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Biomedical subjects

Y Seto

Publications and source records attributed to Y Seto.

At least 127 records · Page 7Linked to original sources

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↗

Recombinant human tumor necrosis factor causes long-lasting and prostaglandin-mediated fever, with little tolerance, in rabbits.

The pyrogenic properties of high purified recombinant human tumor necrosis factor (rHu-TNF) were investigated in rabbits. rHu-TNF produced a clear biphasic fever reaching maximal values at 1 and 5 hr after bolus i.v. injections of 10 and 33 micrograms/kg; the initial febrile response was short-lasting, and not dose-related, but the second one was dose-related and lasted for 10 hr or more. The febrile response to rHu-TNF, unlike lipopolysaccharide, did not decrease after a single or two consecutive doses. A significant reduction in the febrile response, however, was seen after four consecutive doses starting from 7 days after the second dose; the febrile response 3 hr after rHu-TNF was much smaller, but the first peak was hardly smaller. Low anti-rHu-TNF levels were found in serum of rabbits treated repeatedly with rHu-TNF, suggesting that antibody production against rHu-TNF is not responsible for the tolerance formation although it may make some contribution. There was no cross-tolerance between rHu-TNF and lipopolysaccharide. On the other hand, the febrile response to rHu-TNF (33 micrograms/kg i.v.) was inhibited partially or completely blocked by i.v. administration of cyclooxygenase inhibitors or dexamethasone. rHu-TNF produced a marked increase in the cerebrospinal fluid prostaglandin E2 level after bolus i.v. injection. A significant level of rHu-TNF (1.6 and 6.4% of that in serum) was found in cerebrospinal fluid after bolus i.v. injection of 33 and 1000 micrograms/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Homology between mammalian DNA polymerase beta and terminal deoxynucleotidyltransferase.

Nucleotide sequence analysis of the cDNA and the genomic clones for rat DNA polymerase beta revealed the existence of a 1,005-base pair open reading frame capable of encoding a Mr = 38,269 polypeptide of 335 amino acid residues. The region of 174 amino acid residues between the 42nd and 215th residues of the DNA polymerase beta polypeptide has extensive amino acid sequence homology with the region between the 195th and 366th residues of human terminal deoxynucleotidyltransferase. The two enzymes share extensive homology not only in primary structures but also in the computer-derived higher structures in these particular regions. The genes for DNA polymerase beta and terminal deoxynucleotidyltransferase are proposed to be derived from a common ancestral DNA polymerase gene.

Amino Acid Sequence↗

Soybean hydrophobic protein. Isolation, partial characterization and the complete primary structure.

A 9000-Mr protein isolated from a 60% ethanolic extract of soybean (Glycine max) seeds has been characterized and fully sequenced. The protein consists of 80 amino acid residues with four disulfide bonds. It contains a large number of hydrophobic residues and lacks methionine, phenylalanine, tryptophan, lysine and histidine residues. The protein readily crystallizes from water but is quite soluble in aqueous organic solvents like 95% 1-propanol. It aggregates to form large molecules (above 80 kDa) under ordinary denaturing conditions, such as 6 M guanidine X HCl and 8 M urea. Sequence analysis showed that the amino-terminal four-fifths is extremely hydrophobic and most of the acidic residues exist as their amide forms, and only the carboxyl-terminal short segment is rather hydrophilic. A computer search for homology detected an unexpected similarity of this protein to rat prolactin; however, its significance could not be assessed and this protein appears to represent a hitherto unknown protein family. Although no biochemical activity could be detected, the existence in relatively high abundance (approx. 200 mg from 1 kg seeds) of this novel protein may suggest its physiological significance in the plant.

Amino Acid Sequence↗

Chronic active hepatitis with histological features of primary biliary cirrhosis.

A 51-year-old woman was evaluated because of Raynaud's phenomenon, Sjögren's syndrome, and general malaise. There was neither skin itching nor jaundice. Endoscopic retrograde cholangiopancreatography showed a normal extrahepatic as well as intrahepatic biliary tree. Serum GOT and GPT fluctuated with episodes of marked increases. The alkaline phosphatase was slightly increased and total cholesterol was normal. There were marked increases of IgG and IgM. AMA was positive at a titer of 1:320, which was measured by an indirect immunofluorescence method. PBC-specific AMA (anti-M2) was positive, but mixed-form AMA (anti-M4) negative. An LE-cell test, ASMA, ANA, and anti-DNA antibody were all positive on several repeated tests. A wedge liver biopsy tissue showed mixed features of PBC and CAH. A diagnosis of CAH was made on the basis of the clinical, serological, and morphologic findings. The patient responded well to prednisolone treatment with prominent improvement of her symptoms and liver function tests. Subsequently, AMA fell to undetectable levels by indirect immunofluorescence method.

Antibodies↗

Relationship of the distribution of Leu-2+ cells with suppressor cell activities in the spleen and lymph-nodes from gastric cancer.

Tissue distributions of Leu-2+ cells in the spleen and draining lymph-nodes in cases of clinical gastric cancer were investigated, with special reference to suppressor cell function. Significantly higher Concanavalin-A (Con-A) induced suppressor cell activities were evident in spleen cells (SCs), as compared with peripheral blood lymphocytes (PBLs). As for the tissue distribution, the proportion of Leu-2+ (cytotoxic/suppressor) cells within Leu-1+ cells was higher in the spleen than in the lymph-nodes without metastasis. On the other hand, in lymph-nodes with metastasis, the enhanced spontaneous suppressor cell activity was noted. In addition, the proportion of Leu-2+ cells within Leu-1+ cells was the greatest in the lymph-nodes with metastasis, among the lymphoid organs tested. In lymph-nodes without metastasis, lower suppressor cell activities were noted, and numerous Leu-3+ (helper/inducer) cells were present, while Leu-2+ cells were less frequent. NK cell activity against K-562 cells was enhanced by elimination of Leu-2+/OKT-8+ cells with complement-mediated lysis. These results suggest that Leu-2+ cells located in the spleen and lymph-nodes with metastasis may predominantly act as suppressor cells and interact with effector cells.

Adult↗

[The mode of anti-inflammatory action of a topical non-steroidal anti-inflammatory drug, etofenamate].

In order to ascertain the mode of anti-inflammatory action of a topical non-steroidal anti-inflammatory drug, etofenamate which is a diethylene glycol ester of flufenamic acid, the in vitro test for the mechanism of the action were carried out. Etofenamate (3 microM) was hydrolysed to flufenamic acid at a rate of 39.5% and 57.0% of the dose during 30 and 60 min incubation, respectively, when incubated with rat peritoneal macrophages stimulated with starch and bacto peptone in phosphate-buffered saline. PGE2 generation by these cells in MEM medium was dose-relatedly inhibited with etofenamate as well as flufenamic acid at the dosage range of 1 to 30 microM. This suggests that unchanged etofenamate is active, since the highest conversion rate of etofenamate to flufenamic acid was 15% of the dose during the incubation. Etofenamate produced a dose-related inhibition against lipoxygenase prepared from peritoneal polymorphonuclear leucocytes of guinea pigs, and its activity (IC50 = 5.3 X 10(-5) M) was stronger than that of caffeic acid; flufenamic acid was inactive. Inhibitory activity of etofenamate was one-third or less that of flufenamic acid against the hypotonic-hyperthermic lysis of rat erythrocytes and heat-denaturation of bovine serum albumin. From these results, it was suggested that topically applied etofenamate produces its anti-inflammatory action through prostaglandin synthesis inhibition by flufenamic acid produced in the inflammatory tissue and inhibition of prostaglandin synthesis by macrophages and lipoxygenase inhibition by unchanged etofenamate.

Administration, Topical↗

A case of hyperbilirubinemia during treatment with chenodeoxycholic acid.

This is a report of a 27-year-old female with hyperbilirubinemia during treatment with chenodeoxycholic acid (CDCA) for the resolution of gallstones. After CDCA administration, serum bilirubin increased markedly without an apparent obstruction of bile ducts. The histological findings of the liver were compatible with toxic liver injury. Bile acids analysis, however, did not reveal the increment of lithocholic acid, toxic metabolite of CDCA in the serum and the hepatic tissue. The bile acids sulfation and the 6 alpha-hydroxylation of CDCA were also normal. Her jaundice disappeared quickly after discontinuation of CDCA. Presumably, in this case, the stagnation of bile acids in the liver caused by choledochal sands facilitated the toxic effect of CDCA on the damaged hepatocytes.

Adult↗

[Damaging action of human recombinant TNF on tumor vessels as an aspect of its anti-neoplastic action against Meth A sarcoma in mice].

Effect of human recombinant TNF (rHu-TNF) on tumor blood vessels was investigated in relation to its mode of anti-neoplastic action against Meth A sarcoma in BALB/c mice. The extent of the blood vessel lesion was evaluated by measuring the degrees of blueing and hemorrhage after intravenous injection of Evan's blue. When injected intravenously into mice bearing Meth A cells in the abdominal skin transplanted 8 days previously, rHu-TNF, at doses of 3000 and 10,000 units/mouse produced dose-related lesioning of blood vessels in the sarcoma and the adjacent skin but not in the skin distant from the sarcoma. Similar lesioning of blood vessels in the adjacent skin was seen after intravenous administration of 10,000 units/mouse of rHu-TNF in mice with the sarcoma in which the cells had been selectively killed by intratumoral injection of acetic acid (20%, 0.01 ml). On the other hand, rHu-TNF (10,000 units/mouse, i.v.) produced weak lesioning of blood vessels in the granuloma tissue caused by subcutaneous implantation of felt pellets and in the adjacent skin but not in the operation wound in mice with the sarcoma. These results suggest that rHu-TNF damages newly formed blood vessels, particularly those connected with the sarcoma, without influencing blood vessels in normal skin and healing wounds in mice with Meth A sarcoma.

Animals↗

Unusual trihydroxy bile acids in the urine of healthy humans.

The urinary bile acids of 20 adults (aged between 20 and 40 yr), 17 neonates (below 1 week old) and 15 aged men (older than 80 yr old) who were all healthy, were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Frequently, three unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid and omega-muricholic acid were detected as minor components. Our data further suggest that the metabolism of unusual trihydroxy bile acids in the healthy humans is related to age.

Adult↗

Role of the spleen on immunosuppression in esophageal and gastric cancer.

To elucidate the role of the spleen on immunosuppression of gastric and esophageal cancer, suppressor cell activities of spleen cells (SCs), splenic vein lymphocytes (SVLs) and peripheral blood lymphocytes (PBLs) were investigated. Concanavalin-A induced suppressor cell (Con-AS) activity of SCs was significantly higher in patients with gastric cancer than in those with benign diseases. Higher Con-AS activity of SCs was observed in esophageal cancer patients with tumors located in the lower portion of the esophagus. In comparison with suppressor activities of SCs and SVLs, the decrease of the predominance of suppressor precursors in SCs and the increase of the spontaneously activated suppressor cells in SVLs were noted with the advance of the tumors. Culture supernatants from splenic adherent cells significantly induced suppressor cell activities as well as did sera from splenic venous blood. From these results, it is concluded that the generation of suppressor precursors in the spleen is dependent on the location of tumors and that the maturation of suppressor cells occurs in the spleen by factors released from splenic adherent cells, then migrates into the peripheral blood.

Adult↗