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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 1,189 records · Page 66Linked to original sources

Acute effect of thyroid hormone on insulin secretion in rats.

To elucidate the mechanism of thyroid hormone-induced hyperinsulinemia, the acute and direct effect of thyroid hormone administration on insulin secretion was investigated in rats in vivo and in vitro. In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion. The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL, while blood glucose and plasma glucagon were unchanged. This phenomenon was inhibited completely by the preadministration of oxprenolol hydrochloride (2 mg/kg, s.c.), and inhibited partly by the preadministration of metoprolol tartrate (35 mg/kg, s.c.). These results suggest that thyroid hormone induces hyperinsulinemia via beta-adrenergic stimulation in the rat.

Animals↗

Isochromosome 11q in acute monoblastic leukemia (M5a).

An isochromosome 11q in a patient with M5a type acute monoblastic leukemia is reported. The leukemic cells had a few azurophilic and alpha-naphthyl butyrate esterase-positive granules in the cytoplasm. Electron microscopy showed indented nuclei, abundant perinuclear fibrous bundles, and small lysosomes which were characteristic of monocytoid cells. A strong inhibitory activity against urokinase was detected in the cell lysates as compared with other leukemic cells. Cytogenetic analysis of the leukemic cells showed the karyotype 47, XY, +i(11q), which has not been observed hitherto in acute monocytic leukemia.

Chromosome Aberrations↗

Effects of indomethacin and prostaglandin E2 on amylase secretion by rat parotid tissue.

Indomethacin increased the secretion by low concentrations of isoproterenol (IPR, 30-100 nM) and decreased the secretion by a high concentration of IPR (1 microM). Indomethacin also had opposite effects on the secretions induced by low and high concentrations of norepinephrine (NE). PGE2 did not affect the secretions induced by IPR and NE, but it reversed the stimulatory and inhibitory effects of indomethacin. These findings suggest that PG has a role in modulating the amylase secretory response of the rat parotid gland.

Amylases↗

A point mutation in the tyrosinase gene of BALB/c albino mouse causing the cysteine----serine substitution at position 85.

Murine albinism is characterized by complete lack of melanin pigments in skin and retina. In order to study the molecular basis of albinism, we have cloned and characterized the tyrosinase gene of BALB/c mice (c/c). Sequence analysis of this gene reveals a point mutation at nucleotide residue 387 (G----C transversion) causing a Cys----Ser substitution at position 85 in one of the cysteine-rich domains of the tyrosinase molecule. Since this G----C transversion creates an additional DdeI site, we were able to confirm that this mutation is actually present in BALB/c genomic DNA using DNA amplification techniques. In contrast, both C57BL/6 (C/C) and DBA/2 (C/C) mouse strains carry the G residue at the same position, suggesting that this point mutation is specific for the albino mutation at the c locus. Moreover, we were able to show that the tyrosinase containing Ser-85 is not functional in transient expression of its cDNA. We therefore suggest that a G----C transversion at nucleotide residue 387 of the tyrosinase gene could lead to the albino phenotype of BALB/c mouse.

Albinism↗

A plasminogen activator inhibitor-2 from a promyelocytic leukemia cell line, PL-21, binds to the carboxy-terminal chain of plasminogen activators.

A promyelocytic leukemia cell line, PL-21, was found to produce an inhibitor of plasminogen activators (PAI). The PAI reacted to anti-PAI-2 but not anti-PAI-1 anti-serum and had an apparent molecular weight of 43 kDa on unreduced SDS-PAGE. The PAI inhibited not only urokinase-type plasminogen activator (u-PA) but single- and two-chain tissue-type plasminogen activators (t-PAs) on plasminogen-containing fibrin plate. It formed SDS-stable complexes with both t-PA and u-PA but not with prourokinase as demonstrated by both fibrin zymography and immunoblotting using anti-PA and anti-PAI-2 antisera after SDS-PAGE. These complexes were still present even after reduction with dithiothreitol. The PAI appears to bind to the carboxy-terminal chain of both PAs, because the part of the band corresponding to the carboxy-terminal chain of PAs moved to an upper position as a result of complex formation when two-chain form of PAs were incubated with the PAI and analyzed by SDS-PAGE followed by immunoblotting.

Amino Acid Sequence↗

Transient tyrosine hydroxylase-immunoreactive neurons in the region of the anterior olfactory nucleus of pre- and postnatal mice do not contain dopamine.

The transient appearance of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in the anterior olfactory nuclear region of mice was investigated using TH-immunocytochemistry. In this region, a new cell group composed of a small number of neurons immunoreactive to TH was demonstrated for the first time from the embryonic stages of E16-E18. These cells were not shown using antisera against aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl-transferase, dopamine or serotonin. TH-IR cells progressively increased in number until birth. After birth the numbers reached maximum at postnatal days 9-12 and decreased until 4 weeks old, and then mostly disappeared at 6 weeks. Only single TH-IR cells were occasionally observed in this brain area of adult mice. Ultrastructurally some of these TH-IR neurons had immature Golgi apparatus, only a few mitochondria and deformed nuclei along with thin cytoplasma. Some other TH-IR cells, however, had mature Golgi apparatus, many mitochondria and a round nucleus more closely resembling mature cells. These neurons do not belong to the dopaminergic neuron system, because they lack dopamine production, and may be tentatively involved in early limbic circuits.

Aging↗

Inhibition of epidermal growth factor-induced DNA synthesis by tyrosine kinase inhibitors.

We prepared methyl 2,5-dihydroxycinnamate as a stable analogue of erbstatin, a tyrosine kinase inhibitor. This analogue was about 4 times more stable than erbstatin in calf serum. It inhibited epidermal growth factor receptor-associated tyrosine kinase in vitro with an IC50 of 0.15 micrograms/ml. It also inhibited in situ autophosphorylation of epidermal growth factor receptor in A431 cells. Methyl 2,5-dihydroxycinnamate was shown to delay the S-phase induction by epidermal growth factor in quiescent normal rat kidney cells, without affecting the total amount of DNA synthesis. The effect of erbstatin on S-phase induction was smaller, possibly because of its shorter life time.

Animals↗

Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with Alzheimer's disease.

We examined the changes in the intracerebral activities, at the time of postmortem autopsy, in patients with Alzheimer's disease. When compared with the control group, the activity of kallikrein-like enzyme was significantly decreased, while prolyl endopeptidase activity increased, in the patients group. Aprotinin inhibited 50% of the activity of the former enzyme at 2 x 10(-7) M. Taken together with the results of a multivariate study, the above findings may indicate that intracerebral kallikrein deficiency plays an important role in the pathogenesis of Alzheimer's disease.

Aged↗

Aortic endothelial cells synthesize a large chondroitin sulphate proteoglycan capable of binding to hyaluronate.

Confluent cultures of mouse aortic endothelial (END-D) were incubated with either [35S]methionine or 35SO4 2-, and the radiolabelled proteoglycans in media and cell layers were analysed for their hyaluronate-binding activity. The proteoglycan subfraction which bound to hyaluronate accounted for about 18% (media) and 10% (cell layers) of the total 35S radioactivity of each proteoglycan fraction. The bound proteoglycan molecules could be dissociated from the aggregates either by digestion with hyaluronate lyase or by treatment with hyaluronate decasaccharides. Digestion of [methionine-35S]proteoglycans with chondroitinase and/or heparitinase, followed by SDS/polyacrylamide-gel electrophoresis, indicated that the medium and cell layer contain at least three chondroitin sulphate proteoglycans, one dermatan sulphate proteoglycan, and two heparan sulphate proteoglycans which differ from one another in the size of core molecules. Among these, only the hydrodynamically large chondroitin sulphate species with an Mr 550,000 core molecule was shown to bind to hyaluronate. A very similar chondroitin sulphate proteoglycan capable of binding to hyaluronate was also found in cultures of calf pulmonary arterial endothelial cells (A.T.C.C. CCL 209). These observations, together with the known effects of hyaluronate on various cellular activities, suggest the existence of possible specialized functions of this proteoglycan subspecies in cellular processes characteristic of vascular development and diseases.

Aggrecans↗

Sequence determination of unknown cyclic peptide antibiotics by fast atom bombardment mass spectrometry.

The primary structures of unknown cyclic peptides produced by a Bacillus strain have been determined by fast atom bombardment (FAB) mass spectrometry, which has established the peptides as a new family of the iturin group antibiotics. FAB mass spectra of the intact peptides gave the immonium ions characteristic of constituent amino acids which made it possible to distinguish Asn from Asp and Glu from Gln. Collision-induced dissociation (CID) spectra of protonated molecules provided complete information on the connectivity of amino acid residues but did not reveal the direction of peptide bonding, while those obtained for fragment ions allowed us to make a discrimination between the correct sequence and its retro sequence. The amino acid sequences derived are c(Thr-Xaa-Asn-Tyr-Asn-Ser-Glu-Ser) (Xaa: C14 or C15 beta-amino acid) which are closely related to that of bacillomycin L. The structure is confirmed by the FAB mass spectra of the partial acid hydrolysate and the peptide mixture obtained from its single-step Edman degradation. Fragmentation processes involved in the CID spectra of the cyclic peptides are discussed based on the established amino acid sequence.

Amino Acid Sequence↗

Plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action in humans.

Plaunotol, an acrylic diterpene alcohol, is a new antiulcer agent derived from the "plau-noi" plant and has been reported to stimulate the release of endogenous secretin in humans. We investigated the effect of plaunotol on postprandial gastrin release, comparing it to the effect of exogenous secretin in a physiological dose in eight healthy volunteers. Four sets of experiments were performed in each volunteer: (1) meal alone, (2) meal after intravenous ranitidine (50 mg), (3) meal after oral administration of plaunotol (320 mg) in addition to ranitidine, and (4) meal after ranitidine with simultaneous intravenous infusion of secretin (0.03 CU/kg/hr). The postprandial increase in plasma secretin concentration was significantly reduced by ranitidine, while postprandial gastrin release was markedly exaggerated. Plaunotol in combination with ranitidine significantly increased secretin release and inhibited gastrin release after a meal. Intravenous infusion of secretin resulted in significant suppression of postprandial gastrin release exaggerated by ranitidine. The present study indicates that plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action.

Adult↗

Role of secretin and cholecystokinin in oleic acid-stimulated pancreatic secretion in rats.

We investigated the possible role of endogenous secretin and cholecystokinin (CCK) on oleic acid-stimulated pancreatic exocrine secretion in anesthetized rats. Intraduodenal infusion of oleic acid (pH 6.5) in three different doses (0.06, 0.25 and 1 mmole/hr) resulted in dose-related increases in pancreatic juice volume, bicarbonate and amylase outputs (r = 0.665, 0.736 and 0.517, respectively) (P less than 0.001). Plasma secretin and CCK concentrations also elevated significantly in response to oleic acid, in a dose-related manner (r = 0.721 and 0.546, respectively) (P less than 0.001). There were statistically significant correlations between plasma secretin concentrations and bicarbonate outputs, and between plasma CCK concentrations and amylase outputs in response to oleic acid (P less than 0.01). Potent CCK antagonist, CR 1409 (5 mg/kg.hr) administered intravenously suppressed completely increase in amylase output induced by oleic acid, and partially in juice volume and bicarbonate output. It is concluded that both endogenous secretin and CCK play important roles on oleic acid-induced pancreatic secretion in rats.

Amylases↗

Nucleolar organizer regions in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The number of nucleolar organizer regions (NORs) stained by the one-step silver colloid method was measured in preneoplastic and neoplastic bladder lesions induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. Male ACI/N rats, 6 weeks of age, were given 0.05% BBN in drinking water for 5, 8, 12, 18 and 30 weeks to induce preneoplastic and neoplastic transitional cell lesions. The mean numbers of silver-stained NORs (AgNORs) in such lesions were as follows: untreated transitional epithelium (n = 6), 1.26 +/- 0.09; transitional cell epithelium outside focal lesions (n = 10), 1.75 +/- 0.10; simple hyperplasia (n = 10), 2.01 +/- 0.15; papillary or nodular (PN) hyperplasia (n = 10), 2.15 +/- 0.19; transitional cell papilloma (n = 5), 2.37 +/- 0.12; transitional cell carcinoma (n = 5), 3.52 +/- 0.23. Thus, the mean number of AgNORs showed a step-wise increase from untreated and treated, histologically normal transitional epithelium through simple hyperplasia and PN hyperplasia to transitional cell papilloma and carcinoma. These results suggest that the mean number of AgNORs may reflect the proliferative nature of bladder lesions induced by BBN, as reported in preneoplastic and neoplastic lesions in other organs. PN hyperplasias were classified into two types based upon the mean number of AgNORs, indicating that they include reversible and irreversible changes in contrast with simple hyperplasia which is reversible change.

Animals↗