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Biomedical subjects

T Enomoto

Publications and source records attributed to T Enomoto.

At least 73 records · Page 4Linked to original sources

FHIT alterations in cancerous and non-cancerous cervical epithelium.

We have reported a significant frequency of an alteration of the fragile histidine triad (fhit) gene in squamous-cell carcinoma of the uterine cervix (series 1). To further define the role of fhit alteration in the development of cervical carcinoma, we surveyed 36 normal cervical epithelium, 22 cervical intra-epithelial neoplasias (CINs) and 20 additional cases of invasive cervical carcinomas (series 2). fhit transcripts were analyzed using reverse-transcription-polymerase-chain-reaction amplification and sequencing. Loss of expression of fhit was observed in 14 of 48 (29%) invasive carcinomas (8/28, series 1; 6/20, series 2) but not in any normal squamous epithelia or CINs analyzed. Abnormal fhit transcripts, including deletions and/or insertions, were observed in 12 of 48 (25%) invasive carcinomas (9/28, series 1; 3/20, series 2), 6 of 22 (27%) CINs, and 10 of 40 (25%) normal squamous epithelia (0/4, series 1; 10/36, series 2). Point mutation was detected in 9 of 48 (19%) cervical carcinomas (8/28, series 1; 1/20, series 2). Inactivation in both alleles was observed in 18 of 48 cervical carcinomas (38%), but not in any of 22 CINs or 40 normal squamous epithelia. Loss or impaired expression of the fhit-gene product was detected in 13 of 30 (43%) cervical carcinomas by immunohistochemistry, whereas all 6 normal cervical epithelia, or 22 CINs, expressed fhit protein. There was a strong association of impaired fhit protein expression with the disruption of normal fhit transcript in cervical carcinoma. No apparent correlation was observed between fhit inactivation and HPV infection. Our results suggest that fhit-gene inactivation occurs, not as an initiating event, but rather as a later event in cervical carcinogenesis, when the cervical tumor has acquired an invasive character.

Acid Anhydride Hydrolases↗

Variations in the expression of platelet-derived endothelial cell growth factor in human colorectal polyps.

Platelet-derived endothelial cell growth factor (PD-ECGF) has been identified to be an angiogenic factor, and a close relationship between the expression of PD-ECGF and tumor development has been postulated. This study was designed to assess both the role of PD-ECGF in human colorectal polyps as well as its relationship to the expression of other oncogenes during colorectal carcinogenesis. One hundred twenty patients with colon polyps who had undergone a polypectomy were studied. The polyps were classified based on the pathological findings as nonneoplastic or sporadic adenoma. The polyps were immunostained for PD-ECGF and vascular endothelial cell growth factor (VEGF), as well as for Ki-67 antigen and p53. The correlations between expression of PD-ECGF and clinicopathologic factors were examined. PD-ECGF was expressed at significant levels only in adenomas: in 4 of the 20 polyps with severe dysplasia (20%), and in 5 of the 20 cases of carcinoma in adenoma (25%). PD-ECGF was not detected in the nonneoplastic polyps and in adenomas with low-grade dysplasia. The intensity of immunostaining for PD-ECGF in adenomas correlated with the expression of Ki-67 antigen (P < 0.001) but not with that of p53. VEGF was not detected in any types of polyps. Angiogenic factors in colorectal adenomas might play an important role in carcinogenesis. The correlated expression of PD-ECGF and Ki-67 antigen suggests that PD-ECGF might not only act as an angiogenic factor, but also as a tumor growth factor.

Adult↗

Regulation of glycolysis during acclimation of scallops (Patinopecten yessoensis Jay) to anaerobiosis.

Some glycolytic metabolites in the adductor muscle were measured after transfer of scallops from aerobic to anaerobic saltwater for 12 h. The level of octopine increased gradually during the initial 3 h incubation, and thereafter the level increased rapidly up to 12 h. The ATP level also did not show any significant change for the initial 3 h, and then decreased rapidly. The fructose 2,6-biphosphate (Fru 2,6-BP) level increased drastically during the initial 3 h incubation, but thereafter the level did not show any significant change up to 12 h. In the short-term effects of anaerobiosis for 90 min, the level of fructose 6-phosphate (Fru 6-P) increased just after transfer to anaerobiosis, and then its level decreased. In contrast, the fructose 1,6-biphosphate (Fru 1,6-BP) level increased greatly, at the time when both glucose 6-phosphate (Glc 6-P) and Fru 6-P decreased. The Fru 2,6-BP level did not any significant change during the initial 15 min incubation, but thereafter the level increased gradually up to 90 min. Scallop 6-phosphofructo 1-kinase (EC 2.7.1.11) (PFK1) was strongly activated by 1 microM Fru 2,6-BP when 0.2 mM Fru 6-P was used as a substrate, but the activity was not affected at 5 mM Fru 6-P. In view of these results, the regulation mechanism of glycolysis is discussed.

Adenosine Triphosphate↗

Effects of small dose of brotizolam on P300.

Nine healthy men (mean age, 22.2 years) participated in two experimental sessions cross-overed randomly in a double blind manner; one with a placebo and the other with 0.125 mg of brotizolam (BTZ) administered in the morning. Resting electroencephalogram and event-related potential under oddball paradigm was recorded before and 1, 2, 4, 6 and 8 h after the administration. Mean 30-msec bin amplitude from 240 msec to 450 msec after the stimulus was compared between placebo and drug sessions in order to observe P300. Brotizolam reduced the amplitude of P300 at 6 h after administration. It was noted that the effects of BTZ were most marked at Fz.

Adult↗

Activation of nicotinic acetylcholine receptors induces long-term potentiation in vivo in the intact mouse dentate gyrus.

The present study was conducted to clarify the role of nicotinic ACh receptors (nAChRs) on long-term potentiation (LTP) in vivo in the intact mouse dentate gyrus using extracellular recording techniques. Intraperitoneal application of nicotine at a dose of 3.0 mg/kg but not 0.03 or 0.3 mg/kg produced a gradually developing, long-lasting increase for 120 min similar to tetanic LTP. Nicotine at a dose of 9. 0 mg/kg caused a temporary increase followed by depression. The long-lasting potentiation induced by nicotine at 3.0 mg/kg, which was named nicotinic long-term potentiation (LTPn), and tetanic LTP were significantly suppressed by pretreatment with mecamylamine (0.5 mg/kg i.p.), a nonselective nicotinic antagonist, but not affected by postapplication of mecamylamine. Interestingly, choline, a selective alpha7 nAChR agonist, at 3.0-90 mg/kg, induced the long-lasting potentiation similar to LTPn in a dose-dependent manner in vivo in the intact mouse dentate gyrus. The long-lasting potentiation induced by choline (30 mg/kg i.p.) was additionally increased by postapplication of nicotine (3.0 mg/kg i.p.) or tetanic stimulation. The present study revealed that systemic application of nicotine or choline induced the long-lasting potentiation in vivo in the intact mouse dentate gyrus, suggesting that alpha7 nAChRs may contribute to the induction of LTP by nicotine, and supporting in vivo animal studies that nicotine improves learning and memory performance.

Acetylcholine↗

Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms.

Expression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM (P< 0.05) and 12 of 63 (19%) with carcinoma (P < 0.05). Cases with bcl-2 expression showed more favourable prognosis than those without, but the difference was not statistically significant. There was no difference in frequency of Bax and Fas expression between each histologic category. Fas L expression was observed in one of 36 cases (3%) with adenoma, but in 12 of 33 (36%) with LPM (P < 0.001) and 42 of 63 (67%) with carcinoma (P < 0.0001). In carcinomas, cases expressing Fas L showed a less favourable prognosis than those without (P = 0.02). Density of CD8+ lymphocytes, possibly cytotoxic T-cells, was higher in serous carcinoma with negative Fas L expression than those with positive Fas L expression. These findings suggest that Fas L expressing carcinomas induce apoptosis in infiltrating CTL with Fas expression, and escape from immune surveillance.

Adenoma↗

Immunohistochemical localization of telomerase hTERT protein and analysis of clonality in multifocal vulvar intraepithelial neoplasia.

Vulvar intraepithelial neoplasias (VINs) are potentially premalignant lesions of the squamous mucosa. The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population.

Carcinoma in Situ↗

Colocalization of GP125/CD98 with tropomyosin isoforms at the cell-cell adhesion boundary.

Two monoclonal antibodies designated as 1F6 and 4B10 were obtained on screening for reactivities to CD98-associated molecules by sandwich-type enzyme-linked immunosorbent assaying using hybridoma culture supernatants as the solid phase, cell lysates as an antigen source, and a mixture of biotinylated antibodies to CD98HC as a detector. Flow cytometric analysis with microspheres in combination with 1F6, 4B10, and anti-CD98HC also indicated the association of antibody-defined antigen(s) with CD98. 1F6 and 4B10, stained fibrillate components in fixed and permeated cells but were not reactive with unfixed live cells, suggesting that epitopes reside in the cytoskeleton-associated structure in the intracellular region. Two-color immunostaining followed by confocal microscopy revealed the colocalization of the antigen with CD98 at the cell-cell adhesion boundary of HeLa cells. 1F6 detected proteins with relative molecular masses of 33,000 to 43,000 on immunoblotting analysis involving cell lysates of human and rat cell lines. Analysis with a purified tropomyosin specimen from rabbit skeletal muscle demonstrated that 1F6 and 4B10 recognize tropomyosin. Two-dimensional gel electrophoresis followed by immunoblotting analysis revealed that 1F6 recognizes various tropomyosin isoforms. These results indicated that CD98 physically associates directly or indirectly with tropomyosin, and that this association is closely related to the cell-cell interaction.

Actins↗

Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions.

The SGS1 gene of Saccharomyces cerevisiae is a homologue for the Bloom's syndrome and Werner's syndrome genes. The disruption of the SGS1 gene resulted in very poor sporulation, and the majority of the cells were arrested at the mononucleated stage. The recombination frequency measured by a return-to-growth assay was reduced considerably in sgs1 disruptants. However, double-strand break formation, which is a key event in the initiation of meiotic DNA recombination, occurred; crossover and noncrossover products were observed in the disruptants, although the amounts of these products were slightly decreased compared with those in wild-type cells. The spores produced by sgs1 disruptants showed relatively high viability. The sgs1 spo13 double disruptants sporulated poorly, like the sgs1 disruptants, but spore viability was reduced much more than with either sgs1 or spo13 single disruptants. Disruption of the RED1 or RAD17 gene partially alleviated the poor-sporulation phenotype of sgs1 disruptants, indicating that portions of the population of sgs1 disruptants are blocked by the meiotic checkpoint. The poor sporulation of sgs1 disruptants was complemented with a mutated SGS1 gene encoding a protein lacking DNA helicase activity; however, the mutated gene could suppress neither the sensitivity of sgs1 disruptants to methyl methanesulfonate and hydroxyurea nor the mitotic hyperrecombination phenotype of sgs1 disruptants.

Adenosine Triphosphatases↗

Different domains of Sgs1 are required for mitotic and meiotic functions.

The SGS1 of Saccharomyces cerevisiae is a homologue for human Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson's syndrome causative genes. Disruptants of SGS1 show high sensitivity to methyl methanesulfonate (MMS) and hydroxyurea, and hyper recombination phenotypes including interchromosomal homologous recombination in mitotic growth. In addition, sgs1 disruptants show poor sporulation and a reduced level of meiotic recombination as assayed by return-to-growth. We examined domains of Sgs1 required for mitotic and meiotic functions of Sgs1 by transfecting variously mutated SGS1 into sgs1 disruptants. The N-terminal 1-401 amino acid region was required for complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations of sgs1 disruptants in mitotic growth and for complementation of poor sporulation and of reduced meiotic recombination. Although the N-terminal 1-125 amino acid region was absolutely required for the complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations in mitotic growth, it was dispensable for the meiotic functions. In contrast, the highly acidic region (400-596 amino acid) was dispensable for the mitotic functions but a deletion of this region affected the meiotic functions. The C-terminal 1271-1350 amino acid region containing a HRDC (helicase and RNaseD C-terminal) domain was dispensable for the mitotic and meiotic functions. Although DNA helicase activity of Sgs1 was not required for Sgs1 to complement the meiotic functions, a deletion of helicase motifs III-IV (842-1046 amino acid) abolished the complementing activity of Sgs1, indicating that a structurally intact helicase domain is necessary for Sgs1 to fulfill its meiotic functions.

Alleles↗

Localization of telomerase hTERT protein and hTR in benign mucosa, dysplasia, and squamous cell carcinoma of the cervix.

Telomerase has been detected by telomerase repeat amplification protocol (TRAP) assay in cervical dysplasia and squamous cell carcinoma but not in most normal cervical tissues. In the present study, the cellular localization of the protein catalytic subunit of telomerase (hTERT) and the RNA component (hTR) were investigated by a sensitive immunohistochemical technique and by in situ hybridization, respectively. hTERT protein was detected in all diagnostic categories of cervical specimens. hTERT was localized predominantly to the lower suprabasal levels of normal squamous mucosa but was detected throughout virtually all levels of the lesional epithelium in low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and squamous cell carcinoma (SCC). Telomerase expression correlated with hTERT detection in SCC and HSIL but was not detected by TRAP assay in most samples of normal mucosa or LSIL. The distribution of hTR correlated with the localization of hTERT in HSIL and SCC but was restricted to the basal and suprabasal cell layers in normal mucosa and LSIL.

Animals↗

Cecal environment and TBARS level in mice fed corn oil, beef tallow and menhaden fish oil.

To examine the dietary effects of three lipids from different sources on intestinal conditions, diets containing 10% corn oil (CO), 1% corn oil +9% beef tallow (BT) or 1% corn oil + 9% menhaden fish oil (MO) were administered to male mice for 4 wk. Levels of total cholesterol (TC), non-esterified fatty acids (NEFA) and glucose in plasma were lower in mice fed on MO than in mice fed on CO or BT. The plasma phospholipid (PL) level was lower for mice fed MO than in mice fed BT. Levels of the thiobarbituric acid-reactive substances (TBARS), soluble saccharides and soluble proteins in the cecum were significantly higher in mice fed on MO than in mice fed on CO or BT. The number of fecal bacteroidaceae was lower in mice fed on MO than in mice fed on BT. On the other hand, the number of fecal bifidobacteria was greater in mice fed on MO than in mice fed on CO. These results suggest the possibility that menhaden oil affects lower intestinal microflora through the increase of not only oxide products but also saccharides and proteins in the intestine.

Animals↗

[An office technique for myringoplasty without the use of fibrin glue].

A simple method for office closure of eardrum perforation using an atero-collagen graft used for dermal defects (Terdermis) without fibrin glue was developed. Eardrum perforations were successfully closed in 71.4% of all cases (63 ears) after the initial treatment. Neither skin incision nor the use of temporal fascial grafts was necessary in this method. The merit of the method is that there is no possibility of blood infection because no blood materials are used.

Adolescent↗

[A case of biloma caused by early complications of hepatic artery infusion chemotherapy].

We report a 70-year-old male who had biloma as an early complication of hepatic artery infusion chemotherapy. The patient had a history of subtotal gastrectomy for a advanced gastric cancer. Two years after the primary operation on the stomach, a solitary metastatic liver tumor was indicated by follow-up abdominal CT, and a segmental hepatectomy was performed. Soon after the hepatectomy, intraarterial catheter placement was performed via the left subclavian artery for preventive chemotherapy. Infusion chemotherapy of 10.5 g 5-FU and 75 mg CDDP was administered for a month, during which time the patient had liver dysfunction, fever, tenderness, and abdominal fullness. Abdominal CT revealed a large low density mass at a lateral segment of the liver which could not be seen on the previous CT image. Also, extravasation of contrast media was identified by angiography via the reservoir catheter. Using an interventional technique, percutaneous transhepatic drainage for biloma and extubation of the reservoir catheter were performed. The present case is thought to be of an early and rare complication of hepatic artery infusion chemotherapy. The etiology is discussed herein.

Aged↗

[Microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung].

A 67-year-old man who had worked as an aluminum grinder had been given a diagnosis of pneumoconiosis. Ten years later, he was admitted with fever, dyspnea on exertion, and numbness. Chest roentgenograms showed linear-reticular shadows in both lower lung fields. ELISA-based tests were positive for perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens disclosed crescentic glomerulonephritis and angiitis of small arteries. Our diagnosis was microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung. The results of high-energy dispersion X-ray microanalysis indicated that the patient's lungs contained aluminum. His general condition improved with the administration of corticosteroid and immunosuppressive agents, and his chief symptoms disappeared.

Aged↗