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Biomedical subjects

Y Komatsu

Publications and source records attributed to Y Komatsu.

At least 73 records · Page 4Linked to original sources
PubMed2000

Two-terpyridine.Cu(II) complexes-containing antisense systems for rapid and highly site-specific RNA cleavage.

In an approach toward artificial ribonucleases, novel RNA cleaving systems were constructed that contained two terpyridine.Cu(II) residues. The first antisense system used tandem Cu(II) complex--2'-O-methyloligonucleotide 5'- and 3'-conjugates to cleave an RNA substrate. The second system, which will be described in a future paper, contained two contiguous Cu(II) complex residues at an internal site of a 2'-O-methyloligonucleotide. We found that the first system rapidly cleaved RNA with high site-specificity. Based on these results, we expect the second system to also show efficient RNA cleavage.

Base Sequence↗
PubMed2000

Functional domain-assembly in hairpin ribozymes.

Functional structures of hairpin ribozymes have been investigated by constructing various chemically modified molecules. Domain-exchange and linker insertion experiments were performed to find active conformations of the RNA enzyme showing cleavage activity. Our experiments and other evidence suggest that the active structure has a bent conformation, and that domain-interactions are essential for the cleavage activity.

Nepovirus↗
PubMed2000

Early detection of haemobilia associated with percutaneous ethanol injection for hepatocellular carcinoma.

OBJECTIVE: Haemobilia often results from iatrogenic injury caused by therapeutic procedures. The objective of this study was to evaluate the efficacy of early diagnosis of haemobilia based on ultrasonography in patients with hepatocellular carcinoma undergoing percutaneous ethanol injection. PATIENTS AND METHODS: A combination retrospective and prospective study on the early detection of haemobilia caused by percutaneous ethanol injection was conducted on 365 patients in 1995-1996. The retrospective study reviewed the clinical, laboratory and imaging data of 172 patients who had undergone ethanol injection therapy in 1995. The results showed that ultrasonographic changes in the gallbladder, namely the rapid appearance of echogenic material in the gallbladder lumen, are a useful early sign of haemobilia. Based on the results of the retrospective study, a prospective study on the early detection of haemobilia was carried out in 1996. In the prospective study, percutaneous ethanol injection was halted as soon as haemobilia was detected. RESULTS: The incidence of haemobilia in the prospective group (3.6%) was not different from that in the retrospective group (4.7%). However, the mean duration between percutaneous ethanol injection and diagnosis of haemobilia was only 0.3 +/- 0.2 days in the prospective group, compared with 2.8 +/- 2.1 days in the retrospective group (P < 0.001), and the mean duration of jaundice in the prospective group (4.3 days) was significantly shorter than in the retrospective group (40.0 days) (P< 0.05). CONCLUSION: Early diagnosis of haemobilia based on ultrasonographic findings of the gallbladder lumen effectively reduces the severity of haemobilia-related complications due to immediate interruption of the interventional procedure.

Administration, Cutaneous↗
PubMed2000

Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population.

BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are recognized as the major causes of peptic ulcer disease. The status of H. pylori infection in the background population may influence the incidence of H. pylori-negative peptic ulcer disease. OBJECTIVE: To examine the incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs in Japan. PATIENTS: A total of 398 patients who had no eradication therapy for H. pylori prior to this study, including 246 patients with gastric ulcer (GU) and 152 patients with duodenal ulcer (DU), were enrolled. METHODS: H. pylori status was assessed by rapid urease tests, histological examinations (haematoxylin & eosin stain, Giemsa stain and/or immunostaining) and serum IgG antibody. Two biopsy specimens were taken from the antrum within 3 cm of the pyloric and two from the middle corpus of the stomach, along the greater curvature. Patients were asked a series of questions regarding risk factors, including the use of NSAIDs. The presence of gastritis, gastric atrophy and intestinal metaplasia was examined according to the updated Sydney system. RESULTS: Of the 246 patients with GU, 12 patients (4.9%) were considered to be H. pylori-negative. Of the 152 patients with DU, two patients (1.3%) were considered to be H. pylori-negative. Hence, a total of 14 patients were found to be H. pylori-negative. Nine of them were taking NSAIDs. Consequently, the frequency of H. pylori-negative ulcer without intake of NSAIDs was 1.3%. There was no significant difference in the frequencies of H. pylori-negative patients between the GU and DU groups. CONCLUSION: The incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs was very low in the Japanese population.

Adult↗
PubMed2000

Impaired bone resorption by lipopolysaccharide in vivo in mice deficient in the prostaglandin E receptor EP4 subtype.

In a previous study we showed that the involvement of EP4 subtype of the prostaglandin E (PGE) receptor is crucial for lipopolysaccharide (LPS)-induced osteoclast formation in vitro. The present study was undertaken to test whether EP4 is actually associated with LPS-induced bone resorption in vivo. In wild-type (WT) mice, osteoclast formation in vertebrae and tibiae increased 5 days after systemic LPS injection, and urinary excretion of deoxypyridinoline, a sensitive marker for bone resorption, statistically increased 10 days after injection. In EP4 knockout (KO) mice, however, LPS injection caused no significant changes in these parameters throughout the experiment. LPS exposure for 4 h strongly induced osteoclast differentiation factor (ODF) mRNA expression in primary osteoblastic cells (POB) both from WT and EP4 KO mice, and this expression was not inhibited by indomethacin, suggesting prostaglandin (PG) independence. LPS exposure for 24 h further induced ODF expression in WT POB, but not in EP4 KO POB. Indomethacin partially inhibited ODF expression in WT POB, but not in EP4 KO POB. These data suggest that ODF is induced both PG dependently and PG independently. LPS exposure for 24 h induced slightly greater osteoclastgenesis inhibitory factor (OCIF) mRNA expression in EP4 KO than in WT POB. These findings suggest that the reduced ODF expression and apparently increased OCIF expression also are responsible for the markedly reduced LPS-induced osteoclast formation in EP4 KO mice. Our results show that the EP4 subtype of the PGE receptor is involved in LPS-induced bone resorption in vivo also. Since LPS is considered to be largely involved in bacterially induced bone loss, such as in periodontitis and osteomyelitis, our study is expected to help broaden our understanding of the pathophysiology of these conditions.

Animals↗
PubMed2000

Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways.

Brain natriuretic peptide (BNP), a hormone produced primarily by the cardiac ventricle, is thought to be involved in a variety of homeostatic processes through its cognate receptor, guanylyl cyclase A (GC-A). We previously created transgenic mice overexpressing BNP under the control of the liver-specific human serum amyloid P component promoter (BNP-transgenic mice) and demonstrated that they exhibit reduced blood pressure and cardiac weight accompanied by an elevation of plasma cGMP concentrations and marked skeletal overgrowth through the activation of endochondral ossification. To address whether BNP exerts its biological effects solely through GC-A, we produced BNP-transgenic mice lacking GC-A (BNP-Tg/GC-A-/- mice) and examined their cardiovascular and skeletal phenotypes. The GC-A-/- mice are hypertensive with cardiac hypertrophyrelative to wild-type littermates, which is not alleviated by overexpression of BNP in BNP-Tg/GC-A-/- mice. The BNP-Tg/GC-A-/- mice, however, continue to exhibit marked longitudinal growth of vertebrae and long bones comparably to BNP-Tg mice. This study provides genetic evidence that BNP reduces blood pressure and cardiac weight through GC-A, whereas it dramatically alters endochondral ossification in the absence of this receptor. Therefore, the BNP-Tg/GC-A-/- mice provide the first experimental model demonstrating that this natriuretic peptide can signal in a tissue-specific manner through a receptor other than GC-A.

Animals↗
PubMed2000

Ghrelin strongly stimulates growth hormone release in humans.

Ghrelin is a recently identified endogenous ligand for the GH secretagogue receptor and is involved in a novel system for regulating GH release. However, little is known about its GH-releasing activity and other endocrine effects in humans. To address this issue, we studied the GH, ACTH, cortisol, PRL, LH, FSH, and TSH responses to synthetic human ghrelin. In four normal male adults (28-37 yr), iv ghrelin administration released GH in a dose-dependent manner and 0.2, 1.0, and 5.0 microg/kg ghrelin produced 43.3 +/- 6.0, 81.5 +/- 12.7, and 107.0 +/- 10.7 ng/mL of the GH peak values at 30 min, respectively. ACTH, cortisol, and PRL levels were also elevated after ghrelin injection, while the lowest dose (0.2 microg/kg) resulted in only minimum peak values of these hormones (22.8 +/- 3.0 pg/mL, 9.4 +/- 1.9 microg/dL, and 4.6 +/- 0.6 ng/mL, respectively). There were no significant changes in LH, FSH, or TSH levels. This is the first study showing evidence that ghrelin strongly stimulates GH release in humans.

Adrenocorticotropic Hormone↗
PubMed2000

Most clot-bound thrombin activity is inhibited by plasma antithrombin during clot aging, but a very small fraction survives.

Inhibitory effects of thrombin inhibitors against clot-bound thrombin have been evaluated using clots prepared from human plasma as the source of clot-immobilized active enzyme, and the clot-bound thrombin has been reported to be protected from its inhibition by antithrombin. However, we found that the clot-bound thrombin was not intrinsically protected from inhibition by antithrombin, i.e., a large fraction of initially active clot-bound thrombin was inhibited by antithrombin present in human plasma time dependently, and only very small fractions (0.04--0.08%) of the thrombin retained their enzymatic activity after clot-aging. These results suggest that the extent of clot-aging determines the sensitivity of clot-bound thrombin to antithrombin, and that inhibitory effects of drugs against clot-bound thrombin in vitro must be interpreted with caution to estimate their effects in vivo.

Antithrombins↗
PubMed2000

Effects of 9 Kampo medicines clinically used in hypertension on hemodynamic changes induced by theophylline in rats.

We examined the effects of 9 kinds of Kampo medicines, which are clinically used for the treatment of hypertension, on anesthetized rats with increases in arterial blood pressure, heart rate and peripheral blood flow induced by theophylline (5 mg/kg, i.v.) that were partially or completely mediated by endogenous catecholamines. Each Kampo medicine (1 g/kg) was intraduodenaly administered. Shinbu-to caused a severe disturbance of the arterial blood pressure. Saiko-ka-ryukotsu-borei-to, Oren-gedoku-to, San'o-shashin-to and Dai-jyoki-to had hypotensive effects, while Hachimi-jio-gan, Gosha-jinki-gan, Dai-saiko-to and Choto-san did not have such an effect. Moreover, Saiko-ka-ryukotsu-borei-to attenuated the heart rate. In Oren-gedoku-to, San'o-shashin-to and Dai-jyoki-to, a reduction in peripheral blood flow was observed. These results suggest that Saiko-ka-ryukotsuborei-to, Oren-gedoku-to, San'o-shashin-to and Dai-jyoki-to are ameliorative to the hypertension in sympathetic system dominance and Shinbu-to is occasionally dangerous to it.

Animals↗
PubMed2000

Anti-type I allergic mechanisms of mao-bushi-saishin-to in mice.

We investigated the anti-allergic effect of mao-bushi-saishin-to (MBS) on the type I allergy model in mice. When MBS was administered orally at a dose of 0.5 or 1.0 g/kg, edema of the footpad, the amount of plasma IgE and the ratio of eosinophilic leukocytes in peritoneal exudate cells were all dose-relatedly suppressed. Moreover to investigate the anti-type I allergic mechanisms of MBS, enzyme-linked immunosorbent assay was performed to determine the interleukin (IL)-4, IL-5 and interferon (IFN)-gamma production from splenocytes that were stimulated by pokeweed mitogen for 48 h. In addition, we assayed IgE production from splenic B cells stimulated with the lipopolysaccharide and IL-4 for 7 days. MBS inhibited the IL-4 and IFN-gamma production, but IL-5 and IgE production were not affected. Thus possibly, the inhibition of IL-4 production may partially be involved in the expression of the anti-type I allergic effects of MBS.

Animals↗
PubMed2000

Effect of Choto-san, a Kampo medicine, on the cerebral blood flow autoregulation in spontaneously hypertensive rats.

To clarify the mechanism of the benefical effect of Choto-san on cerebral circulation in hypertensive patients, the influence of Choto-san on cerebral blood flow (CBF) during hemorrhagic hypotension was evaluated in 10- to 11-month-old spontaneously hypertensive rats. The lower limit of CBF autoregulation, defined as the mean arterial blood pressure at which CBF decreased by 10% of the baseline value, was dose-dependently lowered when Choto-san (0.5 - 2.0 g/kg per day, p.o.) was administered for 14 consecutive days. Uncariae Ramulus et Uncus (150 mg/kg per day, p.o.), one of the crude drug components of Choto-san, showed an effect equivalent to that of Choto-san. The action of Choto-san (2.0 g/kg per day, p.o.) or Uncariae Ramulus et Uncus on the autoregulatory response of cerebral vessels was eliminated by treatment with N(G)-nitro-L-arginine methyl ester (10 mg/kg, i.v.), an inhibitor of nitric oxide synthase. These results suggested that the activation of nitric oxide synthase by Uncariae Ramulus et Uncus contributed to at least part of the improvement in the cerebral circulation caused by Choto-san.

Animals↗
PubMed2000

[Protective effect of oral administration of several traditional Kampo-medicines on lethal Candida infection in immunosuppressed mice].

The protective effects of a "hozai" type of Kampo medicine, Juzen-taiho-to (Shi-quan-da-bu-tang, TJ-48), Hochu-ekki-to (Bu-zhong-yi-qi-tang, TJ-41) or Ninjin-yoei-to (Ren-shen-yang-rong-tang, TJ-108) on experimental candidiasis in immunosuppressed mice were investigated. ICR mice, which were immunosuppressed by injection of cyclophosphamide or prednisolone, were given these medicines orally andchallenged intravenously with Candida albicans (day 0). Treatments with a daily dose of 1 g/kg/day of TJ-48 or that of 1 or 2 g/kg/day of TJ-108 for 4 consecutive days from day-4 significantly prolonged the survival time of the Candida-infected mice pretreated with cyclophosphamide. Treatments with a daily dose of 1 g/kg/day of TJ-48 for 4 consecutive days from day 0, but not from day -4, significantly prolonged the life span of the Candida-infected mice pretreated with prednisolone. On the basis of these results and previous findings, characteristics of these kampo medicines as therapeutic agents against candidiasis in immunosuppressed hosts were discussed.

Animals↗
PubMed2000

Antioxidative effects of Choi-oki-to and its ability to inhibit the progression of atheroma in KHC rabbits.

Agents which inhibit the oxidative modification of low density lipoprotein (LDL) have been thought to be helpful in preventing the formation of atherosclerotic lesions; the so called "oxidation hypothesis". To test this hypothesis, we examined the antioxidative activities of 127 Kampo medicines in vitro and their inhibitory effects on the development of atheromatous plaque formation in KHC rabbits, a model of spontaneous familial hypercholesterolemia. Some of the 127 Kampo medicines showed scavenging or antioxidative effects equal to or stronger than those of probucol in vitro. Choi joki to, which had the strongest antioxidative effects on LDL in vitro, was chosen for a study in vivo. After 24 weeks, 1 g/kg of Choi joki to successfully inhibited the progression of atherosclerotic lesions in KHC rabbits (P < 0.01). Further investigations regarding the antioxidative effects of Kampo medicines are expected.

Animals↗
PubMed2000

[Recent endoscopic treatment in gastroenterology].

Endoscopic diagnosis and treatment became to be necessary in gastroenterology for last two decades. Indication of endoscopic treatment is amazingly expanding because of developing new techniques and easy-to-use devices. Nowadays, the indication for endoscopic treatment includes the removal of foreign bodies in alimentary tract, the dilatation of stricture lesions by balloon or expandable metallic stent, the resection of polypoid and superficial tumors by polypectomy and EMR (endoscopic mucosal resection) techniques, the injection sclerotherapy and ligation method for gastroesophageal varices, the hemostasis of gastrointestinal hemorrhages by injection method or heat-burn method. In biliary and pancreatic area, there are some endoscopic treatments that are removal and destruction of stones in common bile duct, biliary and pancreatic drainage by tubing method. Our results of endoscopic resection for esophageal and gastric tumors are shown in this papers. In conclusion, complete resection that means histologically tumor negative of lateral and vertical margin of resected specimen is important to prevent recurrence of tumors after resection.

Digestive System Diseases↗
PubMed2000

Can three-dimensional helical CT cholangiography before laparoscopic cholecystectomy be a substitute study for endoscopic retrograde cholangiography?

The study investigated the usefulness of three-dimensional helical computed tomography (3D-CT) before laparoscopic cholecystectomy (LSC) when compared with that of endoscopic retrograde cholangiography (ERC). Forty-five patients referred for LSC, who had undergone 3D-CT cholangiography and ERC simultaneously, participated in the study. Endoscopic retrograde cholangiography and 3D-CT cholangiography were compared in each patient with regard to opacification of the biliary tree, stones, and anatomic variations. Three-dimensional helical CT cholangiography and ERC imaging for predicting operative difficulties in LSC also were compared. The common bile duct and cystic duct were shown in the patients by the images, but the gallbladder was shown in 43 patients (96%) with use of 3D-CT cholangiography and in 36 patients (80%) with use of ERC. A third or more peripheral branches were shown completely with use of 3D-CT cholangiography in 33 patients (73%) and in 32 patients (71%) with use of ERC. Cystic duct stones were found in two of three patients with use of 3D-CT cholangiography and ERC. Common bile duct stones in five of seven patients were detected with use of 3D-CT cholangiography, but all of the common bile duct stones were detected with use of ERC. Anatomic variations of the bile duct were shown in three of four patients by 3D-CT cholangiography and in all patients with use of ERC. No significant differences in findings of the angle of bifurcation and presence of Heister valves between operative easy and complex cases were shown by 3D-CT cholangiography and ERC, despite the more accurate assessment of the cystic duct anatomy with use of 3D-CT cholangiography than with use of ERC. Three-dimensional helical CT cholangiography is useful clinically in preoperative assessment of biliary anatomy, but it is not reliable in the detection of common bile duct stones, and it is not helpful in predicting technical difficulty during LSC.

Adult↗
PubMed2000

[A case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis associated with systemic sclerosis treated by steroid pulse therapy: a case report].

A 57-year-old woman had been diagnosed as systemic sclerosis (SSc) with Raynaud's phenomenon, acrosclerosis and polyarthritis since 1995. She admitted to our hospital in July 1996 because of general fatigue, hemosputa and progressive renal insufficiency. On admission, the blood pressure was normal and laboratory findings showed elevation of the serum creatinin level and a high titer of the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) (> 1000 EU). The renal biopsy revealed crescentic glomerulonephritis. Both renal insufficiency and high titers of MPO-ANCA improved remarkably after methylpredonisolone pulse therapy. This case was suggestive of elucidating the pathogenesis of SSc and MPO-ANCA related glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗