Trp64Arg polymorphism of the beta3-adrenergic receptor is not associated with diabetic nephropathy in Japanese patients with type 2 diabetes.
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Albuminuria↗
Biomedical subjects
S Nakajima
Publications and source records attributed to S Nakajima.
The effect of mast cell on the induction of Helicobacter pylori infection in Mongolian gerbils.
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Journal Article↗
New cytotoxic agents, BE-54238A and B, produced by a streptomycete.
New cytotoxic substances, designated BE-54238A and B, were isolated from the culture broth of Streptomyces sp. A54238. The active principles were extracted from the mycelium by methanol and purified by Diaion HP-20 and Sephadex LH-20 column chromatographies. BE-54238A and B exhibited cytotoxic activity against murine and human tumor cell lines.
Animals↗
New cytotoxic agents, BE-52440A and B, produced by a streptomycete.
New cytotoxic substances, designated BE-52440A and B, were isolated from the mycelium of Streptomyces sp. A52440. The active principles were extracted from the mycelium by methanol and purified by silica gel column chromatography. BE-52440A and B exhibited cytotoxic activity against murine and human tumor cell lines.
Animals↗
Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells.
Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.
Animals↗
[Hospitalization reduction by an asthma tele-medicine system].
We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site randomized control study. In this program, a nurse under physician supervision monitors the patient's airway status at home and provides instructions to individuals via the telephone, helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan. Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and randomly assigned to either the telemedicine or control group. After a six-month study period, an 83% reduction in hospitalization was demonstrated in the telemedicine group versus the control group, with a P value of 0.01. Improvement of peak expiratory flow and symptoms were also shown in the study group. We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring, compliance with prescribed daily prophylactic anti-inflammatory steroid medications, and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration.
Aged↗
[Asthma death among adults in Japan 1995-1997. Analysis of 295 cases reported questionnaires sent to hospitals with more than 100 beds. Asthma Death Investigation Committee].
To clarify recent trends in adult asthma mortality, the Asthma Death Investigation Committee of Japan studied the clinical characteristics of 295 patients who died of asthma between 1995 and 1997. Males were slightly more than females among the death cases. Approximately half of the patients ranged in age from 60 to 79 years. Tendency to increase of death among young male adults continued. One third of the patient deaths involved the asphyxic type, while status asthmaticus was the cause death in 21.9%. Half of the asthmatics died in hospitals or emergency rooms, and places where the fatal attacks occurred were mainly patients' houses. The main cause fatal asthma attacks was respiratory infection, followed by fatigue, stress, and discontinuation of medication. Most of the patients were classified moderate or severe type of asthma 1 month before death. Histories of life-threatening attacks and hospitalization due to severe attacks, irregular visits to the hospital, low compliance, and insufficiency of corticosteroid treatment were suggested as the main risk factors in adult asthma deaths.
Adolescent↗
Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method.
UNLABELLED: The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET.
Adolescent↗
Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression.
To examine the expression of the stromal cell-derived factor 1 (SDF-1)/CXCR4 receptor ligand system in pancreatic cancer cells and endothelial cells, we performed immunohistochemical analysis for 52 pancreatic cancer tissue samples with anti-CXCR4 antibody and reverse transcription-PCR analysis for CXCR4 and SDF-1 in five pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, and PANC-1), an endothelial cell line (HUVEC), and eight pancreatic cancer tissues. We then performed cell migration assay on AsPC-1 cells, HUVECs, and CFPAC-1 cells in the presence of SDF-1 or MRC-9 fibroblast cells. Immunoreactive CXCR4 was found mainly in pancreatic cancer cells and endothelial cells of relatively large vessels around a tumorous lesion. The immunopositive ratio in the pancreatic cancer was 71.2%. There was no statistically significant correlation with clinicopathological features. SDF-1 mRNA expressions were detected in all pancreatic cancer tissues but not in pancreatic cancer cell lines and HUVECs; meanwhile, CXCR4 mRNA was detected in all pancreatic cancer tissues, cancer cell lines, and HUVECs. The results indicate that the paracrine mechanism is involved in the SDF-1/CXCR4 receptor ligand system in pancreatic cancer. In vitro studies demonstrated that SDF-1 significantly increased the migration ability of AsPC-1 and HUVECs, and these effects were inhibited by CXCR4 antagonist T22, and that the coculture system with MRC-9 also increased the migration ability of CFPAC-1 cells, and this effect was significantly inhibited by T22. Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression through tumor cell migration and angiogenesis.
Adult↗
[A case of Sjögren's syndrome with pleural effusion].
A 45-year-old woman was admitted to our hospital because of a fever. A round erythema was noted on the skin, suggesting collagen disease. Bilateral pleural effusion developed during hospitalization, and serum and pleural effusion were positive for antinuclear antibody, RA factor, anti-SS-A antibody, and anti-SS-B antibody. A diagnosis of Sjögren's syndrome was made on the basis of reduced lacrimation and the histological findings in a biopsy specimen from the lip. The cells in the pleural effusion were predominantly lymphocytes, and so a pleural lesion associated with Sjögren's syndrome was suspected, but reports of this condition have been scarce. Good therapeutic results were obtained by corticosteroid administration. Sjögren's syndrome should be considered in the differential diagnosis of pleural effusion associated with collagen disease.
Female↗
[A case of ulcerative colitis with ileus due to extensive stricture of the colon].
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Adult↗
Acute scrotal swelling in Henoch-Schönlein purpura: a case report.
Henoch-Schönlein purpura is a systemic vasculitis and sometimes presents as acute scrotal swelling in children. We report a case of Henoch-Schönlein purpura with acute scrotal swelling, which was correctly diagnosed based upon local physical findings. Scrotal ultrasonography showed normal testes and hydrocele testis around the affected testis 3 hours after the sudden onset of the pain. The scrotal symptoms improved in 2 days with steroid therapy. Scrotal ultrasonography was useful to diagnose Henoch-Schönlein purpura with scrotal involvement. Steroid treatment appeared to be effective for this condition.
Acute Disease↗
Physical properties of the dentin-enamel junction region.
PURPOSE: To determine the physical properties between enamel and dentin at the dentin-enamel junction (DEJ) region of natural tooth structure. MATERIALS AND METHODS: Ultimate tensile cohesive strengths of the DEJ region of human and bovine teeth were measured using a microtensile test, and the nanohardness and Young's modulus from deep enamel to superficial dentin of human teeth were measured using a nanoindentation tester. RESULTS: The mean ultimate tensile cohesive strengths of bovine and human DEJ region were 47.7 MPa and 51.5 MPa, respectively. The nanohardness, dynamic hardness and Young's modulus of the DEJ region showed moderate values between those of enamel and dentin. Comparison of the cohesive strength of the human DEJ region with previous results of the bond strength of resin bonding systems indicate that current resin bonding systems might reproduce the biological adhesion of enamel to dentin in terms of the tensile strength. Moreover, the indentation properties of the DEJ region showed higher values than those of the underlying dentin or of resin impregnated dentin.
Acid Etching, Dental↗
Importance of the G protein gamma subunit in activating G protein-coupled inward rectifier K(+) channels.
The G protein-coupled inward rectifier K(+) channel (GIRK) is activated by direct interaction with the heterotrimeric GTP-binding protein betagamma subunits (Gbetagamma). However, the precise role of Gbeta and Ggamma in GIRK activation remains to be elucidated. Using transient expression of GIRK1, GIRK2, Gbeta1, and Ggamma2 in human embryonic kidney 293 cells, we show that C-terminal mutants of Gbeta1, which do not bind to Ggamma2, are still able to associate with GIRK, but these mutants are unable to induce activation of GIRK channels. In contrast, other C-terminal mutants of Gbeta1 that bind to Ggamma2, are capable of activating the GIRK channel. These results suggest that Ggamma plays a more important role than that of an anchoring device for the Gbetagamma-induced GIRK activation.
Cell Line↗
Analysis of the molecular mechanism for the antagonistic action of a novel 1alpha,25-dihydroxyvitamin D(3) analogue toward vitamin D receptor function.
We have recently reported that 23(S)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9647) efficiently blocks the differentiation of HL-60 cells induced by 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) (Miura, D., Manabe, K., Ozono, K., Saito, M., Gao, Q., Norman, A. W., and Ishizuka, S. (1999) J. Biol. Chem. 274, 16392-16399). To clarify the molecular mechanisms of this antagonism, we examined whether TEI-9647 antagonizes the genomic effects of 1alpha,25(OH)(2)D(3). 10(-7) to 10(-9) M TEI-9647 inhibited the transactivation effect of 10(-8) M 1alpha,25(OH)(2)D(3) in a dose-dependent manner, while TEI-9647 alone did not activate the reporter activity driven by SV40 promoter containing two vitamin D response elements in Saos-2 cells. The antagonistic effect of TEI-9647 was also observed using the rat 24-hydroxylase gene promoter, but the effect was weaker in HeLa and COS-7 cells than in Saos-2 cells. TEI-9647 also exhibited antagonism in an assay system where the VDR fused to the GAL4 DNA-binding domain and the reporter plasmid containing the GAL4 binding site were used in Saos-2 cells, but did not in HeLa cells. TEI-9647 reduced the interaction between VDR and RXRalpha according to the results obtained from the mammalian two-hybrid system in Saos-2 cells, but did not in HeLa cells. The two-hybrid system also revealed that the interaction between VDR and SRC-1 was reduced by TEI-9647 in Saos-2 cells. These results demonstrate that the novel 1alpha,25(OH)(2)D(3) analogue, TEI-9647, is the first synthetic ligand for the VDR that efficiently antagonizes the action of 1alpha, 25(OH)(2)D(3), although the extent of its antagonism depends on cell type.
Animals↗
Facilitation of renal kallikrein-kinin system prevents the development of hypertension by inhibition of sodium retention.
We have previously reported that the renal kallikrein-kinin system suppressed the development of hypertension, using kininogen deficient Brown Norway Katholiek rats. Kinins were degraded in urine mainly by carboxypeptidase Y-like kininase (CPY). Blockade of renal kinin degradation may prevent the experimental hypertension through the facilitation of the renal kallikrein-kinin system. Daily administration of ebelactone B (EB), which is isolated from Actinomycetes and strongly inhibits CPY, from the first day of deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks completely blocked hypertension in Sprague-Dawley rats. This treatment reduced sodium levels in erythrocytes and cerebrospinal fluids (CSF) significantly. By contrast, an ACE inhibitor, lisinopril did not prevent hypertension. The development of hypertension in young spontaneously hypertensive rats was also blunted by EB with reductions in sodium levels in erythrocytes and in CSF. The arterial kinin levels in rats undergoing DOCA-salt treatment were 2.2 +/- 0.2 pg/ml, which were increased significantly to 4.6 +/- 0.4 pg/ml with captopril (10 mg/kg, s.c.). The increased kinin levels were less than those to show hypotension. EB did not increase the arterial kinin levels, with significant increase in urinary kinin secretion. These results suggested that facilitation of the renal kallikrein-kinin system by inhibition of kinin degradation on the luminal side of the renal tubules may effectively prevent hypertension.
Angiotensin-Converting Enzyme Inhibitors↗
A new boronated porphyrin (STA-BX909) for neutron capture therapy: an in vitro survival assay and in vivo tissue uptake study.
A new boronated porphyrin compound (STA-BX909) was developed as a possible agent for boron neutron capture therapy. The boron concentration was measured by an in vivo rat experimental brain tumor model and an in vitro cell culture study. This agent was compared to sodium borocaptate (BSH) which has been used in clinical trials of boron neutron capture therapy. In the 9L rat brain tumor model, STA-BX909 achieved a higher boron tumor/blood ratio 24 h after injection in comparison to BSH. A boron concentration study in cultured glioma cell lines (U-251, U-87, 9L) demonstrated an increased boron concentration as a function of exposure time to STA-BX909, while the boron concentration remained stable with increasing exposure time to BSH. Use of a colony forming assay with thermal neutron irradiation revealed more cytotoxicity with STA-BX909 than BSH when the same concentration of 10B was administered. We concluded that STA-BX909 may be an effective drug for use in boron neutron capture therapy and that it merits further investigation.
Animals↗
Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic-cancer cells.
In this study, we investigated the effect of a novel retinobenzoic acid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), on the growth of 4 human pancreatic-cancer cell lines; BxPC-3, MIAPaCa-2, CFPAC-1 and AsPC-1. TAC-101 significantly inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells in a time- and concentration-dependent manner, but not the proliferation of AsPC-1 cells. Furthermore, the anti-proliferative effects of TAC-101 on BxPC-3 and MIAPaCa-2 cells were stronger than those of all-trans retinoic acid. Flow-cytometric analyses indicated that treatment of BxPC-3 with TAC-101 strongly induces cell-cycle arrest at the G1 phase. The cell-cycle arrest induced by TAC-101 was accompanied by reduction of retinoblastoma-gene product (RB) phosphorylation and an increase of 2 cyclin-dependent kinase (CDK) inhibitors, p21(WAF1/Cip1) (p21) and p27Kip1 (p27). TAC-101 also caused a decrease in cyclin A and thymidylate synthase, which are E2F-regulated gene products. No changes were observed in the expression of cyclin D1, cyclin E on CDK2. In addition, Hoechst staining, gel electrophoresis and flow-cytometric analysis indicated that a marked reduction in the number of BxPC-3 cells with TAC-101 was related to the induction of apoptosis. Our results suggest that TAC-101 inhibits the growth of certain pancreatic-cancer cells by means of G1-phase cell-cycle arrest resulting from the reduction of RB phosphorylation and the up-regulation of p21 and p27 as well as the induction of apoptosis. TAC-101 may therefore be a useful agent for new therapeutic strategies focusing on inhibition of pancreatic-cancer-cell proliferation.
Antineoplastic Agents↗