C-1027-AG, a selective antagonist of the macromolecular antitumor antibiotic C-1027.
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Aminoglycosides↗
Biomedical subjects
Y Minami
Publications and source records attributed to Y Minami.
New antibiotics 4181-A and B from Streptomyces griseus; taxonomy, fermentation, isolation and characterization.
The new antibiotics 4181-A and B were isolated from the fermentation broth of Streptomyces griseus, a soil isolate. Their molecular formulae were determined as C29H21NO9 and C28H19NO9, respectively. The UV, IR and NMR spectra suggest that they possess a quinone moiety in their structures. They were found to have antibacterial, antifungal and antitumor activity.
Animals↗
[Calcium-activated neutral protease and its endogenous inhibitor: structure and function].
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Amino Acid Sequence↗
[Short-term corneal endothelial changes following posterior chamber lens implantation].
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Aged↗
Molecular cloning and sequencing of cDNA for rat cathepsin H. Homology in pro-peptide regions of cysteine proteinases.
A cDNA for rat cathepsin H was isolated and sequenced. The deduced protein comprising 333 amino acid residues is composed of a typical signal sequence (21 residues), a pro-peptide region (92 residues) and a mature enzyme region (220 residues). The amino acid sequence in the pro-peptide region, in particular, residues Phe-(-41) to Ser-(-29) of cathepsin H, is highly homologous to the pro-peptide regions of other cysteine proteinases. This homologous region may play a role in the processing of cysteine proteinases.
Amino Acid Sequence↗
Internalization and cycling of the T cell antigen receptor. Role of protein kinase C.
The dynamics of the T cell antigen receptor on a murine antigen specific T cell hybridoma have been analyzed using a monoclonal anti-receptor antibody. When this antibody, A2B4-2, is bound to surface receptors, no internalization is seen at 4 degrees C. Upon warming to 37 degrees C, between 20 and 30% of the antibody molecules are internalized over 20-30 min as measured by sensitivity to external acid. This level of internalization is identical if monovalent Fab fragments are used. In contrast, cross-linking of the anti-receptor antibody with a second antibody leads to rapid internalization of 100% of prebound surface A2B4-2. Phorbol 12-myristate 13-acetate (PMA) leads to the rapid internalization of up to 65% of the surface A2B4-2 or A2B4-2 Fab fragments. This effect requires protein kinase C and can be completely inhibited by depleting this kinase from the cells by long term treatment with high doses of PMA. Pretreatment of the T cells with PMA leads to a 40-50% drop in surface T cell antigen receptor expression. Despite the loss of surface receptors, the uptake of A2B4-2 in PMA-treated cells at 37 degrees C is identical to that seen in control cells. The total uptake of A2B4-2 at 37 degrees C is 25-30% greater than the number of surface receptors in control cells and about 100-150% greater than the number of surface receptors in PMA-treated cells. At steady state the percentage of total A2B4-2 on the cell surface is 75% for control cells and 38% for PMA-treated cells. The good agreement of these numbers with the percent internalization of a cohort of surface receptors suggests that all receptors are constantly cycling. The effect of PMA is to alter the kinetic parameters of this cycling, thus changing the steady state distribution of receptors between the plasma membrane and internal, presumably endosomal compartments. Measurement of initial rates of internalization suggests that the PMA effect can be largely explained by an increase in the internalization rate constant.
Animals↗
Gas chromatographic-mass fragmentographic determination of propiverine and its metabolites in plasma and urine.
1-Methyl-4-piperidyl diphenylpropoxyacetate hydrochloride has been developed clinically for the therapy of urinary bladder dysfunction. A gas chromatographic-mass fragmentographic method was developed for the determination of this drug and its seven metabolites in plasma and urine. The sample was first treated with a Sep-Pak C18 cartridge, the methanol eluate was evaporated to dryness, and the resulting residue was redissolved in distilled water. This solution was then extracted with chloroform and adjusted to pH 9.0 with 0.1 M sodium borate solution. The acidified aqueous layers were extracted with ethyl acetate. The chloroform layer, which contained non-polar metabolites, was concentrated to dryness, then subjected to trifluoroacetylation, decomposition and methylation. The extract from the plasma sample was trimethylsilylated. The dried residue of the ethyl acetate layer, which contained polar metabolites, was subjected to methylation, trifluoroacetylation and decomposition. Aliquots of each reactant solution were injected into the gas chromatograph-mass spectrometer and analysed by the selected-ion monitoring method using an internal standard. Detection was limited to 1-2 ng/ml of plasma and urine for each metabolite. A precise and sensitive assay for the determination of 1-methyl-4-piperidyl diphenylpropoxyacetate hydrochloride and its metabolites in plasma and urine was thus established, and it should prove useful in basic and clinical pharmacological studies.
Animals↗
Calcium-activated neutral protease and its endogenous inhibitor. Activation at the cell membrane and biological function.
The structures of calcium-activated neutral protease (CANP) and its endogenous inhibitor elucidated recently have revealed novel features with respect to their structure-function relationship and enzyme activity regulation. The protease is regarded as a proenzyme which can be activated at the cell membrane in the presence of Ca2+ and phospholipid, and presumably regulates the functions of proteins, especially membrane-associated proteins, by limited proteolysis. Protein kinase C is hydrolysed and activated by CANP at the cell membrane to a cofactor-independent form. These results are reviewed and the possible involvement of CANP in signal transduction is discussed.
Animals↗
Selective use of the VHQ52 family in functional VH to DJH rearrangements in a B precursor cell line.
AT11-2, an Abelson virus-transformed cell line has DJH complexes on both chromosomes and is able to form functional variable region genes by the joins of VH genes to the DJH complexes during culture. Therefore we examined which VH gene family was used in functional VH to DJH recombinations in AT11-2. Surprisingly, of 32 independent functional VH to DJH recombinational events in AT11-2, 31 events used the VH segments of the VHQ52 family, and the remaining one used the VH segment of the VH7183 family. Thus, we describe here the first B precursor cell line that almost selectively uses the VHQ52 family in functional VH to DJH rearrangements. The selective use of the VHQ52 family in this B precursor cell line strongly indicates nonrandom use of VH gene families, and the existence of a stage at which the VHQ52 family is preferentially used during the normal development of early pre-B cells and has important implications for understanding the ontogeny of VH repertoire development. Furthermore, this cell line should prove extremely valuable in further studies of this kind.
Animals↗
A fragment of an endogenous inhibitor produced in Escherichia coli for calcium-activated neutral protease (CANP) retains an inhibitory activity.
A C-terminal fragment of an endogenous rabbit liver inhibitor for calcium-activated neutral protease (CANP) was produced in Escherichia coli and its inhibitory activity was examined after purification. The truncated inhibitor (373 amino acid residues), which contains two internal repeat structures, inhibits 2 mol CANP whereas the native liver inhibitor (639 residues), containing four internal repeat structures, inhibits 4 mol CANP. This supports the hypothesis that the repeating unit is the functional unit of inhibition. The results also indicate that post-translational modification of the inhibitor is not essential for inhibition.
Amino Acid Sequence↗
Induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells is controlled by the level of intracellular copper.
A study was carried out on the uptake of copper, zinc, or cadmium ions and their induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells. The main difference between Menkes' and normal cells in the uptake of these metal ions was an increased uptake of copper ions in Menkes' cells at a low concentration of CuCl2 (2.1 microM). The CuCl2 concentration necessary to induce metallothionein synthesis in Menkes' cells was 50 microM, whereas that in normal cells was about 200 microM. The levels of zinc or cadmium ions needed to induce metallothionein in Menkes' cells were similar to those in normal cells. At least four isomers of metallothionein were induced by copper, zinc, and cadmium ions in both types of cells. Metallothionein synthesis in Menkes' and normal cells was induced when the amounts of intracellular copper reached a threshold level of approximately 0.2 nmol/10(6) cells, and the rate of metallothionein synthesis in these cells was increased as a function of the amounts of intracellular copper (0.2-1.7 nmol/10(6) cells). These results indicate that the induction of metallothionein synthesis in lymphoblastoid cells is controlled by the level of intracellular copper, suggesting that the major defect in Menkes' cells is not due to the abnormal regulation of metallothionein synthesis but to an alteration of the copper metabolism in cells by which the levels of intracellular copper become larger than those in normal cells and just lower than the threshold level for induction of metallothionein synthesis.
B-Lymphocytes↗
Effect of cholestyramine on bile acid metabolism in conventional rats.
Effects of cholestyramine on biliary secretion of cholesterol, phospholipids and bile acids and fecal excretion of sterols and bile acids were examined in Wistar male rats. Six rats were fed a basal diet, and the other six were fed a basal diet supplemented with 5% cholestyramine for eight days. Bile flow and biliary secretion of bile acids and phospholipids (per hour per rat) decreased with cholestyramine treatment, while biliary cholesterol secretion (per hour per rat) remained unchanged. In the biliary bile acid composition, a marked increase of chenodeoxycholic acid with a concomitant decrease of beta-muricholic acid was observed in cholestyramine-treated rats. Fecal excretion of total sterols and bile acids increased about three- and four-fold, respectively, after cholestyramine treatment. The increase of fecal bile acids derived from cholic acid was more predominant than that derived from chenodeoxycholic acid, resulting in an increase of the cholic acid group/chenodeoxycholic acid group ratio.
Animals↗
Papillary-cystic neoplasm of the pancreas with multiple hepatic metastases: a case report.
We report a case of papillary-cystic neoplasm (PCN) of the pancreas in a 42-yr-old woman. Because of complication with multiple hepatic metastases, the patient could not receive radical operation, and was treated palliatively. The right hepatic tumors decreased in volume by an average of 28% (range: 13-54%) following intra-arterial infusion of doxorubicin and gelatine sponge--i.e. chemoembolization therapy. On the other hand, the left lobe tumor increased by 15% in volume following intra-arterial infusion of doxorubicin alone without selective embolization. A subsequent systemic combination chemotherapy (combinations of 5-fluorouracil, doxorubicin and mitomycin-C) was less effective for both the primary and metastatic sites of PCN of the pancreas. Intra-arterial chemoembolization proved useful--as expected--as a palliative measure. Papillary-cystic neoplasm of the pancreas accompanied by hepatic metastasis is very rare. We present herein its clinical behavior and response to the above treatment as documented by CT scan.
Adult↗
Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma.
The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Selective reduction of hepatic cytochrome P450 content in patients with intrahepatic cholestasis. A mechanism for impairment of microsomal drug oxidation.
Alteration of the components of the mixed-function oxidase system, including cytochrome P450, cytochrome b5, cytochrome P450 reductase, and cytochrome b5 reductase, was examined in liver microsomes prepared from needle biopsy samples of 12 patients with intrahepatic cholestasis. The rate of p-nitroanisole O-demethylation in the microsomes was also measured as the activity of cytochrome P450-dependent drug oxidation. The cytochrome P450 content (0.29 +/- 0.05 nmol/mg microsomal protein) in the patients was significantly lower than that in the 11 control subjects (0.41 +/- 0.09). The rate of p-nitroanisole O-demethylation was also significantly lower in the patients. However, the cytochrome b5 content and the activities of the reduced forms of nicotinamide adenine dinucleotide phosphate- and nicotinamide adenine dinucleotide-cytochrome c reductases did not differ between the two groups. Thus, selective reduction of cytochrome P450 seems to play a major role in the impairment of microsomal drug oxidation during intrahepatic cholestasis. Moreover, the reduction of cytochrome P450 was correlated with the serum concentrations of total bilirubin and bile acid but not with the serum glutamic oxaloacetic transaminase value. These observations suggest that the reduction of cytochrome P450 might be related to the severity of cholestasis.
Adult↗
Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor.
The murine T-cell antigen receptor consists of at least seven chains and six different proteins. The two clonotypic chains alpha and beta are glycoproteins of 40-45 kDa present as a disulfide-linked heterodimer. Four clonally invariant chains include delta (a 26-kDa glycoprotein), gamma (a 21-kDa glycoprotein), epsilon (a 25-kDa protein), and zeta (a 16-kDa protein). zeta is found in the complex as a disulfide-linked homodimer. The clonotypic chains and the invariant chains form a noncovalent complex on the cell surface. We have developed antibodies against each of the chains and used them to examine the assembly of the mature complex in the murine antigen-specific T-cell hybridoma 2B4. Pulse-chase studies of metabolically labeled cells demonstrate that many of the chains are synthesized in great excess over the amount assembled into the mature complex. These excess chains, either as free components or as partially assembled complexes, are rapidly degraded. This degradation most likely takes place in the lysosomes. The complete complex is quite stable with a long half-life. A specific hierarchy of partially assembled complexes can be discerned.
Animals↗
E-F hand structure-domain of calcium-activated neutral protease (CANP) can bind Ca2+ ions.
The cDNA fragments corresponding to the domains with four consecutive E-F hand structures in the large and small subunits of chicken and rabbit calcium-activated neutral protease (CANP) were inserted into an expression vector (pUC8 or pUC18). The resulting plasmids were used to transform E. coli, and isopropyl-1-thio-beta-D-galactoside (IPTG)-inducible expression was performed. The resulting four kinds of E-F hand structure-domains (the chicken large subunit, rabbit high- and low-calcium-requiring large subunits, and rabbit small subunit) were purified and analyzed for their calcium-binding abilities and capacities by the microscale filter assay. Most of the E-F hand structures could bind calcium and 2 or 4 mol of Ca2+ ions bound to the four consecutive E-F hand structures. The calcium-binding affinity of the E-F hand structures in the large subunit roughly corresponds to the calcium concentration required for its CANP activity.
Amino Acid Sequence↗
Studies on algal cytochromes VI: some properties and amino acid sequence of cytochrome c6 from a green alga, Bryopsis maxima.
A photosynthetic c-type cytochrome, cytochrome c6, was extracted from a green alga, Bryopsis maxima, by cutting and immersing the frozen thalli in phosphate buffer, pH 7.0, and purified by acrinol treatment, ammonium sulfate fractionation, DEAE-Sephacel chromatography and Bio-Gel P-10 gel filtration. The ferrcytochrome c6 has absorption maxima at 553.5 (alpha), 523 (beta), 417 (gamma), 318 (delta), and 275 nm, and the ferricytochrome at 695, 528, and 411 (gamma). The molecular weight was estimated to be about 10,000 from Sephadex G-75 gel filtration and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). The midpoint redox potential for the cytochrome was determined by equilibrium titration with a ferro- and ferricyanide system to be 0.385 volt at pH 7.0. Isoelectric points for ferro- and ferricytochromes were determined by density gradient isoelectric focusing electrophoresis to be at pH 3.91 and 4.02, respectively. The complete amino acid sequence of the cytochrome was determined by Edman degradation and by carboxypeptidase digestions of the Cm-cytochrome, 6 staphylococcal protease peptides and 5 lysyl endopeptidase peptides. The cytochrome contained 88 amino acid residues, giving a molecular weight of 9,904 including 1 mol of heme c. The sequence is as follows: GGDLEIGADVFTGNCAACHAGGANSVEPLKTLNKEDVTKYLDGGLSIEAITSQVRNGKGAMPAWSDRLD DEEIDGVVAYVFKNINEGW. A phylogenetic tree of 13 algal cytochromes c6 was constructed by comparing the amino acid differences.
Amino Acid Sequence↗