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M Komuro

Publications and source records attributed to M Komuro.

31 records · Page 2Linked to original sources

Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in human subjects.

The pharmacokinetics of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was studied in healthy male adult volunteers after single ascending oral dose and multiple dosing for 7 days. Serum KC-764 concentration attained the peak in 1 h and declined with a half-life of about 2 h at a single oral dose of 5, 10, 20 and 40 mg. No dose dependent pharmacokinetics of KC-764 was demonstrated. Three metabolites were detected in serum, but their concentrations were lower than that of KC-764. 48-h urinary recoveries after single doses were 41.6-46.6% of dose, not being dose-dependent. Urinary recovery of unchanged KC-764 was 1.1-1.6% of dose. Three metabolites were present in greater amount in urine than unchanged KC-764 and two metabolites were less than KC-764. There was little daily variation of serum concentrations and urinary excretion of KC-764 and its metabolites in the multiple dosing (20 mg twice a day) study. The daily and total urinary recovery were same as those after single doses. Food reduced Cmax and tended to delay tmax, but did not influence AUC0----infinity and urinary recovery. Serum protein binding of KC-764 was about 60%, being not dependent on total serum concentration.

Adult↗

[Successful report of total aortic root replacement by a new technique].

We employed a new procedure of the total aortic replacement in 2 cases which is made of composite graft and reimplantation of the coronary arteries by direct suture technique. These patients took good clinical course and were discharged after operation. We believe that this procedure is a very useful for annuloaortic ectasia or dissecting aortic aneurysm involved coronary artery with aortic regurgitation.

Aged↗

Transformation of Golgi membrane into the envelope of herpes simplex virus in rat anterior pituitary cells.

Envelopment of herpes simplex virus type-1 (HSV-1) was investigated in relation to membrane differentiation in dissociated anterior pituitary cells. The number of cells stained positively with anti-HSV-1 serum was increased from 16 h to 31 h post infection. During this period, electron microscopy revealed that a number of nucleocapsids (unenveloped particles) were accumulated in the Golgi area, where they frequently became surrounded by a double membrane of short Golgi cisternae or by one with a Golgi associated endoplasmic reticulum lysosome (GERL)-like structure. The inner membrane of the cisterna surrounding the nucleocapsids showed regional specialization which was characterized by increased thickness and electron opacity. Acid phosphatase activity, a marker for GERL or trans Golgi cisternae, appeared in the cytoplasmic short cisternae surrounding the nucleocapsids, whereas glucose-6-phosphatase activity, a marker for the nuclear envelope or for endoplasmic reticulum, was not demonstrated in such cisternae. Monoclonal antibody against glycoprotein gD revealed that gD was localized in the trans Golgi membrane as well as in the envelope of the virion. The antibody-binding sites were highly concentrated in the area where Golgi membranes showed increased opacity. Furthermore, nucleocapsids were surrounded exclusively by gD-positive cisternal (Golgi or Golgi-derived) membranes. Thus, our results indicate that the envelope of HSV is derived from trans Golgi cisterna (GERL), and that some viral components, including gD, destined for the envelope may be assembled initially in the Golgi membrane, which is thereby transformed into the envelope of the virus.

Acid Phosphatase↗

Presence of glycoconjugates in prolactin granules of male rats.

Prolactin granules in the anterior pituitary glands of male rats contain densely stained materials at the periphery of the matrix. These occur in both small spherical and large polymorphic types of granules. The presence of densely stained materials around secretory granules may be a useful criterion for identification of prolactin cells since the dense structure was observed in 95% of these cells after conventional staining by uranyl acetate and lead citrate. The localization of glycoconjugates in the prolactin granules was examined by applying concanavalin A (Con A) on the ultrathin sections. HRP-Con A or ferritin-conjugated Con A bound specifically to the densely stained materials in the peripheral region of the prolactin granule matrix, indicating that this densely stained matrix contains glycoconjugates; the significance thereof is discussed with reference to the concentration and packaging of secretory product.

Animals↗

Membrane modification during secretory granule formation in rat somatotrophs.

Somatotrophs from male rat anterior pituitary were used to investigate the formation of secretory granules. When enzymatically dispersed cells were incubated with cationized ferritin (CF) for 15 min, CF labeled immature secretory granules, but not mature granules of somatotrophs. Most immature granules labeled by CF transformed to the mature types within 120 min. This indicates that the fusion of endocytic vesicles with the immature granules occurs during the maturation process of secretory granules. The internalized CF was distributed not only in the immature secretory granules, but also in the peripheral region of trans Golgi cisternae or GERL. Enzyme cytochemistry revealed that acid phosphatase-positive cisternae (GERL) were the main site for secretory granule formation, and was devoid of thiamine pyrophosphatase (TPPase) activity. A small number of secretory granules were also present in the peripheral regions of TPPase-positive Golgi cisternae. The granule-forming sites, however, lacked TPPase activity, while the remaining region of the same cisterna showed the positive enzyme activity. This indicates that the granule-forming region at the periphery of Golgi cisterna is different from the remaining part of the same cisterna in terms of cytochemical properties. This probably results from the insertion of endocytic vesicle membrane, since the same granule-forming sites preferentially fused with CF-labeled small vesicles which lacked cytochemical TPPase activity. Taken together. Our results suggest that the membrane of secretory granules is modified during the granule formation, at least partly by the fusion of endocytic small vesicles with Golgi cisternae (or GERL), and with immature secretory granules.

Animals↗

Localization of sialic acid-containing hormones in GTH cells and ACTH cells of the rat anterior pituitary.

The localization of sialic acid-containing substances in the rat anterior pituitary gland has been studied by light and electron microscopy, using a peroxidase-labeled lectin (limulus polyphemus agglutinin: LPA) which binds specifically to sialic acid residues. LPA stains two types of anterior pituitary cells: (1) round or ovoid cells which are also positively stained with anti-hCG (GTH cell), and (2) small, stellate cells which are unstained with anti-hCG (ACTH cell). All of the LPA-positive cells can be distinguished from TSH cells which are identified by the use of anti-hTSHbeta. On ultrathin sections directly stained with LPA using the postembedding method, the reaction is confined to the secretory granules in GTH cells, and ACTH cells. Of two types of secretory granules in GTH cells, the larger one is intensely stained, whereas the smaller type shows only weak staining with LPA. Since follicle-stimulating hormone (FSH) is known to have high sialic acid contents, the results suggest possible detection of FSH with a technique other than immunohistochemistry. Furthermore, if the sialic acid-containing substances in GTH cells represents FSH, then these results support the hypothesis that LH cells and FSH cells are one cell type.

Adrenocorticotropic Hormone↗

Radioimmunoassay for dexamethasone 17,21-dipropionate and its metabolites in plasma and urine after topical application.

A sensitive radioimmunoassay for dexamethasone 17,21-dipropionate and its four metabolites in human plasma and urine has been developed using single anti-dexamethasone antiserum. The antiserum was obtained by immunizing rabbits with dexamethasone-3-oxime-bovine serum albumin conjugate. All of the endogenous steroids tested cross-reacted less than 0.07%. Before radioimmunoassay, dexamethasone 17,21-dipropionate and dexamethasone 17-propionate were hydrolyzed to dexamethasone, and 6 beta-OH-dexamethasone 17-propionate was hydrolyzed to 6 beta-OH-dexamethasone in 3% ammonia/methanol at 5 C for 16 h. A standard curve was established with a useful range between 0.005 and 2 ng in the case of dexamethasone, between 0.05 and 5 ng in the case of 6 beta-OH-dexamethasone. Measurement of plasma concentrations and percent urinary excretion of the metabolites in healthy men was performed following occlusive dressing of dexamethasone 17,21-dipropionate cream and ointment. The main metabolites in plasma were dexamethasone 17-propionate and dexamethasone, which increased gradually and reached maximum levels (160-200 pg/mL) at 24-32 h after application. The major metabolites observed in urine were 6 beta-OH-dexamethasone 17-propionate and 6 beta-OH-dexamethasone. Total percentage of their urinary excretions within 72 h after application amounted to 0.28-0.50% of the dose administered.

Administration, Topical↗

Gene and protein expression profiles of prostaglandin E2 receptor subtypes in the human corpus cavernosum.

Prostaglandin E1 leads to penile erection, mainly via prostaglandin E2 (EP) receptors. This study aimed to identify the expression profile of EP receptor genes in human corpus cavernosum. Using the quantitative real-time reverse transcription polymerase chain reaction, the mRNA levels of EP receptor subtypes were measured. In addition, expressions of EP receptor subtype proteins were determined by immunohistochemical method. Among the four subtypes, EP4 receptor mRNA expression was the highest, and EP2 receptor mRNA followed, whereas EP1 and EP3 receptor mRNAs were hardly observed. Expression level of EP4 receptor mRNA was significantly higher than that of EP2 receptor mRNA. Expression of both EP2 and EP4 receptor proteins were clearly detected in the cavernous smooth muscle. These results may suggest that EP4 receptor plays an important role among four EP receptor subtypes for relaxation of smooth muscle in the human corpus cavernosum.

Aged↗