Biomedical subjects

Y Komatsu

Publications and source records attributed to Y Komatsu.

At least 91 records · Page 5Linked to original sources

PubMed1999

Effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the survival of mice infected with influenza virus.

The antiviral effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, was investigated using mice infected with influenza virus. TJ-41 was found to increase the survival rate, prolong the mean survival days, suppress viral growth in bronchoalveolar labage fluid (BALF) and inhibit the lung index (lung consolidation) on day 4 after infection in mice infected with influenza, after the agent had been administered orally once daily from day 7 to 2 before infection and from day 0 to 4 after infection. Administration of TJ-41 decreased the BALF concentrations of IL-1alpha, IL-6 and GM-CSF, but not TNF-alpha or interferon-gamma (IFN-gamma), on day 4 after infection. In addition, TJ-41 elevated the level of IFN-alpha in BALF on day 2 after infection. Yet, TJ-41 did not show any inhibitory effect on the growth of influenza virus in vitro. These results suggest that TJ-41 exerts its inhibitory effect on influenza virus infection via enhancement of the host immune responses in this experimental murine system.

Administration, Oral↗

PubMed1999

Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice.

EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity and molecular size, i.e. NP-1-NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.

Animals↗

PubMed1999

Investigation of the recognition of an important uridine in an internal loop of a hairpin ribozyme prepared using post-synthetically modified oligonucleotides.

We introduced 4-thio- ((4S)U), 2-thio- ((2S)U), 4- O -methyluridine ((4Me)U) and cytidine substitutions for U+2, which is an important base for cleavage in a substrate RNA. Oligonucleotides containing 4-thio- and 4- O -methyluridine were prepared by a new convenient post-synthetic modification method using a 4- O - p -nitrophenyl-uridine derivative. A hairpin ribozyme cleaved the substrate RNA with either C+2, (4S)U+2 or (4Me)U+2 at approximately 14-, 6- and 4-fold lower rates, respectively, than that of the natural substrate. In contrast, the substrate with a (2S)U+2 was cleaved with the same activity as the natural substrate. These results suggest that the O4 of U+2 is involved in hydrogen bonding at loop A, but the O2 of U+2 is not recognized by the active residues. Circular dichroism data of the ribozymes containing (4S)U+2 and (2S)U+2, as well as the susceptibility of the thiocarbonyl group to hydrogen peroxide, suggest that a conformational change of U+2 occurs during the domain docking in the cleavage reaction. We propose here the conformational change of U+2 from the ground state to the active molecule during the reaction.

Circular Dichroism↗

PubMed1999

Conformational multiplicity of the antibody combining site of a monoclonal antibody specific for a (6-4) photoproduct.

The antigen binding site of monoclonal antibody 64M5, which possesses a high degree of affinity for DNA containing pyrimidine (6-4) pyrimidone photoproducts, were investigated by use of stable-isotope-assisted NMR spectroscopy. A variety of 64M5 Fab fragments specifically labeled with 13C and 15N at backbone amide groups were prepared. Extensive assignments of amide resonances originating from the variable region of 64M5 were made by using 2D-HN(CO) measurements along with recombination of the heavy and light chains of 64M5. On the basis of chemical shift changes of the amide resonances caused upon addition of d(T[6-4]T) and d(GTAT[6-4]TATG), the binding sites of 64M5 Fab for the (6-4) photodimer and for the oligodeoxynucleotides flanking it were identified. It was revealed that the L1 and L3 segments, which are responsible for the binding to (6-4) photodimer, exhibit conformational multiplicities in the absence of antigens, and take different conformations between the d(T[6-4]T) and d(GTAT[6-4]TATG)-bound forms. On the basis of spectral comparison with another Fab fragment with a similarity in the amino acid sequence of the VL domain of 64M5, we suggest that the conformational multiplicities observed in the present study is caused by a substitution of an amino acid residue at the position of a key residue in L3 canonical structure, which leads to a preferable effect on the antigen binding, and by a specific combination of L1 and L3 canonical structures.

Amino Acid Sequence↗

PubMed1999

In vitro sonographic evaluation of common bile duct stones and fragments with a high-frequency microprobe.

PURPOSE: This study was conducted to evaluate the sonographic characteristics of common bile duct (CBD) stones and stone fragments scanned in vitro with a high-frequency (20-MHz) microprobe. METHODS: We sonographically examined 4 whole CBD stones (1 cholesterol stone with radiant cross section, 1 cholesterol stone with lamellar cross section, 1 black pigment stone, and 1 brown pigment stone), 44 fragments of a cholesterol stone (diameter range, 1.1-3.0 mm; mean diameter, 2.0 mm), and 75 fragments of a black pigment stone (diameter range, 1.1-3.0 mm; mean diameter, 2.0 mm). The chemical composition of all stones was analyzed by infrared absorption spectroscopy. All stones and fragments were placed in a plastic box filled with physiologic saline solution for scanning with a 20-MHz microprobe and a 5-MHz probe. Echogenic foci and acoustic shadows revealed at each frequency were compared. RESULTS: At 5 MHz, the 4 CBD stones showed different sonographic characteristics. The cholesterol stone with radiant cross section showed an echogenic focus but no definite acoustic shadow, whereas the cholesterol stone with lamellar cross section showed an echogenic line, several echogenic spots, and a definite acoustic shadow. The black pigment stone showed an echogenic line with a vague acoustic shadow, and the brown pigment stone showed echogenicity of the whole stone and a definite acoustic shadow. At 20 MHz, the 4 stones showed an echogenic line with a definite acoustic shadow. All fragments appeared as echogenic foci at 20 and 5 MHz. Seventy-seven percent (34) and 5% (2) of 44 cholesterol stone fragments cast a definite acoustic shadow at 20 and 5 MHz, respectively. Sixty-nine percent (52) and 15% (11) of 75 black pigment stone fragments cast a definite acoustic shadow at 20 and 5 MHz, respectively. Among fragments 1.5 mm in diameter and smaller, only 45% (5 of 11) from a cholesterol stone and 30% (6 of 20) from a black pigment stone showed a definite acoustic shadow at 20 MHz. CONCLUSIONS: High-frequency (20-MHz) sonography demonstrates a definite acoustic shadow more frequently among CBD stones and fragments 1.6 mm in diameter or larger than does low-frequency (5-MHz) sonography, but it does not discriminate the chemical composition.

Adult↗

PubMed1999

Effect of Choto-san, a kampo medicine, on impairment of passive avoidance performance in mice.

In mice with procephalic ischaemia loading, disrupted passive avoidance retention performance was dose-dependently improved by Choto-san, but this effect was antagonized by NAN-190, a serotonin1A receptor antagonist. In mice with decreased intracerebral serotonin concentration, Choto-san prevented disturbance in acquiring a passive avoidance response after scopolamine administration, but did not influence the decreased serotonin concentration. These results suggested that Choto-san showed the anti-amnestic effect based on the stimulation of serotonin1A receptors.

Animals↗

PubMed1999

Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active components.

This study was designed to examine the relationship between the antidiarrhoeal effects of Hange-Shashin-To (TJ-14) and its active components. Oral treatment with TJ-14 at 1000 mg/kg significantly inhibited castor oil-induced diarrhoea. Both the 50% methanol eluate fraction (fraction III) and the methanol eluate fraction (fraction IV) showed antidiarrhoeal effects at oral doses of 68 mg/kg and 63 mg/kg, respectively, corresponding to 1000 mg/kg of TJ-14. TJ-14 (1000 mg/kg, p.o.) showed a significant increase in blood corticosterone levels. Increased blood corticosterone was noted after the oral administration of 63 mg/kg of fraction IV. The inhibitory activity of TJ-14 on cyclooxygenase-2 (COX-2) was also observed in fractions III and IV. The main component of fraction III was Scutellariae Radix-derived baicalin. Fraction IV contained Glycyrrhizae Radix-derived glycyrrhizin and isoliquiritin, Coptidis Rhizoma-derived berberine, coptisine and palmitine. Ginseng Radix-derived saponins were also present in fraction IV. These compounds inhibited castor-oil induced diarrhoea at oral doses of 10 or 30 mg/kg. Thus, the present results indicate that Scutellariae Radix, Glycyrrhizae Radix, Ginseng radix and Coptidis Rhizoma-derived components are involved in the antidiarrhoeal action of TJ-14.

Animals↗

PubMed1999

Bioassay of phytoestrogen in herbal medicine used for postmenopausal disorder using transformed MCF-7 cells.

It is well known that plants contain substances with oestrogen activity comparable to that in animals. In animals, oestrogens are steroid hormones while plants contain oestrogen with various chemical characteristics, referred to as phytoestrogens. These especially, may be responsible for part of the effects of Chinese herbal prescriptions for postmenopausal disorders in which oestrogen deficiency is considered the primary cause. In addition, the presence or absence of oestrogen activity in herbal medicine is considered extremely important for patients in whom oestrogen administration is contraindicated. The most important action of oestrogen is the transcriptional regulation of specific genes via oestrogen receptors (ER). Therefore, we have established a highly sensitive bioassay system by placing oestrogen responsive elements (ERE) upstream to the reporter gene, and have used this assay to determine the oestrogen activity in herbal medicine. As a result, phytoestrogens were found in many Chinese herbal prescriptions for postmenopausal disorder, and some prescriptions were considered to effectively administer hormone replacement therapy (HRT). However, since oestrogen activities in most Chinese herbal prescriptions were thought to be weak, it was considered that these prescriptions improved postmenopausal disorder based on a mechanism differing from that of oestrogen replacement therapy.

Biological Assay↗

PubMed1999

A successful surgical repair of the hepatic hydrothorax using pneumoperitoneum: report of a case.

A successful surgical repair of a right hepatic hydrothorax in the absence of ascites is reported. A technetium-99m scintigram that was injected intraperitoneally provided evidence of a one-way flow of fluid from the peritoneal to pleural cavity. To identify any possible minute defects in the diaphragm, carbon dioxide was insufflated into the peritoneal cavity during the operation. We performed a direct suture of the defect observed on the diaphragm. The pleural effusion subsequently vanished after the operation.

Humans↗

PubMed1999

C-Type natriuretic peptide/guanylate cyclase B system in rat osteogenic ROB-C26 cells and its down-regulation by dexamethazone.

There is recent evidence that natriuretic peptides are important regulators of bone and cartilage, although they were originally identified as the cardiac hormones causing natriuresis and hypotension. Three members of natriuretic peptide family are known: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biologically active receptors for these peptides are particulate guanylate cyclases; the two known types are GC-A and GC-B. ANP and BNP have high affinities for GC-A, and CNP is the preferred ligand for GC-B. In this paper we report the results of our study of the expression and possible role(s) of natriuretic peptides in the ROB-C26 cell, which is an osteogenic cell line with multiple potentials for differentiating into myoblast, osteoblast, and adipocyte. ROB-C26 cells produced cGMP in response to natriuretic peptides at both their basal state and after enhanced differentiation into osteoblast which was induced by bone morphogenetic protein [(BMP)-2]. CNP was far more potent than ANP in cGMP production. In contrast, enhanced differentiation into adipocyte by dexamethasone resulted in the marked decrease in their responsiveness to natriuretic peptides. Although the messages for GC-A and GC-B were demonstrated by Northern blot analysis at both the basal stage and after BMP treatment, they were down-regulated after dexamethasone treatment. The presence of CNP was shown by RT-PCR and immunohistochemistry in ROB-C26 cells. C3H10T1/2, which is another and more primitive mesenchymal cell line, also produced cGMP in response to CNP, and less potently to ANP. Culturing ROB-C26 cells with CNP or 8-bromo cGMP decreased [(3)H]thymidine uptake and slightly increased the message for alkaline phosphatase, which is a marker for osteoblast differentiation. These results suggest that the CNP/GC-B system is preferentially expressed in the cells of osteogenic lineage and their expression is down-regulated with differentiation into adipocyte lineage. The CNP/GC-B system is likely to be an autocrine/paracrine regulator of osteoblast growth and differentiation.

Alkaline Phosphatase↗

PubMed1999

Treatment effects of bisphosphonates on ovariectomy-induced osteopenia in rats: comparison between clodronate and etidronate.

We studied the effects of clodronate and etidronate on bone loss induced by ovariectomy (OVX) in rats. Drug administration was initiated 8 weeks after the surgery and continued for 12 weeks (twice per week, s.c.). Lumbar (L4-L5) bone mineral density (BMD) and femoral BMD in the sham-operated group were increased to 113% and 114%, respectively, whereas those in OVX group were suppressed to 98.8% and 105%. Clodronate significantly restored the suppressed BMD over the entire dose range used (4-25 mg/kg). Etidronate restored BMD only at 4 mg/kg. In a histomorphometric analysis of lumbar vertebrae, both bisphosphonates depressed the amount of labeled surface, which was increased by OVX, to 11.9%-20.1% of the OVX group value for clodronate and to 0.23%-9.7% of the OVX group value for etidronate. The osteoid area was significantly increased by etidronate treatment over the entire dose range (OS/BS, 175%-295%). On the other hand, the osteoid area in the clodronate group did not increase at any dose tested (OS/BS, 38.1%-49.9%). Urinary excretion of deoxypyridinoline and plasma level of osteocalcin were elevated in the OVX group (162%-182% and 123%, respectively), suggesting that OVX enhanced bone turnover. Both bisphosphonates suppressed the bone turnover accelerated by OVX, and the data indicated that both bisphosphonates recovered BMD by means of inhibition of bone resorption. These data suggested that clodronate and etidronate reversed osteopenia induced by ovariectomy in rats. As judged from the dose response of BMD and histomorphometric findings, clodronate showed a wider safety margin than etidronate.

Amino Acids↗

PubMed1999

Washout of small stones in the bile duct by saline infusion using a side-holed balloon catheter in patients undergoing endoscopic papillary balloon dilation.

BACKGROUND: Complete bile duct clearance of stones should be achieved in patients managed with endoscopic papillary balloon dilation. However, complete retrieval of small stones or tiny fragments sometimes proves difficult using conventional devices. METHODS: We attempted the removal of fine stone fragments by saline infusion using a specially designed retrieval balloon catheter with a blind tip and a side hole located proximal to the balloon in 14 patients. RESULTS: Using this technique, bile duct clearance was achieved in a single attempt in 13 of 14 patients; 2 attempts were required in 1 patient. Cholecystitis occurred in 2 patients with gallstones in situ after the procedure. CONCLUSIONS: Saline washout using a side-holed retrieval balloon catheter effectively cleans stones and stone fragments from the bile duct in patients treated with endoscopic papillary balloon dilation.

Aged↗

PubMed1999

Characterization of C-terminal-truncated urinary metabolites of a recombinant hirudin in rats.

Although it has been reported that hirudin was excreted in urine mainly as its nonmetabolized form in humans, dogs, and rabbits, no report has been published about the molecular nature of urinary metabolites in rats. We found that nonmetabolized hirudin could not be detected in rat urine after its i.v. administration and that urinary metabolites of recombinant hirudin CX-397 consisted of at least the following six C-terminal-truncated peptides: CX-397(1-49), CX-397(1-50), CX-397(1-51), CX-397(1-52), CX-397(1-54), and CX-397(1-55), in the ratio of roughly 11, 51, 3, 11, 19, and 5%, respectively. In conclusion, the urinary metabolism of recombinant hirudin in rats is different from that in humans, dogs, and rabbits, suggesting that the handling of hirudin in rat kidney is unique among them.

Amino Acid Sequence↗

PubMed1999

Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants.

The amounts of aristolochic acid I and II in four groups of medicinal plants from the Aristolochiaceae and some related plants were determined by high-pressure liquid chromatography, for Aristolochia was reported to produce interstitial nephritis caused by aristolochic acids during chronic use for the treatment of rheumatism, diuretic and analgesic. They were detected in all the plants that originated from the genus Aristolochia (Aristolochiaceae) and in some of the plants from the genus Asarum (Aristolochiaceae). The present results suggest that these medicinal plants should be prohibited to use for remedy due to the harmful effects attributed to aristolochic acids.

Aristolochic Acids↗

PubMed1999

Effect on locomotion of indole alkaloids from the hooks of uncaria plants.

Three predominant Uncariae plants, Uncaria rhynchophylla U. sinensis and U. macrophylla and their indole and oxindole alkaloid constituents were studied for their effect on locomotor response. Water extracts of U. macrophylla and U. sinensis and four indole alkaloids, corynoxine, corynoxine B, isorhynchophylline and geissoschizine methyl ether, significantly decreased locomotor activity after oral administration to mice. The depression of locomotor activity upon administration of these alkaloids appears to be due to mediating of the central dopaminergic system.

Alkaloids↗

PubMed1999

Direct evidence for the intracellular localization of Hsp104 in Saccharomyces cerevisiae by immunoelectron microscopy.

To reveal the intracellular localization of Hsp104 in the yeast Saccharomyces cerevisiae before and after heat-shock, we performed immunoelectron microscopy after immunogold labeling with anti-Hsp104 antibody. At normal temperature (25 degrees C), a small amount of Hsp104 was located in the cytoplasm and nucleus. On exposure to mild heat-shock at 40 degrees C, protein aggregates appeared in the cytoplasm and nucleus, and Hsp104 increased around the aggregates with increasing time of the mild heat-shock treatment. Moreover, at lethal heat-shock temperature (51 degrees C) for 20 min after mild heat treatment at 40 degrees C, the intracellular localization of Hsp104 and intracellular structures were similar to those of the mild heat-shocked cells. However, in the lethally heat-shocked cells, certain intracellular structures were destroyed, and Hsp104 was not expressed. In the hsp104 null mutant strain Deltahsp104 which was treated at 40 degrees C, Hsp104 was not localized around the aggregates. Additionally, in the Deltahsp104 strain, even mild heat-shocked cells at 37 degrees C or 40 degrees C, showed destruction of intracellular structure compared to the wild-type strain. Our data suggest the following: (1) Hsp104 is associated closely with protein aggregates during heat-shock treatment, (2) Hsp104 is important for maintenance of the intracellular structure under lethal heat-shock conditions, (3) acquisition of thermotolerance depends on the amount of Hsp104 produced during mild heat-shock treatment.

Cell Nucleus↗

PubMed1999

Toward artificial ribonucleases: design and synthesis of 2'-O-methyloligonucleotides with a terpyridine-copper(II) complex.

In order to construct an antisense 2'-O-methyloligonucleotide with an internal terpyridine-Cu(II) complex, a novel synthon was synthesized. This synthon was a 2'-deoxy-uridine-3'-phosphoramidite derivative with a terpyridine group at the 5'-O and a dimethoxytritylated hydroxypropyl group at the C-5. The antisense agent cleaved the RNA site-specifically and in a moderate yield.

Base Sequence↗

PubMed1999

Crystal structures of the 64M-2 and 64M-3 antibody Fabs complexed with DNA (6-4) photoproducts.

Crystal structures of the 64M-2 antibody Fab fragment complexed with DNA photoproducts of dT(6-4)T and dTT(6-4)TT, and of the 64M-3 Fab fragment complexed with dT(6-4)T were determined. The 5'-thymine base of the bound dT(6-4)T ligand is in a half-chair conformation, and its base plane is nearly perpendicular to the planar 3'-pyrimidone base. The 64M-2 and 64M-3 Fabs have a common structure suitable for accommodating the dT(6-4)T ligand. In each of the antigen binding sites of the 64M-2 and 64M-3 Fabs, basic residues of His 35H and Arg 95H are located at the bottom of the binding pocket, and are hydrogen-bonded to the base moieties of dT(6-4)T. Two water molecules are involved in the interactions that intervene between the base moieties and the binding site. Aromatic residues of Trp 33H and Tyr 100iH form a side-wall of the pocket and are in van der Waals interactions with the base moieties. The Trp 33H side-chain is placed in parallel to the 3'-pyrimidone base, and the Tyr 100iH side-chain is nearly perpendicular to the 5'-thymine base. His 27dL, Tyr 32L, Leu 93L, and Ser 58H forming another side-wall are located in the vicinity of the sugar-phosphate backbone. In the 64M-2 Fab complex with dTT(6-4)TT, 5'- and 3'-side phosphate groups are also involved in interaction with Fab residues.

Crystallography, X-Ray↗