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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An infant case of acute leukemia (AL) showed lineage infidelity and a chromosome rearrangement involving 11q23. This case was morphologically diagnosed as ALL-L2 according to the FAB classification. However, the blast cells were highly positive for monoclonal antimyeloid antigens (Mol and TG-8) and lymphoid markers (B1, J5 and TdT). These immunologic findings indicated that the blast cells had characteristics of lymphoid B-cell and myeloid lines. In the literature, so-called "11q23 chromosome abnormalities," commonly observed in acute nonlymphoblastic leukemia (ANLL) and in a subtype of acute lymphoblastic leukemia (ALL) with t(4;11) were observed in both lymphoid and myeloid acute leukemias, with some of them recently reported to have lineage infidelity. These unique characteristics may indicate the possibility that the latter is a variation of the former, and support the hypothesis that the chromosomal rearrangement at 11q23 occurs at a multipotent stem-cell level.
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PMID:Infantile acute leukemia with 11q23 chromosome abnormality and lineage infidelity. 316

The joining of various V, (D) and J gene segments during DNA rearrangement of the antigen receptor genes is one of the principle mechanisms responsible for the generation of antibody diversity. In the absence of N-segment variation, the structures of the coding joints formed during light chain rearrangement are thought to be less complex than their heavy chain counterparts. Consequently, the joining of the VL and JL gene segments during recombination account for all of the junctional diversity seen within the third complementarity determining region (CDR3). We generated kappa light chain transcripts from human fetal liver and peripheral blood lymphocytes and found that approximately one third exhibit a variation in the length of CDR3-independent of the JK gene segment utilized. Nucleotide sequence analysis reveals that many of the nucleotides at the VK-JK joint resulting in length variation of CDR3 are directly encoded by the germline VK and JK gene segments used in these transcripts. However, nearly 20% of the transcripts contain N-segment additions consistent with TdT-like activity. These observations suggest that TdT or an analogous enzyme must be active in a significant percentage of human B-lymphocytes during light chain rearrangement. Length variation in light chain CDR3 expands the potential repertoire and thus contributes an additional means of generating diversity in the antibody molecule.
Mol Immunol 1994 Jan
PMID:An apparently common mechanism of generating antibody diversity: length variation of the VL-JL junction. 750 79

Transcription associated with a terminal deoxynucleotide transferase gene initiator element is shown to respond to the transcription factor GAL4-VP16 both in vivo and in vitro. High-level transcription requires both an intact initiator element and bound activator. Transcription from this initiator-directed promoter is synergistic in vivo in that five GAL4 DNA binding sites yield 36 times the expression of a single site. Promoters dominated by initiator and TATA elements respond similarly to several GAL4-based activators, including GAL4-Sp1, GAL4-CTF, GAL4(1-147), GAL4-p53, GAL4-C/EBP, and GAL4-ER(EF), as well as GAL4-VP16 and Sp1. These and other similarities suggest that primary activation of TATA- and initiator-dominated promoters occurs at common steps. Since the initial assembly steps do not appear to be common for the two promoter types, the results place interesting constraints on models for how activation occurs.
Mol Cell Biol 1993 Dec
PMID:Properties of initiator-associated transcription mediated by GAL4-VP16. 824 64

Approximately 25% of arthropod RNA polymerase II-transcribed promoters contain one or more copies of the sequence TCAGT beginning within the interval (-10, +10). The clear statistical overrepresentation of this sequence and, to a lesser extent, of its cognates ACAGT, GCAGT, and TCATT, implies that they may be significant promoter elements. Their collective sequence similarity to vertebrate initiators (Inrs) of the TdT class suggests that the vertebrate and arthropod elements are homologous. Prior work in vertebrate systems has emphasized the role of the Inr in promoters lacking TATA boxes, where it can serve as an alternate staging site for polymerase II initiation. However, it is clear that the Inr sequence is by no means restricted to TATA-deficient promoters. Functional tests using the TATA-containing Drosophila gene Eip28/29 support the idea that the Inr is a facultative promoter element, required for efficient transcription under some conditions. For example, the Inr protects basal expression of Eip28/29 from the silencing effect of ecdysone response elements. In addition, the Inr is required for the function of an enhancer of basal activity in Eip28/29. We conclude that Inrs are promoter elements found sporadically throughout the higher eukaryotes, that the requirement for an Inr depends upon the array of other promoter elements which may be present in a given gene, and that Inrs may permit enhancers to discriminate among promoters.
Insect Biochem Mol Biol 1993 Jan
PMID:The arthropod initiator: the capsite consensus plays an important role in transcription. 848 19

To clarify whether apoptosis is involved in endometriosis, we obtained eutopic endometrial tissues along with endometriotic tissues from the uterus (adenomyosis) (n = 12) and from the ovary (n = 12) from patients undergoing gynaecological surgery. Apoptosis-induced DNA fragmentation was detected by the TdT-mediated dUTP-biotin nick-end labelling method, and immunostaining with a monoclonal antibody against the Fas, Le(y) or B-cell leukaemia/lymphoma-2 (bcl-2) was also performed using the same tissue section. Analysis showed that apoptosis was occurring in all the samples of ovarian endometriotic tissue but in only two of the 12 adenomyotic and in five of the 24 eutopic endometrial tissue samples. In none of these cases was apoptosis correlated with phases of the menstrual cycle. The expression of bcl-2 in the eutopic endometrial and adenomyotic tissues was limited to the proliferative phase, and was observed in only one of the 12 cases of ovarian endometriosis. Fas and Ley were expressed randomly across a wide range in both the eutopic and ectopic endometrial tissues. These results suggest that the features of ovarian endometriosis are different from those of adenomyosis and eutopic endometrium in terms of the involvement of apoptosis. In addition, the regulatory mechanism involved in ovarian endometriosis may differ from that in other endometrial cells.
Mol Hum Reprod 1996 May
PMID:Detection of apoptosis in human endometriotic tissues. 923 97

The structural basis of the recently recognized renal impairment after infusion of trichosanthin (TCS), a type I ribosome inactivating protein, is uncertain, but functionally it appears to be related to a lesion in the renal tubules. In this study, renal dysfunction in experimental rats was induced by a single dose of TCS. Creatinine clearance and tubular proteinuria were used to assess renal function. Light microscopy and ultrastructure of the kidneys were examined and apoptosis in proximal tubules was evaluated by the in situ TdT-mediated nick end labeling technique. TCS-treated rats demonstrated a significant dose-dependent decrease in creatinine clearance together with a mild degree of low-molecular-weight proteinuria. The proximal convoluted tubule was the site of lesions showing individual tubular cell death, which was more abundant in rats receiving high doses of TCS. Apoptotic cell death, together with heterophagosomes and large residual bodies, was observed. DNA fragmentation was confirmed by the in situ technique. There was also a dose-dependent density of apoptotic cells. Other portions of the nephron were spared, and it was not accompanied by any inflammatory infiltrate. In conclusion, these findings are consistent with TCS-induced proximal tubular toxicity resulting in reduction of glomerular filtration rate and tubular proteinuria. The extent of injury is dosage dependent. Both necrotic cell death and apoptosis participated in the loss of cells from the proximal tubules. Such toxicity may be mediated through intracellular events induced by trichosanthin.
Exp Mol Pathol 1997 Apr
PMID:Acute renal failure and proximal tubule lesions after trichosanthin injection in rats. 931 86

Oxygen-derived free radical injury has been associated with several cytopathic conditions. Oxygen radicals produced by chondrocytes is an important mechanism by which chondrocytes induce matrix degradation. In the present study, we extend these observations by studying oxidative processes against osteoblasts. Osteoblasts were mixed in in vitro culture with 200 microM menadione. The cytotoxic effect of menadione-induced oxidative stress was monitored by lucigenin- or luminol-amplified chemiluminescence, tetrazolium assay and immunocytochemical study. Results showed that adding menadione induces an oxidative stress on osteoblasts, via superoxide and hydrogen peroxide production, that can be eradicated by superoxide dismutase (SOD) and catalase in a dose-dependent manner. Catalase and the appropriate concentration of dimethyl sulfoxide have a protective effect on cytotoxicity induced by menadione, whereas SOD does not. Menadione-treated osteoblasts have a strong affinity for annexin V, and the nuclei are strongly stained by TUNEL (TdT-mediated dUTP nick-end labelling). The results suggest that menadione-triggered production of reactive oxygen species leads to apoptosis of osteoblasts.
Cell Mol Life Sci 1997 Dec
PMID:Menadione-induced cytotoxicity to rat osteoblasts. 944 50

Inhaled nitric oxide (NO) is an important new therapeutic agent used to treat pulmonary arterial hypertension in a variety of disease states. However, the effects of NO on cells in the lung are uncertain. Previously, we have shown that NO gas depresses neutrophil oxidative cell function and increases neutrophil cell death. The purpose of this in vitro study was to determine the mechanism of neutrophil death. We hypothesized that NO hastened cell death by inducing apoptosis. To mimic the clinical environment of patients with respiratory failure, we also studied the effects of hyperoxia on neutrophil cell viability and apoptosis. Isolated human neutrophils were exposed to 80% O2 (O2), NO at 20 ppm in room air (NO/RA), 20 ppm NO blended with 80% O2 (NO/O2), or RA alone (control) for 2 to 24 h. Experiments were repeated with NO concentrations of 5 and 50 ppm and with 20 ppm in the presence of superoxide dismutase (SOD). Neutrophils were also incubated in the absence or presence of neutrophil stimulant fMLP (10 nM). Neutrophil cell viability was measured by fluorescence viability/cytotoxicity assay. Neutrophil apoptosis was assessed by cell death detection ELISA for histone-associated DNA fragments, TdT transferase-mediated fluorescence-labeled dUTP nick end labeling (TUNEL) assay, and DNA fragmentation gel electrophoresis. NO/O2-exposed neutrophils showed decreased viability at 2 h (31.7 +/- 3.7%, mean % viability +/- SD) compared with control (94.7 +/- 4.7%), O2 (75.6 +/- 9.3%), and NO/RA (62.8 +/- 14.9%; P < 0.05 by ANOVA; n = 9). Although control neutrophils demonstrated marked apoptosis at 24 h, there was no significant apoptosis at 2, 4, or 6 h (P < 0.001 by Kruskal-Wallis, n = 20) as assessed by ELISA and TUNEL assays. When compared with RA controls at 2 h, neutrophils exposed to NO/O2 showed significantly more apoptosis (292% of control, range: 106 to 2,488%, P < 0.001 by ANOVA and Kruskal-Wallis) but not with exposure to NO/RA or O2 alone. These findings were confirmed by TUNEL assay (n = 4, P < 0.05). NO/ RA and NO/O2-exposed neutrophils demonstrated both evidence of necrosis and enhanced DNA fragmentation at 2 h by gel electrophoresis (n = 2). Fifty parts per million NO produced similar findings, but exposure to 5 ppm NO did not induce significant DNA fragmentation. Coincubation with SOD inhibited NO/ O2-associated apoptosis, suggesting peroxynitrite contributed to cell death. Stimulation with fMLP did not alter apoptosis induced in neutrophils exposed to NO/RA or NO/O2. We conclude that exogenous NO gas, at clinically relevant concentrations under hyperoxic conditions, induces cell death in neutrophils in part by enhancing DNA fragmentation.
Am J Respir Cell Mol Biol 1998 Mar
PMID:Exogenous nitric oxide enhances neutrophil cell death and DNA fragmentation. 949 Jun 60

We show that several transcriptionally inactive genes localize to centromeric heterochromatin in the nucleus of cycling but not quiescent (noncycling) primary B lymphocytes. In quiescent cells, centromeric repositioning of inactive loci was induced after mitogenic stimulation. A dynamic repositioning of selected genes was also observed in developing T cells. Rag and TdT loci were shown to relocate to centromeric domains following heritable gene silencing in primary CD4+8+ thymocytes, but not in a phenotypically similar cell line in which silencing occurred but was not heritable. Collectively, these data indicate that the spatial organization of genes in cycling and noncycling lymphocytes is different and that locus repositioning may be a feature of heritable gene silencing.
Mol Cell 1999 Feb
PMID:Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. 1007 3

Non-obstructive azoospermia accounts for a considerable proportion of male factor infertility. Current therapies for treatment of this kind of infertility include procedures such as intracytoplasmic sperm injection (ICSI), round spermatid injection (ROSI), round spermatid nucleus injection (ROSNI) and elongated spermatid injection (ELSI). All involve injection of haploid germ cells retrieved from testicular biopsies into recipient oocytes. We have investigated a mouse model of azoospermia for quality of haploid germ cell genomes, based on 4,6-diamidino-2-phenylindole (DAPI)/TdT-mediated dUTP nick-end labelling (TUNEL) labelling. The mouse model, a targeted mutation in the protein phosphatase 1cg gene, results in severe depletion of haploid germ cells from the round spermatid stage on. Mice homozygous for the mutation are completely infertile, and produce only the occasional spermatozoon. Spermatozoa and round spermatids retrieved from either the epididymides or the testes of mutant mice displayed very high rates of DNA fragmentation. In contrast, similar cells retrieved from heterozygous or wild-type littermates displayed low levels of DNA fragmentation. In some cases, the high rates of DNA fragmentation in mutant cells could be lowered by inclusion of antioxidants in the retrieval media. High rates of DNA fragmentation were also observed in round spermatids retrieved from testicular biospies of human patients with non-obstructive azoospermia. These results suggest that one of the features of the pathology associated with azoospermia is fragmented DNA in haploid germ cells. This raises questions about the suitability of using these cells for fertility treatment.
Mol Hum Reprod 1999 Apr
PMID:DNA damage in round spermatids of mice with a targeted disruption of the Pp1cgamma gene and in testicular biopsies of patients with non-obstructive azoospermia. 1032 3


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