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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 829 records · Page 46Linked to original sources

[Regulation of aromatase in human choriocarcinoma cells].

To examine the mechanism regulating trophoblastic aromatase, we studied the effects of various agents on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in human choriocarcinoma JEG-3 cells. Aromatase activity was assessed by radioassay with [1 beta-3H] androstenedione. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Human chorionic gonadotropin (hCG) stimulated aromatase activity and increased the P-450arom concentration in a concentration-dependent (0.1-100 IU/ml) manner. Cholera toxin (CT), an adenylate cyclase activator, stimulated aromatase activity and the P-450arom concentration in a concentration-dependent (0.1-10ng/ml) and a time-dependent (12-72h) manner. 12-O-tetradecanoyl phorbol 13-acetate (TPA) (0.1-100ng/ml), a protein-kinase C activator, also stimulated aromatase activity and increased the P-450arom concentration. On the other hand, Ca2+ ionophore A23187, an agent increasing intracellular Ca2+ accumulation, inhibited aromatase activity and reduced the P-450arom concentration. The effects of CT, TPA and Ca2+ ionophore were additive. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in JEG-3 cells the signal transduction system modulates aromatase activity by changing the P-450arom concentration.

Aromatase↗

[Assessment of social disability of patients suffering from chronic mental illness with the role play test].

UNLABELLED: Among the chronic mentally ill patients, disabilities invade most parts of their social functioning, and influences their long term course profoundly. It is important clinical issue to improve disability. Social skills training is assumed to be effective method to improve disability, and it has been disseminated over Japan recently. The assessment system to evaluate disabilities objectively at the viewpoint of social skills must be required to verify effects of social skills training, and to develop further effective therapeutic method. A role play test is the assessment tool for social skills through role plays under specific social conditions. It was reported to be useful as the method of functional assessment before treatment, and as the tool to evaluate effects of treatment to improve disability. PURPOSE: We created the Role Play Test (RPT) which was adapted to Japanese cultural background, and we tried to verify feasibility, reliability, and validity of the RPT. SUBJECTS: Thirty out-patients attending in the Day Hospital attached to Tokyo University Hospital. Twenty-six were schizophrenia, and 4 were other diagnoses. METHOD: Subjects were assessed with the RPT, BPRS, SANS, four rating scales for social functioning, and self-efficacy rating scale. The RPT was designed to assess components of social skills--social perception, role play behavior, and self-efficacy. Role play behaviors were recorded with video tapes for analysis of interrater reliability. The RPT is consisted of 12 scenes to evaluate social skills which are required in daily life. Statistical analyses were done with SAS (Statistical Analysis System). RESULTS: (1) The RPT was presumed to be feasible clinically, because the RPT could be practiced easily and responsibilities of both subjects and testers were not so much. (2) Interrater reliabilities assessed with ANOVA-ICC on 12 items was sufficiently high except one item. (3) Construct validity was certified through factor analysis, and criterion-related validity was certified through correlation analysis with other rating scales of social functioning. (4) Individual profile of the RPT should be useful instrument for functional analysis before social skills training. We also discussed on some hypotheses on the causal relationship between positive and negative symptoms and social skills. The RPT could be used as a tool to research causes of disabilities, and to evaluate improvement of social functioning after psycho-social intervention including social skills training, because the RPT can assess social skills quantitatively according to the cognitive-behavioral model.

Adolescent↗

Cold agglutinin disease following allogeneic bone marrow transplantation.

We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant.

Adult↗

An animal model of chronic ischemic neuropathy with proliferative changes of nerve microvessel wall.

In order to produce a model of ischemic neuropathy with neural microvascular alterations, sodium laurate was injected into a femoral artery and saline into the contralateral artery at the mid-thigh level in Sprague-Dawley rats aged 11 weeks. In view of the dose-related findings, 0.3 mg sodium laurate dissolved in 0.1 ml saline was used for the main experiment. The laurate-injected leg showed paresis during the experimental period. On day 1-7, various stages of Wallerian degeneration and acute microvascular changes were found. At 1 month, regenerating myelinated nerve fibers (MNFs) were found at the central or total fascicular area mainly in the distal tibial nerve. Morphometric analyses suggested that MNFs other than regenerating fibers are atrophic ones. The proliferative changes of nutrient microvascular walls were striking. The percent of closed epineurial microvessels was significantly larger on the laurate-injected sides and inversely associated with the diameter of MNFs. At 7 months, the attenuation of MNFs was more prominent and microvascular alterations were persistently observed. These pathological findings resemble those of chronic ischemic neuropathy including diabetic neuropathy, suggesting that this neuropathy model might provide some valuable and useful clues for clarifying the pathogenesis of chronic ischemic neuropathy.

Animals↗

Alterations in the carbohydrate structures of an abnormal protein from sera of patients with rheumatoid arthritis.

G4-11, an abnormal immunoglobulin G4 (IgG4) glycoprotein, highly purified from the sera of patients with rheumatoid arthritis and from healthy individuals, contains two asparagine-linked sugar chains in one molecule. Comparative studies of the sugar chains released by hydrazinolysis revealed that the structures of the sugar chains of rheumatoid arthritis G4-11 are quite different from those of normal individuals. Although all G4-11 contained biantennary complex-type oligosaccharides like in the case of serum IgGs, samples from patients with rheumatoid arthritis had less galactosylated forms than those from normal individuals. These results indicated that this galactose deficiency of the sugar chains occurs in the abnormal IgG4 molecule of rheumatoid arthritis patients, just as was found in whole serum IgG.

Arthritis, Rheumatoid↗

Effects of taurine on depolarization-evoked release of amino acids from rat cortical synaptosomes.

Effects of taurine on endogenous aspartic acid (Asp), glutamic acid (Glu) and gamma-aminobutyric acid (GABA) release has been investigated using synaptosomes prepared from rat cerebral cortex. Although basal release of these amino acids was not affected, taurine inhibited KCl (30 mM)-evoked overflow of Asp, Glu and GABA in a concentration-dependent manner with potencies (IC50) of 1 microM, 0.8 microM and 5 nM, respectively. Taurine (10 microM) maximally inhibited K(+)-evoked Asp, Glu and GABA overflow by 28, 37 and 65%, respectively. Phaclofen (10 microM, a GABAB receptor antagonist), but not bicuculline (10 microM, a GABAA receptor antagonist), counteracted the inhibition of GABA overflow, although the inhibition of Asp and Glu overflow was not attenuated. These data suggest that taurine may inhibit GABA release through the activation of presynaptic GABAB autoreceptors and, at high concentration, also act on Asp- and Glu-nerve terminals to regulate release of excitatory amino acids in rat cortex.

Amino Acids↗

Peptide histidine methionine and vasoactive intestinal peptide levels in human cerebrospinal fluid: age-related changes and absence of a correlation with serum prolactin.

Serum levels of prolactin (PRL), peptide histidine methionine (PHM) and vasoactive intestinal peptide (VIP) were measured in 97 subjects and cerebrospinal fluid (CSF) levels of PHM and VIP were measured in 50 subjects by specific radioimmunoassays to investigate correlations between them. The chromatographic studies revealed that PHM and C-terminal extended form of PHM, peptide histidine valine occurred in human serum and CSF. Significant age-related increases of CSF PHM (P < 0.02) were observed in both males and females, whereas an age-related decrease of serum PRL level was found in females (P < 0.01). In contrast, neither serum VIP, serum PHM nor CSF VIP changed significantly with age. There was a significant positive correlation (P < 0.002) between VIP and PHM in serum, but not in CSF. The close relation between VIP and PHM in serum meets one's expectation because of their derivation from a common precursor. In CSF, these two peptides did not change in parallel with each other. These results may reflect the alteration in metabolism of PHM in CSF. Finally, there was no correlation between serum PRL concentrations and either serum or CSF levels of the peptides, suggesting that neither VIP nor PHM levels in CSF as well as in serum can influence the basal PRL secretion in subjects without endocrine disorders.

Adolescent↗

E. coli expression and characterization of a mutant troponin I with the three cysteine residues substituted.

A TnI cDNA was cloned from rabbit fast skeletal muscle, and site-directed mutagenesis was applied to replace all the three cysteine residues, Cys-48 and Cys-64 by Ala and Cys-133 by Ser. The mutant and wild-type TnI were expressed in E. coli and purified to homogeneity. No significant functional differences were observed between the mutant and the authentic TnI in terms of the interactions with TnT and TnC, and the ability of the reassembled Tn complex to regulate the acto-S1 ATPase activity in a calcium-dependent manner. These findings suggest that none of the cysteine residues in TnI are essential for the function of this protein and can be replaced to obtain a non-oxidizable mutant TnI which is much easier to handle and suitable as an alternative to the authentic TnI for various purposes, such as crystallization of TnI and the whole Tn, and 1H NMR studies.

Adenosine Triphosphatases↗

Effects of putative cognitive function-enhancing drugs and dopaminergic agents on somatostatin and neuropeptide Y in rat brain.

Reduced levels of somatostatin and neuropeptide Y (NPY) have been demonstrated in the brain of patients with some organic mental disorders. We designed the present study to test whether drugs thought to be effective in improving cognitive functions in these disorders increased the levels of these two peptides. The drugs were given to normal rats for 14 days to examine chronic effects on regional brain somatostatin and NPY levels. Amantadine and bifemelane increased these peptide levels. Idebenone and indeloxazine had little effect. The effect of dopaminergic agents on peptide levels was also tested in rats. 1-Dihydroxyphenylalanine increased somatostatin levels in whole brain, and hypothalamic NPY levels, and reduced NPY levels in the cerebral cortex, hippocampus and striatum. Sulpiride increased the levels of NPY in the striatum and brainstem. 6-Hydroxydopamine decreased cortical somatostatin levels, and increased striatal NPY levels. These findings indicate that some agents used to improve cognitive function impairment in organic mental disorders may increase somatostatin and NPY content in the brain of rats. Also, it is suggest that these peptides are under different influences of the dopaminergic system in the brain.

Animals↗

The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.

The glycosylphosphatidylinositol (GPI) anchor is a membrane attachment structure of many proteins and occurs in a wide variety of eukaryotes from yeasts to mammals. The structure of the core of the GPI anchor is conserved in protozoa and mammals and so is its biosynthetic pathway. A complementary DNA encoding a human protein termed PIG-A (phosphatidylinositol glycan-class A) was cloned. PIG-A was necessary for synthesis of N-acetylglucosaminyl-phosphatidylinositol, the very early intermediate in GPI-anchor biosynthesis.

Amino Acid Sequence↗

Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurologic patients: a replication of neuroendocrine features of major depression.

A blunted thyrotropin (TSH) and an unaltered prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) are widely recognized in neuroendocrinology of depression. We studied effects of repeated TRH administration of 1 mg/day for 10 days on the pituitary-thyroid axis function and PRL secretion in 16 euthyroid patients with neurological disorders. Although levels of serum thyroid hormones and of nonstimulated PRL were not affected by the treatment, baseline TSH levels were markedly inhibited. A blunted response of TSH to TRH was found without a significant effect on a PRL response to TRH after long-term treatment with TRH in four patients in whom a TRH test was performed. These changes are similar to those in depressed patients. TRH administration in this manner replicates a lowered sensitivity of thyrotrophs of the pituitary with a normal responsibility of lactotrophs in depression.

Aged↗

Development of T cells in SCID mice grafted with fetal thymus from AKR mice or F344 rats.

To examine the development of T cells within an allogeneic or xenogeneic environment, we engrafted the fetal thymus from AKR mice or F344 rats under the kidney capsule of SCID mice (mTG and rTG mice). T lymphopoiesis developed in SCID mice 2 months after transplantation, although the ratio of CD4/CD8 in both experimental groups was different from that of normal control. T cells in mTG mice did not show in vitro proliferation or cytotoxicity against either host-type C.B-17 (H-2d) or donor-type AKR (H-2k) cells, while they exerted potent activities against third-party B10 (H-2b) cells. In contrast, T cells in rTG mice exhibited proliferation against both host-type C.B-17 and donor-type F344 rat cells. Consistently, graft-vs.-host disease symptoms developed in these mice and histological examination showed impressive infiltration of lymphocytes into the skin or into the mucosal layers of the stomach. Activated state of T cells in rTG mice was also evidence by the positive expression of interleukin-2 receptor. Taken together, fetal thymus appears to contain progenitor cells which are sufficient for in vivo reconstitution of T lymphopoiesis, but species-specific environment is important for the induction of tolerance. In mTG mice, V beta 6+ T cells reactive to donor Mlsa determinants and V beta 3+ T cells reactive to host Mlsc determinants were deleted, suggesting that tolerance was regulated mainly by clonal deletion. By contrast, V beta 11+ T cells reactive to Mlsf determinants were not deleted possibly due to the lack of their ligands.

Animals↗