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Biomedical subjects

H Ogawara

Publications and source records attributed to H Ogawara.

At least 19 recordsLinked to original sources
PubMed2001

Risk factors for early death in patients undergoing treatment for multiple myeloma.

The survival time of myeloma patients improved from a few months to many years after treatment with melphalan. Perhaps chemotherapy more intensive than melphalan-prednisolone should be administered to patients at risk of early death. Therefore, early death must be accurately predicted. We analyzed 93 patients with recently diagnosed myeloma and found that 13 (14%) died within 6 months (early death). The most common cause of death was bacterial and fungal pneumonia when myeloma became uncontrollable. The response to conventional chemotherapy was poorer in patients at high risk of early death than the control group. Multivariate analysis showed that the serum level of beta-2 microglobulin was the only value that predicted early death.

Aged↗
PubMed2001

Synthesis and chain length-anti-HIV activity relationship of fully N- and O-sulfated homooligomers of tyrosine.

Fully N- and O-sulfated homooligomers from octamer to nonadecamer of tyrosine were obtained as their sodium salts, aO3S-[Tyr(SO3Na)]n-ONa (n = 8-19), from reaction mixtures of tyrosine with sulfur trioxide trimethylamine and pyridine comlexes, respectively, in pyridine. Their anti-HIV activity increased along with the increase of the chain length up to the dodecamer, maintained the same level to the length of the heptadecamer and then decreased. The maximal activity level was the same as or higher than that of dextran and curdlan sulfates.

Anti-HIV Agents↗
PubMed2001

Synthesis and anti-HIV activity of nonatyrosine N- and O1-9-decasulfate.

To develop a potent and effective anti-HIV compound with a definite polyanionic structure, synthesis of oligotyrosine sulfates by oligomerization with simultaneous sulfation of tyrosine was tried. One component was successfully isolated from the mixture containing many products as its sodium salt (Y-ART-4) and was identified as the salt of nonatyrosine N- and O1-9-decasulfate, NaO3S-[Tyr(SO3Na)]9-ONa. Anti-HIV activity of Y-ART-4, determined from the protection it provided against HIV-induced cytopathic effects, was almost the same with that of dextran sulfate and curdlan sulfate.

Anti-HIV Agents↗
PubMed2001

[Genetic and biochemical studies on the regulatory mechanism of the self-resistance and biosynthesis of antibiotics].

The following topics are described: 1. chemistry of beta-lactamases; 2. beta-lactamases from Streptomyces including distribution of beta-lactamases in actinobacteria, properties of beta-lactamases from Streptomyces, cloning and regulatory mechanism of expression of beta-lactamase genes from Streptomyces and evolution and classification of beta-lactamases in general; 3. penicillin-binding proteins from Streptomyces including beta-lactam-producing- and non-producing strains and 4. eukaryotic-type protein kinases from Streptomyces including cloning of the genes and evolution and classification of eukaryotic-type protein kinases in general.

Amino Acid Sequence↗
PubMed1999

A staging system for multiple myeloma based on the morphology of myeloma cells.

The morphology of myeloma cells is reported to be one of the prognostic factors in multiple myeloma (MM) patients. We analyzed the prognostic factors, including morphological classification, in 292 patients with MM in order to select poor-risk patients who should be considered candidates for early intensive chemotherapy, including stem cell transplantation. Multivariate analysis was applied to 90 patients diagnosed between 1989 and 1996, because serum beta-2-microglobulin (beta2M) has been measured regularly since 1989, and showed that serum albumin, serum beta2M, and the morphology of myeloma cells predicted survival. According to these factors, patients were divided into 3 risk groups; a high-risk group (14%), a intermediate-risk group (46%) and a low-risk group (40%). There were significant differences between survival times in these 3 groups (median survival: high-risk, 16; intermediate-risk, 22; and low-risk, 44 months).

Aged↗
PubMed1999

Distribution of beta-lactamases in actinomycetes.

The distribution of beta-lactamase activities in a collection of actinomycete strains was surveyed. Six of 127 strains were found to produce beta-lactamase. This low frequency was in contrast to the case with Streptomyces species. The producing strains were not related phylogenetically. MICs of benzylpenicillin did not correlate with beta-lactamase production.

Actinomycetales↗
PubMed1997

Serum beta-2-microglobulin in patients with multiple myeloma treated with alpha interferon.

In ten patients with multiple myeloma (MM), serum beta-2-microglobulin (B2M) levels were monitored in order to clarify the influence of alpha interferon (IFN) administration. Despite decreases in M-protein and the absence of renal dysfunction, the levels of serum B2M were sustained above those prior to melphalan-prednisolone and IFN therapy in seven patients with MM for six months. Serum B2M did not increase in ten patients with MM treated only by melphalan-prednisolone. Furthermore, serum B2M levels in a patient who achieved a complete response were sustained above her prior level and returned to normal after cession of IFN therapy. Our study suggests that the serum B2M level is increased by treatment with IFN, and does not prove the condition of the disease.

Adolescent↗
PubMed1996

Sulfated pentagalloyl glucose (Y-ART-3) inhibits HIV replication and cytopathic effects in vitro, and reduces HIV infection in hu-PBL-SCID mice.

To evaluate the efficacy of Y-ART-3 as an antiviral drug for HIV infections, its anti-HIV activity was assessed in vitro in cell culture systems and in vivo in hu-PBL-SCID mice. The results indicated that Y-ART-3 invariably inhibited not only HIV-1, but also HIV-2 and SIV strains. Its mechanism of action is ascribed to inhibition of viral adsorption to CD4-positive cells. In an in vivo study, human Ig- and CD4-positive cells were detected at similar levels in Y-ART-3-treated hu-PBL-SCID mice that were infected with HIV, and in PBS-treated control hu-PBL SCID mice that were not infected with HIV. If HIV positivity was calculated using the number of tests in which HIV was detected (i.e. PCR, and p24 from co-cultures of spleen and peritoneal wash cells), a significant effect of Y-ART-3 at a dose of 4 mg/kg was noted. Therefore, Y-ART-3 may be considered to be a potent and effective anti-HIV compound.

Animals↗
PubMed1995

Cloning, sequencing and expression of serine/threonine kinase-encoding genes from Streptomyces coelicolor A3(2).

A 6.3-kb DNA fragment encoding two eukaryotic-type serine/threonine protein kinases (Ser/Thr PK) was cloned from Streptomyces coelicolor A3(2) by using a PCR product obtained with primers based on highly conserved regions of eukaryotic Ser/Thr PK. The nucleotide (nt) sequence of the essential 4.4-kb fragment contained two possible ORFs. One ORF (PkaA) contained 543 amino acids (aa), while another (PkaB) consisted of 417 aa. The N-terminal half of both proteins showed significant similarity with the catalytic domain of eukaryotic Ser/Thr PK. On the other hand, the C-terminal region of PkaA, but not of PkaB, is rich in Pro and Gln residues, indicating that PkaA works as a PK as well as a transcription factor. The pkaB gene was overexpressed in Escherichia coli, and the gene product (PkaB) was found to be phosphorylated mainly at Thr. The pkaA gene was also overexpressed in E. coli, and the gene product (PkaA) was found to be phosphorylated mainly at Thr and slightly at Ser. In the case of PkaA, at least 100 aa residues from the C terminus were not essential for the PK activity. When the PCR product was used as a probe, it hybridized to DNA fragments from all the Streptomyces species tested, indicating that these types of Ser/Thr PK are distributed ubiquitously and play significant physiological roles in the various species of Streptomyces.

Amino Acid Sequence↗
PubMed1995

Cloning, sequencing, and site-directed mutagenesis of beta-lactamase gene from Streptomyces fradiae Y59.

The beta-lactamase gene from Streptomyces fradiae Y59 was cloned and sequenced. To determine which amino acid residues are critical in binding activity to blue dextran, chimera beta-lactamases were constructed and their binding abilities were determined. The results suggested that blue dextran binding may depend more on overall conformation of about two-thirds of the beta-lactamase molecule from the N terminus than on the primary structure.

Amino Acid Sequence↗
PubMed1995

Properties of peptide chain release factor 2 from Streptomyces coelicolor A3(2): conserved primary structure but no frameshift regulation.

A gene was cloned from Streptomyces coelicolor A3(2). It encodes a protein of 368 amino acid residues with a high degree of similarity to prokaryotic release factor 2. However, it has neither an internal stop codon nor the Shine-Dalgarno-like sequence immediately upstream of the assumed frameshift position. The gene is expressed and functional in Escherichia coli as peptide chain release factor 2. The transcription start site is at or adjacent to the translational start site. The size of the mRNA detected by hybridization suggests that the gene (prfB) is monocistronic in S. coelicolor A3(2). However, about 80 bp upstream of the gene there is an operon which is composed of two genes encoding eukaryotic-type serine/threonine kinases.

Amino Acid Sequence↗
PubMed1995

Cochlioquinone A, an inhibitor of diacylglycerol kinase.

The effects of cochlioquinone A, isolated from Drechslera sacchari, were studied in vitro and in vivo. This compound specifically inhibited diacylglycerol kinase activity with Ki = 3.1 microM. The kinetics revealed that cochlioquinone A inhibited diacylglycerol kinase in competition with ATP, and non-competitively with diacylglycerol. The compound inhibited neither protein kinase C, epidermal growth factor receptor-associated protein tyrosine kinase, nor phospholipase C. Cochlioquinone A reduced the concentration of phosphatidic acid in T cell lymphoma with a half maximal concentration of 3 microM, and simultaneously augmented the phosphorylation of 80 kDa protein, a known substrate of protein kinase C. The degree of the phosphorylation of 80 kDa protein in the presence of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 microgram/ml). These results demonstrate that cochlioquinone A is a specific inhibitor of diacylglycerol kinase, which regulates the activity of protein kinase C.

Animals↗
PubMed1994

Daidzein inhibits insulin- or insulin-like growth factor-1-mediated signaling in cell cycle progression of Swiss 3T3 cells.

An isoflavone compound, daidzein, inhibits the cell proliferation of Swiss 3T3 cells. Analysis of entry in S phase of Swiss 3T3 cells reveals that daidzein blocked cell cycle G1 phase progression 4.6 h after stimulation by bombesin plus insulin. After removal of daidzein, insulin or insulin-like growth factors (IGFs) reinitiate cell cycle progression of daidzein-blocked cells without further addition of bombesin. The order in the mitogenic action of insulin or IGFs is as follows: IGF-1 (5 ng/ml) >> IGF-2 (0.5 microgram/ml) congruent to insulin (1 microgram/ml). Studies in vivo of protein kinase activation by mitogenic stimulation reveal that the treatment with daidzein decreased the activation of a MAP2 phosphorylating protein kinase (MAP2 kinase). In vitro kinase assays showed that daidzein inhibits casein kinase II activity, but does not inhibit MAP2 kinase activity. Activation of casein kinase II by polylysine augments the activity of MAP2 kinase in digitonin-permeabilized 3T3 cells. These results suggest that daidzein blocked G1 phase cell cycle progression of Swiss 3T3 by inhibiting the activity of casein kinase II which is required for the commitment of mitogenic signal by insulin or IGF-1 in G1 phase.

3T3 Cells↗
PubMed1993

Cloning, nucleotide sequence and expression of a beta-lactamase gene from Streptomyces lavendulae.

A hybridized DNA fragment was cloned as a 7.6-kb fragment from Streptomyces lavendulae KCCS0263 using a 1.9-kb SacI-XbaI DNA fragment from S. cellulosae as a probe. The latter fragment encoded a beta-lactamase which can bind blue dextran. The hybridized region was reduced to a 2.8-kb KpnI-BclI fragment and the nucleotide sequence was determined. The nucleotide sequence indicated one open reading frame whose amino acid sequence is very similar to that of the beta-lactamase from S. cellulosae. The gene produced beta-lactamase enzyme at a low but significant amount.

Amino Acid Sequence↗
PubMed1993

Cloning, sequence and expression of the argG gene from Streptomyces lavendulae.

The argG gene, encoding argininosuccinate synthetase, was cloned from Streptomyces lavendulae KCCS0055 by colony hybridization using the argG-carrying 2.1-kb fragment of S. coelicolor DNA as a probe. The restriction map of the cloned DNA fragment was very similar to that of S. coelicolor. This DNA fragment could complement the argG mutation of both S. lividans 1326 I10 and Escherichia coli K-12 JE5694, suggesting that the fragment contained a promoter for both E. coli and S. lividans. The subcloning experiment using E. coli K-12 JE5694 as a host has indicated that the essential region for argG is contained in the 2.5-kb DNA fragment. The translational product was identified as a 56-kDa kDa protein in minicells and by conventional gel electrophoresis. Determination of the nucleotide (nt) sequence of the 2.5-kb DNA fragment revealed one open reading frame of 1449 bp. The amino acid (aa) sequence analysis showed that the N-terminus was Ser, and 9 aa from the N terminus were completely identical with those deduced from the nt sequence. Nuclease S1 mapping indicated that the transcription start point is located near the start codon.

Amino Acid Sequence↗
PubMed1993

An inhibitor of inositol-phospholipid-specific phospholipase C.

Q12713 substance, a cyclic peptide from Actinomadura spp., strongly inhibited the enzyme activity of phosphatidylinositol-4,5-bisphosphate-specific phospholipase C (PIP2-PLC) but scarcely inhibited other phospholipases. Kinetic analysis demonstrated that the inhibition of PIP2-PLC activity was competitive with respect to phosphatidylinositol 4,5-bisphosphate. Calcium and magnesium ions had no significant effect on the inhibitory activity. On the contrary, potassium or rubidium ion was essential for the inhibitory activity. Furthermore, NaF and AlCl3-stimulated increase of phosphoinositides was decreased by Q12713 in the cultured 3T3 cells.

3T3 Cells↗
PubMed1993

Sequence of a gene encoding beta-lactamase from Streptomyces cellulosae.

The nucleotide sequence of beta-lactamase (Bla)-encoding gene, bla, from Streptomyces cellulosae KCCS0127 was determined. The deduced amino acid sequence was very close to that of class-A Bla, especially those from Streptomyces species, but completely different from class-D Bla. This is contrary to the result expected from its substrate specificity and its property of binding blue dextran and NADP+.

Amino Acid Sequence↗