Extinction of T cell receptor alpha-chain gene expression accompanied by loss of the lymphoid enhancer-binding factor 1 (LEF-1) in murine somatic cell hybrids.

To investigate the presence of a negative regulatory factor(s) suppressing T-cell receptor alpha-chain (TCR alpha) gene expression in non-T cells, 10 independent cell hybrid clones were generated between mouse T-cell lymphoma EL4 cells (TCR alpha+/beta+) and mouse fibroblast B82 cells. These cell hybrids showed a typical fibroblastic morphology and retained an approximate sum of chromosome numbers derived from both parental cells. No transcripts of the TCR alpha gene were detected in the cell hybrids, although the presence of the rearranged TCR alpha allele from EL4 cells was confirmed.

Liver-specific Induction of NADPH-generating Enzymes by Polychlorinated Biphenyls in Rats.

The induction of NADPH-generating enzymes by polychlorinated biphenyls (PCB) in rats was investigated. The administration of PCB to rats for 3 and 14 days increased the activities of malic enzyme (ME, EC 1.1.

The effect of phlebotomy on serum erythropoietin levels in normal healthy subjects.

We evaluated endogenous serum erythropoietin (Epo) levels in 14 normal subjects (eight males and six females) after a single 400-ml phlebotomy. The subjects were followed up for 56 days. The hemoglobin (Hb) values of both males and females decreased to a nadir on days 3 to 7 post-phlebotomy.

Alteration of serum lipoprotein metabolism by polychlorinated biphenyls and methionine in rats fed a soybean protein diet.

The effects of dietary supplementation of methionine to a 20% soybean protein isolate diet on serum lipoprotein profiles and secretion rate of VLDL in rats receiving polychlorinated biphenyls (PCB) were investigated. Serum cholesterol levels were higher in rats fed PCB or a methionine supplement than in controls. The effects of PCB and methionine were synergistic.

Design, synthesis and antiinflammatory activity of a new indomethacin ester. 2-[N-[3-(3-(piperidinomethyl)phenoxy)propyl]carbamoylmethylthio]ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate.

A novel indomethacin ester prodrug, 2-[N-[3-(3-(piperidinomethyl)phenoxy)propyl]carbamoylmethylthio ]ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate (1) was prepared from a new histamine H2-receptor antagonist, N-[3-(3-(piperidinomethyl)phenoxy)propyl]-2-(2-hydroxyethylthio )acetamide (2) and indomethacin (3). The compound 1 was shown to be essentially similar to 3 in its antiinflammatory action and to almost completely inhibit carrageenin-induced hind-paw edema in the rat at a very high dose of 230 mg/kg (280 mumol/kg), which is comparable to that of 100 mg/kg (280 mumol/kg) of 3, without producing gastric lesions. On a molar basis, the acute gastric lesioning properties of 1 were near one-hundred times less than those of 3, resulting in over a twenty-fold improvement in the ratio of antiedema activity to ulcerogenicity.

Elevated gelsolin and alpha-actin expression in a flat revertant R1 of Ha-ras oncogene-transformed NIH/3T3 cells.

Expressions of gelsolin and alpha-actin have been investigated in a revertant cell line R1 and compared with the parental human activated Ha-ras oncogene-transformed NIH/3T3 (EJ-NIH/3T3), untransformed NIH/3T3 and partially revertant R2 cells. Gelsolin mRNA expression was strongest in R1 cells, intermediate in R2 and NIH/3T3 cells, and low in EJ-NIH/3T3 cells. Southern blot analysis gave neither signs of gross rearrangements nor amplification of the gelsolin gene.

Effect of methionine and threonine on the hypercholesterolemia induced by polychlorinated biphenyls in rats fed a nonprotein diet.

It was previously reported that the hypercholesterolemia induced by polychlorinated biphenyls (PCB) was influenced by dietary protein quantity and quality. On the other hand, the supplementation of methionine and threonine to a nonprotein diet ameliorated the body weight loss and decreased the urinary urea excretion in rats. We examined the effect of methionine and threonine supplements on the hypercholesterolemia induced by PCB in rats fed a nonprotein diet.

Effect of dietary methionine and polychlorinated biphenyls on cholesterol metabolism in rats fed a diet containing soy protein isolate.

The effects of supplementation of methionine to a 20% soy protein isolate diet on serum level of cholesterol. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, cholesterol 7 alpha-hydroxylase activity, and biliary and fecal steroids in rats with or without receiving polychlorinated biphenyls (PCB) were investigated. Supplementation of methionine and PCB did not affect the growth.

A polymorphic monoclonal antibody, PLM10, that reacts with B-cell lines carrying HLA-DPw1, DPw5, and DP "Cp63".

A monoclonal antibody, PLM10, that reacted with B-cell lines of DPw1, DPw5, and DP "Cp63" phenotypes was produced. The antibody was IgM isotype and efficiently lysed B cells but not T cells from approximately 50% of normal Japanese, raising the possibility of serologic typing of the DP polymorphism by the conventional complement-dependent cytotoxicity test.

[Pseudoaneurysm of the left ventricle serially demonstrated from on-set using two-dimensional echocardiography: a case report].

A case of so-called pseudoaneurysm of the left ventricle without pericardial adhesion, serially demonstrated by two-dimensional echocardiography, was reported. A 76-year-old man developed congestive heart failure 10 hours after gastrectomy, and was diagnosed as having acute myocardial infarction. Two-dimensional echocardiography on the 21st day after onset revealed moderate pericardial effusion and an echo-free space in the posterolateral myocardium of the left ventricle.

New synthetic substrate for kallikrein and its application.

We developed a new synthetic substrate, Pro-Phe-Arg-alpha-naphthyl ester, for kallikrein. We found that this substrate had higher specificity and sensitivity for kallikrein and was applied for the preparation of zymogram and for the histochemical demonstration. With Pro-Phe-Arg-alpha-NE as substrate, the minimum detectable concentration of human urinary kallikrein was about 0.

Inhibitory effect of a new synthetic protease inhibitor (FUT-175) on the coagulation system.

The inhibitory effects of 6-amidino-2-naphthyl-4-guanidinobenzoate X dimethanesulfonate (FUT-175) on the human Hageman factor fragment (HFf), factor Xa, thrombin, plasma kallikrein, and plasmin were studied. FUT-175 inhibited plasma kallikrein most (IC50 = 3.0 X 10(-9) M), followed by HFf (IC50 = 3.

Detection of intermediary Clr with complete active site, using a synthetic proteinase inhibitor.

The synthetic proteinase inhibitor, FUT-175 (6-amidino-2-naphthyl-4-guanidinobenzoate), strongly suppressed activation of Clr at 37 degrees C, causing 50% inhibition at 0.03 mM. To clarify whether the inhibitor was incorporated into the active site of intermediary Clr formed during the incubation, determination of the active site was tried using this inhibitor.

New synthetic inhibitor to the alternative complement pathway.

The inhibitory effects of 6-amidino-2-naphthyl 4-guanidinobenzoate (FUT-175) on the activities of factor B, factor D and cobra venom factor (CVF) X Bb were examined. FUT-175 bound specifically to the Bb fragment of factor B or CVF X Bb. FUT-175 was a non-competitive inhibitor of the esterolysis of L-leucyl-L-alanyl-L-arginine naphthylester by factor B and CVF X Bb.

Cytochemical demonstrations of protease in human peripheral blood cells by use of new alpha-naphthyl ester substrates.

The proteases of human leukocytes were cytochemically studied by use of new alpha-naphthyl esters, tosyl-L-lysine-alpha-naphthyl ester (TLNE) and acetyl-L-tyrosine-alpha-naphthyl ester (ATNE). The hydrolytic activities were strong only in neutrophils, with both substrates. They were inhibited completely by DFP and chymostatin, but not by leupeptin and iodoacetate.

A sensitive colorimetric assay for thrombin, prothrombin and antithrombin III in human plasma using a new synthetic substrate.

Benzoyl-L-leucyl-L-alanyl-L-arginine-alpha-naphthylester (Bz-Leu-Ala-Arg-NE) was synthesized as a new substrate for use in the assay of thrombin. In the assay alpha-naphthol released by the enzyme reaction was measured colorimetrically. With Bz-Leu-Ala-Arg-NE as substrate, the minimum detectable concentration of human thrombin was 0.

Inhibition of various immunological reactions in vivo by a new synthetic complement inhibitor.

FUT-175 (6 amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, inhibits the enzyme activities of various proteases, such as Clr, C1 esterase, thrombin, kallikrein, plasmin and trypsin. FUT-175 strongly inhibited complement-medicated hemolysis via the classical and alternative pathways. The effects of FUT-175 on various immunological reactions in vivo were studied.

New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin.

p-Guanidinobenzoate derivates were prepared and their inhibitory effects on trypsin, plasmin, pancreatic kallikrein, plasma kallikrein, thrombin, C1r and C1 esterase were examined. Among the various inhibitors tested, 6'-amidino-2-naphthyl-4-guanidinobenzoate dihydrochloride, 4-(beta-amidinoethenyl)phenyl-4-guanidinobenzoate dimethanesulfonate and 4-amidino-2-benzoylphenyl-4-guanidinobenzoate dimethanesulfonate were the most effective inhibitors of trypsin, plasmin, pancreatic kallikrein. plasma kallikrein and thrombin and they strongly inhibited the esterolytic activities of C1r and C1 esterase, and then strongly inhibited complement-mediated hemolysis.