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Biomedical subjects

A Yoshikawa

Publications and source records attributed to A Yoshikawa.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Therapeutic strategy for advanced non-small cell lung cancer].

This paper describes the recent progress in the treatment of advanced non-small cell lung cancer (NS CLC) as follows: 1) The results of single agent chemotherapy in NSCLC, particularly development of new drugs, are summarized. CPT-11, taxol, taxotere, vinorelbine and gemcitabine have appeared to have a response rate of more than 20%. In addition results of phase I and II trials that involved these agents as part of combination regimens are presented. 2) We summarize 8 randomized trials of combination chemotherapy compared with best supportive care. These studies have provided that combination chemotherapy modestly improves survival of patients with advanced NSCLC. 3) Although several randomized trials with adjuvant or neoadjuvant chemotherapy have reported in the patients with locally advanced NSCLC, we have still not confirmative results. 4) Cisplatin based combination chemotherapy followed by chest irradiation improves outcomes of the patients with stage IIIA or IIIB unresectable NSCLC as compared with chemotherapy alone or radiation therapy alone. In spite of these advances further investigations are necessary to improve the treatment results of patients with advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

The primary structures and properties of non-stomach lysozymes of sheep and cow, and implication for functional divergence of lysozyme.

Lysozymes were purified from the homogenate of cow and sheep kidneys, and their amino-acid sequences as well as some enzymic properties were determined. Like most mammalian lysozymes both sheep and cow kidney lysozymes are composed of 130 amino acids. The sequences of these two lysozymes are the most similar to each other (95% identity), the second most similar to the conventional mammalian lysozymes like human, rat and rabbit lysozymes (74-85% identity), and much less similar to their own stomach lysozymes (65-70% identity). Cow kidney lysozyme is also different from cow milk lysozyme (partial sequence), indicating that cow contains at least three kinds of chicken type lysozymes, that is kidney, milk and stomach lysozymes. The activities of cow and sheep kidney lysozymes were 3% and 29% against Micrococcus luteus at pH 7.0, ionic strength of 0.1 and 30 degrees C, and 57% and 84% against glycol chitin at pH 5.5 and 40 degrees C, which were expressed as percentages relative to hen lysozyme. The net charges of cow and sheep lysozymes at pH 7 were less positive (+1.5 and +2.5, respectively) than human and hen lysozymes (both +8.0) and rather close to the stomach ones (-2 to 0). The decreased net positive charge observed in cow and sheep kidney lysozymes may suggest that the ruminant kidney lysozyme had functioned once as a digestive enzyme in the stomach of an ancestral ruminant.

Amino Acid Sequence↗
PubMed1993

Chimeric hepatitis B virus core particles with parts or copies of the hepatitis C virus core protein.

Either parts or multiple copies of the core gene of hepatitis C virus (HCV) were fused to the 3' terminus of the hepatitis B virus (HBV) core gene with 34 codons removed. As many as four copies of HCV core protein (720 amino acids) were fused to the carboxy terminus of truncated HBV core protein (149 amino acids) without preventing the assembly of HBV core particles. Chimeric core particles were sandwiched between monoclonal antibody to HBV core and that to HCV core, thereby indicating that antigenic determinants of both HBV and HCV cores were accessible on them. Proteolytic digestion deprived chimeric core particles of the antigenicity for the HCV core without affecting that of the HBV core, confirming the surface exposure of HCV core determinants. The density of HCV core determinants on chimeric core particles increased as copies of fused HCV core protein were increased. Hybrid core particles with multiple HCV core determinants would be instrumental as an antigen probe for detecting class-specific antibodies to the HCV core in patients with acute and chronic hepatitis C and for simultaneous detection of antibodies to HBV core and those to HCV core in donated blood.

Amino Acid Sequence↗
PubMed1992

Serodiagnosis of hepatitis C virus infection by ELISA for antibodies against the putative core protein (p20c) expressed in Escherichia coli.

The putative core gene of hepatitis C virus (HCV) was incorporated into a plasmid vector (pCC5-J4), and expressed in Escherichia coli. The product of 180 amino acids (p20c) was purified by gel electrophoresis in the presence of sodium dodecyl sulfate, and used in enzyme-linked immunosorbent assay for antibodies against the putative core protein of HCV (anti-p20c). Anti-p20c was detected in 13 (1.5%) of 873 apparently healthy blood donors. It was detected in 205 (86.5%) of 237 patients with acute or chronic non-A, non-B (NANB) hepatic disease, significantly more frequently (p less than 0.01) than antibodies against the C100-3 protein encoded by nonstructural regions of HCV (anti-C100-3) that was found in 178 (75.1%). Anti-p20c developed in the circulation of a patient with acute NANB hepatitis much earlier than anti-C100-3. HCV RNA was detected by polymerase chain reaction in serum samples from blood donors positive for anti-p20c in high titers, one of which was negative for anti-C100-3. These results indicated that anti-p20c would be useful in complementing anti-C100-3 for the diagnosis of NANB hepatitis and further decreasing the incidence of posttransfusion NANB hepatitis.

Adolescent↗
PubMed1992

p26 protein and 33-nm particle associated with nucleocapsid of hepatitis C virus recovered from the circulation of infected hosts.

Hepatitis C virus (HCV) has not yet been cultured or visualized. We attempted to recover HCV-associated particles from plasma of infected humans to assess the natural properties of the virus. Starting with 720 ml of donor plasma containing high titer of HCV core antigen ELISA activities, we identified HCV core antigen activity and viral RNA enriched in a potassium bromide density gradient fraction with a density of 1.115 g/ml. Icosahedron-shaped particles with an average diameter of 33 nm were liberated by treatment of the fraction with the detergent Tween 80. These particles were selectively visualized with an electron microscope using a grid coated with a murine monoclonal antibody directed to HCV core peptide and were also observed in aggregated forms with an immune electron microscope (IEM) with use of the anti-core antibody. An ultracentrifugation pellet of the above fraction was treated with sodium dodecyl sulfate (SDS) and 2-mercaptoethanol (2ME) and run in SDS-PAGE. A protein that bound antibodies directed to the predicted core protein of HCV was found at a molecular size estimated as about 26,000 Da, significantly greater than the 191 amino acid residues predicted from the presumed core gene of HCV. It is possible that translation initiation and/or the COOH-terminal cleavage site for HCV core protein in vivo may differ from estimates derived from the amino acid sequence of the polyprotein precursor. The nucleocapsid could also be chemically altered in the infected cell, resulting in a gel mobility different from the native protein.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

An ordered clone bank for chromosome I of Saccharomyces cerevisiae.

Chromosome I of Saccharomyces cerevisiae DC5 rho 0 was dissected into segments with an average size of 14.0 kb and cloned into lambda phage vectors. The physical maps of the resultant clones, totaling 205.9 kb, were used to construct an ordered clone bank of this chromosome.

Chromosome Mapping↗
PubMed1991

Construction of an ordered clone bank and systematic analysis of the whole transcripts of chromosome VI of Saccharomyces cerevisiae.

By comparing sequences of restriction enzyme cleavage sites and their distance data, we sorted 384 lambda phage clones containing segments of chromosome VI of S. cerevisiae and constructed an ordered clone bank for this chromosome. The physical length of this bank is 269.7 kb. The bank contains the entire chromosome including the left telomere, but it is not certain whether it contains the right telomere as well. To estimate the number of genes present on this chromosome, we performed a series of Northern hybridization experiments using 157 restriction enzyme fragments prepared from the bank as hybridization probes and total poly(A)+ RNA from vegetatively growing cells. Thus, 97 distinct transcripts were identified. The relative abundance levels of individual transcripts were measured by comparing their band intensity with that of the RPO41 transcript. It was found that the transcripts from the genes located in the telomeric and centromeric regions are less abundant as compared to those from the genes in the central regions of both arms.

Blotting, Northern↗
PubMed1991

Phosphorylation in the carboxyl-terminal domain of the capsid protein of hepatitis B virus: evaluation with a monoclonal antibody.

The capsid protein of hepatitis B virus (p21c) is made of 183 amino acids coded for by the C gene. By using p21c isolated from Dane particles (hepatitis B virus) as an immunogen, a monoclonal antibody (no. 2212) which recognized an epitope dependent on the phosphorylation of p21c was raised. The binding of no. 2212 antibody to authentic p21c was completely inhibited by a synthetic undecapeptide with a sequence of RRRSQSPRRRR, representing amino acids 165 to 175 of p21c, only when the peptide was phosphorylated. Either or both of Ser-168 and Ser-170 were phosphorylated in p21c in vivo, therefore, and contributed to the manifestation of the epitope. No. 2212 antibody bound to p21c from core particles derived from Dane particles or hepatocellular carcinoma tissues (PLC/342) propagated in nude mice but did not bind to p21c from core particles expressed in Escherichia coli or yeast cells, indicating different states of phosphorylation in them. Nonphosphorylated p21c showed a higher affinity for the viral DNA than did phosphorylated p21c. Since the serum from an asymptomatic carrier, with a high titer for antibody to hepatitis B core antigen, specifically bound to phosphorylated undecapeptide (amino acids 165 to 175), the epitope would stimulate humoral antibody responses in the human host.

Amino Acid Sequence↗
PubMed1991

An autoantibody cross-reactive to hepatitis C virus core and a host nuclear antigen.

GOR, an epitope borne by the amino acid sequence, GRRGQKAKSNPNRPL, is recognized by anti-GOR antibodies specifically found in patients with non-A, non-B hepatitis (NANBH). The epitope is not coded for by the hepatitis C virus (HCV), the presumed causative agent for NANBH, but by a single copy gene of the host. Anti-GOR antibodies, distinct from anti-HCV (c100-3) antibodies, were revealed to have dual specificities; they target both the presumed core gene product of HCV and a host component. This cross recognition is probably derived from homologous regions between the GOR epitope and a viral epitope on the core protein in HCV. It is therefore suggested that anti-GOR is an autoantibody induced by HCV infection. This may explain the autoimmune disease like aspect of NANBH pathogenesis.

Amino Acid Sequence↗
PubMed1990

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process.

A cDNA clone (GOR47-1) bearing an epitope with an aminoacid sequence GRRGQKAKSNPNRPL (GOR epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-A, non-B hepatitis (NANBH) agent. The epitope was not encoded by reported sequences of hepatitis C virus (HCV) but instead was coded for by a host cellular sequence. An enzyme-linked immunosorbent assay (ELISA) was developed for antibodies to the GOR epitope (anti-GOR). A patient with acute NANBH produced both IgM and IgG classes of anti-GOR in the acute phase of the illness, with concentrations of IgG class anti-GOR rising when anti-HCV became detectable. Anti-GOR was detected in serum from 59 (81%) of 73 patients with chronic NANBH, 40 (65%) of 62 with NANB liver cirrhosis, and 25 (63%) of 40 NANB patients with primary hepatocellular carcinoma, but in only less than 10% of patients with chronic liver diseases due to hepatitis B virus, alcohol, or an autoimmune disorder, and in only 2% of voluntary blood donors. Circulating HCV-RNA was detected by polymerase chain reaction (PCR) in most patients seropositive for anti-GOR but negative for anti-HCV. Detection of anti-GOR would therefore help in the diagnosis of NANBH and in reducing the occurrence of post-transfusion hepatitis.

Amino Acid Sequence↗
PubMed1990

Deficient activity of nucleotide binding regulatory protein coupled with PGE2 receptor in renal medulla of spontaneously hypertensive rats.

Prostaglandin (PG) E2 receptor-adenylate cyclase system was studied in the kidney of 12-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to evaluate the role of this system in hypertension. PGE2 receptors were determined by a radioligand binding method using [3H]-PGE2. Adenylate cyclase responses to PGE2, sodium fluoride (NaF) and forskolin were also measured. The concentration of PGE2 receptor was increased in SHR compared with WKY. PGE2- and NaF-stimulated adenylate cyclase activities were significantly lower in SHR than WKY. There was no significant difference in forskolin-stimulated adenylate cyclase activity between SHR and WKY. NaF activates the nucleotide binding regulatory protein (G-protein) and forskolin directly activates the catalytic unit. These results indicate that the activity of G-protein coupled with renal PGE2 receptors is deficient in SHR. This defect may contribute to the elevation of blood pressure, through sodium retention.

Adenylyl Cyclases↗