[Serum elastase I and amylase concentrations in non-insulin-dependent diabetes mellitus].
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Biomedical subjects
Publications and source records attributed to H Taguchi.
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Peripheral blood lymphocytes from 2 normal individuals seronegative for human T-cell leukemia virus type I (HTLV-I) were co-cultured with HTLV-I-producing MT-2 cells that had been heated at 56 degrees for 30 min or exposed to 10,000 rad of X-irradiation. HTLV-I-induced lymphocyte transformation was consistently achieved by co-culture with irradiated MT-2 cells but not by co-culture with heated MT-2 cells. The heat treatment was found to be lethal to both MT-2 cells and the virus. These findings are discussed in terms of their potential clinical application for preventing the transmission of HTLV-I.
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Triiodothyronine (T3) uptake as determined with albumin (AT3U) and with charcoal (CT3U) as binders were compared for patients with low-T3 syndrome. Both T3U values were identical in normal subjects and in patients with thyroidal disorders, pregnancy, low thyroxin-binding globulin (TBG), or acute hepatitis with high concentration of TBG. In the low-T3 syndrome, AT3U was significantly higher than CT3U (38.5 +/- 7.2% vs 29.4 +/- 4.9%, mean +/- SD, n = 37, p less than 0.001), and this difference increased as TBG and albumin concentrations decreased. Decreasing the concentration of TBG and albumin in serum by dilution increased the AT3U more than the CT3U value. Adding albumin to serum decreased AT3U, but not CT3U, when serum TBG and albumin concentrations were low. The free-thyroxin (T4) index as calculated by the AT3U ratio and T4 more accurately reflects the concentration of free T4 in low-T3 syndrome than does the index calculated from the CT3U ratio and T4. Thus AT3U is determined primarily by changes in TBG and albumin concentrations, so that the free-T4 index based on the AT3U ratio and T4 may be more useful than the CT3U method for evaluating free-T4 concentrations in low-T3 syndrome, which frequently has concomitant decreases in TBG and albumin concentrations.
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A multilocular lesion was found in the left lobe of the liver in a 70-year-old woman who had complained of jaundice, fever and tumor of epigastrium. There was a continuous and branching cystic lesion in the resected left lobe of the liver diffusely, and communication with the right hepatic duct and the extrahepatic duct was recognized. These cystic spaces were filled with bile and mucus. The inside of the wall was covered with columnar epithelium showing papillay proliferation with marked mucin production. Furthermore, adenocarcinoma was demonstrated in multifoci surrounded by hyperplastic and dysplastic epithelium. This case was diagnosed as congenital dilatation of the intrahepatic bile duct accompanying adenocarcinoma.
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Two cases of human T-cell leukemia virus (HTLV)-positive adult T-cell leukemia (ATL) in brother and sister are presented. Six of 15 members of this family were seropositive for antibodies for ATL-associated antigens (ATLA). The sister of the ATL patient developed overt ATL after 5 years and 8 months of smoldering ATL. Immunologic examinations during the smoldering phase were normal except for negative skin tests for purified protein derivative. Factors leading to the induction of ATL among HTLV carriers remain to be studied.
Holotryptophanase inactivated by oxidation of cysteinyl residues showed a different absorption spectrum from the native enzyme. At pH 8.0, the native enzyme preferentially existed as a 337-nm species (active form), whereas in the inactive enzyme a 420-nm species (inactive form) was dominant. During the reactivation of the enzyme by reduction with dithiothreitol, an increase at 337 nm and a decrease at 420 nm were observed with concomitant increase in enzymatic activity, which was accompanied by the appearance of two cysteinyl residues per monomer. Specific S-cyanylation of cysteinyl residues by nitrothiocyanobenzoic-acid-inactivated apotryptophanase with the modification of one cysteinyl residue per monomer, whereas holotryptophanase was highly resistant to inactivation with nitrothiocyanobenzoic acid. The essential role of the active-site-bound pyridoxal 5'-phosphate in protection against inactivation was confirmed by the agreement of the K1/2 (protection) of 5.0 microM for pyridoxal 5'-phosphate with Km of 2.0 microM in enzyme catalysis. The inactivation by nitrothiocyanobenzoic acid caused a similar shift in the equilibrium between the 337-nm species and 420-nm species, i.e. decrease of the 337-nm species and increase of the 420-nm species. From the pH dependence of the equilibrium between these two species, pKa of 7.9 and 7.4 was obtained for the inactive and the dithiothreitol-activated enzyme, respectively, indicating that cysteinyl residue(s) participated in lowering the pKa of the interconversion between the 337-nm species (active form) and 420-nm species (inactive form). The possible role of cysteinyl residues in the function of tryptophanase is discussed.
Chromosome abnormalities, sister chromatid exchanges (SCE), and cell cycle kinetics were studied in phytohemagglutinin-stimulated lymphocytes from 8 adult T cell leukemia (ATL) patients. In all these cases, chromosome abnormalities were observed in 5-day PHA-stimulated cultures. Four cases had characteristic marker chromosomes; two were due to a balanced translocation, t(9;21), and two to a simple deletion, 5p-. The other four cases, however, had rather complicated chromosome abnormalities, e.g., 1q+, 2q+, 5q+, 6q-, 14q+, 10p-. When chromosome abnormalities were analyzed in previously reported cases, the abnormalities were mostly distributed among chromosomes #1, #2, #5, #6, #14, and #21. These findings suggest that the abnormalities involving #1, #2, #5, #6, #14, and #21 are intimately related to ATL. The SCE frequency was in the normal range in ATL cells. Cell cycle analysis revealed that the duration of two cell cycles in cells labeled with bromodeoxyuridine (BrdU) required approximately 80 hr in ATL cells, whereas the time of two cell cycles in normal cells is 40 hr. These findings indicate that the ATL cell cycle time is about 40 hr, about double that of normal cells (20 hr), in PHA-stimulated cultures. ATL has been known to be a mature T cell leukemia and to respond poorly to chemotherapy. The latter may be due to the elongated cell cycle or to the mature characteristics of the leukemic cells. The association of ATL with cutaneous T cell lymphoma is also discussed.
A rabbit lymphoid cell line (Ra-1) was established by co-cultivation with a human T-cell line (MT-2) carrying human T-cell leukemia virus (HTLV). The Ra-1 cell line is chromosomally male and is persistently infected with HTLV. Ra-1 cells, with or without mitomycin C treatment, were inoculated intravenously (i.v.) into 3 female rabbits. All 3 animals responded with the production of antibodies to HTLV antigens. Lymphocytes from one of these seroconverters were cultured in the presence of T-cell growth factor (TCGF) and HTLV particles were detected in the TCGF-grown lymphocytes which were chromosomally female. Co-cultivation of lymphocytes from the 2 other seroconverters with lymphocytes from 2 anti-HTLV-negative healthy men gave rise to the establishment of an HTLV-producing T-cell line derived from each individual. Blood transfusion from one of the HTLV-infected rabbits into 2 female rabbits also resulted in the seroconversion of both recipients. An HTLV-carrying lymphoid cell line (Ra-2) was established from one of the transfusion-related seroconverters. The Ra-2 cell line was initially TCGF-dependent but later became TCGF-independent. There results indicate that HTLV can be transmitted to rabbits. These animals may provide a suitable model system for studying the mode of transmission and pathogenicity of HTLV.
Two cDNA clones for rat heme oxygenase have been isolated from a rat spleen cDNA library in lambda gt11 by immunological screening using a specific polyclonal antibody. One of these clones has an insert of 1530 nucleotides that contains the entire protein-coding region. To confirm that the isolated cDNA encodes heme oxygenase, we transfected monkey kidney cells (COS-7) with the cDNA carried in a simian virus 40 vector. The heme oxygenase was highly expressed in endoplasmic reticulum of transfected cells. The nucleotide sequence of the cloned cDNA was determined and the primary structure of heme oxygenase was deduced. Heme oxygenase is composed of 289 amino acids and has one hydrophobic segment at its carboxyl terminus, which is probably important for the insertion of heme oxygenase into endoplasmic reticulum. The cloned cDNA was used to analyze the induction of heme oxygenase in rat liver by treatment with CoCl2 or with hemin. RNA blot analysis showed that both CoCl2 and hemin increased the amount of hybridizable mRNA, suggesting that these substances may act at the transcriptional level to increase the amount of heme oxygenase.
Clinical toxicities and pharmacokinetics of methotrexate (MTX), associated with reduced citrovorum factor (CF) neutralization, were studied on 279 infusions in 25 children with various malignancies. MTX, at 1000-8400 mg/m2, was infused during six to 24 hours with multiple schedules of reduced CF rescue. Plasma MTX levels ranged from 7.0 X 10(-5) to 7.0 X 10(-4) M during MTX infusion. The levels declined rapidly with a two-phase elimination pattern (t1/2 = 1.2-2.5 hours, t1/2 = 18-32 hours). The folate level in the plasma ranged from 5 X 10(-7) M to 1.4 X 10(-6) M when CF was administered every six hours or every three hours, respectively. Limited bone marrow suppression was seen in only seven percent of infusions, with moderate elevation of GOT and GPT in 20% of infusions, and stomatitis in only 2.6% of infusions, despite reduction in the total dose of CF from 225 mg to 105 mg and despite delaying CF initiation from nine hours to thirty-six hours after the start of MTX infusion.
The concentration of serum thyroxine (T4)-binding globulin (TBG) not binding T4 (unsaturated TBG, u-TBG) was determined in hyper- and hypothyroidism. u-TBG was expressed as the product of TBG concentration and the ratio of free TBG capacity to maximal TBG capacity as determined by reverse-flow electrophoresis. u-TBG concentration in normal sera (n = 40) was 15.5 +/- 2.3 mg/l (mean +/- SD), or 257 +/- 38 nmol/l for a molecular weight of TBG of 60 000 daltons. u-TBG levels were significantly lower in hyperthyroidism (7.1 +/- 2.3 mg/l, n = 16, P less than 0.001) and higher in hypothyroidism (21.7 +/- 5.0 mg/l, n = 22, P less than 0.001). Based on partial correlation analysis, u-TBG was inversely correlated to serum T4 (r = -0.586, P less than 0.001), but not correlated to triiodothyronine (T3) (r=-0.180, NS). There was a reciprocal correlation between u-TBG concentration and the T3 uptake value (r = 0.748, P less than 0.001). There was also a reciprocal correlation of u-TBG with both % free T4 (r = 0.425, P less than 0.001) and % free T3 (r = 0.377, P less than 0.001), when the data were subjected to partial correlation analysis. These results provide the values for u-TBG concentration in hyper- and hypothyroidism, and support the concept that the free fractions of serum thyroid hormones may be determined by the number of binding sites of the TBG molecule that are not saturated with T4 in hyper-and hypothyroidism.