Search PubMed⌕ Search

Biomedical subjects

E Ito

Publications and source records attributed to E Ito.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pronounced climatic variations in Alaska during the last two millennia.

Paired oxygen-isotopic analyses of abiotic carbonate and benthic-ostracode shells from lake sediments provide a continuous quantitative record of growing-season temperature for the past 2000 years in the northwestern foothills of the Alaska Range. This record reveals three time intervals of comparable warmth: anno Domini (A.D.) 0-300, 850-1200, and post-1800, the latter two of which correspond to the Medieval Climatic Anomaly and climatic amelioration after the end of the Little Ice Age. The Little Ice Age culminated at A.D. 1700, when the climate was approximately 1.7 degrees C colder than at present. A marked climatic cooling also occurred around A.D. 600, coinciding with extensive glacial advances in Alaska. Comparisons of this temperature record with ostracode trace-element ratios (Mg/Ca, Sr/Ca) further suggest that colder periods were wetter and vice versa during the past 2000 years.

Journal Article↗
PubMed2001

Odor responses and spontaneous oscillatory activity in tentacular nerves of the terrestrial slug, Limax marginatus.

We studied the neural oscillatory activity in the peripheral olfactory system of the tentacles in the terrestrial slug, Limax marginatus, by extracellular recording. Recordings from the cut-ends of the inferior tentacular nerves connected to the inferior tentacular ganglia and sensory epithelia showed spontaneous oscillatory activity at frequencies of 0.1-30 Hz. This spontaneous activity was dominated by the 0.6-6 Hz band. Ethanol odor stimulation decreased the amplitude in the 0.6-6 Hz band and increased those in the 6-15 and 15-30 Hz bands. Antagonists of the gamma-aminobutyric acid (GABA) receptor, bicuculline and picrotoxin, resulted in suppression of spontaneous activity and modulated the odor response in the 0.6-6 Hz band. Our results indicate the involvement of GABA-mediated oscillatory activity in the tentacular nerves in the olfactory processing in molluscs.

Animals↗
PubMed2001

Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and prostaglandin production in a human macrophage cell line.

Prostaglandins (PGs) play regulatory roles in a variety of physiological and pathological processes, including the immune response, cytoprotection and inflammation. Desferrioxamine (DFX), an iron chelator, is known to reduce free radical-mediated cell injury and to upregulate certain inflammatory mediators. We investigated the effects of DFX on the production of PGs and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGs, using a human macrophage cell line, U937. Our results showed that COX-2 expression and PGE(2) production are upregulated by DFX treatment and that this upregulation is dependent on both COX-2 promoter activity and alteration of mRNA stability. COX-2 promoter activity may be, at least in part, mediated by activation of the extracellular signal-regulated kinase pathway. These findings suggest that iron metabolism may regulate inflammatory processes by modulating PGs as well as other inflammatory mediators.

Binding Sites↗
PubMed2001

The forkhead-associated domain of NBS1 is essential for nuclear foci formation after irradiation but not essential for hRAD50[middle dot]hMRE11[middle dot]NBS1 complex DNA repair activity.

NBS1 (p95), the protein responsible for Nijmegen breakage syndrome, shows a weak homology to the yeast Xrs2 protein at the N terminus region, known as the forkhead-associated (FHA) domain and the BRCA1 C terminus domain. The protein interacts with hMRE11 to form a complex with a nuclease activity for initiation of both nonhomologous end joining and homologous recombination. Here, we show in vivo direct evidence that NBS1 recruits the hMRE11 nuclease complex into the cell nucleus and leads to the formation of foci by utilizing different functions from several domains. The amino acid sequence at 665-693 on the C terminus of NBS1, where a novel identical sequence with yeast Xrs2 protein was found, is essential for hMRE11 binding. The hMRE11-binding region is necessary for both nuclear localization of the complex and for cellular radiation resistance. On the other hand, the FHA domain regulates nuclear foci formation of the multiprotein complex in response to DNA damage but is not essential for nuclear transportation of the complex and radiation resistance. Because the FHA/BRCA1 C terminus domain is widely conserved in eukaryotic nuclear proteins related to the cell cycle, gene regulation, and DNA repair, the foci formation could be associated with many phenotypes of Nijmegen breakage syndrome other than radiation sensitivity.

Amino Acid Sequence↗
PubMed2001

Repeat renal biopsy in a girl with tubulointerstitial nephritis and uveitis syndrome.

A Japanese girl aged 8 years who presented with a 2-month history of uveitis subsequently developed tubulointerstitial nephritis. A percutaneous renal biopsy revealed massive interstitial mononuclear cell infiltrates consisting of CD4-positive T cells. Despite administration of topical corticosteroids, the ocular symptoms persisted. Systemic corticosteroid therapy dramatically reduced the ocular symptoms and urinary beta2-microglobulin (beta 2MG) concentration. However, reducing the prednisolone dosage induced recurrence of uveitis associated with increased levels of urinary beta 2MG. The CD4-positive T cell infiltration persisted in the second renal biopsy performed 6 months after the first renal biopsy. These observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Although the renal outcome of TINU has been reported to be favorable, prolonged interstitial cell infiltration may affect long-term renal outcome. Selected patients with TINU should be followed with close observation.

Adrenal Cortex Hormones↗
PubMed2001

Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine.

BACKGROUND: The role of antiplatelet therapy with ticlopidine plus aspirin in the prevention of subacute thrombosis after coronary artery stenting has been established. However, restenosis remains a major limitation in coronary artery stenting. METHODS: To compare the effect of cilostazol on restenosis after coronary angioplasty and stenting with that of ticlopidine after coronary artery stenting, 213 patients with 230 lesions who underwent successful coronary interventions were evaluated. Optimal results (residual stenosis less than 30%) were obtained by balloon angioplasty in 112 lesions, 64 lesions were treated with aspirin 81 mg/day (balloon-aspirin group) and 48 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (balloon-cilostazol group). Stent implantation was performed in the remaining 118 lesions; 55 lesions were treated with ticlopidine 200 mg/day and aspirin 243 mg/day (stent-ticlopidine group) and 63 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (stent-cilostazol group). Concomitant medications were continued for 4 to 6 months of follow-up. RESULTS: No adverse events including acute occlusion and subacute thrombosis occurred in any groups. Although immediate gain and minimal lumen diameter immediately after angioplasty were significantly larger in stent groups than those in balloon groups, net gain at follow-up was significantly larger in cilostazol groups (1.54+/-0.83 mm in balloon-cilostazol group and 1.65+/-0.78 mm in stent-cilostazol group) than other groups (1.02+/-0.81 mm in balloon-aspirin group and 1.21+/-0.70 in stent-ticlopidine group) as a result of significantly lower late loss and loss index in cilostazol groups. The restenosis rate was significantly lower in cilostazol groups (12.5% in balloon-cilostazol group and 14.3% in stent-cilostazol group) than other groups (43.8% in balloon-aspirin group and 32.7% in stent-ticlopidine group). The rate of recurrent angina was significantly lower in cilostazol groups (4.3% in balloon-cilostazol group and 1.9% in stent-cilostazol group) than in other groups (17.5% in balloon-aspirin group and 14.0% in stent-ticlopidine groups). CONCLUSIONS: Both optimal balloon angioplasty with cilostazol and coronary artery stenting with cilostazol have a potential to reduce restenosis compared with optimal balloon angioplasty with aspirin or conventional coronary artery stenting with ticlopidine plus aspirin.

Adult↗
PubMed2001

A cyclic AMP-regulated negative feedforward system for neuritogenesis revealed in a neuroblastomaxglioma hybrid cell line.

We examined the role of second messengers during the neuritogenesis that accompanies neuronal differentiation in a neuroblastomaxglioma hybrid cell line (NG108-15). NG108-15 cells extended neurites after treatment with dibutyryl cyclic AMP. This dibutyryl cyclic AMP treatment evoked the synthesis of voltage-dependent Ca(2+) channel proteins in the cells. The number of neurites was decreased by Ca(2+) influx under condition of high K(+). Interestingly, the increase of neurites stimulated by dibutyryl cyclic AMP and the decrease of neurites caused by high K(+) were both reversible. This is the first study to demonstrate that cyclic AMP regulates a negative feedforward system for neuritogenesis, which links with Ca(2+) signaling. Such a dual role of cyclic AMP may play an important part in precise neurite targeting.

Animals↗
PubMed2001

Vasospastic angina accompanied by Brugada-type electrocardiographic abnormalities.

Brugada Syndrome and Vasospastic Angina. We present two patients with vasospastic angina and Brugada-type ECG abnormalities. The first patient complained of chest pain, and transient ST segment elevation was confirmed on ECG. Coronary angiogram showed no organic stenosis. The second patient had syncopal episodes following anginal chest pain, and the same symptoms were reproduced by intracoronary acetylcholine injection that induced vasospasm. In both patients, ECG at rest showed ST segment elevation in leads V1 and V2 and a right bundle branch block pattern that were accentuated by a Class I antiarrhythmic drug. Ventricular fibrillation also was induced by programmed electrical stimulation. Susceptibility to ventricular fibrillation can be modulated by the interaction of coronary vasospasm with Brugada syndrome or vice versa; therefore, it is important to study the clinical implications of the coexistence of the two diseases in such patients.

Aged↗
PubMed2001

Changes in expression and subcellular localization of nuclear retinoic acid receptors in human endometrial epithelium during the menstrual cycle.

The endometrium is a uniquely dynamic tissue in that it undergoes monthly cycles of proliferation and secretory activity, and is regulated by ovarian steroid hormones. In this study, we focused on retinoic acid receptors (RAR and RXR) which are ligand-dependent transcription factors belonging to the large family of steroid hormones and are expected to affect to cell growth and differentiation in the endometrium. We analysed the expression and subcellular localization of the RA receptors in 57 samples of human endometrium by immunohistochemistry and Western blotting. In the nuclei of the endometrial epithelium, the RA receptors were expressed strongly in the proliferative phase. However, RAR were drastically reduced in the epithelial nuclei during the secretory phase in association with changes in serum oestradiol and in the expression of the oestrogen receptor. The expression of RXR was localized in the epithelial nuclei throughout the menstrual cycle. Confocal laser scanning microscopical observation clearly showed the difference in the localization between RAR and RXR in the secretory phase. Furthermore the findings of immuno-electron microscopy showed pooled RAR around the rough endoplasmic reticulum, suggesting that transport of these receptors to the nuclei is inhibited. These findings suggest that RAR and RXR work mainly in the proliferative phase and that in the endometrium RXR may play a different role to RAR during the secretory phase.

Blotting, Western↗
PubMed2001

Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor.

To understand the mechanism of activation of a receptor by its agonist, the excitation and relaxation processes of the vibrational states of the receptor should be examined. As a first approach to this problem, we calculated the normal vibrational modes of agonists (glutamate and kainate) and an antagonist (6-cyano-7-nitroquinoxaline-2,3-dione: CNQX) of the glutamate receptor, and then investigated the vibrational interactions between kainate and the binding site of glutamate receptor subunit GluR2 by use of a semiempirical molecular orbital method (MOPAC2000-PM3). We found that two local vibrational modes of kainate, which were also observed in glutamate but not in CNQX, interacted through hydrogen bonds with the vibrational modes of GluR2: (i) the bending vibration of the amine group of kainate, interacting with the stretching vibration of the carboxyl group of Glu705 of GluR2, and (ii) the symmetric stretching vibration of the carboxyl group of kainate, interacting with the bending vibration of the guanidinium group of Arg485. We also found collective modes with low frequency at the binding site of GluR2 in the kainate-bound state. The vibrational energy supplied by an agonist may flow from the high-frequency local modes to the low-frequency collective modes in a receptor, resulting in receptor activation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

A theoretical study of electronic and structural states of neurotransmitters: gamma-aminobutyric acid and glutamic acid.

As a first approach to understanding the mechanism for the recognition of a ligand by its receptor, we first calculated the electronic and structural states of ionized gamma-aminobutyric acid (GABA) and ionized glutamic acid using the ab initio method with the 6-311++G (3df, 2pd) basis set. We paid special attention to the physicochemical characteristics of these molecules, such as the electric dipole moment, electrostatic potential, and electrostatic force. Even though GABA and glutamic acid are known to exert completely opposite influences in the mammalian brain by binding their specific receptors, the only difference in their chemical structures is that glutamic acid contains one more carboxyl group than GABA. As a result, we succeeded in showing that a difference of only one carboxyl group induces significant differences in the electronic and structural states between these molecules. These differences have a crucial influence on the electric dipole moments, the electrostatic potentials, and the electrostatic forces. The most remarkable finding of the present research is that the electrostatic potential formed by glutamic acid is composed of only negative parts, while that formed by GABA is separated into positive and negative parts. These results strongly suggest that GABA can approach either positively or negatively charged amino acids by adjusting its own orientation, while glutamic acid can approach only a positively charged binding site.

Chemical Phenomena↗
PubMed2001

The promoter of mouse transcription repressor bach1 is regulated by Sp1 and trans-activated by Bach1.

The Maf recognition element (MARE) is regulated by both activators and repressors. Bach1 and Bach2 repress MARE-dependent transcription by forming heterodimers with Maf-related oncoproteins. In order to gain an understanding of the regulation of bach1 gene expression, we analyzed the structure of the mouse bach1 gene. Comparison of the exon-intron structure of the bach1 gene with those of other NF-E2-related genes indicated that bach1 and bach2 constitute an evolutionarily distinct subfamily among bZip factors. The bach1 promoter region contains two GC boxes that are important for its basal activity and are bound by Sp1 in K562 cell extracts. In addition, we found an evolutionarily conserved MARE-like element located downstream of the transcription initiation site. Deletion of this element resulted in a higher promoter activity in K562 cells. Bach1 trans-activated its own promoter depending on the presence of the MARE-like element in co-transfection assays. However, Bach1 did not bind to the MARE-like element in electrophoretic mobility shift assays (EMSA). These results suggest that Bach1 activates its own promoter indirectly by inhibiting the putative repressor. Such a positive feedback regulation by the repressor Bach1 may play an important role in maintaining the expression of Bach1 while consolidating repression of other genes with MARE.

Animals↗
PubMed2001

Reduced expression of laminin alpha 3 and alpha 5 chains in non-small cell lung cancers.

The basement membrane is considered to act as a barrier which hinders cancer cells from invading the surrounding stroma. In order to assess changes in essential components during neoplasia in the lung, we immunohistochemically studied distribution patterns of laminins alpha 3 and alpha 5 in 40 adenocarcinomas and 8 squamous cell carcinomas. The a 5 chain was generally preserved at the periphery, frequently disrupted in foci with alveolar collapse and absent in foci of fibroblastic proliferation within adenocarcinomas. Fragmentation and absence of laminin alpha 3 chain were more prominent than for alpha 5 chain. Laminin alpha 3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from alpha 5 chain. Non-small cell lung cancers with reduced alpha 5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin alpha 3 and alpha 5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express alpha 3 chain and expression of alpha 5 chain was reduced in three. Quantitative RT-PCR analysis also demonstrated expression of laminin alpha 3 chain in adenocarcinoma tissues to be significantly lower than in normal lung tissues. These results suggest that expression of laminin alpha chains is often reduced in lung cancer cells and this might contribute to basement membrane fragmentation and subsequent proliferation of stromal elements, as well as play some role in the process of cancer cell invasion.

Adenocarcinoma↗
PubMed2001

Significance of end-tidal P(CO(2)) response to exercise and its relation to functional capacity in patients with chronic heart failure.

OBJECTIVES: The value of end-tidal PCO(2) monitoring during exercise in patients with chronic heart failure has not been elucidated. The present study was designed to examine end-tidal PCO(2) response to exercise and its relation to functional capacity in patients with chronic heart failure. METHODS AND RESULTS: Maximal upright ergometer exercise with respiratory gas analysis and arterial blood gas analysis were performed in 105 patients with chronic heart failure (34 patients in New York Heart Association [NYHA] class I, 38 patients in NYHA class II, and 33 patients in NYHA class III) and 14 normal control subjects. Peak O(2) uptake, excessive exercise ventilation as assessed by the slope of the relation between expired minute ventilation and CO(2) output (VE-VCO(2)), and the ratio of physiologic dead space to tidal volume (VD/VT) were determined. Cardiac output was also measured during exercise in 28 patients with chronic heart failure. Arterial PO(2) or PCO(2) values at rest and during exercise were not different among the four groups. However, end-tidal PCO(2) was significantly lower, and arterial to end-tidal PCO(2) difference and VD/VT were significantly higher in NYHA class III patients than other groups during exercise. The maximal end-tidal PCO(2) during exercise was significantly reduced as the severity of chronic heart failure advanced (45.7 +/- 4.0 mm Hg in normal control subjects, 43.5 +/- 4.8 mm Hg in NYHA class I patients, 39.7 +/- 5.1 mm Hg in NYHA class II patients, and 34.9 +/- 5.3 mm Hg in NYHA class III patients). The maximal end-tidal PCO(2) during exercise was significantly correlated with peak O(2) uptake (r = 0.68; p < 0.001) and maximal cardiac index (r = 0.73; p < 0.001), and inversely related to Ve-VCO(2) (r = - 0.84; p < 0.001) and VD/VT at peak exercise (r = -0.65; p < 0.001). CONCLUSIONS: The decreased end-tidal PCO(2) during exercise, which is caused by high ventilation/perfusion ratio mismatching, reflects both reduced cardiac output response to exercise and increased exercise ventilation due to enlarged physiologic dead space in advanced chronic heart failure. The end-tidal PCO(2) during exercise can be used to evaluate the functional capacity of patients with chronic heart failure.

Carbon Dioxide↗
PubMed2001

Tubulointerstitial nephritis and uveitis syndrome in two siblings.

Two Japanese sisters with persistent uveitis showed significant increased levels of urinary beta-2 microglobulin. A percutaneous renal biopsy performed in the younger sister revealed tubulointerstitial nephritis (TIN) with helper/inducer T cell infiltrates. Also, abnormal 67-gallium accumulation in the kidneys, suggesting TIN, was observed in the other one at the same time. Although patients with the syndrome of tubulointerstitial nephritis and uveitis (TINU) have been reported to date, its occurrence in siblings has rarely been seen. Both of them shared same human leukocyte antigen (HLA) DR6, suggesting the potential association between HLA-DR6 and TINU.

Adolescent↗
PubMed2001

Improved survival of children with advanced neuroblastoma treated by intensified therapy including myeloablative chemotherapy with stem cell transplantation: a retrospective analysis from the Tohoku Neuroblastoma Study Group.

In the hospitals of the Tohoku Neuroblastoma Study Group (TNBSG), treatment for children with advanced neuroblastoma (NB) was intensified in the mid-1990's with the introduction of myeloablative therapy (MT) with stem cell transplantation (SCT) including the use of autologous peripheral blood stem cells (PBSC) and bone marrow transplantation (BMT). In this report, we examined whether the intensified therapy improved the outcome of children with advanced NB (age> 12 months) who were diagnosed between 1991 and 1997. Patients were 36 children (23 boys and 13 girls) with an average age of 3.4 years (range; 1 to 14 years). Six of them had stage III disease, and the other 30 had stage IV. They were treated initially with induction chemotherapy, surgery, and post-operative chemoradiotherapy, after which 17 of them continued further chemotherapy and the other 19 received MT/SCT (18 with PBSCT and 1 with BMT). Progression-free survival (PFS) rate at seven years from diagnosis was 43.5% for all patients, 66.7% for stage III patients and 38.2% for stage IV patients. The difference between stage III and IV patients was not significant. Among the 30 patients with stage IV disease, PFS at seven years was significantly higher in the 19 patients who received MT/SCT (55.6%) than in the 11 patients who did not receive it (12.5%). There was no difference in clinical and biological risk factors between these two groups, except for the proportion of patients with favorable response to initial therapy (36% and 80% for patients without and with MT/SCT, respectively). Furthermore, the proportion of patients with N-myc amplification was significantly higher in patients with progressive disease (PD) after MT/SCT than in those in CR after MT/SCT. The results of this retrospective study of children with advanced NB suggest that therapy intensification involving MT/SCT might result in lengthened survival time for patients with stage IV disease, and that post-transplant PD remains a risk for patients with high levels of N-myc amplification.

Antineoplastic Agents↗
PubMed2000

A novel function of synapsin II in neurotransmitter release.

Although synapsin has been localized to presynaptic structures, its function remains poorly understood. In the present study, we investigated the presynaptic function of synapsin II using a synaptic vesicle recycling process using synapsin-II-overexpressing NG108-15 cells. Western blot analysis with antibodies for synaptic-vesicle-associated protein indicated that the number of synaptic vesicles was approximately doubled in synapsin II transfectants as reported previously. In differentiated synapsin-II-overexpressing and control cells, the application of high potassium induced strong intracellular calcium elevation along neurites and varicosities after differentiation and a weak calcium rise in the cell bodies. The uptake and release of the fluorescent dye FM1-43 revealed that synaptic vesicle recycling in synapsin-II-transfected cells occurred with the same kinetics in the cell body and neuritic varicosities. Furthermore, the area labeled with FM1-43 fluorescence in the synapsin-II-transfected cells was approximately twice as much as in control cells after stimulation, and ATP released after synaptic vesicle fusion with the plasma membrane in synapsin-II-expressing cells was significantly elevated relative to controls. The number of synaptic vesicles paralleled the amount of transmitter released from the cells leading to the conclusion that the number of releasable synaptic vesicles were increased by synapsin II transfection into NG108-15 cells, suggesting that synapsin II may have a role in the regulation of synaptic vesicle number in presynapse-like structures in NG108-15 cells.

Adenosine Triphosphate↗