A minute rectal carcinoma with massive submucosal invasion and lymph-node metastasis.
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Biomedical subjects
Publications and source records attributed to T Goto.
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We reported previously that nitrous oxide induces pre-emptive analgesia that is partially antagonized by naloxone and totally antagonized by halothane. The aims of this study were to determine if halothane and isoflurane are similar in this respect and to examine if volatile anaesthetics antagonize the analgesic effect of exogenous opioids. We found that 75% nitrous oxide prolonged tail-flick latency by 37% and this analgesia was dose-dependently inhibited by halothane and, less effectively, by isoflurane. In contrast, morphine 1.25 mg kg-1 i.v. also prolonged tail-flick latency by 35% but, unlike nitrous oxide-induced analgesia, this effect was attenuated only by high doses of halothane and was unaffected by isoflurane. Neither halothane nor isoflurane alone altered the tail-flick response. We conclude that both halothane and isoflurane dose-dependently antagonized nitrous oxide analgesia but antagonized morphine-induced analgesia to a lesser extent.
The effect of dietary Ca-bound casein phosphopeptides (CaCPP) on the bones of aged ovariectomized (OVX) rats was studied as a model for post-menopausal bone loss. Three groups of ovariectomized rats were fed a control diet or one of two experimental diets, and one group of sham-operated rats (SHAM) was fed the control diet. The experimental diets contained 0.5% Ca and 0.4% P. In one diet, CaCPP was the sole source of calcium and provided 62.5% of dietary phosphorus (CaCPP diet). In the other, Ca-free CPP provided 100% of dietary phosphorus (Ca-free CPP diet). In the control diet, CaCO3 and KH2PO4 were used. During a 17-wk feeding period, there was little change in femoral bone mineral densities (BMD) of ovariectomized rats fed CaCPP and Ca-free CPP, or in the SHAM rats fed the control diet, whereas the bone mineral densities in the control ovariectomized rats decreased with time. Some of the segmental bone mineral densities of the excised femurs from the rats fed CaCPP were significantly higher than those from the control ovariectomized rats, but the values of the Ca-free CPP group were similar to those of the control ovariectomized rats. In the Ca-free CPP group, the discrepancy in bone mineral densities obtained between in vivo results and excised specimens might have been the result of a loss in bone mass due to their significant loss in body weight. There were no significant differences in serum inorganic phosphorus, alkaline phosphatase activity, osteocalcin or 1 alpha-25-dihydroxycholecalciferol concentrations among the ovariectomized groups. In the CaCPP and Ca-free CPP groups, urinary phosphorus excretion decreased and urinary calcium excretion increased significantly with time. The inhibitory effect on bone loss in aged ovariectomized rats could be due to the effects of dietary CaCPP on phosphorus and calcium metabolism.
The ultrastructure and morphogenesis of human immunodeficiency virus (HIV) were elucidated by observation with several techniques including immunoelectron microscopy and cryo-microscopy. The virus particle consists of an envelope, a core and matrix. The virus particles were observed extracellularly as having one of three profiles: (1) a centric or an eccentric electron-dense core, (2) rod-shaped electron-dense core, and (3) doughnut-shaped. HIV-1 particles in the hydrated state were observed by high resolution electron cryo-microscopy to be globular, and the lipid membrane was clearly resolved as a bilayer. Many projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially head parts, were found to vary in each projection. By isolation with Nonidet P40 and glutaraldehyde, HIV-1 cores were confirmed to consist of p24 protein by immunogold labeling. When the virus enters the cell, two entry modes were found: membrane fusion and endocytosis. No structures resembling virus particles could be seen in the cytoplasm after viral entry. In HIV-1-infected cells, positive reactions by immuno-labeling suggest that HIV-1 Gag may be produced in membrane-bound structures and transported to the cell surface by cytoskeletons. Then a crescent electron-dense layer was first formed underneath the cell membrane. Finally, the virus particle was released from the cell surface. Several cell clones producing defective particles were isolated from MT-4/HIV-1 cells. Among them, doughnut-shaped or teardrop-shaped particles were seen to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins faced each other against the inner electron dense ring, suggesting that the inner ring consists of a precursor Gag protein.
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BACKGROUND: The Drosophila gene runt plays multiple roles during embryogenesis, including one as a pair-rule class segmentation gene. The runt protein (Runt) contains an evolutionarily conserved domain (the Runt domain) that is found in several mammalian proteins including the human protein AML1, which is involved in many chromosome translocations associated with leukaemia. Specific DNA binding activity of a mammalian Runt domain is enhanced by a partner protein called PEBP2beta/CBFbeta. DNA binding activity of Drosophila Runt is also stimulated by this protein, suggesting the existence of a similar Runt partner protein in Drosophila. RESULTS: We report here the cloning of two closely linked Drosophila genes, runt domain partner (rp) beta1 and beta2, that encode homologues of mouse PEBP2beta/CBFbeta. They are highly homologous to each other and to the mammalian counterpart. Either of the rpb proteins is capable of forming a complex with Runt and stimulating its DNA binding activity, but their temporal and spatial distributions are quite dissimilar, suggesting that functional specificity of Runt may be conferred by the interacting partner. Runt represses transcription dominantly when coexpressed with either partner in cultured cells, a function consistent with a direct role for Runt in regulating expression of the even-skipped gene in Drosophila embryos. CONCLUSIONS: Drosophila Runt can interact with either of two Runt domain partners, and the resulting complex functions as an active repressor of transcription.
We present a case of polycystic ovary syndrome (PCOS) that developed simultaneous intra- and extra-uterine pregnancy with ovarian hyperstimulation syndrome (OHSS) after induction of ovulation with pure FSH-HCG. At 9 weeks of pregnancy, the bilateral tubal pregnancy caused an imminent spontaneous abortion, and both Fallopian tubes were resected. After the laparotomy, the pregnancy progressed without problems until 31 weeks and 5 days of pregnancy, when signs of spontaneous abortion appeared, and healthy twin female babies were delivered by cesarean section. The incidence of heterotopic pregnancy is increasing in cases in which inducers of ovulation or ART, such as IVF-ET and GIFT, have been employed. One must be well aware that the danger of heterotopic pregnancy following induction of ovulation is imminent, particularly in cases with risk factors of multiple and/or extra-uterine pregnancy, such as PCOS, a history of tubal restoration, and sexually transmitted disease(s).
The production of aflatoxins B1 and B2 by Aspergillus tamarii (subgenus Circumdati section Flavi) is reported for the first time. The fungus was isolated from soil collected from a tea (Camellia sinensis) field in Miyazaki Prefecture, Japan. Three single-spore cultures, NRRL 25517, NRRL 25518, and NRRL 25519, were derived from subcultures of the original isolate 19 (MZ2). Each of these single-spore cultures of A. tamarii produced aflatoxins B1 and B2 and cyclopiazonic acid, as well as black, pear-shaped sclerotia. The demonstration of aflatoxin production by A. tamarii is examined in connection with A. tamarii phylogenetic relationships, chemical ecology, and potential use in food fermentations.
We investigated the relationships between hyperinsulinemia (a major indicator of the insulin resistance syndrome), blood pressure, dyslipidemia, and coagulation factors in 2606 community-dwelling Japanese individuals as part of the Jichi Medical School Cohort Study. An age-related decrease of the fasting insulin level was found in men but not in women. Body mass index, systolic and diastolic blood pressure, triglyceride and fasting glucose levels, and factor VII activity all increased in both sexes as the insulin level became higher, while the HDL cholesterol level decreased. In addition, total cholesterol and LDL cholesterol levels increased as the insulin level became higher and lipoprotein(a) levels decreased in the men. Fibrinogen levels were not related to the insulin level in either sex. Multiple logistic regression analysis revealed that fasting insulin levels were positively correlated with body mass index and fasting glucose and factor VII activity levels, whereas they were negatively correlated with HDL cholesterol in both sexes. In addition, fasting insulin levels were positively correlated with LDL cholesterol levels in men and with triglyceride levels in women. Our results indicate that hyperinsulinemia is associated with high factor VII activity in a general Japanese population as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.
The even-skipped (eve) pair-rule gene plays a key role in the establishment of the anterior-posterior segmental pattern of the Drosophila embryo. The continuously changing pattern of eve expression can be resolved into two phases. Early expression consists of seven broad stripes in the blastoderm embryo, while late expression, which occurs after cellularization, consists of narrow stripes with sharp anterior borders that coincide with the odd-numbered parasegment boundaries. Previous studies have shown that these two phases are controlled by separate classes of cis elements in the eve promoter. Early stripes are expressed by multiple stripe-specific elements under the control of maternal-effect genes and gap genes, while late stripes are expressed by a single regulatory element, the 'late element', under the control of pair-rule genes including eve itself. We report here that paired (prd), a pair-rule gene which had been considered to be below eve in the regulatory hierarchy of pair-rule genes, in fact plays a critical role in the regulation of late eve expression. Transgenic analysis shows that this regulation is largely mediated by an evolutionarily conserved sequence within the late element termed PTE (Paired Target Element). In vitro analysis shows that the Prd protein binds strongly to this sequence. Interestingly, PTE contains juxtaposed binding sites for the two DNA-binding domains of the Prd protein, the paired domain and the homeodomain. Mutagenesis of either binding site leads to significant reduction in the activity of the late element, indicating that both DNA-binding domains in the Paired protein are required for regulation.
Drosophila paired, a homolog of mammalian Pax-3, is key to the coordinated regulation of segment-polarity genes during embryogenesis. The paired gene and its homologs are unusual in encoding proteins with two DNA-binding domains, a paired domain and a homeodomain. We are using an in vivo assay to dissect the functions of the domains of this type of molecule. In particular, we are interested in determining whether one or both DNA-binding activities are required for individual in vivo functions of Paired. We constructed point mutants in each domain designed to disrupt DNA binding and tested the mutants with ectopic expression assays in Drosophila embryos. Mutations in either domain abolished the normal regulation of the target genes engrailed, hedgehog, gooseberry and even-skipped, suggesting that these in vivo functions of Paired require DNA binding through both domains rather than either domain alone. However, when the two mutant proteins were placed in the same embryo, Paired function was restored, indicating that the two DNA-binding activities need not be present in the same molecule. Quantitation of this effect shows that the paired domain mutant has a dominant-negative effect consistent with the observations that Paired protein can bind DNA as a dimer.
Monosodium 2-[(R*s,9S*)-(4-methoxy-6,7,8, 9-tetrahydro-5H-cyclohepta-[b]pyridin-9-yl)sulfinyl]-1H-benzimidazole (3A), a novel antiulcer agent previously reported by us, was found to be easily decomposed in weakly acidic solutions. In order to improve the stability of the parent compound, 3A, the preparation of 1-substituted benzimidazoles (4A) was attempted. However, the inhibitory effect of 4A against gastric acid secretion was less potent than that of 3A. Then 3A was solvated by EtOH or H2O to afford 5A or 6A, respectively. On the other hand, an another diastereoisomer, (R*s,9R*)-3B, was not solvated by EtOH or H2O under the same conditions. The thus obtained solvates (5A, 6A) are much more stable than that of 3A. The antiulcer activities of 5A and 6A were found to be similar to that of the parent compound (3A). Consequently, 6A was selected as an antiulcer agent for the development.
We demonstrated the release of follistatin, an activin-binding protein, from cultured rat anterior pituitary cells by measuring immunoreactive (ir-) follistatin in a specific immunoradiometric assay. Ir-follistatin release gradually increased in cultures over 1-18 days and reached its maximal level at 12-15 days of incubation. The basal ir-follistatin levels in the culture media increased about 3- (P < 0.01) and 5-fold (P < 0.001) in 2 and 10% fetal calf serum for 6 days, respectively. LHRH and activin A caused an approximately 2.0- (P < 0.05) and 1.8-fold (P < 0.05) rise in ir-follistatin release, respectively, in contrast to the lack of significant FSH effects. The culture medium condensed on sulfate-cellulofine gel was resolved by polyacrylamide gel electrophoresis and blotted with anti-follistatin polyclonal antibody, resulting in at least three protein bands ranging from 35 to 50 kDa under non-reducing conditions. These results indicated that follistatin is produced in anterior pituitary cells and that its secretion is regulated at least in part by LHRH and activin, implying an autocrine/paracrine role of activin and follistatin in the pituitary.
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A 45-year-old man underwent a distal arch and descending aortic replacement through a left thoracotomy. His chronic type A dissecting aortic aneurysm had the entry at the proximal descending aorta. After 9 years of his first dissection, he suffered from a second dissection. In computerized tomogram (CT), the ascending and descending aorta enlarged to 6.0 cm and 7.0 cm in diameter, respectively and descending aorta showed a three channeled dissection. The open proximal anastomosis technique was used under the deep hypothermic circulatory arrest (HCA) followed by selective cerebral perfusion (SCP). Surgical repair included the obliteration of the proximal false lumen at the level between the left carotid and subclavian artery. A thrombosed retrograde dissection in the ascending aorta was revealed in postoperative evaluation, and decreased in size at follow up CT.
An eight day old neonate with coarctation of aorta (CoA), ventricular septal defect (VSD), and severe left ventricular outflow tract obstruction (LVOTO) underwent a successful staged repair following a new palliative operation, which comprised aortic arch reconstruction, PTFE bypass graft between main pulmonary artery and descending thoracic aorta, and pulmonary artery banding (PAB) distal to the graft. Insertion of the bypass graft was aimed to allow enough systemic blood flow and reduces after load of ventricles after PAB. The second staged definitive operation was performed 21 days after the first operation and the procedure comprised partial resection of posterioly deviated infundibular septum via VSD, patch closure of VSD, and division of the graft. No evidence of progression of LVOTO was noted until the second stage operation despite the tight PAB. This new palliative operation, which does not need aid of cardiopulmonary bypass, is particularly effective for those with LVOTO, and can be safely applied even to seriously ill neonate. Thus, for the staged repair in aortic arch obstructive disease with VSD and severe LVOTO, this procedure can be a good alternative for palliative operation.
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