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Biomedical subjects

Y Seto

Publications and source records attributed to Y Seto.

At least 109 records · Page 6Linked to original sources

Expression cloning of a receptor for murine granulocyte colony-stimulating factor.

Two cDNAs encoding the receptor for murine granulocyte colony-stimulating factor (G-CSF) were isolated from a CDM8 expression library of mouse myeloid leukemia NFS-60 cells, and their nucleotide sequences were determined. Murine G-CSF receptor expressed in COS cells could bind G-CSF with an affinity and specificity similar to that of the native receptor expressed by mouse NFS-60 cells. The amino acid sequence encoded by the cDNAs has demonstrated that murine G-CSF receptor is an 812 amino acid polypeptide (Mr, 90,814) with a single transmembrane domain. The extracellular domain consists of 601 amino acids with a region of 220 amino acids that shows a remarkable similarity to rat prolactin receptor. The cytoplasmic domain of the G-CSF receptor shows a significant similarity with parts of the cytoplasmic domain of murine interleukin-4 receptor. A 3.7 kb mRNA coding for the G-CSF receptor could be detected in mouse myeloid leukemia NFS-60 and WEHI-3B D+ cells as well as in bone marrow cells.

Amino Acid Sequence↗

Unusual trihydroxy bile acids in the urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis.

Urinary bile acids from 20 patients treated with chenodeoxycholate, 18 treated with ursodeoxycholate, 15 treated with rifampicin and 8 patients with advanced cirrhosis were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Occurrence rates and amounts of three so-called unusual trihydroxy bile acids, hyocholate, ursocholate and omega-muricholate, were increased in patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and decreased in cirrhotic patients as compared with those in untreated healthy adults. These data suggest that chenodeoxycholate and ursodeoxycholate are hydroxylated to produce unusual trihydroxy bile acids in bile acid-loaded humans and that this metabolism may be related to the induction of hepatic microsomal enzymes by rifampicin. In contrast, the hydroxylation of chenodeoxycholate and ursodeoxycholate may be impaired by severe hepatic damage. Because the urine is a secretory pathway for internal bile acids, the occurrence of unusual trihydroxy bile acids in the urine may be used as an indicator of hepatic ability to metabolize "hydrophobic" dihydroxy bile acids to their secretory forms.

Bile Acids and Salts↗

Fragment peptide library for classification and functional prediction of proteins.

From protein sequence comparison data found in the literature, a library was organized using peptide fragment sequences which are common to related proteins. Each of the fragments was then examined for its occurrence in all the protein superfamilies defined by the NBRF-PIR data base. We have selected those fragment peptides that appear exclusively in one or a few superfamilies, and thus made a library of fragment peptides that characterize specific superfamilies. Such characteristic peptides are, in general, five to seven residues long and contain unusually high proportions of glycine and cysteine. This collection is a useful resource for the classification and functional prediction of protein molecules.

Amino Acid Sequence↗

Three different mRNAs encoding human granulocyte colony-stimulating factor receptor.

Three cDNAs for the human granulocyte colony-stimulating factor (G-CSF) receptor were isolated from the cDNA libraries of human U937 leukemia cells and placenta by using a murine G-CSF receptor cDNA as the probe. The human G-CSF receptor containing 813 amino acids had a marked homology (62.5%) with its murine counterpart and consisted of extracellular, transmembrane, and cytoplasmic domains. The WSXWS motif found in members of the newly identified growth factor receptor family was also present in the extracellular domain of the human G-CSF receptor. Expression of the cloned cDNA in monkey COS cells gave rise to a protein that could specifically bind G-CSF with a high affinity (Kd, 550 pM). Two other classes of the human G-CSF receptor were also identified, one of which had a deletion of the transmembrane domain and seemed to encode a secreted, soluble receptor. The third class of the G-CSF receptor contained a 27-amino acid insertion in the cytoplasmic domain and was highly expressed in placenta.

Amino Acid Sequence↗

Calcium-associated cytoprotective effect of taurine on the calcium and oxygen paradoxes in isolated rat hepatocytes.

Our study was designed to determine the calcium and oxygen paradoxes in isolated rat hepatocytes, and to evaluate the cytoprotective effects of taurine on hepatocytes during oxygenation, hypoxia, and on these paradoxes. The calcium and oxygen paradoxes were clearly revealed in isolated rat hepatocytes. As the formation of the superoxide radical was accelerated by the hyperbaric conditions and the calcium ions, drugs such as superoxide dismutase and a calcium channel blocking agent (verapamil), prevented these paradoxes. Taurine decreased the oxygenation-induced lipid peroxidation of hepatocytes, and prevented the hypoxia-induced hepatocyte death in a calcium-containing medium, but not in a calcium-free medium. Taurine also protected the hepatocytes from injuries associated with the calcium and oxygen paradoxes due to the inhibition of sudden calcium influx into the hepatocytes.

Animals↗

[A calcified mucinous adenocarcinoma of the stomach--case report].

The paper discusses the case of a 44-year-old woman with an epigastric discomfort at Hiroshima University Hospital. A barium study of the stomach showed rigidity and a giant fold. A subsequent abdominal roentgenogram and CT disclosed calcification throughout the stomach wall. Thus, is hopes of effecting a cure, a total gastrectomy, a partial resection of transverse colon, a splenectomy and a pancreatic tail resection were performed. A surgical specimen macroscopically presented an inelastic and thickened wall of the entire stomach, and deposits of whitish calcium were visible within the gastric wall. The pathological diagnosis indicated a mucinous adenocarcinoma, se, INF alpha, v2, ly3, n4 (No. 221), with calcification of this mucinous adenocarcinoma in the stomach.

Adenocarcinoma, Mucinous↗

Size fractionation of oligosaccharides by liquid chromatography on a cation-exchange column.

Oligosaccharides, labelled with 2-aminopyridine at their reducing ends, were satisfactorily fractionated according to the sugar sizes on Shodex RSpak DC-613, a cation-exchange resin column (Na+ form), with water-acetonitrile as the eluent in the presence of sodium acetate or triethylammonium acetate buffer. For the fractionation of sugar samples, dextran hydrolyzates, chitin oligomers and oligosaccharide moieties of ovomucoid were used. The oligosaccharides were strongly adsorbed to the resin column with solvents containing less water and at lower temperature, and were eluted in order of increasing molecular size above the critical concentration of acetonitrile. Baseline separation of a dextran hydrolyzate up to oligomers having 20 glucose units was observed by gradient elution. The separation efficiency and elution pattern were investigated by changing the buffer concentration, mobile phase pH and temperature.

Chromatography, Ion Exchange↗

N-(cyclohexylcarbonyl)-D-phenylalanines and related compounds. A new class of oral hypoglycemic agents. 2.

A series of analogues of N-(cyclohexylcarbonyl)-D-phenylalanine (5) have been synthesized and evaluated for their hypoglycemic activity. Relationships were studied between the activity and the three-dimensional structure of the acyl moiety, which was characterized by high-resolution 1H NMR spectroscopy and MNDO calculations. The role of the carboxyl group of the phenylalanine moiety was also studied by comparing the activities of the enantiomers, the decarboxyl derivative, the esters, and the amides of the phenylalanine derivatives. Thus, the structural requirements for possessing hypoglycemic activity was elucidated and a highly active compound, N-[(trans-4-isopropylcyclohexyl)carbonyl]-D-phenylalanine (13) was obtained, which showed a 20% blood glucose decrease at an oral dose of 1.6 mg/kg in fasted normal mice.

Administration, Oral↗

Normal somatomedin-C activity measured by radioimmunoassay in Perthes' disease.

In recent years, the association between somatomedin and Perthes' disease has been investigated. Somatomedin activity measured by different methods (i.e., bioassay and radioreceptor assay) has generated variable results. The purpose of this study was to examine plasma somatomedin-C activity in Perthes' disease using radioimmunoassay. Somatomedin-C activity in affected boys and girls between six and 11 years of age was normal compared to the standard data on normal children. It is difficult to prove a functional pituitary somatomedin target axis. Therefore, caution is advisable before hypothesizing an etiology of Perthes' disease on the basis of results of plasma somatomedin concentration.

Child↗

Structure-activity relationship of reversible cholinesterase inhibitors including paraquat.

The inhibitory effect of paraquat on cholinesterase activity was investigated in comparison with four paraquat derivatives, six monoquaternary ammoniums and six anticholinergic drugs. Inhibitor concentrations to cause 50% inhibition (I50) and Hill coefficients for three enzymes, human erythrocyte acetylcholinesterase (AChE), Electrophorus electricus AChE and human plasma butyrylcholinesterase (BuChE) were measured. The results obtained were as follows. The I50 for erythrocyte AChE was similar to the I50 for eel AChE. Secondary to edrophonium, diethylparaquat, paraquat, morfamquat and monoquat showed lower I50 for AChE, and possessed higher inhibition selectivity (IS), expressed as the ratio of I50 for BuChE to I50 for erythrocyte AChE. However, diquat showed higher I50 for AChE and lower IS, similar to the other monoquaternary ammoniums. A negative correlation was observed between log [I50 for erythrocyte AChE] and log [IS], among paraquat and its derivatives, monoquaternary ammoniums and anticholinergic drugs, respectively. With respect to Hill coefficients, these inhibitors could be classified into four groups, [1] competitive inhibitors: diquat, edrophonium, choline, tetramethylammonium and trimethylphenylammonium, [2] inhibitors showing negative cooperativity: paraquat, diethylparaquat, morfamquat, d-tubocurarine, atropine, gallamine and nicotine, [3] moderate type inhibitors: monoquat, hexamethonium and decamethonium. [4] the other type inhibitors showing positive cooperativity for erythrocyte AChE: tetraethylammonium and ethyltrimethylammonium.

Animals↗

Immunocytochemical study on the variation in estrogen receptors of primary and nodal metastases of breast cancer.

The variation in estrogen receptors (ER) between primary and regional nodal metastatic lesions was examined by an estrogen receptor immunocytochemical assay (ER-ICA) in 25 mammary carcinoma patients. The ER status was evaluated in terms of the percentage of ER positive stained cells, staining intensity and distribution of those stained cells. The overall ER status was consistent in both sites, however, the percentage of ER positive cells and the staining intensity were not always consistent. A decrease in the percentage of ER positive cells and staining intensity was demonstrated in the nodal metastatic lesions of 4 and 3 cases out of a total 14 ER positive cases, respectively. The mean percentage of ER positive cells in the nodal metastatic lesions was 57 per cent compared with 73 per cent in primary lesions. Thus, a tendency of both the percentage of ER positive cells and the staining intensity to decrease in nodal metastases as when compared with primary lesions in breast cancer was demonstrated.

Antibodies, Monoclonal↗

N-acylphenylalanines and related compounds. A new class of oral hypoglycemic agents.

N-Benzoyl-DL-phenylalanine (1) was found to possess hypoglycemic activity. A series of the analogues of compound 1 were prepared and evaluated for their blood glucose lowering activity. Both the steric effects of the phenylalanine moiety and the effects of variations in the acyl moiety were investigated. This study elucidated some of the structure-activity relationships and led to the development of N-(4-ethylbenzoyl)-D-phenylalanine (34), which was 50 times more potent than the initial compound 1.

Animals↗

[A correlation between the species differences in anti-inflammatory activity of AD-1590, a non-steroidal anti-inflammatory drug, and its plasma level].

Authors have reported that the oral potency ratio of AD-1590 to indomethacin varies with the animal models employed; the ratio is 4, 2.3 and 31 in the tests of acetic acid-induced vascular permeability (male mice), carrageenan hind paw edema (male rats) and UV-erythema (female guinea pigs), respectively. Thus, the relationship between the difference in the anti-inflammatory activity of AD-1590 among animal models and the species difference of the plasma AD-1590 level was investigated in experimental animals in order to ascertain the cause of the difference in the potency ratio. Inhibitory potency of AD-1590 on UV-erythema and increased vascular permeability induced by acetic acid in male rats was about 2.1 and 2.3 times, respectively, that of indomethacin. On the other hand, after a single oral administration of 5 mg/kg, the highest plasma AD-1590 level was seen in female guinea pigs (AUC9-8 hr = 63.1 micrograms.hr/ml); and followed by that in mice (male, 32.1; female, 36.1) greater than male dogs (11.5) greater than or equal to rats (male, 9.02; female, 12.5), male rabbits (9.17) greater than male monkeys (9.34 at 6 mg/kg). Hucker et al. have reported that the plasma level of indomethacin in rats is several times higher than that in guinea pigs, rabbits and monkeys. These results suggest that most of the species difference in the relative potency of AD-1590 to indomethacin in the anti-inflammatory activity results from the species difference in the plasma level of both drugs.

Animals↗