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Biomedical subjects

Y Minami

Publications and source records attributed to Y Minami.

At least 217 records · Page 12Linked to original sources

[Induction therapy with CDDP and ADM for stage D prostatic cancer and its clinical response].

From September 1983 to September 1989, 20 patients with newly diagnosed stage D prostatic cancer were treated with cis-platinum (CDDP) and adriamycin (ADM) as the induction therapy. Analysis of histological and clinical effects on the induction therapy revealed partial response (PR) in 13 cases and no change (NC) in 7 cases according to Shimazaki's response criteria, and PR in 4 cases, NC in 15 cases and progression (PD) in 1 case according to NPCP criteria. Histological Ef 0-b effect was found in 2 cases, Ef 1 in 7 cases, Ef 2 in 3 cases, Ef 3 in 2 cases and Ef 4 in 2 cases. Analysis of long-term results revealed relapse in 9 cases and cancer death in 6 cases. The 1-year, 3-year and 5-year continued response rates for all cases were 85.7, 40.2 and 32.1%, respectively. The 1-year, 3-year and 5-year survival rates were 100, 64.3 and 53.6% respectively. Histologically, low responsive cases showed a tendency of relapse and cancer death more frequently than high responsive cases. These results suggest that CDDP and ADM therapy is more effective than hormone therapy in newly diagnosed stage D prostatic cancer as an induction therapy.

Adenocarcinoma↗

A novel member of the calcium-dependent cysteine protease family.

In the course of cDNA cloning of the large subunits of human mu- and mCANPs, a novel cDNA clone encoding a putative calcium-dependent cysteine protease homologous to but distinct from both mu- and m-types was found. The encoded protein, designated tentatively as p94, is composed of four domains similar to those found in other CANP large subunits, but includes three unique regions that have no homology to other CANPs. These unique sequences might be involved in regulating the activation and/or determining the intracellular localization of p94. Since the mRNA for p94 is five times more abundant than that for the CANP small subunit in skeletal muscle, it is possible that p94 does not associate with the small subunit in vivo. In contrast to the ubiquitous expression of mu- and m-types, the mRNA for p94 is expressed only in skeletal muscle. Besides acting as a protease, p94 may act as a skeletal muscle specific regulatory protein like troponin C.

Amino Acid Sequence↗

Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types. Specific expression of the mRNA in skeletal muscle.

Two types of calcium-dependent protease with distinct calcium requirements (termed muCANP and mCANP) are known in mammalian tissues. These two isozymes consist of different large (80-kDa) subunits (mu- or m-types) and identical small (30-kDa) subunits. By screening human and rat muscle cDNA libraries with a cDNA probe for the chicken CANP large subunit, which has a structure similar to both the mammalian mu- and m-types, a cDNA clone encoding a novel member of the CANP large subunit family was obtained. The encoded protein (designated "p94") consists of 821 amino acid residues (Mr 94,084) and shows significant sequence homology with both human mu-type (54%) and m-type (51%) large subunits. p94 can be divided into four domains (I-IV) as reported for the CANP large subunit family. Domains II and IV are potential cysteine protease and calcium-binding domains, respectively, and have sequences homologous to the corresponding domains of other CANP large subunits. However, domain I of p94 is significantly different from others. Moreover, p94 contains two unique sequences of 62 and 77 residues in domains II and III, respectively. In contrast to the ubiquitous expression of mu- and m-types, Northern blot analysis revealed that the mRNA for p94 exists only in skeletal muscle with none detected in other tissues including heart muscle and smooth muscles such as intestine.

Amino Acid Sequence↗

T cell activation induces rapid tyrosine phosphorylation of a limited number of cellular substrates.

Activation of murine T cells by antigen, antibodies binding the T cell antigen receptor, or stimulatory anti-Thy-1 antibodies results in rapid phosphorylation of the T cell receptor zeta chain on tyrosine residues. The T cell receptor is itself unlikely to be a tyrosine kinase; rather, it is probable that this receptor is coupled to a nonreceptor tyrosine kinase. To understand further this protein kinase pathway, additional targets of the tyrosine kinase have been sought by comparing anti-phosphotyrosine antibody immunoblots of cellular proteins from unactivated and activated T cell hybridomas. In addition to the T cell receptor zeta chain, two proteins of 53 and 62 kDa are phosphorylated on tyrosine residues after T cell activation. These phosphorylations require stimulatory anti-Thy-1 antibodies, antigen, or antireceptor antibody stimulation. The 53-kDa protein is preferentially phosphorylated by antigen or antireceptor antibody. Of interest is that variants of the murine T cell hybridoma lacking the T cell receptor zeta chain or lacking surface antigen receptor can nonetheless be stimulated by anti-Thy-1 antibodies to phosphorylate the 62-kDa substrate. In contrast to the tyrosine kinases of oncogenic viruses, the kinase coupled to the T cell antigen receptor appears to have a limited number of targets. These proteins are candidates for critical substrates in this protein tyrosine kinase pathway.

Animals↗

Antipyrine clearance per unit liver volume in cirrhotics with and without hepatocellular carcinoma indicating a correlation with histological change of the liver.

The antipyrine metabolizing capacity was studied in 12 patients with cirrhosis of the liver and 12 with cirrhosis and hepatocellular carcinoma (HCC). Antipyrine clearance (Cl) and liver volume (LV) were measured and the antipyrine clearance per unit liver volume (Cl/LV) was calculated. The patients with HCC showed a significantly lower Cl value than those without HCC but there was no significant difference in Cl/LV between the two groups. This suggested that the lower Cl values in the HCC patients resulted from a decrease in residual liver mass. Cl/LV showed positive correlation with % parenchymal cell mass as an indicator of residual parenchymal cell mass per unit volume of liver. This result showed a correlation of Cl/LV with histological change of the liver in cirrhotics.

Adult↗

Identification and characterization of inhibitory sequences in four repeating domains of the endogenous inhibitor for calcium-dependent protease.

We reported previously the cDNA cloning of the endogenous inhibitor for calcium-dependent protease (CANP inhibitor, calpastatin) and the expression of its fragments in Escherichia coli. The CANP inhibitor has four internal repeating domains each spanning about 140 amino acid residues. The inhibitory activity arises from these domains which have a well-conserved sequence, TIPPXYR, in their central positions. The inhibitory activities of various fragments expressed in E. coli suggest the involvement of the regions around the well-conserved sequences. In this report, we describe further detailed investigation on the interaction site of the CANP inhibitor with CANP by truncating inhibitor fragments and by using chemically synthesized peptides. The results clearly indicate that the sequence around the well-conserved sequence, TIPPXYR, is an interaction site. A peptide as short as 23 amino acid residues retained inhibitory activity, but a 9-residue peptide corresponding to the conserved sequence, VTIPPKYRE had none. The inhibitory sequence is suggested as LGXKDREXTIPPXYRXLL. The analysis of the competition between an inhibitor peptide and an irreversible inhibitor, E-64 for the reaction with the active site suggests no involvement of the active site cysteine residue of CANP in the inhibitory interaction between CANP and the CANP inhibitor. The high specificity of the CANP inhibitor to CANP arises from its interaction with residues other than the active site cysteine residue, possibly the subsite for substrate-binding of CANP.

Amino Acid Sequence↗

Endothelium-dependent and -independent mechanisms of action of acetylcholine in monkey and dog isolated arteries.

In helical strips of monkey coronary and mesenteric arteries and dog mesenteric arteries partially contracted with prostaglandin (PG)F2 alpha, the mechanism of action of acetylcholine (ACh) has been analyzed by the use of pharmacological antagonists and by the endothelium-derived relaxing factor (EDRF) bioassay and the 6-keto PGF1 alpha radioimmunoassay. In conclusion, ACh releases vasodilator substance(s) from endothelium (EDRF) and also PGs from subendothelial tissues. Vasoconstrictor PGs appear to counteract the dilator action of EDRF in monkey coronary arteries, whereas vasodilator PG, possibly PGI2, appears to facilitate the relaxation caused by EDRF in monkey and dog mesenteric arteries.

6-Ketoprostaglandin F1 alpha↗

Alterations in fructosamine and glycated albumin levels during childhood.

Age-related changes in the blood concentrations of glycated proteins during childhood and adolescence were examined by measuring the blood fructosamine (FA), glycated albumin (GA), glucose levels and total serum protein levels in 611 healthy children (325 boys and 286 girls) aged 0-18 years old. These levels were compared with those of 130 healthy adults. GA was measured by a newly developed, highly precise method of high-performance liquid chromatography (inter-assay coefficient of variation, 4.9%). The FA values of all groups of up to 15 years old (grouped in two year age brackets) were significantly lower than those of adults. The mean serum concentrations of GA in infants up to four years old were also significantly lower than in adults. A slight but statistically significant positive correlation was found between age and values of FA (r = 0.36, P less than 0.001), but not of GA (r = 0.04). Levels of total serum proteins showed a positive correlation with those of FA (r = 0.47, P less than 0.001) but a weak correlation with those of GA (r = 0.29). These results suggest that age should be taken into account when the FA levels of children and the GA values of infants are evaluated.

Adolescent↗

Role of endothelium in the response to prostaglandin H2 in isolated dog arteries.

Prostaglandin (PG) H2 produced a transient contraction followed by a relaxation in helical strips of dog coronary, mesenteric and renal arteries contracted with PGF2 alpha. The contraction was in the order of mesenteric greater than renal greater than coronary artery. Removal of endothelium abolished the contraction in these arteries and significantly potentiated the relaxation only in mesenteric arteries. The relaxation was greater in mesenteric arteries than in renal and coronary arteries, denuded of endothelium. PGI2-induced relaxations were not influenced by endothelium denudation. In the arteries contracted with K+, PGH2-induced relaxations were attenuated, compared to those contracted with PGF2 alpha. Treatment with ONO3708, an antagonist of vasoconstrictor PGs, abolished the PGH2-induced contraction and potentiated the relaxation in the K+-contracted arteries. The relaxant response was suppressed by diphloretin phosphate, a PG receptor antagonist, as was the response to PGI2. PGH2-induced contractions in dog coronary, mesenteric and renal arteries would be due to vasoconstrictor PGs produced preferentially in the endothelium. However, production of PGI2 from PGH2 in endothelial and subendothelial tissues do not appear to differ.

Animals↗

Extraluminally applied acetylcholine and substance P on the release of EDRF.

Acetylcholine, substance P and nitroglycerin applied intra- and extraluminally to the perfused dog femoral artery segment with endothelium caused depressor responses. Endothelium denudation abolished the responses to acetylcholine and substance P. EC50 ratios of extra- versus intraluminal acetylcholine and substance P were 43 and 79, respectively, whereas those of nitroglycerin did not differ. Physostigmine potentiated the response to extraluminal acetylcholine. Acetylcholine seems to be degraded partly by cholinesterase in the arterial wall. Acetylcholine and substance P applied extraluminally are expected to reach the endothelium and release endothelium-derived relaxing factor.

Acetylcholine↗

New glutarimide antibiotics, S-632-B1 and B2. I. Taxonomy of producing strain, fermentation and biological properties.

Strain S-632 was found to produce new glutarimide antibiotics, S-632-B1 and B2, which were isolated from the culture fluid. A taxonomic study on strain S-632 was carried out, and the taxonomic characterization demonstrated that it belonged to the species Streptomyces hygroscopicus. The strain was given the name S. hygroscopicus S-632. These antibiotics were active against Saccharomyces sp., but inactive against filamentous fungi and bacteria, and had cytotoxic activity against KB tissue culture cells.

Antifungal Agents↗

New glutarimide antibiotics, S-632-B1 and B2. II. Isolation, physico-chemical properties and chemical structure.

Antifungal antibiotics S-632-A1,A2,B1 and B2 were extracted with ethyl acetate from the filtered broth of Streptomyces hygroscopicus S-632 and isolated through a combination of conventional and reversed-phase silica gel column chromatography. On the basis of the spectral data, S-632-B1 and B2 were found to be new members of the glutarimide family of antibiotics. The chemical structures of these components were elucidated as two stereo-isomers of 3-(5,7-dimethyl-8,9-epoxy-2-hydroxy-4-oxo-6-decenyl)glutarimide.

Antifungal Agents↗

Possible involvement of 5-lipoxygenase products in the generation of endothelium-derived relaxing factor.

Acetylcholine and substance P applied to the donor tissue, dog femoral artery segments with endothelium, produced moderate relaxations of the assay tissue, endothelium-denuded dog coronary artery strips. The relaxation was attenuated markedly by treatment of the assay tissue with hydroquinone and abolished by oxyhemoglobin or methylene blue. In this bioassay system, the effect of AA861 and TMK777, new 5-lipoxygenase inhibitors, was evaluated. When the donor tissue was treated with AA861 or TMK777, the responses to acetylcholine and substance P were attenuated moderately, whereas the relaxation by nitroglycerin was not influenced by AA861. However, the inhibitors when infused just below the donor tissue did not attenuate relaxant responses to acetylcholine and substance P. Application of superoxide dismutase (SOD) to the donor tissue caused a relaxation of the assay tissue, and potentiated the relaxation by acetylcholine and substance P. AA861 and TMK777 suppressed the relaxant responses to acetylcholine and substance P, respectively, in the presence and absence of SOD to a similar extent and abolished the SOD-induced relaxation. Pyrogallol abolished the relaxation by acetylcholine, but did not inhibit the response when the donor tissue was pretreated with SOD. Therefore, it appears that AA861 and TMK777 do not degrade endothelium-derived relaxing factor (EDRF) in the perfusate via generation of superoxide anion or block the action of EDRF on vascular smooth muscle, but interfere with the synthesis and/or release of EDRF. The findings obtained so far support the idea that lipoxygenase products participate in the generation of EDRF.

Acetylcholine↗

Infrequent utilization of the immunoglobulin heavy chain variable region(s) identical or closely related to that of MOPC315 myeloma protein in the functional V region formation in B-precursor cell lines.

We raised anti-VH315 antibodies by immunization of rabbits with VH315 fragments, the variable portions of the immunoglobulin heavy chains of MOPC315 myeloma protein. Inhibition radioimmunoassay using various immunoglobulins as inhibitors showed that the anti-VH315 antibodies specifically reacted with the variable portions of the heavy chains of MOPC315 myeloma protein. When the variable region (VH) gene of the heavy chains was cloned and sequenced from the cells producing the heavy chains detected by the anti-VH315 antibodies, the VH gene was closely related (82% homology at amino acid level) to the VH gene of MOPC315. When we examined the frequency with which the variable region(s) detected by the anti-VH315 antibodies were expressed in eight Ignull Abelson virus-transformed cell lines (DJ/DJ or VDJ-/DJ), which were able to generate functional V regions during culture, only one cell line, AT8-1, produced a small number of intracytoplasmic mu-positive cells (VH315+ cells) stained by the anti-VH315 antibodies. The percentage of the total number of the VH315+ cells to the total number of intracytoplasmic mu-positive cells was 0.91% in AT8-1. In the remaining seven cell lines, no VH315+ cells were detected. In the present study we estimate, for the first time at the individual cell level, the frequency of the utilization of the heavy chain variable region(s) identical or closely related to that of MOPC315 in the functional V region formation during early B-cell development.

Amino Acid Sequence↗

Molecular cloning and expression of human leukotriene A4 hydrolase cDNA.

We have isolated a near full-length cDNA encoding human leukotriene A4 (LTA4) hydrolase from a human spleen cDNA library. The mature form of the enzyme consists of 610 amino acid residues and its molecular weight is calculated to be 69,153. The cDNA was inserted into an expression vector (pUC 9) and expressed in Escherichia coli. The fusion protein (EX85) possessed the LTA4 hydrolase activity with kinetic properties similar to the native enzyme.

Amino Acid Sequence↗