Mapping of the eukaryotic initiation factor eIF-1A gene, Eif1a, to mouse chromosome 12D-E by FISH.
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Biomedical subjects
Publications and source records attributed to M Tada.
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Cellular damage secondary to reperfusion following ischemic insult has been hypothetically attributed to an inflammatory cascade concerted by cell-to-cell interactions. While the role of several cytokines and adhesion molecules in reperfusion injury of the brain has been explored to a certain extent, their regulatory and temporary profiles remain unclear. We have addressed the temporal features of the induction of mRNA for proinflammatory cytokines, adhesion molecules and chemokines at an acute phase subsequent to reperfusion in rat forebrain. Semiquantitatively calibrated reverse transcription-polymerase chain reaction analysis was employed to assess the relative expression of mRNA for intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1 alpha, IL-1 beta, 1L-2, 1L-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, monocyte-chemoattractant protein (MCP)-1, and macrophage migration inhibitory factor (MIF). The increase in mRNA from the basal levels after reperfusion followed one of two different patterns; an increase occurring as early as 1 h, or a slight increase continuing up to 24 h after reperfusion. The former pattern was seen for ICAM-1, IL-1 alpha, IL-1 beta, TNF-alpha, and MCP-1, and the latter for IL-6 and MIF. These results were consistent with the proinflammatory properties of the immediately induced cytokines, which may be involved in the initiation step of the inflammatory cascade, causing the secondary cellular responses and finally leading to further brain damage.
BACKGROUND: We compared the accuracy of endoscopic ultrasonography (EUS) for staging depth of invasion of early gastric cancer with that of conventional endoscopy. PATIENTS AND METHODS: We assessed the depth of invasion of 108 lesions (104 patients) using EUS with a thin 20 MHz probe and compared the results with those of conventional endoscopy and of histologic examination of endoscopically or surgically resected specimens. RESULTS: The overall accuracy rates for staging depth of invasion for conventional endoscopy and EUS were 72.2% and 64.8%, respectively. Lesions that were classified as limited to the mucosa on both conventional endoscopy and EUS were very likely (92.2%) to be limited to the mucosa on histologic examination. The rates for understaging and overstaging were 16.7% and 11.1%, respectively, for conventional endoscopy; and 7.4% and 24.1%, respectively, for EUS. The highest rate for understaging based on conventional endoscopy occurred for lesions in the gastric body (including cardia, 23.9%). CONCLUSIONS: EUS appears to be useful in combination with conventional endoscopy for staging depth of invasion of early gastric cancer. In particular, the two techniques in tandem may accurately predict that a lesion is limited to the mucosa, and EUS may be useful to overcome the potential for understaging by conventional endoscopy, particularly in the gastric body.
BACKGROUND: Although the presence of Epstein-Barr virus has been documented in approximately 7% of patients with gastric carcinoma, the clinical features of Epstein-Barr virus-associated carcinoma have not been well documented. We studied the histologic and endoscopic characteristics of Epstein-Barr virus-associated gastric carcinoma. METHODS: We tested 124 gastric carcinomas from 117 patients using in situ hybridization for Epstein-Barr virus encoded small RNA1. The histologic and endoscopic findings in the Epstein-Barr virus-associated groups and the negative control groups were analyzed and compared. RESULTS: Twelve tumors (9.7%) were identified as Epstein-Barr virus associated. These lesions were located mainly in the upper part of the stomach (p < .05) and had a diffuse-type histology (p < .05) compared with those in the control group. Six of seven (85.7%) early Epstein-Barr virus-associated lesions were type 0 IIc (superficial depressed) or a combined type, and 42.9% were accompanied by submucosal nodules of carcinoma with lymphoid stroma. Four of five (80%) advanced Epstein-Barr virus-associated tumors were type 3 (ulcerated without definite limits), thought to be the advanced shape of superficial depressed lesions. CONCLUSIONS: Epstein-Barr virus-associated gastric carcinomas often appear as superficial depressed or ulcerated lesions in the upper part of the stomach and have a diffuse-type histology with lymphoid infiltration.
Many reports have shown inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on the progression of atherosclerotic plaque lesions in vascular tissue of experimental models. However, no report has shown alterations of ACE activity in vascular tissue during the process of atherosclerosis. We measured ACE activity in plasma and aortic tissue in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the blood pressure response to angiotensin (Ang) I and II. These data were compared in untreated rabbits and in rabbits receiving chronic treatment with an ACE inhibitor, enalapril (3 mg/kg/day for 10 weeks). ACE activity in aortic tissue, but not in plasma, in cholesterol-fed rabbits was gradually but significantly increased compared with that in noncholesterol-fed rabbits even after the 4-week feeding period, when no atherosclerotic lesion was observed in the aortic tissue. Treatment with enalapril for 10 weeks, but not 4 weeks, significantly reduced the ACE activity in aortic tissue in association with the reductions in the elevated Ang II level and the atherosclerotic plaque area of the aortic tissue. These results indicated that ACE activity in aortic tissue was increased during the early phase of atherosclerotic process.
There is extensive evidence that Moyamoya disease has a tendency for multifactorial inheritance, although the pathogenesis of Moyamoya disease is not clear. The authors report five cases showing familial occurrence of Moyamoya disease and analyse its clinical characteristics. In the past 15 years, we have encountered 68 cases of Moyamoya disease. Among these, 14 cases (10 females and four males, five family pedigrees, asymptomatic 1 case) of familial occurrence were observed. In this series, mother-to-child inheritance was observed in five cases, although there were no cases showing father-to-child inheritance. Ten patients were children with an initial onset of cerebral ischemia, at a mean age of 9.7 years. One mother was asymptomatic and two mothers had a past history of cerebral ischemia. Only one patient was a 37-year-old woman with clinical onset of intracerebral hemorrhage. There were no specific clinical characteristics in familial Moyamoya disease compared with those in sporadic Moyamoya disease.
To investigate the conservation of mechanisms for mesodermal patterning between zebrafish and Xenopus, we isolated two cDNA clones encoding bone morphogenetic protein (BMP)-related proteins from a zebrafish cDNA library. Based on their predicted amino acid sequences, these two clones were designated as zbmp-2 and zbmp-4. Whole-mount in situ hybridization analysis revealed that in gastrula embryo, both genes were localized in the ventral part of the embryo, consistent with the proposed function of Xenopus BMP-4 in ventral mesoderm specification. zbmp-4 expression, however, was also seen in the embryonic shield, the most dorsal mesodermal structure. To examine the ability of zbmp-2 to ventralize mesoderm, we injected synthetic mRNA into zebrafish embryos and found that overexpression of this gene eliminated dorsal structures including notochord at both morphological and molecular level. In contrast, expression of ventral marker gene eve1 was expanded to the dorsal side. These effects are analogous to the ventralization of embryos caused by ectopic xBMP-4 expression. Taken together, one may conclude that the developmental mechanisms for mesodermal patterning regulated by BMPs are evolutionarily conserved between amphibians and teleosts.
1. Ischaemic preconditioning (IP) protects the myocardium against irreversible ischaemic injury by activating protein kinase C (PKC). The mechanism by which PKC protects the myocardium is unknown. We have shown that PKC increases the activity of ecto-5'-nucleotidase (ecto-5'-N) and thereby the production of adenosine in cardiomyocytes which may protect the myocardium against ischaemia-reperfusion injury in vivo. 2. The objective of this study was to elucidate the possible role of PKC-induced activation of ecto-5'-N in the cardioprotection associated with IP in the canine heart. 3. IP increased the activities of both ecto-5'-N and PKC, and minimized ischaemic damage (infarct size: 7.5 +/- 1.8 vs. 42.3 +/- 2.8%, P < 0.01 vs. the control group). Treatment with the PKC activator (4 beta-phorbol 12-myristate-13-acetate) also reduced infarct size (13.5 +/- 2.9%, P < 0.01 vs. the control group). 8-Sulfophenyltheophylline (an antagonist of adenosine receptors) or alpha,beta-methyleneadenosine 5'-diphosphate (an inhibitor of ecto-5'-N) eliminated the cardioprotective effect of the PKC activator (infarct size: 36.6 +/- 3.9 and 34.7 +/- 4.2%, respectively), suggesting that PMA limits infarct size by increasing the activity of ecto-5'-N and the adenosine level. 4. The PMA-induced cardioprotection was blunted by GF109203X (an inhibitor of PKC, infarct size: 36.2 +/- 3.1%), but not by pretreatment with dexamethasone (infarct size, 14.2 +/- 2.6%). 5. We conclude that the PMA- and IP-induced cardioprotection is attributable to phosphorylation and activation of ecto-5'-N.
BACKGROUND AND STUDY AIMS: In the treatment of rectal carcinoid tumors, confusion arises in the choice between radical surgery and local endoscopic resection, since the malignancy of individual tumors differs widely. We investigated the appropriateness of using endoscopic therapy for this disease. PATIENTS AND METHODS: Twenty-two patients were diagnosed with rectal carcinoid tumors at the First Department of Internal Medicine, Yamaguchi University School of Medicine and its affiliated hospitals, from 1977 to 1994. The tumors were resected and examined regarding their size, depth of invasion, and histological atypia. The post-treatment course in patients whose tumors were completely resected without atypia was observed by colonoscopy and ultrasonography at yearly intervals. RESULTS: In 21 patients, tumor invasion did not extend beyond the submucosal layer, and there were no signs of atypia. The size of the tumor varied from 2.2 mm to 10.0 mm in diameter, with an average of 5.4 mm. After endoscopic resection of the tumors in 18 patients and surgical local resection in three patients, no local recurrences or liver metastases were experienced. The patients survived for a minimum of 29 months and a maximum of 237 months; the mean survival period was 72.8 months. In one patient, the tumor showed cellular atypia invading into the tunica muscularis, and measured 25 mm in diameter. The patient underwent surgery, but died ten months later due to liver metastasis. CONCLUSIONS: Endoscopic treatment of rectal carcinoid tumors was found to be appropriate when the tumor measured 10 mm or less in diameter, did not infiltrate beyond the submucosal layer, and had no histological atypia.
OBJECTIVE: Radiation-induced glioma is a rare but serious complication of radiotherapy. Underlying radiation-induced mutations in oncogenes or tumor suppressor genes have not previously been described. CLINICAL PRESENTATION: A 16-year-old female patient developed a glioblastoma in the right frontal lobe 10 years after treatment of a suprasellar germ cell tumor with 50 Gy ionizing radiation. The glioblastoma was undetectable on a high-resolution magnetic resonance image obtained 3 months before diagnosis. METHODS AND RESULTS: A p53 functional assay was used to examine the transcriptional competence of the p53 tumor suppressor gene. This assay scores the content of mutant p53 alleles in tumor and blood samples quantitatively as a percentage of red yeast colonies. The glioblastoma contained 95% mutant p53 alleles, whereas blood from the patient and her parents contained only normal background levels of red colonies. Sequencing revealed that the mutation in the tumor was a 3-base pair deletion affecting codons 238 and 239. Intragenic deletion within the p53 deoxyribonucleic acid binding domain is uncommon in sporadic tumors but would be entirely consistent with misrepair of a radiation-induced double-strand deoxyribonucleic acid break in this case. CONCLUSION: This is the first case in which a causative underlying genetic event has been identified in a radiation-induced glioblastoma. We infer that mutation of one p53 allele occurred at the time of radiotherapy, and the sudden appearance of the tumor 10 years later occurred after loss of the remaining wild-type allele and/or other genetic alterations, such as chromosome 10 loss and epidermal growth factor receptor gene amplification.
OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a cytokine that has the potential to immobilize and activate monocytes/macrophages. To examine whether MIF may potentially be involved in the pathogenesis of reperfusion injury of the brain, we investigated the expression of MIF in a rat model of reperfusion. METHODS: A four-vessel occlusion procedure was performed for 30 minutes using male Wistar rats to obtain a moderate reperfusion in the forebrains. Semiquantitatively calibrated reverse-transcription polymerase chain reaction analysis was conducted to examine temporal profiles of messenger ribonucleic acid (mRNA) expression for MIF and macrophage chemoattractant protein 1. MIF protein assays expression was assessed with specific Western blot analysis. For anatomic mapping of MIF, an immunohistochemical study was performed. RESULTS: Reverse-transcription polymerase chain reaction demonstrated that the mRNA level of MIF increased depending on the duration of reperfusion (< or = 24 h) subsequent to global ischemia. The macrophage chemoattractant protein 1 mRNA was also observed to increase after reperfusional stress, but its maximum expression was reached earlier (1 h after the stress) than was MIF mRNA. Increase of MIF protein was also shown by Western blot. MIF-positive staining was observed in the neuronal processes (neuropil) in the cortex and basal growth ganglia of a rat forebrain. CONCLUSION: This protein is up-regulated and may modulate immunological reaction in secondary brain damage after ischemia and reperfusion stress.
OBJECTIVE AND IMPORTANCE: Hemifacial spasm is rarely caused by facial nerve lesions in the temporal bone. Intratemporal facial nerve hemangiomas may initially present as facial spasm. CLINICAL PRESENTATION: A 30-year-old woman developed right hemifacial spasm. Physicians observed slight weakness on the right side of her face, in addition to the hemifacial spasm, but routine radiological examinations did not detect any abnormal findings along the course of the facial nerve. Although the patient underwent neurovascular decompression, the spasm persisted postoperatively. Two years after surgery, the right facial palsy progressed. Concurrently, the hemifacial spasm diminished. High-resolution computed tomography demonstrated a small mass lesion expanding the cortex of the right petrosal bone involving the geniculate ganglion of the facial nerve. INTERVENTION: The patient underwent a second craniotomy through a subtemporal extradural route, and the tumor was completely removed. A pathological examination demonstrated a cavernous hemangioma. CONCLUSION: Routine radiological examinations may fail to detect small intratemporal facial nerve hemangiomas, particularly at the geniculate ganglion. Therefore, when physicians encounter atypical facial spasm, the intratemporal portion of the facial nerve should be carefully examined using high-resolution computed tomography.
Endoscopic variceal ligation (EVL) using 'O' rings is widely accepted as a treatment of oesophageal varices that is at least as effective as endoscopic injection sclerotherapy but which produces fewer complications. Endoscopic variceal ligation using detachable snares has attracted attention as a safe and easy method of endoscopic treatment for gastric varices. Nineteen patients with acute bleeding from oesophageal or gastric varices were treated in the present study. Of these, 14 patients were treated with EVL using 'O' rings and five patients were treated with EVL using detachable snares and the treatment results were evaluated. Haemostasis was achieved in all patients. No serious complications of the procedures were observed. However, recurrences and rebleeding were observed in some patients during the maximum follow-up period of 24 months. Endoscopic variceal ligation using 'O' rings and detachable snares is useful for achieving haemostasis in cases of acute bleeding from oesophageal or gastric varices. However, additional endoscopic sclerotherapy may be needed to eliminate the variceal feeding vessels to further improve the long-term prognosis of these patients.
Analysis of gene function in Xenopus development frequently involves over-expression experiments, in which RNA encoding the protein of interest is microinjected into the early embryo. By taking advantage of the fate map of Xenopus, it is possible to direct expression of the protein to particular regions of the embryo, but it has not been possible to exert control over the timing of expression; the protein is translated immediately after injection. To overcome this problem in our analysis of the role of Brachyury in Xenopus development, we have, like Kolm and Sive (1995; Dev. Biol. 171, 267-272), explored the use of hormone-inducible constructs. Animal pole regions derived from embryos expressing a fusion protein (Xbra-GR) in which the Xbra open reading frame is fused to the ligand-binding domain of the human glucocorticoid receptor develop as atypical epidermis, presumably because Xbra is sequestered by the heat-shock apparatus of the cell. Addition of dexamethasone, which binds to the glucocorticoid receptor and releases Xbra, causes formation of mesoderm. We have used this approach to investigate the competence of animal pole explants to respond to Xbra-GR, and have found that competence persists until late gastrula stages, even though by this time animal caps have lost the ability to respond to mesoderm-inducing factors such as activin and FGF. In a second series of experiments, we demonstrate that Xbra is capable of inducing its own expression, but that this auto-induction requires intercellular signals and FGF signalling. Finally, we suggest that the use of inducible constructs may assist in the search for target genes of Brachyury.
A stringent test for imprint control elements is to examine their function at ectopic loci in transgenic experiments. Igf2 and H19 are part of a larger imprinting region and as a first step, we examined these reciprocally imprinted genes in transgenic experiments using a 130 kb YAC clone. After paternal inheritance, H19 was appropriately repressed and Igf2 was expressed, irrespective of copy number or genetic background. After maternal inheritance H19 was consistently expressed, albeit with some variability. The levels of H19 expression per copy of the transgene inversely correlated with Igf2 (-lacZ) expression in cis. The consistent imprinting of H19 from this YAC contrasts with the previously described imprinting of mini-H19 transgenes, which only occurs at multi-copy loci, is inconsistent, and is prone to genetic background effects. We propose a novel model in which silencing of the H19 gene is the default state and its activation after maternal inheritance is the key mechanistic event for imprinting in this region. In addition, in situ analysis of the Igf2-lacZ reporter indicates that additional mesoderm-specific enhancers are present within the YAC clone. No obvious phenotype was detected from the excess gene dosage of H19.
A 24-year-old female presented with basilar invagination and kyphoscoliosis of the cervical spine associated with a large intercarotid paraganglioma. She had suffered from pharyngeal discomfort from the age of 9 years due to the tumor. The tumor had originated from the right carotid body and extended in the parapharyngeal space compressing the upper cervical spine. Presumably the slowly growing tumor had caused the kyphoscoliosis and disturbed osseous development of the occipito-atlanto-axial complex, resulting in anterior basilar invagination, hypoplasia of the clivus, and aplasia of the posterior arch of the atlas.
Recently, the presence of Epstein-Barr virus(EBV) in almost 7% of gastric carcinoma lesions was reported. From our observation, EBV-associated gastric carcinomas located mainly in the gastric body, and moderate to poorly differentiated adenocarcinoma with lymphoid infiltration, as currently reported. Macroscopically, there were mainly thick and ulcerated lesions, EBV-associated gastric carcinomas had close relation with intestinal metaplasia, and EBV could be suspected to provide the immortalized epithelial cells.
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