Surgical treatment for primary oral malignancy with pulmonary metastases: report of 4 cases.
Explore the source record for details and available documents.
Adenocarcinoma↗
Biomedical subjects
T Iijima
Publications and source records attributed to T Iijima.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
A novel case of Wilms' tumor followed by colon cancer, both showing microsatellite instability.
Explore the source record for details and available documents.
Adult↗
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↗
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↗
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↗