Search PubMed⌕ Search

Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 955 records · Page 53Linked to original sources

[Side effects of antithyroid drugs].

In order to investigate the incidence of side effects of antithyroid drugs and to study if there were any factors related to the onset of the side effects, clinical and laboratory findings were examined in 71 untreated Graves' patients. The overall incidence was 28.2% among 71 cases who were initially administered methimazole or propylthiouracil. The incidences were 23.2% (13 of 56 cases) for methimazole and 46.7% (7 of 15 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Seventeen of 20 cases with side effects under the drug of first choice were administered the another antithyroid drug. Four of 17 (23.5%) cases successively had side effects. The side effects were observed within 1.5 months of administration of less than 150 tablets in total in most of the cases. The serum concentration of Ig-E and peripheral eosinophils(/mm3) at the onset of the side effects were significantly higher than those before treatment. These results suggest that allergic mechanism rather than accumulating may concern the onset of side effects. Since in cases without the side effects the peripheral eosinophils at 3 to 4 weeks after administration were significantly higher than those before treatment and 19 of 51 (38.0%) cases without side effects had a high concentration of Ig-E of more than 500 u/ml, it is suggested that allergic mechanism may be triggered in most of Graves' patients who were administered methimazole or propylthiouracil. Thus, immunological disturbances in Graves' disease seems to be the cause of the side effects of antithyroid drugs, although there was no correlation between antithyroid autoantibodies and development of the side effects.

Adolescent↗

The degradation of urate in liver peroxisomes. Association of allantoinase with allantoicase in amphibian liver but not in fish and invertebrate liver.

Allantoinase and allantoicase were co-purified from frog (Rana catesbeiana) liver. The ratio of the two enzyme activities remained constant during purification and was unchanged by a variety of treatments of the purified enzyme. These results suggest that allantoinase and allantoicase are located in the same protein. It was found that the two hepatic enzyme activities are also associated with the same protein in other frogs (Xenopus laevis and Rana nigromacultata), tadpoles (R. catesbeiana), and newts (Triturus pyrrhogaster). In contrast, allantoinase and allantoicase were found to be different proteins in marine fish and invertebrate liver.

Amidohydrolases↗

Induction of rat liver malic enzyme messenger RNA activity by insulin and by fructose.

The effects of insulin treatment and fructose feeding on malic enzyme [EC 1.1.1.40] mRNA in liver of diabetic rats were investigated. A high fructose diet, even without insulin treatment, increased the mRNA activity, much more than a high starch diet, but to a lesser extent than insulin treatment. The increase of malic enzyme activity was approximately comparable to the change in mRNA activity, but occurred 12 hr and 30 hr after the increase of mRNA in the fructose-fed rats with and without insulin treatment, respectively. Thus, insulin and fructose appear to induce malic enzyme primarily by increasing the activity of translatable mRNA.

Animals↗

Expression in Escherichia coli of chemically synthesized gene for the human immune interferon.

A 454 base pair fragment of double stranded DNA consisting of a gene for a human immune interferon (hIFN-gamma), initiation and termination signals plus appropriate restriction endonuclease sites, was totally synthesized. The synthesis involved preparation of 62 oligodeoxyribonucleotides by rapid, solid phase procedures, and enzymatic ligation of the oligonucleotides. This synthetic gene was expressed in E. coli under the control of the lac UV5 promoter. The product has antiviral activity which was acid labile and completely neutralized by antiserum to hIFN-gamma but not by antiserum to hIFN-alpha or hIFN-beta. Molecular weight of hIFN-gamma produced by E. coli was estimated to be about 32,000 and 17,000 by gel filtration and SDS-polyacrylamide gel electrophoresis respectively.

Amino Acid Sequence↗

Expression of chemically synthesized alpha-neo-endorphin gene fused to E. coli alkaline phosphatase.

An alpha-neo-endorphin (alpha NE) gene, which we previously synthesized chemically and inserted into E. coli beta-galactosidase gene of pK013 plasmid, has been excised and fused to E. coli alkaline phosphatase (APase) gene. One of the transformants was named E15/pA alpha NE1. Under the APase gene regulation, APase-alpha NE chimeric protein was expressed at 1.3 X 10(6) molecules per cell, and accounted for about 60% of total cellular proteins. The HPLC pattern of CNBr treated E15/pA alpha NE1 was very simple reflecting the high content of the chimeric protein and low numbers of methionine residues in it. A series of genes encoding APase-alpha NE chimeric proteins in which 30 to 94 C-terminal amino acid residues were replaced by (met)-alpha NE, was cloned in E. coli. Transportation of the chimeric proteins to periplasmic space was studied. All chimeric proteins were apparently processed by signal peptidase but few, if any, was transported to the periplasmic space.

Alkaline Phosphatase↗

Separation of tetrodotoxin and paralytic shellfish poisons by high-performance liquid chromatography with a fluorometric detection using o-phthalaldehyde.

Tetrodotoxin (TTX) and a variety of paralytic shellfish poisons (PSPs) were extracted from toxic specimens of puffer and scallop, and quantitated by high-performance liquid chromatography with a fluorometric detection using o-phthalaldehyde. Fluorescence spectra for the TTX- and PSP-fluorophors in 0.05 M borate buffer (pH 10) showed maxima at 453 nm with 332-nm excitation. The fluorescence intensity per nM of TTX was found to be 3 and those of PSP to be 4-12. This fluorometric technique may be useful for the simultaneous quantitation of TTX and PSP in small volumes of toxin extracts.

Animals↗

Selective in vitro toxicity of purothionin conjugated to the monoclonal antibody 225.28S to a human high-molecular-weight melanoma-associated antigen.

The toxic agent purothionin was conjugated to the monoclonal antibody 225.28S to a human high-molecular-weight melanoma-accociated antigen. The toxic conjugate displayed in vitro toxicity to cultured human Colo 38 melanoma cells as indicated by reduced uptake of 3H-thymidine following a 24-h incubation and loss of cell viability following a 7-day incubation. The effect is dose-dependent and is specific since addition of the toxic conjugate to a cultured Raji B lymphoid cells did not affect their 3H-thymidine uptake or their viability.

Antibodies, Monoclonal↗

Poor myelination in the central nervous system of "dilute-lethal mutant mice" (d1/d1).

The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), as a marker for myelinogenesis, was measured in different parts of the nervous system of dilute-lethal mutant mice (d1/d1). The activity in terms of micromoles of 2'-AMP formed per milligram of protein of homogenate per minute was found to be exceedingly reduced in the cerebrum, brain stem, and medulla oblongata, slightly reduced in the cerebellum and cervical spinal cord, but not reduced in the thoracic spinal cord and the optic and sciatic nerves. These results clearly indicate that dilute-lethal mutant mice show poor myelination in the cerebrum, brain stem, and medulla oblongata.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Occurrence of saxitoxin and other toxins in the liver of the pufferfish Takifugu pardalis.

Highly toxic livers of the pufferfish Takifugu pardalis were extracted with acidic ethanol. The toxins extracted were partially purified by chromatography on Bio-Gel P-2 and then Bio-Rex 70, resulting in separation into three fractions I, II and III. ratios of total mouse units per fraction were approximately 0.1:100:0.01, respectively, with tetrodotoxin (TTX) as standard. By TLC, electrophoresis and a TTX analyzer, Fr. II was identified as TTX and, unexpectedly, Fr. III as saxitoxin, while Fr. I remains unidentified.

Animals↗

Faulty development of cortical neurons in the Snell dwarf cerebrum.

In the Snell dwarf motor cortex, area 6 of Caviness, the cell number, the stratification of neurons and the portion of layer-widths were absolutely identical to those of the controls. By means of the Golgi-Cox method modified by Ramon-Moliner, however, the pyramidal neuron was found to have small perikarya, short primary dendrites with sparse branchings, and a low spine density on the dendrites. The corpus callosum of the dwarf contained a reduced number of fibers compared to that of the controls, and the staining for myelin basic protein revealed a considerable reduction of positive-fibers of radiation in this area. The content of Thy-1 antigen in the cerebrum, cerebellum and brainstem, was significantly lower than that of controls, but the monoamine content was normal in the cerebrum and brainstem. From these results, it appears that the Snell dwarf cerebrum shows retarded neuronal growth; a reduction in size of neurons, an underdevelopment of axons and dendrites, and a retarded maturation of spine, in addition to arrested glial proliferation. At present, it is unclear which hormone deficient in these mutants, growth hormone or thyroxine, is the essential potentiator for neuronal growth.

Animals↗

Intestinal absorption of calcium in rats given diets containing casein or amino acid mixture: the role of casein phosphopeptides.

1. In an attempt to investigate calcium absorption in the rat during the postprandial period, with the least alteration of the physical environment, the undisturbed small intestine was ligated in situ 2.5 or 3.0 h after ingestion of a diet containing 200 g casein/kg or an equivalent amino acid mixture, or 925 g casein/kg. Estimation of Ca absorption was made by comparing the amount of soluble 40Ca or 45Ca in the contents of segments from the rats receiving 45Ca by intubation 30 min after withdrawal of food, ligated after a further 30 min, then killed after 0 or 30 min. 2. Under conditions such that the estimated amount of a marker, polyethylene glycol, in segments ligated in a defined position was little changed in rats killed 30 min apart, the difference in the amount of soluble 40Ca was much higher in the rats fed on the basal diet containing 200 g casein/kg than in other groups. 3. This specific effect on Ca absorption, particularly in the distal portion of the small intestine, could be seen also after 45Ca was directly injected into ligated segments in situ. The amount of 45Ca in the portal blood 15 min after injection of the label was also highest in the rats given the basal diet. 4. The results were in agreement with our previous findings that the formation and accumulation of casein phosphopeptides causes an increase in the amount of soluble Ca in the distal small intestine.

Amino Acids↗

Effect of protein quality on dietary induction of hepatic ornithine decarboxylase.

Dietary induction of ornithine decarboxylase (ODC) in rat liver depended on the quality of protein in the diet. Zein did not induce ODC unless it was supplemented with the deficient amino acids, tryptophan and lysine. Similar phenomena were observed with gelatin (tryptophan and methionine) and hemoglobin (isoleucine). However, ODC was found to be significantly induced by an amino acid mixture simulating zein. The difference between amino acid diet and protein diet effects could not be explained by digestibility of zein. Unphysiologically rapid influx of amino acids appeared to induce ODC by a mechanism different from that by which dietary protein induced ODC. After ingestion of zein, the concentration of tryptophan and lysine decreased markedly in plasma and liver. However, it was confirmed that their supply from intracellular protein degradation continued even after feeding. In contrast to ODC, tyrosine aminotransferase was induced by zein as well as by casein, indicating that the requirement of tryptophan and lysine as precursor amino acids for enzyme synthesis was satisfied by reutilization of the amino acids liberated by intracellular protein degradation. Therefore, it was concluded that good quality protein was required for ODC induction mainly as a signal but not as a source of precursor amino acids.

Amino Acids↗

Release of tetrodotoxin and paralytic shellfish poison from puffer liver by RNase.

A nontoxic high-molecular fraction was separated from the extracts of toxic liver of a puffer, Takifugu poecilonotus, by Sephadex G-50 gel filtration. This fraction became toxic when digested with RNase T2. The toxins were partially purified by activated charcoal treatment, followed by chromatography on Bio-Gel P-2 and Bio-Rex 70, and were analyzed by TLC and electrophoresis. The results showed that most of the toxicity is accounted for by tetrodotoxin, and the remainder by saxitoxin and other unidentified toxins. The corresponding high-molecular fraction separated from nontoxic liver of another puffer, T. rubripes, did not release any toxin on RNase digestion.

Animals↗

Biopotency and nuclear binding of glucocorticoids.

Nuclear binding abilities of 3 glucocorticoids, dexamethasone (Dex), prednisolone (Pred) and corticosterone (Cort), which exhibited different biopotencies were compared in vitro. cytosols labelled with 3H-Dex, 3H-Pred and 3H-Cort from the rat liver prepared by incubation at 0 degrees C for 16 hr were bound to isolated liver nuclei in rates of approximately 25%, 9% and 1% of added radioactivity, respectively. Nuclear binding rates observed were correlated with biopotencies of these steroids. Time course studies of the cytosol binding revealed that the difference in the nuclear binding ability of these ligands was attributable, at least in part, to the metabolic transformation of ligands during the incubation period. A significant portion of 3H-Pred and 3H-Cort was transformed to polar metabolite(s) even under the incubation conditions at 0 degrees C. Kd's of the cytosol binding to 3H-Dex which was metabolically stable were decreased with the length of incubation time, significantly lower Kd being observed in the cytosol incubated for 16 hr than in those incubated for 2 and 6 hr. Kd's and the number of maximum binding sites were erratic when the ligands received biotransformation during the course of incubation. Transformed 3H-Pred and 3H-Cort during the incubation still exhibited features of the protein bound state. Besides biotransformation of ligands, structure related difference in the nuclear binding ability of these glucocorticoids was also observed. These observations suggest that metabolic susceptibility as well as structure related ability of the nuclear binding may contribute to the biopotency of glucocorticoids.

Animals↗