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K Terashima

Publications and source records attributed to K Terashima.

At least 55 records · Page 3Linked to original sources
PubMed1996

Purification and partial characterization of an indomethacin hydrolyzing enzyme from pig liver.

PURPOSE: Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. METHODS: An indomethacin hydrolyzing enzyme was purified to homogeneity from pig liver microsomes using columns of Q-Sepharose, Red-Sepharose and Blue-Sepharose. The enzyme activity was assayed by measuring of rho-chlorobenzoic acid liberated from indomethacin by HPLC. RESULTS: The purified enzyme effectively hydrolyzed the amide linkage in indomethacin but not those in alpha-naphthylacetate and rho-nitrophenylacetate, which are typical substates for carboxylesterase. The subunit molecular mass of the enzyme was 65 kDa according SDS-polyacrylamide gel electrophoresis. The Michaelis constant (K(m)) and maximum velocity (Vmax) values for indomethacin were 67.8 microM and 9.02 nmol/min/mg protein, respectively. The amino acid sequence analysis of the enzyme after cyanogen bromide cleavage showed high homology with a mouse carboxylesterase isozyme designated as ES-male. The activity of indomethacin hydrolysis was relatively high in the pig, rabbit and human liver homogenate, but not in those from rat and mouse. On the other hand, purified human liver carboxylesterases pl 5.3 and 4.5, and pig liver carboxylesterases have no catalytic activity for indomethacin. CONCLUSIONS: These results indicate that the hydrolysis of amide-linkage of indomethacin in humans would be associated with an enzyme similar to the indomethacin hydrolyzing enzyme from pig liver microsomes described here.

Animals↗
PubMed1996

[Study of twenty-three cases of pediatric testicular tumors].

Twenty-three cases of testicular tumor (10; malignant, 13; benign) in childhood are reported. The age at diagnosis was between 3 months old and 8 years old. Twelve patients visited the clinic within a month of first appearance of symptoms. All but one patient received high orchiectomy. One patient had resection of tumor because of its benign property. Eight of the 10 patients with malignancies received 30-50Gy of retroperitoneal radiation, including one patient (stage IIa) with retroperitoneal lymph node dissection. Two patients (stage I and IIa) with post-operative metastasis in lungs, brain and mediastinal lymph nodes were treated with chemotherapy repeatedly, but they died. Our latest therapy is; 1) high orchiectomy recommended for benign and stage I malignant testicular tumors in childhood, 2) retroperitoneal radiation and/or lymph node dissection limited for patients with stage II malignancy, and 3) Systemic chemotherapy for stage III malignant tumors. At least three years of follow up would be needed. Those who received radiation or chemotherapy should be followed longer.

Age of Onset↗
PubMed1996

[A case of aphallia].

We report a case of aphallia in a male neonate. The phallus was completely absent. The urethral meatus was located between the well developed bifid scrotum containing normal testes. Voiding cystourethrography revealed grade II VUR on the right side. The karyotype was 46XY. Other urogenital anomalies were not detected. Bilateral orchiectomy was performed at 2 months of age. The sex assignment and management of aphallia were discussed.

Humans↗
PubMed1995

Studies on antiulcer agents. II. Antiulcer properties of N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides inhibiting release of histamine from passively sensitized rat peritoneal mast cells.

With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.

Animals↗
PubMed1995

Studies on antiulcer agents. I. Synthesis and pharmacological properties of ethyl 2-[(1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate, a new H+/K(+)-ATPase inhibitor possessing mucosal protective activity.

Ethyl 2-[1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate (2) has been synthesized and evaluated for antiulcer properties. Compound 2 is a H+/K(+)-ATPase inhibitor that affords mucosal protection against absolute ethanol-induced gastric lesions in rats after oral and parenteral administrations. On the other hand, omeprazole, a representative H+/K(+)-ATPase inhibitor, showed mucosal protective action only after oral administration, indicating that it required gastric acid secretion to generate activity. The antiulcer activity of 2 in animal models, such as water-immersion stress-induced gastric ulcer in rats and acidified aspirin-induced gastric ulcer in rats, was three times higher than that of cimetidine.

Animals↗
PubMed1995

Studies on antiulcer agents. III. Plausible mechanism of antisecretory action of ethyl 2[(1H-benzimadazol-2-yl)sulfinylmethyl]-4-dimethylamino- 5-pyrimidinecarboxylate, an H+/K(+)-ATPase inhibitor, based on its reaction with thiols.

To explore the mechanism of the gastric antisecretion activity of ethyl 2-[(1H-benzimidazol-2-yl)sulfinylmethyl]- 4-dimethylamino-5-pyrimidinecarboxylate (5), a potential H+/K(+)-ATPase inhibitor, in the acid compartment of parietal cells, its reaction with some alkylthiols in the presence of hydrochloric acid was investigated. Upon treatment with 2-mercaptoethanol under acidic conditions, 5 gave a characteristic 1:2 adduct, ethyl 4-[2-(2-hydroxyethyldithio)- 1-(2-hydroxyethylthio)ethylidenamino]pyrimido[1,2-a]benzimid azole-3- carboxylate (6), instead of providing a disulfide of type 3, 2-(2-alkyldithiomethylpyridino)benzimidazolide, the product predicted to be formed according to the reaction mechanism of common H+/K(+)-ATPase inhibitors, such as omeprazole or lansoprazole, with mercaptans. With a large excess of 2-mercaptoethanol, 5 provided 2-(2-hydroxyethylthio)-1H-benzimidazole (8) and ethyl 4-dimethylamino-2-(2-hydroxyethyldithio)-5-pyrimidinecarboxylat e (9) as well as 6. The transformation mechanisms and their implications are discussed.

Anti-Ulcer Agents↗
PubMed1995

Studies on antiulcer agents. IV. Antiulcer effects of 2-benzylthio5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds.

With a view to finding more effective antiulcer agents, a series of 2-benzylthio-5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds were synthesized and evaluated in a histamine-stimulated gastric secretion model. The sodium salt of the 2-(dimethylamino)benzylthio derivative (8) showed gastric mucosal protection and gastric antisecretion activities, and was also effective against experimental gastric and duodenal ulcers induced by some ulcerogenic agents. Based on a comparison of the antiulcer properties of 8 with those of the lead compounds (1 and 2) and cimetidine, it appears that, for improvement of antiulcer activity, the reduction of gastric acidity is a more important factor than the reduction of gastric volume output or gastric total acid output.

Animals↗
PubMed1995

[Four cases of true hermaphroditism].

We report four cases of true hermaphroditism. The first patient (legal sex female, karyotype of 46, XX/46, XY, bilateral ovotestis) was changed to a male at 2 years old. The second patient (karyotype of 46,XX/47, XXY/48, XXYY, hypospadia, and right undescended testis) was referred to us at 6 months old, and turned out to have a uterus, an ovary on the left side and a testis on the right side. The third patient (6 months old, karyotype of 46, XX/46, XY, hypospadia) had an ovotestis on the right side and a testis on the left side. The fourth patient (1 year and 6 months old, a karyotype of 46,XX, hypospadia) had bilateral ovotestis. All four patients showed a variety of responses of testosterone to human chorionic gonadotropin stimulation. They were grown as males. It is difficult to treat a case of true hermaphroditism including determination of sex. We should consider the results of chromosomal analysis, hormone values, imaging studies and histology of gonads, and determine appropriate sex.

Child, Preschool↗
PubMed1994

Testicular juvenile granulosa cell tumor in an infant with X/XY mosaicism clinically diagnosed as true hermaphroditism.

We report a testicular juvenile granulosa cell tumor (T-JGCT) with characteristic clinical and histopathological features. The tumor was present in the left abdominal testis of a 7-month-old infant with a 45,X/46,XY karyotype and ambiguous genitalia. Preoperatively, the infant was diagnosed as having functional testicular and ovarian elements based on elevated levels of serum testosterone and estradiol following human chorionic gonadotropin and human menopausal gonadotropin administration, respectively. Histologically, the left gonad contained a tumorous lesion composed of an admixture of cellular areas and multiple cystic follicles that had some continuity with the adjacent testicular tubules. Some tumor cells showed immunoreactivity for estradiol. The right gonad was a streak gonad containing small irregular nests of sex cord-type cells. No maturing ovarian follicle was present in either gonad. To our knowledge, this is the fifth reported case of T-JGCT with abnormal sex chromosomes, and the first case of T-JGCT confirmed to have not only the morphological but also the functional characteristics of granulosa cells.

Disorders of Sex Development↗
PubMed1994

[Urological problems in Prader-Willi syndrome].

Prader-Willi syndrome is rather a rare disease. However, as it includes 4 features (hypogonadism, hypomentia, hypotonia, and obesity), urologist may see the patients with this syndrome for their gonadal problem. We studied all the 27 cases in our hospital of which data were precisely collected. Among males, 67% of patients had presented themselves first to the department of pediatric internal medicine. One third of the patients were not diagnosed as the syndrome and referred to our clinic because of urological abnormalities. Chromosomal abnormality was seen in 40.9%. We found cryptorchism in all the cases and micropenis in 56%. In females, delayed menarche over 15-year-old was seen in 75%. From endocrinological studies, 75% male showed low reaction against HCG stimulation. Low gonadotropin responses to LH-RH were seen in 80% of all patients. We performed orohiopexy for cryptorchism, but testicular development was poor. And we do not actively utilize hormonal therapies for these patients.

Adolescent↗
PubMed1994

Anti-ulcer effect of 1,6-dihydro-2-[2-(2-methylpropoxy) anilino]-6-oxo-5-pyrimidinecarboxylic acid on experimental gastric ulcers in rats.

The effects of 1,6-dihydro-2-[2-(2-methylpropoxy) anilino]-6-oxo-5-pyrimidinecarboxylic acid (MAR-99, CAS 98772-05-5) on various experimental gastric ulcers were studied in rats. MAR-99 (3-100 mg/kg, p.o. or i.d.) showed the anti-ulcer effect in Shay-, stress, acetylsalicylic acid (ASA)- and compound 48/80-ulcer models and significantly accelerated healing of acetic acid-induced gastric ulcer in rats. In addition, MAR-99 (1-10 mg/kg p.o.) decreased dose-dependently the gastric mucosal damage induced by necrotizing agents such as 99.5% ethanol, 0.6N HCl and 0.2 N NaOH. These results indicate that MAR-99 may be useful for the treatment of gastric ulcer in human.

Acetates↗
PubMed1994

Effect of 1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarboxylic acid on gastric mucosal defensive factors and gastric secretion in rats.

1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarbo xylic acid, (MAR-99, CAS 98772-05-5) (10-30 mg/kg i.g.) improved the reduction of gastric blood flow rate induced by the administration of 99.5% ethanol or acidified-acetylsalicylic acid (ASA). In addition, MAR-99 (3 x 10(-6)-3 x 10(-5) mol/l) protected dose-dependently the damage of epithelial cells induced by ulcerogenic agents such as ethanol or acidified-ASA. MAR-99 (1-10 mg/kg p.o.) prevented dose-dependently the reduction of hexosamine content in glandular stomach. Furthermore, MAR-99 (10-30 mg/kg i.g.) improved the decrease in gastric potential difference induced by 99.5% ethanol and acidified-ASA. MAR-99 (10-30 mg/kg p.o.) significantly inhibited the lesion formation induced by 99.5% ethanol and such effect of this compound was not attenuated by the pretreatment with indomethacin. Furthermore MAR-99 (10 and 30 mg/kg p.o.) had no effect on the prostaglandins (PGE2 and I2) contents in the stomach of normal rats. In pylorus-ligated rats, MAR-99 (3-100 mg/kg i.d.) showed a weak or no effect on acidity and pepsin activity in gastric juice, although this compound decreased dose-dependently the volume of gastric juice. In perfused stomachs, MAR-99 (30-100 mg/kg i.d.) slightly prevented the acid secretion induced by carbachol and pentagastrin. However, MAR-99 did not affect the acid secretion stimulated by histamine. These results indicated that anti-ulcer effect of MAR-99 was mainly due to maintenance of the gastric mucosal resistance.

Animals↗
PubMed1994

A case of infant with bilateral multicystic kidney and ureteropelvic junction obstruction; surgical treatment after percutaneous nephrostomy.

We report a case of bilateral multicystic kidney and left ureteropelvic junction (UPJ) obstruction in a female infant. She was diagnosed to have severe cystic disease from 20 weeks of gestation. After birth with cesarean section, she was transferred to the neonatal intensive care unit (NICU) of our hospital. One day after birth, she was referred to our department for progression of azotemia. We placed a nephrostomy catheter into the largest renal cyst, but it did not work. One week later, we placed another nephrostomy catheter into another cystic lesion inside of the first one. It worked well for nine months and azotemia was improved. At the age of nine months her upper urinary tract was reconstructed by pyeloplasty. We observed peristalsis of ureter and first urination from bladder.

Female↗
PubMed1992

Histopathological study of balloon embolization: silicone versus latex.

Bilateral, symmetrical, experimental aneurysms were produced with anastomosed vein flap in the carotid arteries of 24 mongrel dogs. Aneurysms were occluded with latex or silicone balloons on each side and observed angiographically from 2 weeks to 2 months. A histopathological study was performed subsequently using light and scanning electron microscopy. Rupture after balloon embolization occurred in five aneurysms; all of which were incompletely occluded by a silicone balloon. On subsequent angiograms, four silicone balloons and one latex balloon were found to have migrated into the aneurysm, resulting in aneurysmal expansion. Parent artery occlusion was more common with latex balloons than silicone balloons. Histopathologically, residual fresh thrombi, decreased proliferation of fibroblasts within the aneurysmal cavity, and poor endothelialization were present around the silicone balloon. These results suggest that the intra-aneurysmal organization, as seen in the aneurysm occluded by the silicone balloon, will be delayed because the balloon is not fixed within the aneurysm, and that this free-floating and rotating balloon causes repeated trauma to the aneurysm wall, contributing to subsequent enlargement and rupture of the aneurysm. The superior antithrombogenic nature of silicone may be responsible for the bias of such phenomena toward the silicone balloon.

Aneurysm↗
PubMed1992

Follicular dendritic cell and ICCOSOMES in germinal center reactions.

The development and destination of immune complex coated bodies (ICCOSOMES) was investigated at the ultrastructural level in the germinal centers (GC) of murine lymph nodes after secondary-immunization with horseradish peroxidase. Immediately after a booster injection, large amounts of immune complex (IC) were trapped on the surface of the cytoplasmic extensions of follicular dendritic cells (FDC). Cytoplasmic extensions, consisting mainly of FDC processes with associated IC, formed complex lamellar labyrinth-like structures (LBS). We describe here morphological changes of LBS. Lamellar or stationary LBS before the injection sequentially changed into distorted, filiform, glomerated and transitional LBS. Around day 1, IC-coated cytoplasmic extensions developed into glomerated LBS (G-LBS) which were invaginated into their own cytoplasmic ends, which swelled up to several microns in diameter. Around day 2, tufts of the glomerated LBS were unlaced and dispersed as (ICCOSOMES) in the interstitium. Some ICCOSOMES were endocytosed by germinal center cells (GCCs) and transported to the Golgi apparatus and perinuclear space. These ICCOSOME-bearing GCCs were B220-positive and some produced specific antibody (spAb) in the perinuclear space indicating they are in the B cell lineage. ICCOSOME-ingesting GCCs are thought to be able to process the antigen and present it to T cells. This may be important in the development of plasma cells and memory cells which developed from the GC B cells.

Animals↗