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Biomedical subjects

Y Komatsu

Publications and source records attributed to Y Komatsu.

At least 271 records · Page 15Linked to original sources
PubMed1994

[Sequential methotrexate/5-fluorouracil therapy with 5'-deoxy-5-fluorouridine against advanced gastric cancer: comparison between bolus injection and drip infusion of 5-fluorouracil administration. Hirosaki Cooperative Study Group for Cancer Chemotherapy].

Forty-two patients with gastric cancer were entered in this study. Forty-one of them were eligible and administered sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR). 5-FU was administered intravenously by drip infusion for 2 hours in 22 cases (group A), and was infused by bolus injection in 19 cases (group B). The treatment schedules were as follows: MTX 100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. 5'-DFUR 1,200 mg/body/day was given orally on 5 consecutive days per week. Three of 20 cases (15%) in group A showed PR, while 5 of 15 cases (33%) in group B showed PR. Median survival time was 2.8 months in group A and 3.7 months in group B. There was, however, no statistical difference. Gastrointestinal toxicity was commonly observed. Leukocytopenia was more severe in group B. Alopecia was more frequently observed in group B (p < 0.025). These results suggested bolus injection of 5-FU was a promising way of administration in sequential MTX/5-FU therapy.

Administration, Oral↗
PubMed1994

[Management for subarachnoid hemorrhage with negative initial angiography].

Subarachnoid hemorrhage (SAH) is commonly caused by ruptured aneurysm or arteriovenous malformation which is detected by cerebral angiogram. However, since angiograms sometimes cannot show the origin of SAH, we review 12 cases (6.3% of total SAH) to assess the management of these cases. We divided the 12 cases into three groups. Group A (occulted aneurysm group) consisted of six cases of which aneurysms were detected by repeated angiographies in four, and by surgical procedures in two. Group U (unknown etiology group) consisted of five cases. Their follow up periods varied from 7 months to 7 years 11 months, and all of them recovered well and had no episode of rebleeding. Group R (rebleeding group) consisted of one case which fatally re-bled on the second day. Group A tended to be Hunt and Hess grade 3, and Fisher group 3 or 4. In contrast, group U tended to be H and H grade 1 or 2, and Fisher group 2. However by their clinical and neuroradiological findings alone, it was not possible to distinguish the two groups certainly. This means that the patients whose initial angiography does not show the origin of bleeding must be cared for as an occult aneurysm case. Twice repeated angiograms should be programmed. In our cases the first was carried out on the seventh day in the hope that the reason for vasospasm of the parent artery might be shown to be a hidden aneurysm. The second was carried out sometime between the 14th and 21st day because of thrombolysis in the aneurysm, and because it was necessary to relieve vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Increased release of KC/gro protein, intercrine cytokine family, from hepatocytes of the chronically ethanol fed rats.

In an attempt to clarify the mechanisms of neutrophil-accumulation in the liver of alcoholics, release of KC/gro protein (intercrine cytokine family) from hepatocytes in the chronically ethanol fed rats was examined. Chemotactic activity for rat neutrophils was demonstrated in the culture supernatant of hepatocytes isolated from the ethanol fed rats, which was then inhibited in the presence of antibody against rat KC/gro protein. Immunoblot analysis revealed that the peptide reacted with antiserum against KC/gro protein was demonstrated at a molecular weight of 20-23kDa, and an amount of KC/gro protein released from the hepatocytes of the chronically ethanol fed rats was increased, as compared with that of the control rats.

Alcoholism↗
PubMed1993

CX-397, a novel recombinant hirudin analog having a hybrid sequence of hirudin variants-1 and -3.

To elucidate the differential roles of N- and C-terminal halves of hirudins in thrombin inhibition, we produced novel recombinant hirudin analogs, CX-397 and CX-397R, having a hybrid amino acid sequence of hirudin variants-1 (HV-1) and -3 (HV-3). CX-397 is composed of the N-terminal half of HV-1 (HV-11-36) combined with the C-terminal half of HV-3 (HV-337-66). CX-397R is the opposite combination. Their anti-thrombin activity was determined by a fluorogenic enzyme assay and compared with that of recombinant HV-1 (rHV-1) and rHV-3. The order of the magnitude of dissociation constants (Ki) of these four hirudin analogs in thrombin inhibition was as follows: CX-397R (0.294 pM) > rHV-1 (0.148 pM) > rHV-3 (0.0593 pM) > CX-397 (0.0433 pM), indicating that CX-397 is the strongest inhibitor among them.

Amino Acid Sequence↗
PubMed1993

Central action of C-type natriuretic peptide on vasopressin secretion in conscious rats.

The effect of intracerebroventricular injection of C-type natriuretic peptide (CNP) on arginine vasopressin (AVP) secretion was studied in conscious rats, and was compared to that of atrial natriuretic peptide (ANP). The AVP secretion induced by central injection of 0.1 nmol angiotensin II was significantly suppressed by the pretreatment with 1 nmol CNP. ANP at a dose of 0.1 nmol elicited almost equivalent suppressive action to 1 nmol CNP. Considering that CNP is a specific ligand for ANP-B receptor, while ANP is that for ANP-A receptor, the result demonstrates that CNP possesses the similar central action to ANP, and suggests that the distribution of ANP-A and ANP-B receptors and/or their affinity towards each natriuretic peptide are different in the central nervous system.

Angiotensin II↗
PubMed1993

Postnatal development of NMDA receptor-mediated synaptic transmission in cat visual cortex.

Postnatal development of N-methyl-D-aspartate (NMDA) receptors in cat visual cortex (area 17) was studied by intracellular recording from cortical cells in slice preparations obtained from kittens aged 0-20 weeks after birth and adult cats. Cells were sampled from layer IV and the lower half of layer II-III, where it is known that most cells receive direct inputs from lateral geniculate nucleus. Excitatory postsynaptic potentials (EPSPs) evoked in cortical cells by white matter stimulation were mediated by both non-NMDA and NMDA receptors, because bath application of a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), left slow depolarizing responses which were abolished by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid. The contribution of NMDA receptors to the synaptic transmission was assessed by the ratio of the initial rising slope of EPSPs in the presence of DNQX to that in control solution. The NMDA receptor-mediated component of monosynaptic EPSPs was small at 0-2 weeks after birth, steeply increased to the peak value at 5-6 weeks and then declined gradually to the almost initial value by 20 weeks. This time-course agrees with the developmental changes in susceptibility of ocular dominance preference of visual cortical cells to monocular deprivation, suggesting that NMDA receptors play a role in plastic changes in geniculocortical synapses.

2-Amino-5-phosphonovalerate↗
PubMed1993

On the cytosolic and perinuclear mortalin: an insight by heat shock.

We have identified, cloned and characterized a 66-kD protein from cytosolic fractions of mouse embryonic fibroblasts and named it mortalin (Wadhwa et al., J. Biol. Chem., 268, in press, 1993). Immortal fibroblasts were seen to harbor the same or very similar protein, however, localized in the perinuclear locale. The present report is on the differentially localized forms of p66 protein which are biochemically and structurally found to be widely the same. In fact, heat shock treatment could translocate the cytosolic form to the perinuclear position without any detectable biochemical modification. The observed phenomenon adds to the unique identity of mortalin in hsp70 family. Besides, it confers that only the minor differences in the protein probably enroute its differential cellular distribution and the associated function.

3T3 Cells↗
PubMed1993

Hydrostatic pressure is like high temperature and oxidative stress in the damage it causes to yeast.

A comparison of barotolerance, thermotolerance and oxygen tolerance was made under different physiological conditions, such as heat shocked and recovered state, different growth phases and changes of physiological conditions by mutations. The three kinds of tolerance showed similar features under different physiological conditions. We suggest that the damage caused by hydrostatic pressure may be essentially the same as that due to high temperature and oxidative stress in yeast.

Hot Temperature↗
PubMed1993

Cross-ligation and exchange reactions catalyzed by hairpin ribozymes.

The negative strand of the satellite RNA of tobacco ringspot virus (sTobRV(-)) contains a hairpin catalytic domain that shows self-cleavage and self-ligation activities in the presence of magnesium ions. We describe here that the minimal catalytic domain can catalyze a cross-ligation reaction between two kinds of substrates in trans. The cross-ligated product increased when the reaction temperature was decreased during the reaction from 37 degrees C to 4 degrees C. A two-stranded hairpin ribozyme, divided into two fragments between G45 and U46 in a hairpin loop, showed higher ligation activity than the nondivided ribozyme. The two stranded ribozyme also catalyzed an exchange reaction of the 3'-portion of the cleavage site.

Base Sequence↗
PubMed1993

Identification and differential expression of yeast SEC23-related gene (Msec23) in mouse tissues.

We have isolated a yeast SEC23-related clone (Msec23) from mouse fibroblast cDNA library. It has an open reading frame of 1721 bp (64% homologous to SEC23-2.3 kb) which can potentially encode a 64.7 kDa protein (61% homologous to 85.4 kDa product of SEC23). The deduced Msec23 protein (Msec23p) sequence contains three successive Ig-like domains at the N-terminus followed by amphipathic alpha-helical regions, suggesting the potential of Msec23p to interact with other protein components. Further, Msec23 is differentially expressed in mouse tissues with its high level in brain and fibroblasts.

Amino Acid Sequence↗
PubMed1993

Quantification of sinusoidal cell function in vivo.

Although the clearance and distribution of ligand molecules in circulation represent the function of hepatic sinusoidal cells, these mechanisms revealed a network that is more intricate than would at first seem, since several receptors are common to not only one type of cell, but also to two or three types of cells in the liver. In the case of latex particles in which their uptake by a particular cell type seems to be determined by their size, sinusoidal endothelial cells are able to internalize particles up to 0.23 microns under physiologic conditions, in vivo, and larger particles are taken up by Kupffer cells. However, when the phagocytic function of Kupffer cells is impaired by frog virus 3 or alcohol, endothelial cells have been found to take up particles larger than 1 micron in diameter after the injection of an excess amount of latex particles. Endothelial cells would thus constitute a second line of defense in the liver in that they remove foreign materials from the blood when Kupffer cell phagocytic function is totally disturbed. This potential role may not, however, be fully expressed under physiologic conditions when Kupffer cells are active in clearing foreign substance from the circulation. The functions of liver sinusoidal cells are varied and complex and these cells can be regarded as "a sinusoidal cell unit." This cellular interaction must be taken into account for any quantitative analysis.

Animals↗
PubMed1993

Long-term modification of inhibitory synaptic transmission in developing visual cortex.

The long-term modification of inhibitory postsynaptic potentials (IPSPs) was studied in visual cortex slices taken from developing rats. IPSPs evoked by layer IV stimulation were intracellularly recorded from layer V cells while excitatory synaptic transmission was blocked by NMDA and non-NMDA receptor antagonists. High-frequency conditioning stimulation of layer IV induced long-term potentiation of IPSPs. By contrast, long-term depression (LTD) of IPSPs was induced by the same conditioning stimulation applied while NMDA receptor-mediated synaptic transmission was unmasked by removing the NMDA antagonist from and adding a GABAA receptor antagonist to the medium. The LTD of IPSPs was also induced by NMDA application to the cells. The plasticity of IPSPs might explain the postnatal development of selective responsiveness of visual cortical cells.

2-Amino-5-phosphonovalerate↗
PubMed1993

Cloning and nucleotide sequence of anaerobically induced porin protein E1 (OprE) of Pseudomonas aeruginosa PAO1.

The porin oprE gene of Pseudomonas aeruginosa PAO1 was isolated. Its nucleotide sequence indicated that the structural gene of 1383 nucleotide residues encodes a precursor consisting of 460 amino acid residues with a signal peptide of 29 amino acid residues, which was confirmed by the N-terminal 23-amino-acid sequence and the reaction with anti-OprE polyclonal antiserum. Anaerobiosis induced OprE production at the transcription level. The transcription start site was determined to be 40 nucleotides upstream from the ATG initiation codon. The control region contained an appropriately situated E sigma 54 recognition site and the putative second half of an ANR box. The amino acid sequence of OprE had some clusters of sequence homologous with that of OprD of P. aeruginosa, which might be responsible for the outer membrane permeability of imipenem and basic amino acids.

Amino Acid Sequence↗
PubMed1993

Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells.

We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from the porcine brain, is produced by endothelial cells and proposed that CNP can exert local control over vascular tone and growth as a local regulator from endothelial cells. Since cytokines play pivotal roles in the control of vascular tone and structure, we have examined effects of various cytokines on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP. While interleukin (IL)-2 had no significant effect on CNP secretion, IL-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha stimulated CNP secretion in a time- and dose-dependent manner. Among them, TNF-alpha, one of the key mediators for inflammation and vascular remodeling, induced more than two orders of magnitude increase in CNP secretion. In addition, lipopolysaccharide (LPS) potently stimulated CNP secretion. These results indicate that IL-1, TNF-alpha and LPS, the endotoxin itself, can regulate local vascular tone and growth through the activation of CNP secretion from endothelial cells. Therefore, CNP could be of clinical relevance as an autocrine/paracrine regulator from endothelial cells for systemic and local cytokine-associated disorders, such as endotoxin shock and atherosclerosis.

Animals↗
PubMed1993

Quantitative structure-activity relationships of antibacterial agents, 7-heterocyclic amine substituted 1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acids.

Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6,8-difluoro-1,4-dih ydro-4- oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidines to potentiate antibacterial activity. A good parabolic relationship seemed to exist between the relative mean antibacterial activity indices against five representative gram-negative bacteria, GNM, and the calculated hydrophobic parameters, CLOG P, of these molecules. The CLOG P value of the most potent derivative was predicted to be around 2.3. On the other hand, against five representative gram-positive bacteria, the relative mean antibacterial activity indices, GPM, remained high and rather constant regardless of structural variation in the azetidine moiety. In order to confirm these findings, the QSAR analysis was extended with success to the quinolonecarboxylic acids, 26-34, which bear various substituted pyrrolidine, piperazine and piperidine derivatives instead of azetidines. The findings showed that the introduction of any amide substituent group to these heterocyclic amine moieties would lead to marked decrease in GNM, whereas incorporation of some amino substituent groups at a position two or three carbons remote from the N-1 position resulted in great enhancement of GNM. As azetidine quinolones exhibited somewhat low in vivo antibacterial activities, possibly reflecting their lesser bioavailability, we finally selected 3-amino-4-methoxypyrrolidine as one of the most promising C-7 substituent groups based on our QSAR analysis.

Anti-Bacterial Agents↗