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Biomedical subjects

H Ueda

Publications and source records attributed to H Ueda.

At least 631 records · Page 35Linked to original sources
PubMed1991

Novel cerebroprotective agents with central nervous system stimulating activity. 1. Synthesis and pharmacology of 1-amino-7-hydroxyindan derivatives.

To develop a novel cerebroprotective agent with central nervous system (CNS) stimulating activity, a series of 1-amino-7-hydroxyindan derivatives was synthesized, and their effects on the survival time of mice under hypoxic conditions were tested. CNS-stimulating activity was also evaluated by examining the promotional effect on the recovery from cerebral concussion induced coma in mice. Several compounds prolonged the survival time of mice in hypoxic conditions at a dose of 30 mg/kg (sc or ip) and 100 mg/kg (po). They also exhibited the promotional effects on recovery from coma at a dose of 100 mg/kg po. The three most potent compounds in both tests, 1-amino-7-hydroxy-6-(1-methylpropyl)indan, 1-amino-7-hydroxy-4, 6-dimethyl-2-phenylindan, and 1-amino-7-hydroxy-2,2,4,6-tetramethylindan were selected for further investigations. Structure-activity relationships were also discussed.

Animals↗
PubMed1991

Expression of a synthetic gene for human cap binding protein (human IF-4E) in Escherichia coli and fluorescence studies on interaction with mRNA cap structure analogues.

An artificial gene coding for the human cap binding protein (hCBP: human IF-4E) was chemically synthesized and expressed in Escherichia coli under the control of a trp promoter. The DNA duplex of 662 bp was designed and constructed from 44 oligodeoxynucleotide fragments of typically 30 nucleotides in length. Although the hCBP gene was not directly expressed in E. coli HB101, we succeeded in its high-level expression as a fusion protein connected with a portion of human growth hormone through a tetradecapeptide (Asp-Asp-Pro-Pro-Thr-Val-Glu-Leu-Gln-Gly-Leu-Val-Pro-Arg) that contains the recognition sequence for a site-specific protease alpha-thrombin. Upon induction with 3-indoleacrylic acid, the fusion protein accumulated with a yield of about 20% of the total proteins of the host cell. Upon the treatment of the fusion protein with alpha-thrombin, which recognizes the sequence "Val-Pro-Arg," specific proteolysis at the fused junction occurred efficiently. In this system, nonspecific digestion by alpha-thrombin was not marked. About 15 mg of recombinant hCBP was obtained from a 1-liter culture. Association constants between the recombinant hCBP and mRNA cap structure analogues were determined by fluorescence spectroscopy. The values obtained for the m7GpppA, m7GTP, and m7GMP were almost the same as those reported for the IF-4E isolated from human erythrocyte cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Synergy between cyclosporine and anti-IL-2 receptor monoclonal antibodies in rats. Functional studies of heart and kidney allografts.

Although cyclosporine has improved results of organ transplantation, treatment regimens using multiple agents are being evaluated both experimentally and clinically in attempts to diminish its often profound nephrotoxicity; some therapies act synergistically by differential inhibition of distinct steps of the rejection cascade. The effects on graft function of a full dose or a subclinical dose of CsA, ART-18, a monoclonal antibody (mAb) directed against the IL-2 receptor expressed on activated host cells, and a combination of low-dose CsA and ART-18, have been tested in rat recipients of both heart and kidney allografts. Renal graft function was assessed by several classic techniques; heart function by isolated perfusion methods. Full-dose CsA and combination treatment were most effective in both organ graft systems, with at least one-third of grafts surviving indefinitely. At seven days after transplantation, glomerular filtration rates and renal plasma flow of all grafted recipients were decreased as compared with normal; at 14 days, function in the best treatment groups had improved toward that of isografts. Similarly, cardiac output and stroke work index of best treatment groups were comparable to that of isografts. These functional studies complement previously reported immunological and immunohistological findings stressing that synergy occurs between subclinical doses of CsA and anti-IL-2-R mAb in two rat organ graft systems.

Animals↗
PubMed1991

A case of idiopathic vulvar calcinosis: the first in Japan.

Idiopathic calcinosis of the scrotum is a rare condition of unknown etiology. As counterparts of this male disorder, only two female cases have been reported. We report a third case, the first of its kind, in Japan. Histochemical stains revealed acid mucopolysaccharide (acid-MPS) within the calcinosis and many infiltrated mast cells near it; these might histogenese the calcium deposition. Immunohistochemically, polyclonal carcinoembryonic antigen (CEA) and keratin stains revealed no positive cells near the calcium depositions.

Calcinosis↗
PubMed1991

L-arginine induces relaxation of rat aorta possibly through non-endothelial nitric oxide formation.

1. The relaxation of rings of rat thoracic aorta induced by L-arginine and its derivatives was investigated. 2. L-Arginine (0.3-100 microM), but not D-arginine, induced relaxation of the arteries, which was detectable after 2 h and maximal after 4-6 h on its repeated application; it was endothelium-independent. 3. L-Arginine methyl ester, N alpha-benzoyl L-arginine and L-homo-arginine had essentially similar effects to those of L-arginine. 4. NG-nitro L-arginine methyl ester (L-NAME, 3 microM), NG-nitro L-arginine (L-NNA, 1 microM) and NG-monomethyl L-arginine (L-NMMA, 10 microM), inhibitors of nitric oxide (NO) formation from L-arginine, inhibited or reversed the L-arginine-induced relaxation, irrespective of the presence or absence of the endothelium. In contrast, NG-nitro D-arginine was without effect. 5. Haemoglobin (Hb, 10 nM) and methylene blue (MB, 0.3 microM) inhibited or reversed the L-arginine-induced relaxation. 6. L-Arginine (1-100 microM), but not D-arginine, increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in the tissues that relaxed in response to L-arginine. This effect of L-arginine was suppressed by Hb (3 microM), MB (1 microM) and L-NAME (100 microM). Removal of the endothelium did not significantly alter the L-arginine-induced cyclic GMP production. 7. These results suggest that L-arginine itself caused a slowly developing relaxation of rat aorta, possibly via formation of NO by an endothelium-independent mechanism.

Animals↗
PubMed1991

Protein-secretory patterns of normal and abnormal human placentas with special reference to human chorionic gonadotropin.

[35S]Methionine-labeled protein-secretory patterns resolved by two-dimensional polyacrylamide gel electrophoresis in abnormal hydatidiform-mole placentas were compared with those in normal full-term placentas with special reference to human chorionic gonadotropin (hCG) by means of immunoblotting and immunoelectron-microscopic techniques. Although basic protein-secretory patterns of both placentas were similar to each other, four polypeptide spots appeared and one spot disappeared in the hydatidiform-mole samples. Among four newly synthesized and secreted spots, three were immunoreacted with anti-hCG serum by an immunoblotting experiment. Ultrastructural localization of hCG showed that the labeling intensity of anti-hCG serum in hydatidiform-mole placentas was much heavier than that in full-terms ones. Particularly, the Golgi apparatus, middle-sized granules and large bodies were highly immunoreactive. The present study reveals that hydatidiform-mole placentas have different protein-secretory functions especially in hCG synthesis and secretion from those of normal pregnancy.

Autoradiography↗
PubMed1991

Ultrastructure of the red pulp in spleen innervation in horse and pig.

The innervation of the red pulp in the spleen of horse and pig was investigated by electron microscopy. In addition, the neurilemma was studied by immunohistochemistry specific for S-100 protein. In the pig, a large population of smooth-muscle cells extending from the smooth-muscle trabeculae was present in the red pulp. The cytoplasmic processes of reticular cells enwrapped the smooth-muscle cells, and nerve fibres were distributed between the smooth-muscle cells and the reticular cells. The nerve terminals clustered toward the facing of the smooth-muscle cells. Nerve fibres and terminals were not disclosed within the sheathed artery. Immunohistochemically the neurilemma showed a reaction positive for S-100 protein. In the horse, no smooth-muscle cells were noted in the red pulp. The nerve fibres terminated around the cytoplasmic processes of the reticular cells. Nerve fibres and terminals were disclosed within the sheathed artery, and the terminals contained both large and small dense-cored vesicles. Immunohistochemically the neurilemma showed a reaction negative for S-100 protein. These findings support the presence of the axon-bearing reticular cells described earlier in the horse spleen.

Animals↗
PubMed1991

Electron microscopy of histamine-induced contraction of the in vitro swine coronary artery.

Dose-dependent contractions of the in vitro swine coronary artery were induced by application of histamine and acetylcholine, but not of angiotensin II, ergonovine, noradrenaline, prostaglandin F2 alpha and serotonin. Ultrastructural changes especially of the tunica intima during the contractions were observed at 2, 5 and 30 min after application of histamine and acetylcholine. The intimal gutter spirally running along the longitudinal axis of the vessel was obscured, and the intimal surface became extensively indented. Exclusively in the histamine-treated samples, the increase in number and size of the intracellular vacuoles and the dilation of the intercellular clefts to the extent of the intercellular vacuoles were observed in the endothelium. Moreover, the enhancement of the endothelial permeability was indicated by the marker experiments using horseradish peroxidase. Such endothelial cell damages and the enhancement of the endothelial permeability may amplify the coronary artery contraction.

Acetylcholine↗
PubMed1991

Spectroscopic study on interaction of nucleic acid base with tryptophan-containing tripeptides: acetyl-Trp-X-Trp-NHCH3 (X = Gly, Asn, Asp, Gln and Glu).

As part of a series of peptides designed to have binding ability selective for each of the nucleic acid bases, five tripeptides consisting of N-acetyl-Trp-X-Trp-NHCH3 (X = Gly, Asn, Asp, Gln and Glu) were synthesized, and their abilities to form complexes with four different nucleotides were examined by the fluorescence and phase distribution methods. The association constants obtained indicated that, depending on the sort of X residue, the peptides showed a variation in their interaction with guanosine monophosphate (GMP), while no noticeable selectivity was observed for other nucleotides adenosine monophosphate (AMP), uridine monophosphate (UMP) and cytidine monophosphate (CMP). The binding mode of N-acetyl-Trp-Asp-Trp-NHCH3 for the guanine base was further investigated using the proton nuclear magnetic resonance (1H-NMR) method. The mode was suggested to involve intimate cooperation of (1) the hydrogen bond formation between the carboxyl group of the Asp side chain and the guanine C2-amino group, and (2) the stacking interaction of the base with two terminal Trp residues of the peptide. Such interaction was strengthened by the protonation of the guanine base. A tentative binding mode is proposed based on these results.

Molecular Structure↗
PubMed1991

Effects of dietary zinc deficiency on protein secretory functions of the mouse testis.

The effects of dietary zinc deficiency on testicular protein secretion, mainly that by Sertoli cells, were examined by electron microscopy and two-dimensional polyacrylamide gel electrophoresis of [35S] methionine-labeled secretory proteins from mouse testes. Zinc deficiency caused a significant decrease in the gonadosomatic index and a distinct increase in deoxyribonucleic acid concentration. Sertoli cells maintained normal fine-structural features; junctional complexes among Sertoli cells continued to divide seminiferous tubules into basal and adluminal compartments in the zinc-deficient mouse testes. Severe atrophic changes were observed in spermatogenic cells after meiotic division in the adluminal compartment, but not in spermatogonia located in the basal compartment. Zinc replacement treatment caused spermatogenesis to recover normally. Although total protein secretion was not affected by zinc deficiency, one polypeptide spot appeared due mainly to the loss of its target spermatogenic cells. The present study indicates that zinc is indispensable for spermatogenic cells after meiosis and that testicular protein secretory functions can be preserved in the absence of zinc.

Animals↗
PubMed1991

Utilization and metabolism of [U-14C]4' galactosyllactose (O-beta-D-galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rats.

O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl- (1----4)-D-glucopyranose (designated as 4'GL) are produced from lactose with Cryptococcus laurentii OKN-4. Excretion and metabolism of 4'GL in rats were examined using a radioisotope technique. [U-14c]4'GL was synthesized from [U-14C]lactose by Cryptococcus laurentii OKN-4. The 14CO2 in expired air was counted after oral administration of [U-14C]4'GL or [U-14C]lactose in conventional rats, rats treated with antibiotics and germ-free rats. The rate of 14CO2 excretion from conventional rats given [U-14C]4'GL was slower than that from those administered [U-14C]lactose. When [U-14C]4'GL was orally administered to rats given antibiotics, there was a 2-h delay in 14CO2 excretion, as compared to conventional rats. In germ-free rats, total excretion of 14CO2 from [U-14C]-4'GL decreased to about one-third of that of conventional rats during a 24-h period. Radioactivities in the serum, liver, and carcass of the [U-14C]4'GL oral administration group were lower than those of the [U-14C]lactose oral administration group. Radioactivities in the feces and urine however, were higher in [U-14C]4'GL group than in [U-14C]lactose group.

Animals↗
PubMed1991

Multiple opioid receptors and GTP-binding proteins.

We believed that GTP-binding protein (G-protein)-coupling receptor always transduces stimulatory signals to G-proteins. From our recent experiments using reconstitution techniques, however, it was revealed that some receptors transduce an inhibitory or no signal to G-proteins in specific tissues, despite some interaction between them. Here we discuss the molecular basis of mechanisms of such diverse modes of functional coupling between different subtypes of opioid receptors and G-proteins.

Animals↗
PubMed1991

[Kyotorphin like substance in human cerebrospinal fluid of patients with persistent pain].

Kyotorphin is an analgesic neuropeptide isolated from the bovine brain in 1979. Further studies showed that kyotorphin produces an analgesia through an increased release of met-enkephalin in the brain and the spinal cord. We showed that it is also found in the human cerebrospinal fluid and the concentrations of kyotorphin in normal human CSF is 1.19 +/- 0.51 pmol.ml-1. We also found that it is lower in patients with persistent pain (0.24 +/- 0.04 pmol.ml-1). Above results suggest that kyotorphin acts as a putative neuromediator and/or an endogenous pain modulator in the human brain.

Adult↗
PubMed1991

Cadmium toxicity on cultured neonatal rat hepatocytes: biochemical and ultrastructural analyses.

The effects of cadmium exposure on the protein secretory functions of cultured neonatal rat hepatocytes were analyzed by both two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and electron microscopy. [35S]Methionine-labelled protein secretion was significantly depressed by cadmium exposure in a dose-dependent manner (1, 10 and 100 microM). Protein secretory patterns resolved by 2D-PAGE and analyzed by autoradiography showed that besides albumin and transferrin, three polypeptide spots decreased their radiolabelling intensities, whereas four spots appeared due to cadmium exposure. Ultrastructural alterations in cultured neonatal rat hepatocytes induced by cadmium exposure were characterized by condensation of the nuclear chromatin, appearance of intra-nuclear inclusions, decrease in number of microvilli, increase in number of intra-mitochondrial granules and transformation of rough endoplasmic reticulum to cytoplasmic vesicles in a dose-dependent manner. Both biochemical and ultrastructural findings indicate that cadmium adversely affects the protein secretory functions of cultured neonatal rat hepatocytes.

Animals↗