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T Iijima

Publications and source records attributed to T Iijima.

At least 145 records · Page 8Linked to original sources
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↗
PubMed2000

Clonal proliferation of B lymphocytes in the germinal centers of human reactive lymph nodes: possibility of overdiagnosis of B cell clonal proliferation.

Clonal expansion of the germinal center B cells of human reactive lymph nodes was analyzed. By micromanipulation, 28 germinal centers were microdissected from three nonneoplastic lymph nodes that had been fixed with formalin. Immunoglobulin heavy chain variable (V) region gene rearrangement was examined by seminested polymerase chain reaction (PCR) using two sets of primers (FR2-J and FR3A-J). An oligoclonal development (one to five clones) was found in each germinal center. Depending on the primer used, four or five (16%) of the germinal centers showed a single rearrangement band. The average number of B-cell clones in each germinal center was approximately 2.5. Next, the authors analyzed 50 endoscopic biopsy specimens from 6 patients with non-mucosa-associated lymphoid tissue (MALT) type gastric lymphoma, 25 patients with chronic gastritis, and 19 patients with nonspecific colitis. In addition to the samples from the 6 patients with malignant lymphoma, 8 of 44 biopsy samples (18.2%) from patients diagnosed as having chronic gastritis or nonspecific colitis showed one or two amplified bands. These results indicate that PCR analysis of immunoglobulin heavy chain V region gene rearrangement in small biopsy specimens could be misleading, causing overdiagnosis of reactive lymphoid tissue as B-cell clonal proliferation.

Adenocarcinoma↗
PubMed2000

Pathogenesis of non-familial colorectal carcinomas with high microsatellite instability.

AIMS: Microsatellite instability (MSI) was first observed in hereditary non-polyposis colorectal carcinoma (HNPCC) and was subsequently seen in non-familial colorectal carcinoma. The relation between MSI and cancer associated genes in non-familial colorectal carcinomas has yet to be evaluated. To clarify this matter, changes in cancer associated genes were examined in non-familial colorectal carcinomas. METHODS: Alterations in the adenomatous polyposis coli (APC), p53, and Ki-ras genes were analysed in 24 MSI high (alterations in four to seven of seven loci), nine MSI low (alterations in one to three of seven loci), and 31 MSI negative non-familial carcinomas. The hMSH2 and hMLH1 genes were also analysed in 24 MSI high carcinomas. RESULTS: Both the frequencies and types of alterations in the APC and p53 genes in MSI high carcinomas were the same as those in MSI low and MSI negative carcinomas; however, they were different from those seen in HNPCC. The frequency of Ki-ras mutation was significantly lower in the MSI high cases (two of 24; 8%) than in the others (15 of 38; 39%). Somatic mutation of hMSH2 or hMLH1 was detected in six of 24 (25%) of the MSI high cases. CONCLUSIONS: These results suggest that APC and p53 alterations occur irrespective of microsatellite instability status in non-familial colorectal carcinomas, and that Ki-ras mutation is not involved in MSI high non-familial colorectal carcinoma. The pathogenesis of these carcinomas may differ from both the usual adenoma-carcinoma sequence and HNPCC carcinogenesis.

Base Sequence↗
PubMed2000

Optical recording study of granule cell activities in the hippocampal dentate gyrus of kainate-treated rats.

In the epileptic hippocampus, newly sprouted mossy fibers are considered to form recurrent excitatory connections to granule cells in the dentate gyrus and thereby increase seizure susceptibility. To study the effects of mossy fiber sprouting on neural activity in individual lamellae of the dentate gyrus, we used high-speed optical recording to record signals from voltage-sensitive dye in hippocampal slices prepared from kainate-treated epileptic rats (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a large depolarization in almost the entire molecular layer in which granule cell apical dendrites are located. The signals were identified as postsynaptic responses because of their dependence on extracellular Ca(2+). The depolarization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the granule cell layer. In the inner molecular layer, a good correlation was obtained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicuculline enlarged the depolarization in granule cell dendrites. Our data indicate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAergic inhibition partly masks the synaptic depolarization. However, despite the large dendritic excitation induced by the sprouted mossy fibers, seizure-like activity of granule cells was never observed, even when GABAergic inhibition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.

Animals↗
PubMed1999

Estrogenic antagonists bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore.

Dicarba-closo-dodecaboranes (carboranes), which have spherical geometry and hydrophobicity, are applicable as a hydrophobic pharmacophore of biologically active molecules. We have designed and synthesized estrogenic antagonists based on the structure of the potent agonist 1-hydroxymethyl-12-(4-hydroxyphenyl)-1,12-dicarba-closo-d odecaborane, which we have developed. The compounds showed potent antagonistic activity in luciferase reporter gene assay using COS-1 cells transfected with rat ER alpha-expression plasmid and an appropriate reporter plasmid.

Animals↗
PubMed1999

Structure-activity study of estrogenic agonists bearing dicarba-closo-dodecaborane. Effect of geometry and separation distance of hydroxyl groups at the ends of molecules.

Dicarba-closo-dodecaboranes (carboranes), which have spherical geometry and hydrophobicity, are applicable as a hydrophobic pharmacophore of biologically active molecules. We have investigated structure-activity relations based on the structure of the potent estrogenic agonist, 1-hydroxymethyl-12-(4-hydroxyphenyl)-1,12-dicarba-closo-d odecaborane, which we have previously reported. The geometry and separation distance of the phenolic and alcoholic hydroxyl groups play a critical role in the appearance of biological activity.

Animals↗
PubMed1999

High-speed CCD imaging system for monitoring neural activity in vivo and in vitro, using a voltage-sensitive dye.

We have designed and constructed a high-speed CCD imaging system for optically detecting neural activity from preparations stained externally with a voltage-sensitive dye, and have used this system to image evoked and epileptiform neural activity in the rat somatosensory cortex. The imaging system uses a commercially available 1/3-in. CCD chip, and it can continuously capture images for more than 8 s, at 1000 frames/s, with a spatial resolution of 128 x 62 pixels. The spatial/temporal resolution of the CCD sensor is variable by changing the geometry of on-chip binning pixels, which can be controlled by a PC/AT computer. Dye bleaching correction was not necessary for long-term imaging of epileptiform neural events, since the sensitivity of the CCD sensor was increased by combining the signal from adjacent pixels.

Animals↗
PubMed1999

Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by defective DNA mismatch repair, which results in genetic instability of tumors; however, only a few target genes have been recognized. Our previous study detected a low frequency of APC gene mutation (21%) in colorectal tumors from HNPCC patients, in contrast to a high frequency of APC gene alteration (>70%) in non-HNPCC tumors. Because both beta-catenin and ACP gene mutations have recently been shown to activate the same signaling pathway, we analyzed beta-catenin mutation in HNPCC tumors. A notable frequency of beta-catenin gene mutation (43%, 12 of 28) was found to occur in HNPCC colorectal tumors. Beta-catenin mutations were not detected in tumors with APC mutations. All beta-catenin mutations detected in HNPCC tumors existed within the regulatory domain of beta-catenin. Immunohistochemical staining of tumors with this mutation showed accumulation of beta-catenin protein in nuclei. These and previous data from our laboratory suggest that activation of the beta-catenin-Tcf signaling pathway, through either beta-catenin or APC mutation, contributes to HNPCC colorectal carcinogenesis in approximately 65% of cases.

Base Pair Mismatch↗
PubMed1999

Optical recording of cortical activity after in vitro perfusion of cerebral arteries with a voltage-sensitive dye.

Cortical neuronal architecture and connectivity can be analyzed with high-resolution optical imaging after staining the in vitro isolated guinea pig brain preparation by circulating the voltage-sensitive dye RH795 via the arterial system. To establish this new technique, electrical field potentials evoked in the piriform and entorhinal cortices by lateral olfactory tract stimulation were correlated to the optical signal. The depth analysis of the optical response was performed by evaluating the contribution of the mono- and poly-synaptic components of the signal generated in different layers after applying a pair-pulse stimulation protocol. The tangential propagation of neuronal activity in olfactory cortices was evaluated by gathering several 4.2 x 4.2 mm images recorded from adjacent cortical areas. The real-time optical imaging technique applied to the isolated guinea pig brain can be successfully utilized to study the integrative properties of cortical neurons ensembles.

Animals↗
PubMed1999

Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis.

We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without distant metastasis, 6/17 (35%) in primary invasive carcinoma with distant metastasis, and 11/36 (31%) in distant metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as distant metastasis, in human colorectal carcinogenesis.

Colorectal Neoplasms↗
PubMed1999

Amino acid release during spreading depression in a flow-compromised cortical area.

The glutamate concentrations in dialysate samples obtained from microdialysis probe implanted in the cortex were assayed during artificially induced spreading depression (SD) and SD with hypoperfusion. The glutamate concentrations did not differ even after SD induction with hypoperfusion (all p>0.05 cf. control), whereas anoxic depolarization caused significantly high glutamate release. Prolonged SD in hypoperfused area did not expose cerebral neurons to high glutamate concentrations.

Alanine↗
PubMed1999

Giant trichoblastoma mimicking malignancy.

We report a case of giant trichoblastoma, a rare benign hair germ tumor. A 73-year-old man presented with a soft-tissue mass on his upper arm. Magnetic resonance imaging analysis revealed an unique mosaic pattern on T2-weighted images. Needle biopsy disclosed a keratinizing tumor suggesting squamous cell carcinoma. The size of the tumor was 9.5 x 7 x 9.5 cm, one of the largest trichoblastomas ever reported. The rarity and gigantic size of the tumor, together with its misleading clinical features, prompted us to report our case.

Aged↗
PubMed1999

Inhibition by genistein of the hyperpolarization-activated cation current in porcine sino-atrial node cells.

1 The hyperpolarization-activated cation current (If) was recorded in single pacemaker cells of the porcine sino-atrial node, and the effects of genistein, an isoflavone inhibitor of tyrosine-specific protein kinases was investigated by the whole-cell patch clamp technique. 2 Genistein (20-500 microM) decreased If in a dose-dependent manner with an IC50 value of 62.3 microM and a maximum inhibition of 45.3%. 3 The effect on If appeared without altering the half-activation potential (control, -88.3+/-2.8 mV; genistein, -87.0+/-1.8 mV) and the slope factor (control, 8.0+/-0.3 mV; genistein, 8.6+/-0.7 mV) of the steady-state activation curve. No significant voltage-dependency was detected in the fully-activated current-voltage relation measured by the double-pulse protocols. 4 The inactive form of genistein analogue, daidzein (500 microM) or genistin (200 microM), were without effect. If was not affected by another tyrosine kinase inhibitor, tryphostin-47 (100 microM), but tyrphostin-25 (100-200 microM) suppressed If in an irreversible manner. 5 Neither bath nor intracellular application of the tyrosine phosphatase inhibitor, orthovanadate, affected If, and subsequent application of genistein inhibited If significantly. 6 These data indicate that the inhibition of If by genistein is not mediated through tyrosine kinase inhibition but through nonselective block of the If channels.

Animals↗