Detection of ETV6/MDS1/Evi-1 chimeric transcripts in a patient with acute myelocytic leukemia and t(3;12)(q26;p13)
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Biomedical subjects
Publications and source records attributed to Y Nishimura.
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Jutokuin-Genyu studied medicine under Dohsan-I when he was young. He lived at Shinzaike in Kyoto and, as the Manase's fellow pupil, he exchanged visits and elegantly associated with upper-class people. During that time he complied medical books, wrote, served the Edo Shogunate as a physician, and also went to Kagoshima. In his last years he was granted a rank of Ingoh, Hoh-in. He died on April 3, 1644 (the 21st year of the Kan-ei period). His age at death is unknown, though it appears that he was considerably long-lived, since his death was half a century after his teacher, Dohsan, who died in 1594 (the third year of the Bunroku period). His grave is at the Ryuh-un-in temple at Edo. His wife was once Shojun Kohtokuin's widow. Genjun, who afterward succeeded to the Jutoku-in family and became the second generation thereof, came from the Kohtoku-in family.
Recent studies have raised the possibility that DNA-based vaccination may prove useful for generating virus-specific cytotoxic T-lymphocytes (CTL) responses. Recently, a plasmid containing the human elongation factor 1alpha(EF1-alpha) promoter, pEF321, was reported to be a versatile expression vector for gene expression in mammalian cells in vitro. In the present study, we assessed the capability of a novel plasmid, pEFCE1E2, encoding hepatitis C virus (HCV) structural proteins (core, E1 and E2) under the EF1-alpha promoter to generate CTL against HCV in vivo. BALB/c mice were immunized with the pEFCE1E2 but not with a plasmid possessing the same cDNA under the cytomegalovirus developed HCV-specific effector cells by a single immunization. These effector cells elicited by pEFCE1E2 immunization were CD8(+) and major histocompatibility complex class I restricted. These studies provided evidence for the potential utility of the EF1-alpha promoter for development of DNA vaccines against HCV infections.
The non-Mendelian inheritance of organelle genes is a phenomenon common to almost all eukaryotes, and in the isogamous alga Chlamydomonas reinhardtii, chloroplast (cp) genes are transmitted from the mating type positive (mt(+)) parent. In this study, the preferential disappearance of the fluorescent cp nucleoids of the mating type negative (mt(-)) parent was observed in living young zygotes. To study the change in cpDNA molecules during the preferential disappearance, the cpDNA of mt(+) or mt(-) origin was labeled separately with bacterial aadA gene sequences. Then, a single zygote with or without cp nucleoids was isolated under direct observation by using optical tweezers and investigated by nested PCR analysis of the aadA sequences. This demonstrated that cpDNA molecules are digested completely during the preferential disappearance of mt(-) cp nucleoids within 10 min, whereas mt(+) cpDNA and mitochondrial DNA are protected from the digestion. These results indicate that the non-Mendelian transmission pattern of organelle genes is determined immediately after zygote formation.
We have recently reported that freeze-dried alginate gel, which was developed in our laboratory, enhanced peripheral nerve regeneration. The purpose of this study was to examine whether alginate gel is capable of promoting nerve regeneration in the severed spinal cord of adult mammals. Using Wistar rats at 30 days of age (P30), the T9-T10 spinal cord was totally resected and alginate gel was implanted across the gap. Forty-five days after surgery myelinated and unmyelinated axons regenerated throughout the gap with remaining alginate gel. The elongated axons established electrophysiologically functional projections across the gap. In conclusion, freeze-dried alginate gel could be a promising material as an artificial nerve guide for repair of injured central nervous system.
We have recently reported that the burst firing neurons are found in layer III as well as in layer V of cat sensorimotor cortex in vitro. In the present study, we examined the synaptic excitability of layer III neurons by white matter stimulation and compared with their firing patterns against the current injections through the recording microelectrodes. The firing patterns of layer III neurons were classified into three main classes as in our previous study, i.e., (1) regular spiking (RS), i.e., the tonic firing that often exhibited spike-frequency adaptation, (2) burst-and-single spiking (BS), i.e., the initial bursting followed by tonic firing, (3) repetitive-bursting (RB), the burst firing that recurred at fast frequency. In RS cells, single action potential was superimposed on the largest EPSPs among all cell types analyzed. BS cells also fired single action potential and never exhibited burst firing synaptically. Only in a part of RB cells, synaptic bursting instead of single action potential was evoked on smaller EPSPs. IPSPs could be observed in about 60% of all the recorded RS and BS cells, however, they were observed in only 10% of the RB cells.
Capillary electrophoresis (CE) with two different detection methods, mass spectrometry (MS) and UV absorption spectroscopy with photodiode array detection (UV/DAD), was used for the analysis of the degradation products of dyestuffs. We have studied wet oxidation with solid catalyst as the treatment method of wastewaters containing dyestuffs. When the Orange II (C.I. Acid Orange 7) solution was used as the model wastewater, treated solution contained unknown highly polar degradation products. We were able to determine the molecular masses of some products by CE-MS. From this clue, we tried to identify these products by CE-UV/DAD. By means of the comparison of the migration time and UV spectra of standard samples, three degradation products were identified. The separation of degradation products was successful within 15 min.
BACKGROUND: Clinical results of external beam radiation therapy (RT) with or without intraluminal brachytherapy (IBT) for patients with superficial esophageal carcinoma were evaluated retrospectively. METHODS: Between 1985 and 1996, 21 patients with superficial esophageal squamous cell carcinoma were treated by external beam RT, with or without high dose rate IBT, with curative intent. There were 18 males and 3 females; their median age was 67 years (range, 51-85 years). Eight patients were treated by external beam RT alone (60-69 gray [Gy]), whereas the remaining 13 patients were treated by IBT after external beam RT. Most patients in the IBT group received 2 or 3 fractions of IBT of 4 Gy after external beam RT of 50-56 Gy. RESULTS: All of the 21 tumors showed complete regression at the end of RT. Local recurrence was noted in 4 patients in the group that received external beam RT alone and in 2 patients in the IBT group. Salvage therapy was successful for 4 patients. Local control probability and cause specific survival probability for the IBT group were significantly higher than those for the group that received external beam RT alone (P < 0.05 for both). The 3-year local control and cause specific survival rates for the IBT group were 85% and 100%, respectively, whereas those for the external beam RT group were 45% and 67%, respectively. Transient esophageal ulcers were noted in two patients in the IBT group. CONCLUSIONS: External beam RT and IBT is a safe and effective treatment modality for patients with superficial esophageal carcinoma.
The proliferative responses of a human CD4+ T cell clone 29.15.2, reactive with a self-K-ras-derived peptide (3EYKLVVVGAGGVGKSALT20), were tested using a set of X9 combinatorial peptide libraries containing the flanking residues (EYKLVXXXXXXXXXSALT, where X indicates random amino acids). Certain peptide libraries, such as EYKLVXXXXXX M XXSALT and EYKLVXXXXXXX H XSALT, stimulated a marked proliferation of 29.15.2. However, no combinations of substitutions tested, such as EYKLVXXXXXX MH XSALT, exhibited additive effects. We subsequently synthesized peptides with degenerate sequences (a mixture of 480 species), where each position is composed of the wild-type (wt) residue or of amino acids that induced the proliferation of 29.15.2, in positional scanning. Interestingly, one fraction of degenerate peptides, separated by reverse-phase HPLC, stimulated much higher proliferation than did the wt; in addition, the retention time of this fraction was distinct from that of the wt. Mass spectrometry analysis of this fraction and flanking fractions identified five peptide species that exhibit strong signals in a manner that parallels the antigenic activity. Finally, 17 candidate peptide sequences were deduced from mass spectrometry and hydrophobicity scoring results, of which two peptides (EYKLVVVGAGG ML KSALT and EYKLVVVGAGG MI KSALT) did induce 52- and 61-fold stronger proliferation, respectively, compared with the wt. These findings indicate that: 1) synthetic peptides that carry "the best" residue substitution at each position of combinatorial peptide libraries do not always exhibit superagonism, and 2) such a drawback can be overcome with the use of mass spectrometry. This approach provides new perspectives for the accurate and efficient identification of peptide superagonists.
Platelet-activating factor (PAF) plays an important role in the pathogenesis of bronchial asthma. To investigate the role of PAF in the maintenance and remodeling of the extracellular matrix, we evaluated the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 from human bronchial epithelial cells after PAF treatment. Gelatin zymography of human bronchial epithelial cell-conditioned media showed major pro-matrix metalloproteinase-9 and minor pro-matrix metalloproteinase-2 expression and these expressions were totally inhibited by the metalloproteinase inhibitor EDTA. The identification of matrix metalloproteinase-9 was confirmed by Western blot analysis. Northern blotting and zymography demonstrated that PAF induced the mRNA of matrix metalloproteinase-9 from human bronchial epithelial cells and an increase in the gelatinolytic activity of pro-matrix metalloproteinase-9 but not in that of pro-matrix metalloproteinase-2. Lyso-PAF did not induce matrix metalloproteinase-9 mRNA or the gelatinolytic activity of pro-matrix metalloproteinase-9. CV6209, an receptor antagonist of PAF, reduced the increases of pro-matrix metalloproteinase-9 mRNA and gelatinolytic activity induced by PAF. Another receptor antagonist of PAF, hexanolamine PAF, did not inhibit the increases in the synthesis or release of pro-matrix metalloproteinase induced by PAF. Based on these results, we propose that matrix metalloproteinase-9 may be actively involved in the PAF-induced physiopathological remodeling in human bronchial epithelial cells.
Activating transcription factor-2 (ATF-2) is a transcription factor that binds to cAMP response element (CRE). ATF-2 contains two functional domains, an N-terminal transactivation domain and a C-terminal DNA-binding domain. The DNA-binding domain contains the basic leucine zipper (bZip) motif. Here, the three-dimensional structure of the transactivation domain of ATF-2 has been determined by NMR. The transactivation domain consists of two subdomains: the structure of an N-terminal half (N-subdomain) is well determined, while a C-terminal half (C-subdomain) takes a highly flexible and disordered structure. The architecture of the N-subdomain is very similar to that of the well-known zinc finger motif found in DNA-binding domains, consisting of an antiparallel beta-sheet and an alpha-helix. The zinc atom is tetrahedrally coordinated to two cysteine residues and two histidine residues. Amino acids that form the hydrophobic core in all of the DNA-binding zinc fingers are well conserved in the N-subdomain of the transactivation domain, whereas some amino acids that are responsible for binding to the phosphate backbone of DNA in the DNA-binding zinc fingers are substituted with other amino acids. The flexible C-subdomain, which contains two threonine residues that the stress-activated protein kinases phosphorylate, is likely to undergo a conformational change by specific binding to a target protein.
p16, an inhibitor of cell cycle machinery, is frequently inactivated in non-small cell carcinoma of the lung (NSCCL). To clarify the significance of p16 inactivation in the progression of lung adenocarcinoma, we immunohistochemically evaluated p16 protein status and Rb, p53 and cyclin D1 expression in 51 surgically resected adenocarcinomas that were less than 3 cm in diameter (median follow-up period: 52.5 months). Twenty-one of 51 adenocarcinomas showed negative immunostaining for p16. Twenty adenocarcinomas were also negative for Rb, while 31 and 13 were positive for p53 and cyclin D1, respectively. Loss of p16 expression was significantly correlated with scar grade, lymphatic permeation, lymph node metastasis and clinical stage. Rb protein expression was also inversely correlated with scar grade, pleural involvement and vascular invasion. When the cases were stratified according to the expression of both proteins, the Rb-/p16- subset (7/51) consisted of poorly differentiated adenocarcinoma with a higher grade of invasion. While Rb, p53 and cyclin D1 protein status showed no significant correlations with prognosis, p16 inactivation was significantly correlated with poor prognosis, and the prognosis of Rb-/p16- was the worst among the 4 subsets. Inactivation of p16 may play a role in accelerating scar formation and lymph node metastasis, and may contribute through these mechanisms to poor prognosis in patients with small-sized lung adenocarcinoma.
We have identified human and rat homologues of the VAMP-associated protein (VAP) of 33 kDa of Aplysia californica (aVAP-33), which we designated VAP-A, VAP-B, and VAP-C. Human VAP-A (hVAP-A) was found to be identical to the recently reported protein hVAP-33, with the exception of two amino acid residues. VAP-B contained a coiled-coil domain and a transmembrane domain (TMD). Human VAP-B (hVAP-B) was 46 and 60% homologous of the amino acid level to aVAP-33 and hVAP-A, respectively. Human VAP-C was a splicing variant of hVAP-B, lacking both the coiled-coil domain and the TMD. hVAP-B had VAMP-binding ability. Moreover, hVAP-A and hVAP-B associated with each other through their respective TMDs. These results suggest that complex formation by VAPs might be important in the trafficking of mammalian vesicle.
We have developed a novel artificial nerve guide composed of biodegradable freeze-dried alginate gel covered by polyglycolic acid mesh, and evaluated its effect on peripheral nerve regeneration, using a 50-mm gap cat sciatic nerve model. Functional reinnervation of motor and sensory nerves occurred 13 weeks after implantation, as demonstrated by recovery of compound muscle action potential (CMAP) and somatosensory evoked potential (SEP). For histologic evaluation, samples of tissue were harvested from the grafted material segment 7 months after operation. Many newly developed nerve fasciculi were found, and the implanted nerve guidance material had completely disappeared with little inflammation. These results indicate that freeze-dried alginate gel allows the nerve to regenerate across longer gaps than described in previous literature.
A previously reported patient presenting sensory-dominant neuropathy with antiganglioside antibodies, bound preferentially to polysialogangliosides including GD1b, was autopsied. While axonal degeneration was predominant in the sural nerve, many demyelinated fibers were present in the spinal roots. Dorsal roots had undergone significant damage. These pathological findings were well correlated with the electrophysiological results showing decreased F-wave conduction velocities and conduction blocks in motor nerves and decreased or absent sensory action potentials in sensory nerves, with distribution of GD1b in nerve tissues such as dorsal root ganglia and paranodal myelin in the ventral and dorsal roots.
Alginate dressings are currently used in the management of epidermal and dermal wounds, and provide a moist environment that leads to rapid granulation and reepithelialization. However, a cytotoxic effect on proliferation of fibroblasts and residual material with inflammation in healing wounds have been reported recently. We have developed a new alginate dressing (AGA-100), which does not have an inhibitory effect on proliferation of fibroblasts. The purpose of this study was to evaluate the new alginate dressing with respect to wound healing in full- and partial-thickness pig wounds and with respect to biodegradation following implantation into rabbit muscle. Kaltostat and Sorbsan, both well-established commercial dressings, were used as control. The closure rate of full-thickness wounds treated with AGA-100 was significantly higher on day 15 compared with that with Kaltostat and Sorbsan. Reepithelialization rate of partial-thickness wounds treated with Sorbsan was statistically significantly lower on day 3 than those with the other two dressings. As to dressing debris remained in the healing wound, a large amount of foreign debris was noted in all the full-thickness wounds treated with Kaltostat or Sorbsan, while only about one-third of wounds treated with AGA-100 showed a little dressing debris. AGA-100 implanted into the muscle of rabbits was bioresorbed completely within 3 months. Therefore, dressing residue in AGA-100-treated full-thickness wounds might be fully absorbed in a few months. In conclusion, it is shown that our newly developed AGA-100 possesses superior properties compared with typical alginate dressings.
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