCG beta in one carcinoid tumor. Immunoreactive cells for isolated hCG beta appeared much more frequently in non-SCCL than in SCCL. Most non-SCCL containing hCG beta-positive cells did not show alpha-subunit-immunoreactivity. Thus, immunohistochemical distribution of hCG-subunits was unbalanced and hCG-subunits may be expressed through an independent mechanism, commonly in the lung and lung tumors. The significance of isolated alpha-subunit is further discussed in light of multidirectional differentiation of lung neoplasms (14, 17).

Adult↗
PubMed1986

Malignant fibrous histiocytoma arising in the liver.

A unique type of hepatic sarcoma in an adult was composed of pleomorphic fibrohistiocytic cells with benign cystic structures. The malignant mesenchymal component was morphologically similar to malignant fibrous histiocytoma of the soft tissue. The cystic epithelial structures appeared to be formed by the cystic transformation of the entrapped bile ducts and ductules. Malignant fibrous histiocytoma can arise in the liver, but the original architecture of the liver may affect or modify the histologic characteristics of the sarcoma.

Female↗
PubMed1986

[Clinical correlation and modification of the subrenal capsule assay].

A prospective study using 10 cases with miscellaneous tumors was performed. Discoid (columnar) tumors were measured three-dimensionally (volume method). Modified criteria for evaluability and for both absolute and relative quantitative sensitivities were employed. The evaluability was 9/10 (90%) and by the volume method true positives (more than PR) were 2/2, true negatives (less than PR) were 9/10 and overall predictive accuracy was 11/12 (92%), and accordance in relative sensitivity ranking (e.g. A drug is better than B drug) was seen in 4/4. However using the original method (mean diameter method) the corresponding figures were 0/0, 9/12, 9/12, (75%) and 2/4, respectively. The utility of this assay in the field of clinical chemotherapy therefore seems very promising.

Antineoplastic Agents↗