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Biomedical subjects

S Matsuki

Publications and source records attributed to S Matsuki.

At least 19 recordsLinked to original sources
PubMed1998

Bone marrow transplantation in a Holstein heifer with bovine leucocyte adhesion deficiency.

Bone marrow transplantation (BMT) was performed in a 9-month-old heifer with bovine leucocyte adhesion deficiency (BLAD). Clinical and haematological findings, selected neutrophil function and CD18 expression of neutrophils in a B2 integrin-deficient heifer were examined. Twelve months after BMT, a small fluorescent region in the CD18-positive area of a flow cytometric profile was demonstrated and estimated to represent 0.3-0.5% of the CD18-positive neutrophils as measured by flow cytometric analysis following immunomagnetic separation. The animal's clinical condition appeared to improve and stabilize over our observation period of 28 months following BMT. Newly expressed CD18 seemed to play an important role in ameliorating the clinical signs of BLAD in this heifer.

Animals↗
PubMed1998

Seroprevalence and field isolation of bovine immunodeficiency virus.

A seroprevalence study of bovine lentivirus, known as bovine immunodeficiency virus (BIV), was conducted in 12 different dairy herds in Hokkaido, where some herds were a high prevalence of bovine leukemia virus (BLV) infection. Amongst 611 cattle, 28.6% of cattle were BLV-seropositive, and 11.7% of cattle were seropositive for BIV, while 4.2% of cattle were seropositive for both BIV and BLV. For the isolation of BIV, 19 samples of peripheral blood mononuclear cells (PBMC) and one sample of milk-derived leukocytes were prepared from BIV-seropositive cows. These PBMC and leukocyte preparations were then co-cultivated with cc81 cells, a cat cell line transformed by mouse sarcoma virus. BIV was isolated from 17 PBMC and one milk-derived leukocyte samples. The isolated viruses showed slow replication and syncytia formation. Major core antigen, p26 from these isolates were reacted with anti-BIV (American isolate R-29) serum. In addition, proviral DNA was detected in blood and milk samples by nested polymerase chain reaction and subsequent Southern blot hybridization. Nucleotide sequence analysis of the amplified pol gene products showed its 99.0 to 99.7% homology to that of BIV R-29. These results indicate that the Japanese BIV isolates appear to be antigenically and genetically similar to the American R-29. Since BIV was isolated from milk samples, BIV could possibly be transmitted through milk. This is the first report of BIV isolation in Japan.

Amino Acid Sequence↗
PubMed1998

Survival of transfused CD18-positive granulocytes and their chemiluminescent response in a heifer with leukocyte adhesion deficiency.

Granulocyte transfusion (GT) was performed in an 8-month-old heifer with leukocyte adhesion deficiency (BLAD) to monitor the changes in transfused CD18-positive neutrophils and associated neutrophil chemiluminescent (CL) response in beta 2-integrin-deficient host. The CD18-positive neutrophils were detected in blood from the BLAD heifer during the first 3 hr after 2.6 x 10(9) cells were infused by GT, and disappeared by 5 hr after GT. The CL response of neutrophils was increased 1.7 to 2.8-fold in the BLAD heifer during the first 3 hr after GT, thereafter CL response decreased gradually from 2 to 5 hr after GT.

Animals↗
PubMed1997

Structure-activity relationships of penem antibiotics: crystallographic structures and implications for their antimicrobial activities.

Twelve closely related crystal structures of the penem derivatives revealed a characteristic short contact of the oxygen atom in the C2 side-chains with the S1 atom. The side-chain conformations of the crystal structures showed a good correlation with the antimicrobial activity. In particular, the penems which show high antimicrobial activity have similar torsion angles for S1-C2-C1'-C2', suggesting that the disposition of the C2' atom would be important for binding to penicillin-interacting enzymes. Two conformations of the C6 hydroxyethyl group were observed in the crystal structures. Of those two, the conformation with a larger torsion angle (delta = 179.2 degrees) is deduced to be the enzyme-bound conformation in the Michaelis complex.

Anti-Bacterial Agents↗
PubMed1995

Role of antennary structure of N-linked sugar chains in renal handling of recombinant human erythropoietin.

To elucidate the role of the branched structure of sugar chains of human erythropoietin (EPO) in the expression of in vivo activity, the pharmacokinetic profile of a less active recombinant human EPO sample (EPO-bi) enriched with biantennary sugar chains was compared with that of a highly active control EPO sample enriched with tetraantennary sugar chains. After an intravenous injection in rats, 125I-EPO-bi disappeared from the plasma with 3.2 times greater total body clearance (Cltot) than control 125I-EPO. Whole-body autoradiography after 20 minutes of administration indicated that the overall distribution of radioactivity is similar, but 125I-EPO-bi showed a higher level of radioactivity in the kidneys than control 125I-EPO. Quantitative determination of radioactivity in the tissues also indicated that radioactivity of 125I-EPO-bi in the kidneys was two times higher than that of control 125I-EPO. The difference in plasma disappearance between 125I-EPO-bi and control 125I-EPO was not observed in bilaterally nephrectomized rats. The distribution of 125I-EPO-bi to bone marrow and spleen was similarly inhibited by simultaneous injection of excess amounts of either the nonlabeled EPO-bi or control EPO. These results indicate that the low in vivo biologic activity of EPO-bi results from rapid clearance from the systemic circulation by renal handling. Thus, the well-branched structure of the N-linked sugar chain of EPO is suggested to play an important role in maintaining its higher plasma level, which guarantees an effective transfer to target organs and stimulation of erythroid progenitor cells.

Animals↗
PubMed1995

A highly sensitive enzyme immunoassay for G-CSF in human plasma.

We have developed a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) to measure granulocyte colony-stimulating factor (G-CSF) in human plasma. This ELISA employs a combination of a mouse monoclonal antibody (MAb) as the first antibody and an affinity-purified sheep polyclonal antibody conjugated with beta-D-galactosidase as the second antibody. The coefficients of intra- and interassay variations were 2.2 to 3.6% and 8.3 to 10.2%, respectively. The assay had no cross-reactivity with four other human cytokines. Plasma G-CSF levels in healthy volunteers could easily be measured because the detection limit was 0.5 pg/mL. The mean plasma G-CSF concentration in 57 healthy volunteers (aged 19 to 47; 27 males and 30 females) was 10.5 +/- 4.5 pg/mL standard deviation [SD]). There was no statistically significant relationship between plasma G-CSF concentration and absolute neutrophil counts in those healthy volunteers (r = 0.259; p = 0.052).

Adult↗
PubMed1994

Pharmacological effects of recombinant human granulocyte colony-stimulating factor modified by polyethylene glycol on anticancer drug-induced neutropenia in mice.

1. To clarify the pharmacological effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) conjugated to polyethylene glycol (PEG), its effects on the number of circulating neutrophils in mice made neutropenic by cyclophosphamide (CPA) or 5-fluorouracil (5-FU) were compared with rhG-CSF lacking PEG. 2. In normal mice, PEG-conjugated rhG-CSF (PEG-rhG-CSF, 10 micrograms protein/kg) induced an increase in neutrophils which lasted for 72 h after injection whereas the effect of rhG-CSF (10 micrograms protein/kg) disappeared by 24 h after injection. 3. In CPA or 5-FU-induced neutropenic mice, PEG-rhG-CSF inhibited neutropenia or accelerated recovery from neutropenia and its potency was higher than that of rhG-CSF. 4. These results indicate that PEG-rhG-CSF has a longer duration of action than rhG-CSF and is more effective in the recovery from neutropenia.

Animals↗
PubMed1992

Chemical modification of recombinant human granulocyte colony-stimulating factor by polyethylene glycol increases its biological activity in vivo.

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Escherichia coli was chemically modified by polyethylene glycol (PEG) of molecular weights 4,500 or 10,000. The neutrophils observed at 32 hours after intravenous injection of the rHuG-CSF modified with PEG (4,500) or PEG (10,000) to mice were, respectively, 2.5 times and 5 times more than that observed after the injection of the unmodified rHuG-CSF. These results show that the covalent attachment of PEG to rHuG-CSF enhanced its pharmacological activity in vivo and that the modification with the larger PEG molecule is more effective to enhance the in vivo activity of rHuG-CSF.

Animals↗
PubMed1992

The substitution of cysteine 17 of recombinant human G-CSF with alanine greatly enhanced its stability.

Human recombinant granulocyte-colony stimulating factor (rhG-CSF) has one free cysteine at position 17 and has two disulfide bridges (Cys36-Cys42 and Cys64-Cys74). The Cys17 of rhG-CSF was substituted with Gly, Ala, Ser, Ile, Tyr, Arg, and Pro, or deleted using site-directed mutagenesis in order to improve its thermostability. With the exception of Pro17-rhG-CSF, all mutant proteins retained biological activity which promotes the growth of mouse bone marrow cells in vitro. Among these mutant proteins, Ala17-rhG-CSF had more than 5 times higher stability than rhG-CSF. But Ser17-rhG-CSF had almost same stability as rhG-CSF and other mutant proteins had only lower stability.

Alanine↗
PubMed1992

Is necrosis induction therapy relevant to hepatocellular carcinoma? Prognostic evaluation viewed from necrosing feature in HCC occluding the main portal vein after treatment with DBcAMP and MMC.

Intraarterial infusion therapy combining dibutyryl adenosine 3',5'-monophosphate and mitomycin C was administered to 27 patients with hepatocellular carcinoma (HCC) occluding the main portal vein. Twelve patients (44%) survived more than 6 months, among them nine (75%) whose tumors were non-necrosing before treatment. When patients were compared for the presence or absence of necrosis in the tumor, those with necrosis responded poorly to treatment; only 3 of 11 (27%) survived more than 6 months. Although the combination therapy exerted a salutary effect on HCC occluding the main portal vein, the presence of necrosis in the tumor was an unfavorable sign for the prognosis, which casts doubt upon the use of the necrosis-inducing method for the treatment of HCC.

Adult↗
PubMed1991

Pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol in rats.

The pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol (PEG-rhG-CSF) and rhG-CSF were studied in male Sprague-Dawley rats. The serum concentration after i.v. administration at a dose of 100 micrograms protein/kg was investigated by a bioassay. The serum rhG-CSF concentration decreased steadily after injection with a terminal half-life of 1.79 h. The PEG-rhG-CSF concentration after injection decreased much more slowly with a half-life of 7.05 h. The slower disappearance of PEG-rhG-CSF resulted in a greater area under the concentration-time curve. The neutrophil count after 100 micrograms of protein/kg of rhG-CSF administration reached a peak 12 h after injection and returned to the control level 48 h after injection. The neutrophil count after 100 micrograms of protein/kg of PEG-rhG-CSF administration was identical to that of rhG-CSF after 12 h but the highest level was maintained for 24 to 72 h after injection and returned to the control level after 168 h. These data indicated that PEG-rhG-CSF administration exerted a sustained biological effect on peripheral blood neutrophils. It is expected that PEG-rhG-CSF may contribute greatly to human G-CSF treatment because it has a prolonged neutrophil-proliferating activity enabling fewer administrations.

Animals↗
PubMed1991

Selective DNA cleavage by elsamicin A and switch function of its amino sugar group.

We report guanine-specific recognition and selective cleavage of DNA by the antitumor antibiotic elsamicin A equipped with an amino sugar and compare these results with cleavage by chartarin and chartreusin antibiotics. The preferential cutting sites of DNA strand scission with elsamicin A are on the bases adjacent to the 3'-side of guanine residues such as 5'-GN sites, in particular 5'-GG sites. The present results also indicate that (1) the aglycon portion binds intercalatively to the 3'-side of guanine in host DNA, (2) the guanine 2-amino group has an important effect on selective DNA binding of elsamicin A, and (3) the amino sugar residue of elsamicin A facilitates the drug binding into the minor groove of B-DNA. In addition, we found that an acetylation of the amino group on the elsamicin A sugar portion plays an interesting switch function for the activity of elsamicin A. The biological implication of this switch has also been discussed.

Aflatoxin B1↗
PubMed1991

Mutant protein of recombinant human granulocyte colony-stimulating factor for receptor binding assay.

A new mutant protein of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was produced for the studies on receptors for human G-CSF. The mutant protein [(Tyr1, Tyr3]rhG-CSF), the biological activity of which was almost equal to that of rhG-CSF, was prepared by the replacement of threonine-1 and leucine-3 of rhG-CSF with tyrosine. The radioiodinated preparation of the mutant protein showed high specific radioactivity and retained full biological activity for at least 3 weeks. The binding capacity of the radioiodinated ligand was compared with that of [35S]rhG-CSF. Both radiolabeled ligands showed specific binding to murine bone marrow cells. Unlabeled rhG-CSF and human G-CSF purified from the culture supernatant of the human bladder carcinoma cell line 5637 equally competed for the binding of labeled rhG-CSFs in a dose-dependent manner, demonstrating that the sugar moiety of human G-CSF made no contribution to the binding of human G-CSF to target cells. In contrast, all other colony-stimulating factors and lymphokines examined did not affect the binding. Scatchard analysis of the specific binding of both labeled ligands revealed a single class of binding site with an apparent dissociation constant (Kd) of 20-30 pM and 100-200 maximal binding sites per cell. These data indicate that the radioiodinated preparation of the mutant protein binds the same specific receptor with the same affinity as [35S]rhG-CSF. The labeled mutant protein also showed specific binding to human circulating neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗