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Biomedical subjects

T Iijima

Publications and source records attributed to T Iijima.

At least 19 recordsLinked to original sources
PubMed2001

Expression of mouse igf2 mRNA-binding protein 3 and its implications for the developing central nervous system.

Functional analyses of neural RNA-binding proteins have focused mainly on their roles as modulators of posttranscriptional gene regulation, e.g., alternative splicing, dendritic mRNA localization, and local translation. Here we identified a mouse homologue of human IMP3, which is known to bind to and repress the translation of igf2 leader 3 mRNA. The mouse igf2 mRNA-binding protein 3 (mIMP3) is a member of the zipcode binding protein-1 (ZBP-1) family previously reported in chick fibroblast cells. mIMP3 was expressed in undifferentiated neuroepithelial cells and some postmitotic neurons at early embryonic stages (E10.5--E12.5), and its expression level decreased after the midembryonic stage (E12.5) until birth. The expression profile of mIMP3 is very similar to that of mouse igf2 leader 3 mRNA. In vitro UV cross-linking experiments showed that mIMP3 preferentially bound to igf2 leader 3 mRNA rather than igf2 leader 4 mRNA and did not bind the zipcode region of beta-actin or c-myc mRNA. Furthermore, persistent expression of mIMP3 protein in an undifferentiated P19 cell line revealed that mIMP3 inhibited neuronal differentiation morphologically and immunohistochemically. Taken together, these observations raise the possibility that mIMP3 represses neuronal differentiation through the regulation of igf2 mRNA expression.

5' Untranslated Regions↗
PubMed2001

Measurement of B(0)(d)-B_(0)(d) mixing rate from the time evolution of dilepton events at the upsilon(4S).

We report a determination of the B(0)(d)-&B_(0)(d) mixing parameter Deltam(d) based on the time evolution of dilepton yields in Upsilon(4S) decays. The measurement is based on a 5.9 fb(-1) data sample collected by the Belle detector at KEKB. The proper-time difference distributions for same-sign and opposite-sign dilepton events are simultaneously fitted to an expression containing Deltam(d) as a free parameter. Using both muons and electrons, we obtain Deltam(d) = 0.463+/-0.008 (stat)+/-0.016 (syst) ps(-1). This is the first determination of Deltam(d) from time evolution measurements at the Upsilon(4S). We also place limits on possible CPT violations.

Journal Article↗
PubMed2001

Measurement of the CP violation parameter sin2 phi(1) in B(0)(d) meson decays.

We present a measurement of the standard model CP violation parameter sin2 phi(1) (also known as sin2beta) based on a 10.5 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) collider. One neutral B meson is reconstructed in the J/psiK(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psiK(L), or J/psipi(0) CP-eigenstate decay channel and the flavor of the accompanying B meson is identified from its charged particle decay products. From the asymmetry in the distribution of the time interval between the two B-meson decay points, we determine sin2 phi(1) = 0.58(+0.32)(-0.34)(stat)+0.09-0.10(syst).

Journal Article↗
PubMed2001

Kat1-antigen--a reliable immunological marker for identifying osteoclast precursors of rats: detection of subpopulations among precursors and initiation of osteoclastogenesis.

Previously we found a unique cell surface antigen [Kat1-antigen (Kat1-Ag)] expressed on rat osteoclasts. In the present study, we focused on the expression of this antigen in preosteoclasts, mononuclear precursors of osteoclasts. Immunohistochemical and immunoelectron microscopic observations of the Kat1-Ag expressed in vivo showed the antigen to be present on mononuclear cells having the morphological features of preosteoclasts. The relationship between Kat1-Ag expression and calcitonin receptor (CTR) expression was examined in detail by a double-detection technique for CTR and Kat1-Ag by use of autoradiography and immunocytochemistry, respectively. In a culture system for forming mononuclear preosteoclast-like cells, almost 100% of the mononuclear cells expressing Kat1-Ag also expressed CTR, demonstrating that Kat1-Ag is a reliable immunological marker for identifying preosteoclasts. Interestingly, a significant number of the CTR-positive mononuclear cells did not express the Kat1-Ag. Detection of these cells expressing CTR but not Kat1-Ag strongly suggests the presence of subpopulations in preosteoclasts. We also obtained evidence suggesting that expression of the Kat1-Ag is initiated during the postmitotic stage of the osteoclast progenitors.

Animals↗
PubMed2001

Neuroanatomical discrimination between manipulating and maintaining processes involved in verbal working memory; a functional MRI study.

We used functional magnetic resonance imaging (fMRI) to investigate neural correlates of processes concerning store and manipulation in verbal working memory. We prepared a revised lag 1 digit span, digit span and a simple number detection task. Specific activities in association with manipulating process were identified in the right middle (BA 9/46) and left precentral gyrus (BA 6). Activated areas specific to maintaining process were detected in the right middle (right BA 11/10) and medial (BA 6) frontal gyri, the right inferior parietal lobule (BA 40), and the left middle (BA 9) and inferior frontal gyri (BA 44). The process-nonspecific activated areas common to two processes were identified in the right inferior frontal gyrus (BA 47) and the left superior parietal lobule (BA 7). Using the signal percent change of each subject, we calculated the correlation coefficients among each activated area. The results of this analysis showed that two processes of verbal working memory were clearly discriminated. The two essential processes of manipulation and maintenance in working memory seem to activate process-specific and overlapping (process-nonspecific) areas, but the patterns of combination were definitely different.

Adult↗
PubMed2001

Potent estrogen agonists based on carborane as a hydrophobic skeletal structure. A new medicinal application of boron clusters.

BACKGROUND: Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable thermal stability and exceptional hydrophobicity. Applications of the unique structural and chemical properties offered by icosahedral carboranes in boron neutron capture therapy have received increasing attention over the past 30 years. However, these features of carboranes may allow another application as a hydrophobic pharmacophore in biologically active molecules that interact hydrophobically with receptors. RESULTS: We have designed candidate estrogen-receptor-binding compounds having carborane as a hydrophobic skeletal structure and synthesized them. The most potent compound bearing a carborane cage exhibited activity at least 10-fold greater than that of 17beta-estradiol in the luciferase reporter gene assay. Estrogen receptor-alpha-binding data for the compound were consistent with the results of the luciferase reporter gene assay. The compound also showed potent in vivo effects on the recovery of uterine weight and bone loss in ovariectomized mice. CONCLUSION: Further development of the potent carborane-containing estrogenic agonists described here, having a new skeletal structure and unique characteristics, should yield novel therapeutic agents, especially selective estrogen receptor modulators. Furthermore, the suitability of the spherical carborane cage for binding to the cavity of the estrogen receptor-alpha ligand-binding domain should provide a basis for a similar approach to developing novel ligands for other steroid receptors.

Animals↗
PubMed2000

Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous melanin deposition, and increased risk of cancer, mainly in the gastrointestinal tract. We examined mutations of the LKB1, beta-catenin, APC, K-ras, and p53 genes in 27 gastrointestinal hamartomatous polyps from 10 patients in nine PJS families. Of these hamartomatous polyps, one intestinal polyp had an adenomatous lesion, and one gastric polyp contained adenomatous and carcinomatous lesions. Germ-line mutations of the LKB1 gene were detected in six PJS families. Somatic mutations of the LKB1 gene were found in 5 polyps, whereas loss of heterozygosity (LOH) at the LKB1 locus at 19p was seen in 14 other polyps. In adenomatous lesions microdissected from hamartomatous polyps, both beta-catenin mutation and 19p LOH were detected. Furthermore, a carcinomatous lesion in a gastric hamartomatous polyp was found to contain a mutation of the p53 gene and LOH at the p53 locus in addition to LOH at the LKB1 locus and a beta-catenin mutation. K-ras mutations were detected in a few polyps, whereas no APC mutation or 5q LOH was detected in hamartomatous polyps. These results suggest that gastrointestinal hamartomatous polyps in PJS patients develop through inactivation of the LKB1 gene by germ-line mutation plus somatic mutation or LOH of the unaffected LKB1 allele, and that additional mutations of the beta-catenin gene and p53 gene convert hamartomatous polyps into adenomatous and carcinomatous lesions.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Properties of the delayed rectifier potassium current in porcine sino-atrial node cells.

Whole-cell currents were recorded in single, spontaneously active cells dissociated from porcine sino-atrial node, and the conductance and gating properties of the delayed rectifier K+ current (IK) were investigated. The isolated cells exhibited spontaneous action potentials at a rate of 80.5 +/- 5.4 min-1 (mean +/- s.e.m., n = 11). Under Ca2+ current block, depolarization from -40 mV to various potentials activated a time-dependent outward current (IK). The activation curve of IK showed a half-activation potential (V½) of 20.5 +/- 2.1 mV and a slope factor (S) of 16.4 +/- 1.2 mV (n = 8). As the duration of the depolarizing pulse to either +10 or +60 mV was prolonged, the amplitude of the tail current increased in proportion to that of the activated outward current during depolarization. E4031 (2-5 µM), a selective blocker for the rapidly activating component of IK (IK,r), hardly affected IK, but chromanol 293B, a selective blocker for the slowly activating component (IK,s), inhibited IK with an IC50 of 8.79 µM. The reversal potential of IK was -75.2 +/- 2.3 mV with 5.4 mM external and 150 mM internal K+. The time courses of activation and deactivation of IK were fitted by the sum of two exponential functions at various potentials. The relationship between the time constants and membrane potential showed a bell-shaped curve with a peak at around -10 mV for both fast and slow components. The results indicate that in porcine sino-atrial node cells IK is largely derived from IK,s and that IK,s plays a functional role in the slow diastolic depolarization. IK,s may, in part, account for the relatively slower heart rate of pigs than that of rabbit in which IK,r is a functionally dominant component of IK.

Journal Article↗
PubMed2000

Properties of the delayed rectifier potassium current in porcine sino-atrial node cells.

1. Whole-cell currents were recorded in single, spontaneously active cells dissociated from porcine sino-atrial node, and the conductance and gating properties of the delayed rectifier K+ current (I(K)) were investigated. 2. The isolated cells exhibited spontaneous action potentials at a rate of 80.5 +/- 5.4 min(-1) (mean +/- S.E.M., n = 11). Under Ca2+ current block, (depolarization from -40 mV to various potentials activated a time-dependent outward current (I(K)). The activation curve of I(K) showed a half-activation potential (V1/2) of 20.5 +/- 2.1 mV and a slope factor (S) of 16.4 +/- 1.2 mV (n = 8). 3. As the duration of the depolarizing pulse to either +10 or +60 mV was prolonged, the amplitude of the tail current increased in proportion to that of the activated outward current during depolarization. 4. E4031 (2-5 microM), a selective blocker for the rapidly activating component of I(K) (I(K,r)), hardly affected I(K), but chromanol 293B, a selective blocker for the slowly activating component (I(K,s)), inhibited I(K) with an IC(50) of 8.79 microM. 5. The reversal potential of I(K) was -75.2 +/- 2.3 mV with 5.4 mM external and 150 mM internal K+. The time courses of activation and deactivation of I(K) were fitted by the sum of two exponential functions at various potentials. The relationship between the time constants and membrane potential showed a bell-shaped curve with a peak at around -10 mV for both fast and slow components. 6. The results indicate that in porcine sino-atrial node cells I(K) is largely derived from I(K,s) and that I(K,s) plays a functional role in in the slow diastolic depolarization. I(K,s) may, in part, account for the relatively slower heart rate of pigs than that of rabbit in which I(K,r) is a functionally dominant component of I(K).

Action Potentials↗
PubMed2000

Inhibition by antisense oligonucleotides of plasma membrane Ca(2+) ATPase in vascular endothelial cells.

Antisense oligodeoxynucleotides were used to knock down plasma membrane Ca(2+) ATPase, and the role of plasma membrane Ca(2+) ATPase was investigated in human aortic endothelial (HAE) cells. The peak of thapsigargin-evoked intracellular Ca(2+) concentration ([Ca(2+)](i)) was higher in antisense-treated than in untreated cells, but the declining time course was unaffected by the antisense treatment. The declining time was prolonged in both antisense-treated and untreated cells by reducing external Na(+), but the prolongation was more marked in the antisense-treated cells. These results provide the evidence of a functional role of plasma membrane Ca(2+) ATPase, although other mechanisms including Na(+)/Ca(2+) exchange may play the primary role in regulating [Ca(2+)](i).

Calcium↗
PubMed2000

Immunohistochemical study of NGF and its receptors in the synovial membrane of the ankle joint of adjuvant-induced arthritic rats.

To study the role of nerve growth factor (NGF) in local inflammation, we investigated the expression of NGF and its receptors, trkA and p75, in the ankle joints of adjuvant-induced arthritic rats. Infiltrated mononuclear cells revealed a positive immunoreactivity for NGF and trkA; they were also positive for immunostaining for W3/25 and ED1, which mainly stain T cells and macrophages, respectively. Changes in the ratios of NGF-positive cells to mononuclear cells showed a relatively similar pattern for trkA-positive cells, which peaked at weeks 2 to 3 after the adjuvant injection. In double-immunofluorescence staining, 80% and 65% of NGF-positive cells stained for W3/25 and ED1, respectively. Similarly, 67% and 80% of trkA-positive cells also corresponded to W3/25- and ED1-positive cells, respectively. However, p75 immunoreactivity localized on the nerve fibers but not on the cells of the ankle joints. Dense meshworks of p75-positive nerve fibers with numerous terminal varicosities were observed at weeks 2 to 4. The present findings suggest that infiltrated mononuclear cells may secrete NGF in an autocrine or paracrine manner in the inflamed synovium. An upregulation of NGF in these mononuclear cells and an increase in density of the synovial nerve fibers may be involved in the development of adjuvant arthritis in rats.

Animals↗
PubMed2000

Specific mutation in exon 11 of c-kit proto-oncogene in a malignant gastrointestinal stromal tumor of the rectum.

Gastrointestinal stromal tumor (GIST) in the distal third of the rectum was detected in a 57-year-old man who underwent an abdominoperineal resection of the rectum. Because the tumor expressed CD34 and c-kit gene product, but did not express smooth muscle actin or S-100 protein, it was diagnosed as an uncommitted type of GIST. Moreover, a specific mutation in the sequence coding the juxtamembrane domain in exon 11 of the c-kit proto-oncogene was revealed by a polymerase chain reaction-single-strand conformation polymorphism method. One year after resection, the patient developed multiple liver metastases. It is suggested that a specific mutation in exon 11 of the c-kit proto-oncogene may have played an essential role in the development of the liver metastases.

Exons↗
PubMed2000

Molecular evidence for multicentric development of thyroid carcinomas in patients with familial adenomatous polyposis.

Familial adenomatous polyposis is characterized by multiple colorectal adenomas and an increased incidence of colorectal carcinomas. Patients also develop various extracolonic tumors, of which, thyroid carcinoma is common in young females. The occurrence of multiple carcinomas in one thyroid is frequently observed, although some carcinomas are solitary. To clarify whether each carcinoma develops independently or metastatically spreads from the first one formed, we analyzed the adenomatous polyposis coli (APC) gene mutation in each carcinoma. We found that each carcinoma had a different somatic mutation of the APC gene. This is molecular confirmation for the multicentric development of thyroid carcinomas in familial adenomatous polyposis through biallelic inactivation of the APC gene.

Adenomatous Polyposis Coli↗
PubMed2000

Difference in glutamate release between retina and cerebral cortex following ischemia.

The difference in ischemic tolerance between the retina and cerebral cortex may be attributable to a difference in glutamate release during ischemia. Glutamate release in the retina and the cerebral cortex was compared in rats. A dialysis electrode for real-time glutamate measurement was perfused with L-glutamate oxidase, and the current evoked between two voltage-clamped electrodes was detected. Two electrodes were implanted in the retina through the choroid and cerebral cortex in 12 anesthetized rats, each mounted on a stereotaxic frame. Global ischemia was induced by ligation on both carotid arteries and hypotension was induced by blood withdrawal. Under control conditions, the glutamate concentration in the retina was 164 +/- 231 (mean +/- standard deviation) microM, being significantly higher (P < 0.05) than that in the cerebral cortex (83 +/- 105 microM). In 10 of the 12 animals, the glutamate concentration in the retina decreased to a minimum of 134 +/- 149 microM (P < 0.01, compared with the value for the cerebral cortex), but that in the cortex increased to 410 +/- 305 microM (averaged highest value). Immediately after the start of reperfusion, the glutamate concentration in the cortex decreased rapidly to 101 +/- 27 microM, but that in the retina increased gradually to almost the control level (148 +/- 204 microM). In the other two animals, the glutamate concentration remained unchanged. In conclusion, glutamate release in the retina does not proceed as rapidly as that in the cerebral cortex during 20 min of ischemia, and in fact decreases. This opposite trend shown by the two organs may be due to the slow depletion rate of ATP in the retina. This may explain the differing neuronal tolerance to ischemia in these two organs.

Animals↗
PubMed2000

Expression of heat shock proteins in osteosarcoma and its relationship to prognosis.

The prognosis of osteosarcoma has been improved by chemotherapy. Heat shock proteins (HSPs) assist in folding proteins at posttranslation and degeneration under stress. We investigated the effect of HSPs on survival in osteosarcoma. Conventional osteosarcomas of the extremities from 70 patients aged 30 years or younger were used. Preoperational chemotherapy was performed in all cases. Tissues at surgery and biopsy were immunohistochemically stained with anti-HSP27, HSP47, HSP60, HSP70, HSP90alpha, HSP90beta, and p53 antibodies. We classified the cases in which more than 10% of tumor cells were positive into the overexpressing group. Overall survival was compared between the groups either overexpressing HSPs or not using Wilcoxon's test and Cox's proportional hazard model. The overexpression rate at biopsy was 22% (HSP27), 88% (HSP47), 66% (HSP60), 48% (HSP70(, 47% (HSP90alpha), 31% (HSP90beta), and 17% (p53), respectively. The rate at surgery was 33% (HSP27), 94% (HSP47), 60% (HSP60), 49% (HSP70), 28% (HSP90alpha), 40% (HSP90beta), and 17% (p53), respectively. HSP27 and p53 overexpression at biopsy had a negative prognostic value. HSP27 showed the strongest negative prognostic value in osteosarcoma. It is therefore important to investigate further its function in cellular regulation and drug resistance.

Bone Neoplasms↗
PubMed2000

Time-dependent block of the slowly activating delayed rectifier K(+) current by chromanol 293B in guinea-pig ventricular cells.

The slowly activating delayed rectifier K(+) current (I(Ks)) was recorded in single myocytes dissociated from guinea-pig ventricles and the mechanism underlying the block of I(Ks) by a chromanol derivative, 293B, was investigated. In the presence of 1 - 100 microM 293B, activation phase of I(Ks) was followed by a slower decay during 10 s depolarizing pulses. Both the rate and extent of the decay were increased in a concentration-dependent manner. The relationship between the concentration of 293B and the block showed a Hill's coefficient of approximately 1. The half-inhibitory concentration was approximately 3.0 microM and did not differ significantly at various membrane potentials from +20 to +80 mV. A mathematical model for the 293B block was constructed on the basis of multiple closed and open states for the I(Ks) channels, and the blocking rate was calculated by fitting the model to the original current traces. The blocking rate constant showed a linear function with the 293B concentration, indicating 1 : 1 binding stoichiometry. At +80 mV the blocking rate was 4x10(4) M(-1) s(-1) and the unblocking rate was 0.2 s(-1). The results indicate that 293B is an open channel blocker with relatively smaller blocking rate than those reported so far for time-dependent blockade of various ionic channels.

Algorithms↗
PubMed2000

The epileptogenic properties of the volatile anesthetics sevoflurane and isoflurane in patients with epilepsy.

UNLABELLED: No study comparing epileptogenicity of sevoflurane to other volatile anesthetics has been performed. We compared the epileptogenic properties of sevoflurane to isoflurane in patients with epilepsy. In 24 mentally and/or physically disabled patients, 12 with epilepsy and 12 without epilepsy, electroencephalograms were recorded under anesthesia with 1.0 minimum alveolar anesthetic concentration (MAC), 1.5 MAC, and then 2.0 MAC sevoflurane or isoflurane under three ventilatory conditions: (A) 100% oxygen, and end-tidal CO(2) partial pressure (ETCO(2)) = 40 mm Hg, (B) 50% oxygen, 50% nitrous oxide, ETCO(2) = 40 mm Hg, and (C) 100% oxygen, ETCO(2) = 20 mm Hg. Spike activity was evaluated as a spike-and-wave index (% durations of spike and wave). The spike-and-wave index increased (P<0.05) from 1.99%+/-0.96% during 1.0 MAC sevoflurane to 6.14% +/- 4.45% during 2.0 MAC sevoflurane in (A) in the epilepsy group, while no spike activity was observed in the nonepilepsy group. Only a few spikes were observed under isoflurane anesthesia, 0.04% +/- 0.04% in (A), with no spikes in (B) and (C). Supplementation with 50% nitrous oxide or hyperventilation (P<0.05) suppressed the occurrence of spikes. Sevoflurane has a stronger epileptogenic property than isoflurane, but nitrous oxide or hyperventilation counteracts this specific epileptogenic property. IMPLICATIONS: The stronger epileptogenicity of sevoflurane than isoflurane was confirmed in a controlled study in patients with epilepsy. Hyperventilation and supplementation of nitrous oxide under sevoflurane anesthesia suppressed epileptogenicity. A combination of sevoflurane and nitrous oxide may be a safer method for seizure-prone patients than the use of sevoflurane alone.

Adolescent↗