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Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 757 records · Page 42Linked to original sources

Resistance of nerves from certain toxic crabs to paralytic shellfish poison and tetrodotoxin.

The inhibitory effect of paralytic shellfish poison and tetrodotoxin on nerves from toxic and nontoxic crabs was examined. The toxins at concentrations of 10(-3) - 10(-4) M partially or completely inhibited the action potential of nerves isolated from the legs of toxic crab species (Zosimus aeneus, Atergatis floridus and Platypodia granulosa), but had no effect at 10(-6) M, the concentration at which the action potential of nerves from a nontoxic crab (Plagusia dentipes) was inhibited completely. A xanthid crab Daira perlata was intermediate in respect to the resistance to toxins. These results agree with the previous results obtained by i.p. administration of both toxins into those crabs.

Action Potentials↗

Tetrodotoxin in two species of ribbon worm (Nemertini), Lineus fuscoviridis and Tubulanus punctatus.

Extracts of two species of ribbon worm, Lineus fuscoviridis and Tubulanus punctatus, had lethal potencies in mice from 15-503 MU/g of worm and from less than 10-540 MU/g, respectively. The toxins were partially purified by ultrafiltration and column chromatography using Bio-Gel P-2 and Bio-Rex 70 (H+ form). Thin-layer chromatographic, high performance liquid chromatographic and gas chromatography-mass spectrometric analyses revealed the presence of tetrodotoxin and anhydrotetrodotoxin plus some unidentified compounds.

Animals↗

Increased production of prostacyclin (PGI2) by vascular intimal smooth muscle cells from atherosclerotic rabbit aorta.

In vitro PGI2 synthesis by aortic strips obtained from thoracic aorta of rabbits fed a high cholesterol diet was examined and compared with that of control rabbits fed a normal diet. In this report, the amounts of PGI2 produced were shown as 6-keto-PGF1 alpha per microgram of aortic tissue DNA instead of per mg wet weight. We also investigated PGI2 synthesis by cultured smooth muscle cells (SMC) obtained from atherosclerotic intima. Basal PGI2 production by aortic strips from atherosclerotic rabbit aorta was significantly augmented compared with that of controls. Arachidonic acid (AA)-induced PGI2 production by atherosclerotic aorta was also significantly higher than that of controls. PGI2 producing capacities of intimal and medial layers, separated from atherosclerotic aorta, were examined and the intimal layer was found to elicit a significantly greater PGI2 production than the medial layer. Furthermore, cultured intimal SMC obtained from atherosclerotic rabbit aorta produced a greater amount of PGI2 than medial SMC from normal rabbit aorta at various cultured conditions. These results suggest that the possibility of enhanced PGI2 production by atherosclerotic aorta may well be considered as a defence mechanism of the vessel wall against damaging stimuli.

Animals↗

The effects of estrogen, insulin and dexamethasone on the synthesis and secretion of egg white proteins in primary cultured oviduct cells of laying Japanese quail (Coturnix coturnix japonica).

1. The effects of estrogen, insulin and dexamethasone on the synthesis of egg white proteins were investigated by employing primary cultured oviduct cells of laying Japanese quails. 2. It was demonstrated that oviduct cells require insulin and dexamethasone, besides estrogen, to synthesize and secrete egg white proteins maximally.

Animals↗

Pyruvate kinase isoenzyme transitions in cultures of fetal rat hepatocytes.

Changes in the expression of two isoenzymic forms of pyruvate kinase in fetal hepatocyte cultures derived from 15- and 19-day gestation rats are studied by immunocytochemical localization of the respective antigens. Initially, in cultures established from 15-day gestation rats only the 'embryonic' form of the enzyme (M2-PK) is detected in all cells. Cells which stain positively for the liver specific form of the enzyme (L-PK) are not observed. After 2 days' culture, a significant number of cells have become positive for L-PK. All the positive cells have a morphology which is typical of liver parenchymal cells. However, the majority of parenchymal cells remain negative for L-PK while retaining M2-PK. In contrast, all cells which display a fibroblastic morphology, as well as clear epithelial cells are M2-PK positive, but L-PK negative. In 5-day-old cultures, all hepatocytes have become L-PK positive. Hepatocytes derived from 19-day gestation rat liver stain positively for L-PK on day 1 of culture in agreement with previously published biochemical data. A minor population of negative cells is non-parenchymal in appearance. All parenchymal cells are negative when the culture is stained with M2-PK specific antibody. Five days after the culture is established, many non-parenchymal cells are present. Such cells are L-PK negative and M2-PK positive and their presence in cultures derived from both 15- and 19-day gestation rats explains the persistence of M2-PK. This study reveals that during enzymic differentiation of fetal hepatocytes, all immature hepatocytes are initially capable of expressing M2-PK while they do not produce L-PK. During culture, a sub-population of these cells initiates synthesis of L-PK, indicating that only a fraction of the cells differentiate. At the same time, hepatocytes which do not stain for M2-PK appear, which suggests that cells which initiate L-PK synthesis have ceased to make M2-PK. Eventually all hepatocytes are L-PK positive and M2-PK negative, indicating that a switchover in expression of the pyruvate kinase isoenzymes has occurred.

Animals↗

Intermediate peptides of insulin degradation in liver and cultured hepatocytes of rats.

1. Bestatin, a microbial aminopeptidase inhibitor, induced accumulation of low-molecular weight intermediate peptides of insulin degradation in liver of rats in vivo and in primary cultured rat hepatocytes. However, bestatin did not affect the association and internalization of the hormone into hepatic cells. 2. Results of the HPLC analyses showed that the intermediate peptides of insulin degradation are small ones and specifically accumulate only in the presence of bestatin. 3. The above results, together with those employing other protease inhibitors, show that cytosolic bestatin-sensitive protease(s), trypsin-like protease(s) and thiol protease(s) play an important role in the intracellular degradation process of insulin.

Aminopeptidases↗

Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents.

A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.

Alkaloids↗

Further studies on the nutritional factors affecting the urinary excretion of acid-soluble peptides in rats.

1. Nutritional factors affecting the urinary excretion of acid-soluble peptides (ASP) were studied in rats. The ratio, total urinary nitrogen: ASP-form leucine + valine was lowest in the rats fed on a protein-free diet and increased as retained N: absorbed N decreased. The ratio was not affected by dietary protein level when the level was below the National Research Council (1978) recommended requirement, but increased greatly when it exceeded the recommended requirement. 2. The excretion of ASP-form leucine + valine per kg body-weight was significantly lower in the protein-deficient rats than in those fed on protein-adequate diets. This variable decreased during the stage of rapid growth, but did not change as markedly after the onset of adolescence. It increased again when the rats became older. The patterns of change in the rate of excretion of ASP-form amino acids during growth and that of Nr-methylhistidine were different. 3. When labelled amino acids were injected into rats, the largest amount of the ASP-form label was excreted on the 1st day of injection. From the 2nd day the excretion of ASP-form label decreased exponentially. 4. The findings suggest that the rate of urinary excretion of ASP-form amino acids can be employed as an index of protein metabolism, particularly as a simple index of the assessment of the status of protein nutrition.

Aging↗

Recurrent primary leptomeningeal astrocytoma of the lumbosacral spinal cord resembling schwannoma. A case report.

Primary leptomeningeal astrocytoma has been considered to be derived from ectopic glial cells in the leptomeninges. A case of recurrent primary leptomeningeal astrocytoma of the lumbosacral spinal cord is described. The original tumor was localized in the extramedullary space at the level of the 12th thoracic vertebra, and was solely composed of interlacing bundles of monomorphous spindle-shaped cells. The tumor was therefore diagnosed as schwannoma. The recurrent tumor removed one year after the first operation showed two distinct histologic patterns with increased nuclear atypia and mitosis. Namely, both schwannoma-like areas and astrocytomatous areas were observed. Silver impregnation clearly demonstrated an alveolar pattern in the schwannoma-like area. Immunohistochemically, the tumor cells revealed a positive reaction for glial fibrillary acidic protein. This case particularly emphasizes the usefulness of silver impregnation in differential diagnosis from schwannoma.

Astrocytoma↗

Differentiation of erythroid progenitor (CFU-E) cells from mouse fetal liver cells and murine erythroleukemia (TSA8) cells without proliferation.

Erythropoietin (epo) appears to play a significant role in influencing the proliferation and differentiation of erythroid progenitor (CFU-E) cells. To determine the mechanism of action of epo, the effect of drugs on the in vitro colony formation of CFU-E cells induced from a novel murine erythroleukemia cell line, TSA8, was examined. While cytosine arabinoside inhibited colony formation and terminal differentiation of the CFU-E cells responding to epo, herbimycin, which is a drug that inhibits src-related phosphorylation, inhibited colony formation only. The same effect of herbimycin was observed with normal CFU-E cells from mouse fetal liver cells. These results suggest that epo induces two signals, one for proliferation and the other for differentiation, and that the two signals are not linked in erythroid progenitor cells.

Animals↗

Albumin gene transcription is enhanced in liver of nephrotic rats.

The level of albumin mRNA and the transcription rate of the albumin gene were studied in the liver of control rats and rats with nephrosis induced by injection of the aminonucleoside of puromycin. Total RNA was extracted from liver by the guanidium thiocyanate method. The albumin mRNA level was measured by cDNA-RNA dot-blot hybridization, and the transcription rate of the albumin gene was measured by the "run-on" transcription assay using isolated nuclei. Urinary protein excretion in nephrotic rats was significantly higher than in control rats (258 +/- 132 vs. 12 +/- 2 mg/day), and the serum albumin concentration in nephrotic rats was significantly lower. There was no difference in body weight, liver weight, serum creatinine, or urea nitrogen between the two groups. Both the level of albumin mRNA and the transcription rate of the albumin gene in the nephrotic liver were about twice as high as those in the control liver. There was no difference in the level of beta-actin mRNA between the two groups. Northern blot analysis showed that both putative precursor RNA and the mature form of albumin mRNA were increased in nephrotic rats. We conclude that albumin synthesis is increased in the liver of nephrotic rats and a transcriptional process is responsible for this increase.

Actins↗

Reduced vasoactive intestinal polypeptide immunoreactivity in the pituitaries of hormone-deficient mutant mice.

The prolactin-producing cells of the bovine anterior pituitary were found to contain a vasoactive intestinal polypeptide (VIP) immunoreactive substance, thus suggesting a role for VIP in the regulation of prolactin release. The pituitaries of the dw and lit strains of mutant mice, congenitally deficient in prolactin-producing cells, and hyt mice, which were found to have reduced numbers of prolactin-producing cells, showed a markedly reduced VIP immunoreactivity. Hypothalamic VIP immunoreactivity, however, was found to be unchanged in the three strains of mutant mice, indicating that the high concentration of VIP in the hypothalamus does not derive from the adenohypophysis through retrograde flow. The deficiency in the mutant mice seems to be due to the lack of prolactin target cells in the pituitary.

Animals↗

The distribution and structure of the lymphatic system in dog atrioventricular valves.

A morphological study of the lymphatic system in atrioventricular (AV) valves of adult dogs and puppies was carried out using a series of techniques including India ink injection, a hydrogen peroxide technique, light microscopy, and electron microscopy. Lymphatic capillaries were found in all cusps of the AV valves, and were shown to extend delicate networks in the subendocardium of the atrial side of the valves. The extent of their development varied among cusps, being most prominent in the anterior cusp of the mitral valve. Marked differences were noted in the intravalvar distribution between lymphatic capillaries and blood microvessels. The ultrastructures of the lymphatic capillaries in the AV valves were also demonstrated.

Animals↗