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Biomedical subjects

Y Matsuo

Publications and source records attributed to Y Matsuo.

At least 181 records · Page 10Linked to original sources
PubMed1997

[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics].

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Adolescent↗
PubMed1996

Autocrine loop through cholecystokinin-B/gastrin receptors involved in growth of human leukemia cells.

The cholecystokinin (CCK)-B/gastrin receptor binds two brain-gut hormones, CCK and gastrin, with high affinities. These peptides have a trophic effect on gastrointestinal cells expressing the receptor in vivo as well as in vitro. Recently, this receptor mRNA was reported to be expressed in immunocytes localized in the lamina propria of normal rat stomach mucosa. Here, we studied the receptor expression in human hematopoietic cells in order to determine whether they play a role in cell growth. The CCK-B/gastrin receptor mRNA was detectable in the polymorphonuclear (PMN) cells but not in the mononuclear cells of normal peripheral white blood cells by reverse transcription-polymerase chain reaction. The receptor transcript was, however, expressed in human leukemia cell lines (14 of 18 cell lines tested) derived from not only myeloid, but also T- and B- lymphoid lineages. The CCK-B/gastrin receptors on several leukemia cell lines were shown to be biologically active by demonstrating ligand-dependent cell proliferation in serum-deprived medium. Interestingly, a human CCK-B/gastrin receptor specific antagonist, YM022, but not its stereotype isoform, selectively inhibited the DNA synthesis of THP-1, MOLT-16, MOLT-14, and CCRF-CEM in the absence of exogenous peptide ligands. Further investigation revealed that these leukemia cell lines and normal PMN cells also expressed gastrin mRNA. These results suggest that growth of human leukemia cells is promoted by an autocrine mechanism through the CCK-B/gastrin receptors.

Cell Division↗
PubMed1996

Denitrification, a novel type of respiratory metabolism in fungal mitochondrion.

Subcellular localization and coupling to ATP synthesis were investigated with respect to the denitrifying systems of two fungi, Fusarium oxysporum and Cylindrocarpon tonkinense. Dissimilatory nitrate reductase of F. oxysporum or nitrite reductase of C. tonkinense could be detected in the mitochondrial fraction prepared from denitrifying cells of each fungus. Fluorescence immunolocalization, cofractionation with mitochondrial marker enzymes, and cytochromes provided evidence that the denitrifying enzymes are co-purified with mitochondria. Respiratory substrates such as malate plus pyruvate, succinate, and formate were effective donors of electrons to these activities in the mitochondrial fractions. Moreover, nitrite and nitrate reduction were shown to be coupled to the synthesis of ATP with energy yields (P:NO3- or P:2e ratios) of 0.88 to 1.4, depending upon whether malate/pyruvate or succinate were provided as substrates. Nitrate or nitrite reductase activity was inhibited by inhibitors such as rotenone, antimycin A, and thenoyltrifluoroacetone. Thus, fungal denitrification activities are localized to mitochondria and are coupled to the synthesis of ATP. The existence of these novel respiration systems are discussed with regard to the origin and evolution of mitochondria.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Structurally altered Evi-1 protein generated in the 3q21q26 syndrome.

Overexpression of the Evi-1 gene appears to be a consistent feature of the 3q21q26 syndrome, an association of myeloid leukemias/myelodysplastic syndrome with a specific chromosomal aberration involving both 3q21 and 3q26, such as t(3;3)(q21;q26) or inv(3)(q21q26). The rearrangement in 3q26 has been reported to occur near the Evi-1 locus, implicating that it is the critical gene deregulated in the 3q21q26 syndrome. Here we present a structural abnormality of Evi-1 protein in a case with the 3q21q26 syndrome. In this case carrying typical inv(3)(q21q26), the 3q26 breakpoint is located within an intron of the Evi-1 gene, and resulted in overexpression of normally unexpressed, an aberrant form of Evi-1 protein, in which the C-terminal 44 amino acids of wild-type Evi-1 protein were truncated and replaced by five amino acids. The truncated Evi-1 protein is shown to increase AP1 activity when expressed in NIH3T3 cells as its wild-type counterpart. We also show that the origin of this peculiar type of rearrangement of the Evi-1 gene is not an artifact during establishment of the cell line, but is the event that occurred in the primary leukemic cells. Our results strongly support that the primary target for the 3q21q26 syndrome is the Evi-1 gene, and provide the first evidence that the structurally altered Evi-1 gene may be involved in the 3q21q26 syndrome.

3T3 Cells↗
PubMed1996

Genetic analysis of the cytochrome P-45OIIC18 (CYP2C18) gene and a novel member of the CYP2C subfamily.

The CYP2C18 gene was investigated in order to characterize its molecular basis in the CYP2C subfamily. A mutation of the CYP2C18 gene was identified at the 5'-flanking region of the gene, which could be detected by digestion with DdeI. The allele frequency of the mutant CYP2C18 gene was 21.4%. Genotypes of the polymorphic DdeI site of the CYP2C18 gene were found to be completely consistent with that of the polymorphic CYP2C19 gene (the m1 mutant). The CYP2C18 and CYP2C19 genes were suggested to be linked and located close together on the chromosome. Clones containing the 5'-flanking region of a member of the CYP2C subfamily were obtained from the PCR products from human genomic DNA. The nucleotide sequence of the clone proved to be 90.5% identical to the corresponding region of the CYP2C18 gene. This is very likely to be a novel member of the CYP2C subfamily.

Alleles↗
PubMed1996

Analysis of heterophilic cell adhesion mediated by CD66b and CD66c using their soluble recombinant proteins.

The heterophilic cell adhesion mediated by CD66b (carcinoembryonic antigen (CEA) gene family member 6, CGM6) and CD66c (nonspecific cross-reacting antigen, NCA), both CEA family members expressed on neutrophils, was investigated using their soluble recombinant proteins prepared in silkworm larvae. The recombinant CD66b and CD66c immobilized on plastic bound CHO transfectants expressing CD66c and CD66b, respectively. Their deglycosylated forms retained the adhesion activity, suggesting that their carbohydrate portions are not prerequisite for the binding. This cell adhesion appeared to be mediated via interaction between the N domains of CD66b and CD66c, because CD66 antibodies recognizing their N domains inhibited the binding. Neutrophils, when activated, adhered to the immobilized CD66b and CD66c. In addition, the binding of primed neutrophils to the antigens induced superoxide anion release. The cell adhesion mediated by CD66b and CD66c may play a role in interaction between neutrophils or between neutrophils and epithelial cells expressing CD66c in vivo.

Animals↗
PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗
PubMed1996

The 1.8-A X-ray structure of the Escherichia coli PotD protein complexed with spermidine and the mechanism of polyamine binding.

The PotD protein from Escherichia coli is one of the components of the polyamine transport system present in the periplasm. This component specifically binds either spermidine or putrescine. The crystal structure of the E. coli PotD protein complexed with spermidine was solved at 1.8 A resolution and revealed the detailed substrate-binding mechanism. The structure provided the detailed conformation of the bound spermidine. Furthermore, a water molecule was clearly identified in the binding site lying between the amino-terminal domain and carboxyl-terminal domain. Through this water molecule, the bound spermidine molecule forms two hydrogen bonds with Thr 35 and Ser 211. Another periplasmic component of polyamine transport, the PotF protein, exhibits 35% sequence identity with the PotD protein, and it binds only putrescine, not spermidine. To understand these different substrate specificities, model building of the PotF protein was performed on the basis of the PotD crystal structure. The hypothetical structure suggests that the side chain of Lys 349 in PotF inhibits spermidine binding because of the repulsive forces between its positive charge and spermidine. On the other hand, putrescine could be accommodated into the binding site without any steric hindrance because its molecular size is much smaller than that of spermidine, and the positively charged amino group is relatively distant from Lys 349.

Amino Acid Sequence↗
PubMed1996

A distant evolutionary relationship between bacterial sphingomyelinase and mammalian DNase I.

The three-dimensional structure of bacterial sphingomyelinase (SMase) was predicted using a protein fold recognition method; the search of a library of known structures showed that the SMase sequence is highly compatible with the mammalian DNase I structure, which suggested that SMase adopts a structure similar to that of DNase I. The amino acid sequence alignment based on the prediction revealed that, despite the lack of overall sequence similarity (less than 10% identity), those residues of DNase I that are involved in the hydrolysis of the phosphodiester bond, including two histidine residues (His 134 and His 252) of the active center, are conserved in SMase. In addition, a conserved pentapeptide sequence motif was found, which includes two catalytically critical residues, Asp 251 and His 252. A sequence database search showed that the motif is highly specific to mammalian DNase I and bacterial SMase. The functional roles of SMase residues identified by the sequence comparison were consistent with the results from mutant studies. Two Bacillus cereus SMase mutants (H134A and H252A) were constructed by site-directed mutagenesis. They completely abolished their catalytic activity. A model for the SMase-sphingomyelin complex structure was built to investigate how the SMase specifically recognizes its substrate. The model suggested that a set of residues conserved among bacterial SMases, including Trp 28 and Phe 55, might be important in the substrate recognition. The predicted structural similarity and the conservation of the functionally important residues strongly suggest a distant evolutionary relationship between bacterial SMase and mammalian DNase I. These two phosphodiesterases must have acquired the specificity for different substrates in the course of evolution.

Amino Acid Sequence↗
PubMed1996

Preparation and characterization of two human carcinoembryonic antigen family proteins of neutrophils, CD66b and c, in silkworm larvae.

As a step to investigate the cell adhesion mechanism and physiological roles of two CD66 antigens in human neutrophils, carcinoembryonic antigen gene family member 6 (CGM6, CD66b) and nonspecific cross-reacting antigen (NCA, CD66c), we prepared their soluble recombinant forms in silkworm larvae. Each cDNA fragment for CGM6 and NCA was ligated into the transfer vector pBK283 after modification to encode the protein lacking the membrane anchor. The resultant vectors were introduced to the Bombyx mori nuclear polyhedrosis virus, with which silkworm larvae were infected. Recombinant proteins secreted into the hemolymph of larvae at concentrations up to 1.3 mg/ml were purified by cation exchange followed by gel filtration or antibody affinity chromatography. The smaller apparent masses of the antigens compared with those of the native antigens appeared to be primarily due to incomplete glycosylation. Both recombinant antigens are quite similar to the corresponding native antigens in terms of the antigenic reactivity against a panel of CD66 monoclonal antibodies. In addition, the recombinant CGM6 and NCA exhibited cell binding activity against CHO cells expressing NCA and CGM6, respectively. Thus the two biologically active recombinant CD66 antigens prepared in large quantities in silkworm larvae should be useful for their functional studies, and our present system will be available for the production and purification of other carcinoembryonic antigen family members, whose biological functions are also unknown.

Animals↗
PubMed1996

Inflammation of the brain after ischemia.

Cytokines which promote emigration of leukocytes from the vascular lumen into the injured brain tissue are produced at the site of incipient cerebral infarction. The blood-borne invaders then accelerate the decomposition of brain cells by their toxic by-products, phagocytic action, and by the immune reaction. Recently accumulated data in our laboratories and other research facilities show that depleting the amount of circulating leukocytes or administering anti-inflammatory chemicals such as cytokine blocking agents, anti-adhesion molecule antibodies, and immunosuppressants effectively minimize the size of ischemia induced cerebral infarction. Based on the fact the leukocyte invasion of the affected brain tissue occurs 6 to 24 hours after onset of ischemia, administration of an anti-inflammatory therapy may widen the therapeutic window against stroke.

Acute-Phase Reaction↗
PubMed1996

The retroperitoneal approach to aortoiliac surgery associated with a horseshoe kidney: report of a case.

The presence of a horseshoe kidney associated with aortoiliac vascular disease poses technical difficulties in terms of vascular reconstruction. The renal isthmus, position of the renal pelvis and ureters, and variable blood supply to the horseshoe kidney can complicate aortoiliac reconstruction. The left retroperitoneal approach provides excellent exposure of the abdominal aorta in patients with a horseshoe kidney without dividing the renal isthmus and avoids the risk of injury to a ureter in an anomalous position. We herein report the case of a patient with a horseshoe kidney who underwent a successful reconstruction of aortoiliac vascular disease using the left retroperitoneal approach.

Aged↗
PubMed1996

Molecular evolution of the paired gene in Drosophila: cloning and characterization of the partial paired gene from Drosophila willistoni.

A partial paired gene of Drosophila willistoni containing the paired box and extended homeo box was amplified by PCR and the nucleotide sequence of 1141 bp was determined. Comparison of the paired genes in D. willistoni and D. melanogaster showed that the proportions of identical nucleotide sites in the coding region and identical amino acid sites were 73.8 and 86.5%, respectively. The amino acid sites in the N-terminal region, the paired box, and the extended homeo box were 88.5, 95.3, and 98.6% identical in the two species. The rates of amino acid substitution for these regions were estimated to be 1.73 x 10(-9), 0.67 x 10(-9), and 0.19 x 10(-9)/site/year, respectively. In contrast, the connecting region between the two boxes has been highly diverged and evolved very rapidly, 18.3 x 10(-9)/site/year, suggesting almost no functional constraint in the connecting region.

Amino Acid Sequence↗
PubMed1996

Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2.

We purified a neutrophil chemotactic factor from a culture fluid of the PHA-activated human T-cell leukemia SKW-3 cells. The factor showed a 16-kDa basic protein by Tricin-SDS-polyacrylamide gel electorophoresis and analysis of amino acid composition. The primary amino acid sequence revealed that the chemotactic factor was significantly different from other known chemotactic factors, indicating a novel protein designated LECT2. The sequence revealed homology with the myb-induced myeloid protein-1 (Mim-1), which is expressed from gene in immature and normal granulocytes of chicken. Its biological function had not yet been identified. LECT2 and Mim-1 may be involved in the regulation of neutrophil functions in an as yet unidentified way.

Amino Acid Sequence↗
PubMed1996

Genotype analysis of the CYP2C19 gene in the Japanese population.

A polymorphic CYP2C19 gene was analyzed in 233 Japanese subjects, including 63 with Parkinson's disease, 92 with chronic liver diseases (35 chronic hepatitis, 19 liver cirrhosis, 16 hepatocellular carcinoma, 10 primary biliary cirrhosis and 12 autoimmune hepatitis), 14 with lung cancer (squamous cell carcinoma) and 64 healthy subjects to determine the genotype distributions of the CYP2C19 gene and to investigate its involvement in the diseases. Among Japanese healthy subjects 14.1% are predicted to be poor metabolizers (PM) of mephenytoin. The frequencies of the m1 and the m2 mutations of the CYP2C19 gene in the healthy subjects were 21.9% and 11.7%, respectively. Though the number of patients was small, patients with lung cancer (squamous cell carcinoma) are believed to have reduced enzyme activities of CYP2C19.

Aryl Hydrocarbon Hydroxylases↗
PubMed1996

The Fas antigen is detected on immature B cells and the representative cell lines show Fas-mediated apoptosis.

The expression and functions of Fas antigen, a major regulator of apoptosis, in T-cell selection have been intensively investigated, but little is known about its expression i immature B cells which are also selected in the bone marrow, and plasma cells which are at the terminal stage of B-cell differentiation and are designed to die. We examined bone marrow cells and found Fas antigen on these cells at low levels. Next we analysed Fas expression and susceptibility to anti-Fas antibody-mediated apoptosis on B-cell lines representing various stages of differentiation. We also examined the expression of Bcl-2 and Bax on these lines, which were intimately related to apoptosis. Fas antigen was almost negative on pre-pre-B cell lines and was detected on pre-B-cell lines at low levels. All plasma cell lines expressed Fas at a low to moderate level. Some cell lines with peripheral B-cell phenotype expressed Fas antigen. Except for the Burkitt cell lines and one plasma cell line, susceptibility to Fas-mediated apoptosis depended on Fas expression. Bcl-protein was detected on all but one cell line and Bax was detected on 15/23 lines, but neither were related to cellular differentiation or Fas expression.

Apoptosis↗