Biomedical subjects

T Nagai

Publications and source records attributed to T Nagai.

At least 109 records · Page 6Linked to original sources

PubMed2001

Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor.

Using mouse osteoclast-like cells (OCs), we have shown that treatment with glucocorticoids (GCs) resulted in an increase in calcitonin (CT) binding by enhancing CT receptor (CTR) gene transcription. Additionally, treatment with GCs demonstrated increased sensitivity to CT. There is, however, scant information on the effects of GC or CTR regulation by GCs in human osteoclasts. In this study we examined CTR regulation by GCs and the effects of GCs and CT together in human OCs. OCs were prepared by treatment of peripheral blood mononuclear cells in vitro with soluble receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor. Treatment of mature OCs with dexamethasone (Dex) resulted in a dose- and time-dependent increase in [(125)I]salmon CT (sCT) binding capacity. Treatment with Dex enhanced CTR messenger RNA (mRNA) expression, suggesting that CTR up-regulation is at least partly due to an increase in de novo CTR synthesis. Triamcinolone and prednisolone reproduced the Dex effect on [(125)I]sCT-specific binding and CTR mRNA expression, but 17beta-estradiol, progesterone, dehydroepiandrosterone, and aldosterone did not. A Scatchard plot analysis showed that Dex enhanced CTR number with a minimal change in the affinity to sCT. Autoradiographic studies using [(125)I]sCT showed that Dex enhanced the CTR density on individual multinuclear OCs. Up-regulation of [(125)I]sCT-specific binding and CTR mRNA expression was seen even in the presence of sCT, but the enhancement diminished subsequently at later times (36-48 h after sCT removal), which was consistent with our previous observation in mouse OCs. This suggests that GCs and CTs act on CTR expression differently, consistent with our previous work using mouse OCs, in which we found that GCs increased transcription of CTR gene expression, whereas CT reduced CTR mRNA stability. The results obtained in this study show that GC increased CTR expression and sensitivity to CT in cells of the human osteoclast lineage and provide the basis for understanding the beneficial effects of combination treatment with GCs and CTs in malignancy-associated hypercalcemia.

Acid Phosphatase↗

PubMed2001

Promoting mechanism of menthol derivative, 1-O-ethyl-3-buthylcyclohexanol, on the percutaneous absorption of ketoprofen.

Menthol derivatives were synthesized and evaluated for their promoting activity on the percutaneous absorption of ketoprofen and skin irritation in vivo, choosing O-ethylmenthol (MET) as the mother compound. The compound having a C-3 positionned n-butyl group (1-O-ethyl-3-n-buthylcyclohexanol, OEBC) indicated the most promoting activity and caused relatively little skin irritation. In order to understand enhancement mechanism of OEBC an in vitro permeation study of ketoprofen was performed. The time course of the cumulative amounts of drug permeated through the rat skin exhibited a linear relation after an initial lag time. This was analyzed in membrane diffusion model and the diffusion and partition parameters of ketoprofen were estimated. Both parameters were remarkably enhanced when a hydrogel containing a small quantity of OEBC (0.5%) was applied. Furthermore, to clarify the site of action of OEBC, we also investigated in vitro permeation study of ketoprofen employing different skins of state, reversed skin and stratum corneum stripped skin. When OEBC was added to the hydrogels which were applied to the reversed and stripped skins, almost no changes of the flux were observed compared with the control (without OEBC). These results suggested that the site of action of OEBC was stratum corneum. Morphological changes of the stratum corneum surface were microscopically observed with 0-2% OEBC. The spaces between the stratum corneum cells treated with 0.5-2% OEBC became extended and the shape of each cell became clear. This may suggest that the site of action of OEBC was the intercellular of stratum corneum. Furthermore, an electron spin resonance study was performed to investigate the effect of OEBC on the intercellular lipid bilayer fluidity of the stratum corneum and the rotational correlation times were calculated. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were used as the spin label. In use of OEBC, the fluidity of TEMPO labeled the stratum corneum lipid increased as the addition of OEBC. The results suggested that OEBC promote the penetration of drugs by enhancing fluidity of the local lipid bilayers around TEMPO.

Algorithms↗

PubMed2001

Cloning, sequencing, and expression of the gene encoding 4-hydroxy-4-methyl-2-oxoglutarate aldolase from Pseudomonas ochraceae NGJ1.

A DNA fragment that carried the gene (proA) encoding 4-hydroxy-4-methyl-2-oxoglutarate aldolase was cloned from the chromosomal DNA of Pseudomonas ochraceae NGJ1, and the coding region was assigned to the nucleotide sequence based on the N-terminal amino acid sequence of the enzyme purified from the organism. The proA gene was 684 bp long, corresponding to a protein of 227 amino acid residues with a calculated molecular mass of 24,067 Da. The genes encoding a putative transporter and a 4-oxalomesaconate hydratase were upstream, and a 3'-truncated gene encoding 2-pyrone-4,6-dicarboxylate lactonase was downstream from the proA gene in the same orientation on the DNA fragment. The proA gene product was overproduced in Escherichia coli and briefly purified to homogeneity from the crude extract by a two-step purification. The molecular and catalytic properties of the gene product were similar to those of the P. ochraceae enzyme.

Amino Acid Sequence↗

PubMed2001

Serotonin transporter gene variation is a risk factor for sudden infant death syndrome in the Japanese population.

OBJECTIVE: Serotonin (5-HT) in the nervous system is a major factor in facilitation of the brain center for respiration. Variations in the promoter region of the 5-HT transporter (5-HTT) gene have been shown to potentially regulate 5-HT activity in the brain. Therefore, we aimed to identify the possibility that specific allele variants of the 5-HTT gene can be found as a genetic background for sudden infant death syndrome (SIDS). METHODS: Polymorphisms in the 5' regulatory region of the 5-HTT gene were determined in genomic DNA obtained from 27 SIDS victims and 115 age-matched health control participants. RESULTS: There were significant differences in genotype distribution and allele frequency of the 5-HTT promoter gene between SIDS victims and age-matched control participants. The L and XL alleles were more frequently found in SIDS victims than in age-matched control participants. CONCLUSION: Efficiency in the transportation of 5-HTT with the L allele is known to be higher than that with the S allele. The excitatory function by 5-HT is considered to be lower in the respiratory center of individuals with the L allele compared with those with S allele. The XL allele variant has shown another novel biological risk factor for SIDS.

Carrier Proteins↗

PubMed2001

Platelet-derived growth factor and its receptors are expressed in areas of both active inflammation and active fibrosis in inflammatory bowel disease.

The aim of the present study is to clarify in situ expression of platelet-derived growth factor (PDGF) and its receptors in different phases of inflammatory bowel disease (IBD). Tissues samples were obtained from 20 patients with ulcerative colitis (UC) and 29 with Crohn's disease (CD) at surgery. In situ hybridization and immunohistochemistry on frozen sections were performed for PDGF-A and -B and its alpha and beta receptors (alphaR and betaR). The area of active inflammation was infiltrated by abundant polymorphonuclear and mononuclear leukocytes, of which the latter expressed mRNA and proteins of PDGF-A, -B, and -alphaR and mRNA for PDGF-betaR. The area of active fibrosis, characterized by activated fibroblasts/ myofibroblasts, was juxtaposed to ulceration, which is induced as a repair process to tissue destruction. In these areas, activated fibroblasts/myofibroblasts were positive for mRNA and protein of PDGF-A, -B, -alphaR, and -betaR. The expression of PDGF-A, -B, and -alphaR declined significantly in the scar area. Our results suggest that PDGF is not only important as an inducer of fibrosis in the repair phase but also it is involved in the active inflammatory phase possibly as a chemoattractant for mononuclear inflammatory cells.

Adolescent↗

PubMed2001

Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide.

We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.

Aged↗

PubMed2001

Acute gastric dilatation accompanied by diabetes mellitus.

A 72-year-old man with diabetic triopathy was hospitalized with methicillin resistant staphylococcus aureus pneumonia. Six hours after the admission, his abdomen was fully expanded. An abdominal X-ray showed gastric dilatation. After insertion of a gastric tube to extract gastric air, his abdomen was flat and gastric dilatation improved. A positive Schellong test and decreased coefficient of RR interval in electrocardiogram variation indicated autonomic neuropathy, which may explain the reason for gastric hypomotility. Acute gastric dilatation in this patient may have occurred due to gastric hypomotility as a result of diabetic autonomic neuropathy in addition to gastric motility inhibition resulting from gastric autonomic nerve stimulation by bacterial toxin.

Acute Disease↗

PubMed2001

CAM-cytarabine, aclarubicin plus macrophage colony-stimulating factor in the treatment of acute myelogenous leukemia with trilineage dysplasia: usefulness of in vitro apoptosis in leukemic cells.

A 67-year-old woman was treated for acute myelogenous leukemia with trilineage dysplasia (AML-TLD) by combination chemotherapy with cytarabine, aclarubicin plus macrophage colony-stimulating factor (M-CSF) (referred to as CAM therapy). Complete remission was achieved after two courses of CAM therapy. After coculture of her bone marrow mononuclear cells with M-CSF in vitro, differentiation of leukemic cells into macrophages with apoptotis was observed. This case confirms an earlier report that an effect of M-CSF inducible by differentiation with apoptotic phenomena, against human leukemic cells was shown both in vitro and in vivo when achieving complete remission.

Aged↗

PubMed2001

[Non-operative management of dens fracture in an elderly patient with severe complications].

An 82-year-old woman was diagnosed with hypertension at the age of 50 and had been treated with antihypertensive agents. Proteinuria was detected at age 60 and her renal function subsequently deteriorated. Hemodialysis was started on February 14, 2000. She fell out of the bed and hit her neck in the early morning on February 15. Neck X-ray tomography revealed Anderson type III dens fracture. Since she had several complicating conditions including angina pectoris and arrhythmia, she was treated by external fixation using a halo-vest. The neck pain improved gradually. During her clinical course, she experienced delirium due to immobilization. However, bone union was complete 5 months later. Physicians should be aware of the possibility that even minor injury can cause dens fracture in elderly patients. Conservative management of type III dense fracture should be considered for elderly patients with a compromised condition.

Aged↗

PubMed2001