[The cellular target proteins of adenovirus gene products].
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Adenovirus Early Proteins↗
Biomedical subjects
M Shindoh
Publications and source records attributed to M Shindoh.
High malignant transformation rate of widespread multiple oral leukoplakias.
OBJECTIVE: This study was undertaken in order to investigate clinicopathologic characteristics and malignant potential of widespread multiple oral leukoplakias. PATIENTS AND METHODS: The present study includes 12 patients with widespread multiple leukoplakias (widespread patients) and 99 with localized lesions (localized patients), and all patients were followed for more than 6 months with the mean follow-up period of 4 years. RESULTS: Gingiva and tongue were the major affected sites of leukoplakias in the localized patients, whereas gingiva and buccal mucosa were predominantly affected in the widespread patients. The rate of developing carcinoma was significantly (P < 0.02) higher in the widespread patients (3/12) than in the localized patients (5/99), although there was no significant difference in the rate of dysplastic lesions between these groups. CONCLUSION: These results indicate that the widespread leukoplakias have a higher potential for the development of carcinoma than do the localized lesions.
Adult↗
The enhancing effect of excess retinol palmitate on induction of odontogenic tumors and inhibitory effect on squamous cell carcinoma of the gingiva in hamsters treated with N-methylnitrosourea.
The influence of excess retinol palmitate on induction of tumors in the oral region was examined histopathologically. Sixty-three weanling Syrian golden hamsters were divided into five groups and received either 0.2% N-methylnitrosourea (MNU) (1 mg/100 g body weight) or retinol palmitate (RP) (25,000 IU/100 g body weight) twice a week for 16 weeks, singly or in combination. Animals received RP intraperitoneally or intragastrically and then, 6 hours later, the animals received intragastric administration of MNU. To accelerate the cell activity of the incisal tooth buds, intentional disocclusion of the left upper and lower incisor of all hamsters was carried out by repeated cutting with cooled diamond disks to a level just above the inter-dental papilla twice a week for 12 weeks. The right incisors were left in occlusion. In all animals exposed to RP + MNU, while the induction of squamous cell carcinomas of the gingiva and forestomach were prevented, the notable findings were a significantly increased incidence of odontogenic tumors in cut incisal regions of the animals with intragastric administration of RP + MNU and an induction of maxillary neurogenic tumors. The incidence of MNU-induced disturbances in odontogenesis in the incisors was reduced but marked disturbances were increased. RP seemed to have opposite effects of prevention and enhancement for development of neoplastic changes in the oral region.
Animals↗
Oral clonidine to control hypertension after head injury.
Clonidine, an alpha2 agonist, was administered through a nasogastric tube for the treatment of hypertension in a head-injury patient with elevated plasma catecholamines. Haemodynamic parameters were stabilized with a reduction in sympathetic nervous activity. The plasma clonidine concentration, measured by radioimmunoassay, rapidly increased following the administration. After cessation of oral administration of clonidine, mean arterial blood pressure gradually increased. So clonidine was again administered orally and good blood pressure control was achieved and no change in consciousness level was observed. Oral clonidine was useful and effective for hypertension in this head injury patient.
Administration, Oral↗
Induction of apoptosis by the p53-273L (Arg --> Leu) mutant in HSC3 cells without transactivation of p21Waf1/Cip1/Sdi1 and bax.
Codon 273 is one of the hot spots of missense mutation of the p53 tumor suppressor gene found in human cancers. We have previously reported that a mutation at codon 273, p53-273L (Arg --> Leu), suppresses cell growth despite its having no p53-specific transactivation activity. To further elucidate the mechanism of growth suppression caused by p53-273L, we used squamous cell carcinoma cell line HSC3 to isolate subclones containing Zn2+-inducible wild-type (wt) p53, p53-175H, and p53-273L. Northern blot hybridization of the HSC3 cells possessing an inducible function of p53 as well as a luciferase assay for the p21Waf1/Cip1/Sdi1 promoter showed that only wt p53 could induce p21Waf1/Cip1/Sdi1 transcription. Meanwhile, the expression of bax remained unchanged between, before, and after the induction of any analyzed p53s. When wt p53 was induced in HSC3 cells cultured in medium containing 5% fetal bovine serum, cell growth was suppressed through G1 arrest. On the other hand, in medium with 0.1% fetal bovine serum, the growth of HSC3 cells expressing p53-273L was suppressed to a greater degree than that of cells expressing wt p53. Flow cytometric analysis and DNA ladder formation revealed that, unlike wt p53-SN3- and p53-175H-expressing HSC3 cells, p53-273L-expressing cells contained a larger sub-G1 fraction under this culture condition. These findings suggest that p53-273L can induce apoptosis in HSC3 cells without transactivation of p21Waf1/Cip1/Sdi1 and bax.
Amino Acid Substitution↗
The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor.
Urokinase plasminogen activator (uPA) has been associated with invasion and metastasis in breast cancer. The expression of uPA and 92 kDa type IV collagenase (gelatinase B/MMP-9) is regulated by growth factors, receptor-type tyrosine kinases and cytoplasmic oncoproteins. Here, we have identified transcriptional requirements for the induction of uPA and 92 kDa type IV collagenase by epidermal growth factor (EGF). EGF stimulates the motile and invasive activities specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of extracellular matrix-degrading proteases including type I collagenase/MMP-1, 92 kDa type IV collagenase/MMP-9, uPA and uPA receptor were induced. EGF also transiently stimulated expression of the transcription factors Ets-1 and Ets-2. Reporter transfection assays revealed the activation of uPA and MMP-9 collagenase promoters by EGF and the requirement of each of the composite Ets and AP-1 transcription factor binding sites for an EGF response. Most notably, transfections with the Ets-1 and Ets-2 expression vectors potentiated uPA and MMP-9 promoter activation in response to EGF. Mutation of the threonine 75 residue of chicken Ets-2 conserved in the Pointed group of the Ets family proteins abrogated the ability of Ets-2 to collaborate with EGF. Ets-1 and Ets-2 were highly expressed in invasive breast tumor cell lines. Our results suggest that Ets-1 and Ets-2 provide the link connecting EGF stimuli with activation of uPA and 92 kDa type IV collagenase promoters and may contribute to invasion phenotypes.
Breast Neoplasms↗
A case of crush syndrome occurring during alcohol withdrawal: extended disturbance of consciousness with development of persistent Korsakoff's psychosis.
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Adult↗
Flow cytometric analysis of cell cycle fractions in oral leukoplakia.
Flow cytometric analysis of cell cycle fractions and DNA ploidy was performed on 39 biopsy specimens of oral leukoplakia. The aneuploidy rate of these leukoplakias was 9/39 (23.1%) and the mean DNA index of the aneuploid lesions was 1.34. The aneuploidy rate was significantly higher in severely dysplastic lesions (8/17) than in mildly dysplastic (1/15, P<0.02) and nondysplastic (0/7, P<0.05) lesions. No significant differences in the percentages of each cell cycle fraction were seen between the diploid and the aneuploid leukoplakias. However, the S-phase fraction of the severely dysplastic lesions (23.0%) among the diploid leukoplakias was higher than those of the mildly dysplastic (12.4%) and nondysplastic (15.5%) lesions, and the difference between the severely dysplastic and the mildly dysplastic lesions was statistically significant (P<0.001). These results suggest that flow cytometric analysis of cell cycle fractions and DNA ploidy might offer additional information for assessing the malignant potential of oral leukoplakias.
Aneuploidy↗
Oral clonidine for sedation and analgesia in a burn patient.
Clonidine has both analgesic and sedative actions, and it has been used in a variety of settings as a sedative, or both. We administered oral clonidine with intravenous ketamine to a burn patient to control severe pain. Clonidine produced good analgesia and sedation. In addition, clonidine counterbalanced the sympathetic stimulation of ketamine by virtue of its action in reducing sympathetic outflow. The combination of these two drugs may be useful for burn patients with hypertension or myocardial ischemia.
Administration, Oral↗
Detection of human papillomavirus type 2 related sequence in oral papilloma.
Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma.
Adult↗
High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay.
To determine the timing and actual incidence of p53 mutations in oral epithelial lesions, we examined 33 primary squamous cell carcinomas (SCCs), 14 dysplasias and six hyperplasias from Japanese patients by a combination of yeast functional assay and DNA sequencing. The assay detects mutations of p53 mRNA between codons 67 and 347 on the basis of the DNA-binding activity of the protein. Twenty-six SCCs (79%) and five dysplasias (36%) were positive for p53 mutation, while all six hyperplasias were negative for the mutation. Human papillomavirus type 16 E6 mRNA was detected in one of seven p53 mutation-negative SCCs by reverse transcription polymerase chain reaction (RT-PCR). We further examined p53 mutations in 17 Sri Lankan oral SCCs using the yeast functional assay and the single-strand conformation polymorphism analysis of PCR-amplified DNA fragments (PCR-SSCP) of exon 5-8. The mutations were confirmed by DNA sequencing and the detection sensitivity was compared between the two methods. Six samples (35%) were positive for p53 mutation in PCR-SSCP analysis, while nine samples (53%) were positive in yeast functional assay. This suggests that the incidence of p53 mutations has been considerably underestimated in the conventional SSCP analysis. The present data indicate that p53 mutations are extremely frequent in oral cancers in the Japanese, and suggest that the timing and significance of p53 mutation in oral tumor progression vary in different ethnic populations and areas.
Adult↗
Activation of the p21(Waf1/Cip1) promoter by the ets oncogene family transcription factor E1AF.
p21(Waf1/Cip1) is one of the key regulatory proteins in cell cycle, terminal differentiation, and apoptosis. Its promoter was shown to be transactivated by the wild-type p53 protein as well as in a p53-independent manner. In this report, we demonstrate that E1AF, an ets-related transcription factor, activates the human p21(Waf1/Cip1) promoter by interacting with the ets-binding sites located close to the two previously identified p53-responsive elements. Northern blot analysis revealed that p21(Waf1/Cip1) and E1AF were correlatively upregulated in response to cisplatin treatment in SiHa cells. Transient expression assays demonstrated that E1AF can activate the p21(Waf1/Cip1) promoter-driven luciferase reporter gene in SiHa cells. The p21(Waf1/Cip1) promoter activity was also increased in p53-null Saos2 osteosarcoma cells, but was markedly reduced when the ets-binding sites were deleted. These results indicate that E1AF positively regulates transcription from the p21(Waf1/Cip1) promoter in response to genotoxic stresses.
Adenovirus E1A Proteins↗
Predominant expression of the src homology 2-containing tyrosine phosphatase protein SHP2 in vascular smooth muscle cells.
src homology 2 (SH2)-containing protein-tyrosine phosphatase SHP2 is known to transduce positive signals from activated receptor protein-tyrosine kinases such as platelet-derived growth factor receptor (PDGFR) beta and insulin receptor. Here, we demonstrate the physiological expression of SHP2 in rats. In northern and western blot analyses, SHP2 expressions were recognized in all tissues, but their expression levels varied significantly among tissues: it is lowest in the liver and kidney. Immunohistochemical staining and in situ hybridization showed SHP2 was expressed ubiquitously but predominantly in vascular smooth muscle cells (SMC). During the development of granulations. SHP2 was expressed predominantly in vascular SMC and also highly expressed in capillary cells. The functional associations of SHP2 with PDGFR beta, which transduces major growth signals in vascular SMC, identify a crucial function of SHP2 in blood vessels in consert with PDGFR beta.
Actins↗
Crush syndrome sustained in the 1995 Kobe, Japan, earthquake; treatment and outcome.
STUDY OBJECTIVE: To assess the treatment and outcome of patients with crush syndrome sustained in an earthquake disaster. METHODS: We conducted a retrospective analysis of eight patients with crush syndrome and subsequent acute kidney failure who were treated in the ICU of a university hospital. All eight patients had been extricated from buildings that collapsed in the 1995 Kobe, Japan, earthquake. Crush injury involved the upper extremities in one patient and the lower extremities in seven. Each patient received intravenous fluid infusion and diuretic drugs and underwent hemodialysis. Emergency fasciotomy was performed in some patients, 17 to 100 hours after extrication. RESULTS: All patients were conscious and lucid on admission, and blood pressure and heart rate were normal. All the patients demonstrated kidney failure with increased concentrations of serum creatinine (1.9 to 9.6 mg/dL [169 to 852 mumol/L]). Six patients were oliguric. Hyperkalemia (5.6 to 8.8 mEq/L) was present in six patients. We found close correlations between the serum potassium and creatine kinase concentrations, between the serum myoglobin and potassium concentrations, and between the serum myoglobin and creatine kinase concentrations. All the patients were weaned from hemodialysis. The serum creatinine concentration decreased to a normal level within 20 to 52 days of admission in all patients. No patients underwent amputation. Muscle weakness and sensory deficits persisted in all patients 6 months after the earthquake. CONCLUSION: Our findings support current therapeutic strategies for crush syndrome, despite the long delay to initiation of intensive therapy. All the patients recovered kidney function and were weaned from hemodialysis; none required amputation.
Acute Kidney Injury↗
Expression of E1AF, an ets-family transcription factor, is correlated with the invasive phenotype of oral squamous cell carcinoma.
E1AF is a newly identified ets-oncogene family transcription factor. Previous reports have noted that E1AF can upregulate promoter activities of several matrix metalloproteinase (MMP) genes and showed that invasive potentials of oral squamous cell carcinoma-derived cell lines are correlated with expression of E1AF and MMPs. The invasive phenotype is restrained by transfection with an antisense E1AF expression vector. Thus, E1AF is thought to be highly correlated with malignant potentials of cancer cells. However, little is known about E1AF expression and cancer cell malignancies in in vivo tumours. In the present study, 27 oral squamous cell carcinoma (SCC) specimens were examined using RT-PCR, Southern blot hybridisation and in situ hybridisation (ISH) and compared to the clinicopathological parameters. Among the 27 patients, E1AF was detected in 15 cases. E1AF mRNA was detected in 13 of 17 invasive SCCs, whereas the majority of SCCs not expressing E1AF showed an expansive growth pattern. Increased prevalence of E1AF-positive oral SCC was observed in cases with nodal metastasis. These results indicate that E1AF may be involved in cancer cell malignancies through its ability to promote invasive potential.
Adenovirus E1A Proteins↗
Salivary gland scintigraphy with 99mTc-pertechnetate in Sjögren's syndrome: relationship to clinicopathologic features of salivary and lacrimal glands.
Salivary gland scintigraphy was performed on 52 patients who were suspected of having Sjögren's syndrome (SS), and the results were compared with clinicopathologic features of the salivary and lacrimal glands. The time-activity curves which were obtained from computer-assisted analysis of 99mTc-pertechnetate (99mTc) scintigraphy were classified into four types (normal, median, flat and sloped types). The stimulated parotid flow rate decreased and the incidence of SS-related sialographic and histopathologic findings increased significantly as the scintigraphic abnormality advanced. In addition, the lacrimal gland function decreased and the proportion of patients diagnosed as having keratoconjunctivitis sicca (KCS) increased significantly as the scintigraphic abnormality advanced. These results indicate that the results of scintigraphy are related not only to the clinicopathologic features of the salivary glands but also to the lacrimal gland function in SS.
Chi-Square Distribution↗
Comparison between submucosal (extra-nodal) and nodal non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region.
Fifty-two cases of non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region, comprising 31 submucosal (extra-nodal) and 21 cervical node NHLs, were investigated. The patients' ages ranged from 5 to 86 years, with a bimodal age distribution among young people below 12 years of age (average 8 years) and in those aged 30 years or older (average 60.3 years). The male-to-female gender difference ratio was 1.3:1. Patients presented with swelling as the major symptom. Histologically, diffuse, large cell malignant lymphoma was the most frequent type and 67.9% of lymphomas were of intermediate malignancy as defined by the Working Formulation for Clinical Usage. All submucosal lymphomas showed diffuse proliferation patterns, although follicular proliferation was identified in 5 of the 21 nodal lymphomas. Immunohistochemistry showed that the B-cell type was predominant, especially in nodal lymphomas.
Adolescent↗
Restricted expression of cell adhesion kinase-beta in rat tissues.
Cell adhesion kinase-beta (CAK-beta) is a protein tyrosine kinase of the focal adhesion kinase subfamily, which contains large amino- and carboxyl-terminal domains. We studied the tissue distribution of CAK-beta and its mRNA by immunohistochemical staining and in situ hybridization. In rat brain, CAK-beta was mainly found in the medulla whereas CAK-beta mRNA was expressed in most neurons, especially pyramidal cells and Purkinje cells. In the small intestine, CAK-beta protein and mRNA were detected in the absorptive epithelial cells, and the protein was concentrated in the brush border. Double immunostaining for CAK-beta and actin showed that they co-localized in the brush border of small intestine cells. Immunoelectron micrography revealed that the anti-CAK-beta antibody localized within microvilli. In the kidney, the protein was mainly expressed in proximal tubular cells, which have well developed microvilli, although CAK-beta mRNA was observed in most urinary tubular cells. In other tissues, the ciliated cells of the epididymis strongly expressed CAK-beta mRNA and CAK-beta localized in the cilia. In addition, alpha- and beta-tubulin were identified in the rat brain lysates immunoprecipitated with anti-CAK-beta antibody. The present results demonstrate that CAK-beta is present at relatively high levels in cilia, axons, and microvilli. This suggests that CAK-beta may play important roles in the functions of these structures or that the CAK-beta-related signaling pathway is closely associated with cytoskeletal components.
Animals↗