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Biomedical subjects

A Seth

Publications and source records attributed to A Seth.

At least 145 records · Page 8Linked to original sources
PubMed1994

Management of urinary tract calculi by extracorporeal shock wave lithotripsy.

From July 1989 to April 1993, Extracorporeal Shockwave Lithotripsy (ESWL) was performed on 642 patients, of which 21 were from the pediatric age group. All treatments were done on a second generation lithotriptor-Siemens Lithostar, which does not require any modification for positioning of children. Fragmentation was achieved in all the patients (100%). A complete stone free rate was achieved in 17/21 patients (80.9%). Three (14.3%) patients had insignificant residual fragments whereas 1 (4.8%) had a residual fragment approximately 4 mm in size. 5640 shocks were required on an average. We have used low energy shockwaves with good results. General anesthesia was required for lithotripsy in only one child. The average fluoro exposure time was 1.6 minutes. We conclude that ESWL is a safe and effective method for treating urinary tract calculi in children.

Adolescent↗
PubMed1994

Ureteral obstruction following acute pancreatitis.

A patient with hydronephrosis caused by extrinsic right ureteral obstruction due to extension of pancreatic inflammation is reported. At surgery, pyonephrosis was detected and nephrectomy had to be carried out. We recommend a careful ultrasonographic follow-up of all patients with acute pancreatitis for back pressure changes in the kidneys.

Acute Disease↗
PubMed1993

Double-negative T cells from MRL-lpr/lpr mice mediate cytolytic activity when triggered through adhesion molecules and constitutively express perforin gene.

The lpr gene induces in mice, accumulation of large numbers of CD4-CD8- (double negative [DN]) T lymphocytes which bear adhesion molecules not characteristic of normal resting T cells. These cells fail to acquire interleukin 2 (IL-2) receptors, produce IL-2, and proliferate when activated with mitogens or monoclonal antibodies (mAbs) against the T cell receptor (TCR). Because of these poor functions in vitro, the nature and significance of DN T cells in the autoimmune disease process is not clear. In the current study, we describe a surprising finding that mAbs against CD3-TCR-alpha/beta complex can strongly trigger the lytic activity of the DN T cells to induce redirected lysis of Fc receptor-positive targets. Similar redirected lysis was also inducible using mAbs against CD44 and gp90MEL-14, molecules involved in the binding of lymphocytes to endothelial cells. The spontaneous cytotoxic potential of the DN T cells was further corroborated by demonstrating that the lpr DN T cells constitutively transcribed perforin gene but failed to express granzyme A. The current study suggests that DN T cells are capable of mediating lysis of autologous cells bearing the specific ligands for adhesion molecules involved in the signaling of cytotoxicity. These findings provide a novel insight into the functional significance of DN T cells in lpr mice and their potential role in the pathogenesis of autoimmune disease.

Animals↗
PubMed1993

The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation.

The Ets family of genes encodes a class of transcription factors. Ets1 is predominantly expressed in the lymphoid organs of neonatal and adult mice, whereas Ets2 is expressed in every organ examined. In this study, we investigate the expression of Ets1 and Ets2 during murine embryonic development. Our data show that Ets1 expression increases in embryos after implantation and during organogenesis such that it is expressed in all the organs of day-15 embryos studied. In later fetal stages, Ets1 expression is predominant in the lymphoid tissues, brain, and organs that are undergoing branching morphogenesis (e.g., lung) but is dramatically reduced in other organs such as the stomach and intestine. In neonatal development, Ets1 is expressed only in the lymphoid organs and brain. In situ hybridization analysis demonstrates that expression of Ets1 occurs in mesenchymal cells of developing organs, in the nervous system, and in forming bone. Furthermore, expression of Ets1 is upregulated in P19 cells induced to differentiate into mesoderm-like cells. Ets2, on the other hand, is expressed in differentiated and undifferentiated P19 and F9 cells and in all organs of embryonic, neonatal, and adult mice studied. These data suggest that Ets1 plays an important role in mesodermal cells associated with morphogenetic processes such as organ formation and tissue modeling, whereas Ets2 plays a more fundamental role in cells.

Animals↗
PubMed1993

Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62.

The product of the human c-myc protooncogene (Myc) is a sequence-specific DNA binding protein. Here, we demonstrate that the placement of the specific Myc DNA binding site CACGTG upstream of a luciferase reporter gene conferred Myc-stimulated expression that was inhibited by the overexpression of the basic-helix-loop-helix/leucine zipper protein Max. It was observed that Myc was phosphorylated in vivo within the NH2-terminal domain at Thr-58 and Ser-62. Replacement of these phosphorylation sites with Ala residues caused a marked decrease in Myc-stimulated reporter gene expression. In contrast, the replacement of Thr-58 or Ser-62 with an acidic residue (Glu) caused only a small inhibition of transactivation. Together, these data demonstrate that the NH2-terminal phosphorylation sites Thr-58 and Ser-62 are required for high levels of transactivation of gene expression by Myc.

Amino Acid Sequence↗
PubMed1993

cPLA2 is phosphorylated and activated by MAP kinase.

Treatment of cells with agents that stimulate the release of arachidonic acid causes increased serine phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). Here we report that cPLA2 is a substrate for mitogen-activated protein (MAP) kinase. Moreover, phosphorylation by MAP kinase increases the enzymatic activity of cPLA2. The site of cPLA2 phosphorylation by MAP kinase, Ser-505, is identical to the major site of cPLA2 phosphorylation observed in phorbol ester-treated cells. Replacement of Ser-505 with Ala resulted in a mutant cPLA2 that is not a substrate for MAP kinase and causes little or no enhanced agonist-stimulated arachidonate release from intact cells. Taken together, these data indicate that MAP kinase mediates, at least in part, the agonist-induced activation of cPLA2.

Amino Acid Sequence↗
PubMed1993

Successful aortic balloon valvuloplasty in critical aortic stenosis with shock.

Emergency balloon valvuloplasty was performed in a 42 year old male with critical aortic stenosis, severe congestive heart failure, and shock. Hemodynamic and clinical improvement occurred and he underwent elective aortic valve replacement. Balloon aortic valvuloplasty may provide a "bridge" to aortic valve replacement in patients with critical aortic stenosis and shock.

Adult↗
PubMed1993

Clinical and coronary arteriographic features and outcome of recent onset unstable angina.

Fifty consecutive patients (43 male and seven female; mean age 51.8 years) with recent onset angina (24.6% of all admissions for unstable angina during a 1-year period) underwent coronary arteriography. Most patients (96.8%) presented with severe angina (Canadian Cardiovascular Society Class III-IV) with admission ECG changes of myocardial ischemia in 46%. Echocardiography (within 2 days of admission) showed normal left ventricular function (LVEF > 50%) in 80% and mild or moderate impairment (LVEF 35-49%) in 12% of patients. Segmental wall motion abnormalities were noted in a small number (12.9%). Coronary angiography revealed significant (> or = 70% diameter stenosis) disease in one vessel in 14 (28%), in two vessels in seven (14%), three vessels in 22 (44%) and no disease in seven (14%) patients. Significant left main stenosis (> or = 50% diameter stenosis) was present in two (5%) patients. Left anterior descending artery was more commonly involved (66%) as compared to the other arteries. A significantly higher incidence of multivessel disease was observed in patients with diabetes mellitus (P < 0.003) and in smokers (P < 0.04). Multiple coronary artery involvement was more common in patients with three or more risk factors for coronary artery disease (P < 0.005). In-hospital non fatal myocardial infarction occurred in three (6%) patients. During follow-up (average 13 +/- 1.28 months) 30 (60%) patients underwent coronary artery bypass surgery, 13 (26%) required coronary angioplasty while seven (14%) were managed by drugs alone with no further mortality and significant symptomatic relief. Patients with recent onset angina, in our setting, frequently have severe multiple vessel coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus.

The mitogen-activated protein (MAP) kinase signal transduction pathway represents an important mechanism by which growth factors regulate cell function. Targets of the MAP kinase pathway are located within several cellular compartments. Signal transduction therefore requires the localization of MAP kinase in each sub-cellular compartment that contains physiologically relevant substrates. Here, we show that serum treatment causes the translocation of two human MAP kinase isoforms, p40mapk and p41mapk, from the cytosol into the nucleus. In addition, we report that p41mapk (but not p40mapk) is localized at the cell surface ruffling membrane in serum-treated cells. To investigate whether the protein kinase activity of MAP kinase is required for serum-induced redistribution within the cell, we constructed mutated kinase-negative forms of p40mapk and p41mapk. The kinase-negative MAP kinases were not observed to localize to the cell surface ruffling membrane. In contrast, the kinase-negative MAP kinases were observed to be translocated to the nucleus. Intrinsic MAP kinase activity is therefore required only for localization at the cell surface and is not required for transport into the nucleus. Together, these data demonstrate that the pattern of serum-induced redistribution of p40mapk is different from p41mapk. Thus, in addition to common targets of signal transduction, it is possible that these MAP kinase isoforms may differentially regulate targets located in distinct sub-cellular compartments.

Amino Acid Sequence↗
PubMed1993

ETS family proteins activate transcription from HIV-1 long terminal repeat.

ets is a multigene family and its members share a common ETS DNA-binding domain. ETS proteins activate transcription via binding to a purine-rich GGAA core sequence located in promoters/enhancers of various genes, including several that are transcriptionally active in T cells. The ETS1, ETS2, and ERBG/Hu-FLI-1 gene expression pattern also suggests a role for these genes in cells of hematopoietic lineage. The HIV-1 LTR core enhancer contains two 10-base pair direct repeat sequences (left and right) that are required for regulation of HIV-1 mRNA expression by host transcription factors, including NF kappa B. Two ETS-binding sites are present in the core enhancer of all the HIV-1 isolates reported so far. In our studies, we utilized HIV-1 HXB2 and HIV-1 Z2Z6 core enhancers because the Z2Z6 strain has a single point mutation flanking the right ETS-binding site. We demonstrate that the ETS1, ETS2, and ERGB/Hu-FLI-1 proteins can trans-activate transcription from both the HXB2 and Z2Z6 core enhancer when linked to a reporter (cat) gene. In addition, we show that the DNA binding and trans-activation with the Z2Z6 core enhancer is at least 40-fold higher than that observed with the HXB2 core enhancer. Further, we provide evidence that the marked increase in binding and trans-activation with Z2Z6 core enhancer sequences is due to the substitution of a flanking T residue in HXB2 TGGAA) by a C residue in Z2Z6 (CGGAA) isolate, thus generating an optimal ETS-binding core (CGGAA) sequence.

Animals↗
PubMed1993

Cell cycle regulation of the c-Myc transcriptional activation domain.

The product of the c-myc gene (c-Myc) is a sequence-specific DNA-binding protein that has previously been demonstrated to be required for cell cycle progression. Here we report that the c-Myc DNA binding site confers cell cycle regulation to a reporter gene in Chinese hamster ovary cells. The observed transactivation was biphasic with a small increase in G1 and a marked increase during the S-to-G2/M transition of the cell cycle. This cell cycle regulation of transactivation potential is accounted for, in part, by regulatory phosphorylation of the c-Myc transactivation domain. Together, these data demonstrate that c-Myc may have an important role in the progression of cells through both the G1 and G2 phases of the cell cycle.

Animals↗
PubMed1993

Day care urology in a hospital based setting.

From January 1, 1991 to December 31, 1992, 3078 operations were performed on day care basis and 1185 operations on in-patient basis. Surgery performed on day care basis included ureteric stone basketing, ureteroenoscopic stone retrieval, JJ stenting, cystolithotripsy, TUR-BT, TUR-P and internal urethrotomy. Failure of complication rate was 0.97%. Most of the complications (26/29) could be detected early and managed by conversion of short admission into a regular one. Only 3 patients (0.1%) were admitted later on through the emergency. There was no mortality. In conclusion, we recommend urologic operative procedures on carefully selected patients on day-care basis to achieve two of the government's primary goals a) the provision of high quality services and b) the reduction of health care costs. Simultaneously a word of caution that it is unique challenge to be handled with care.

Adult↗
PubMed1993

Transactivation of GATA-1 promoter with ETS1, ETS2 and ERGB/Hu-FLI-1 proteins: stabilization of the ETS1 protein binding on GATA-1 promoter sequences by monoclonal antibody.

Ets family proteins activate transcription via binding to the GGAA core sequence located in the promoter/enhancer elements of many cellular and viral genes. GATA-1 is an erythroid-specific transcription factor. The promoter of the chicken GATA-1 gene contains multiple ets binding sites (EBS), two of them are present in palindromic form. The GATA-1 promoter has been shown to be activated by the E26 virus. In this study, we have analysed whether the palidromic EBS of the chicken GATA-1 promoter is a target for binding and activation by members of the cellular ets gene family products. The results herein indicate that both EBS in the palindrome are required for DNA-binding because mutations in either site reduces the activity by at least 95%. Moreover, DNA binding of ETS1 to the EBS palindrome is dramatically stabilized in the presence of a specific monoclonal antibody whose epitope maps between amino acid positions 240-260. Although each of the single sites bind, the efficiency of binding is extremely low. Furthermore, for efficient binding the two sites must be in an inverted configuration because of the fact that the oligonucleotide containing the left and right EBS in the same orientation binds 10-fold less than the oligonucleotide containing the EBS palindrome. Additionally, we show that the transcription of a reporter gene (CAT) either linked to the GATA-1 EBS palindrome or GATA-1 promoter can be activated by cotransfection with ETS1, alternatively-spliced ETS1, ETS2 or ERGB/Hu-FLI-1 expression vectors.

Animals↗
PubMed1992

Signal transduction within the nucleus by mitogen-activated protein kinase.

The nucleus is an important target of signal transduction by growth factor receptors that stimulate mitogen-activated protein (MAP) kinases. We tested the hypothesis that MAP kinases have a signaling role within the nucleus by examining the effect of the expression of a human MAP kinase isoform (p41mapk) in tissue culture cells. The expressed p41mapk was found to be localized in both the cytoplasmic and nuclear compartments of the cells. Significantly, the expression of p41mapk caused an increase in the phosphorylation of a nuclear substrate: Ser62 of c-Myc. Phosphorylation at Ser62 stimulated the activity of the NH2-terminal transactivation domain of c-Myc. Thus, p41mapk causes the phosphorylation and regulation of a physiologically significant nuclear target of signal transduction. These data establish that at least one MAP kinase isoform has a nuclear role during signal transduction.

Amino Acid Sequence↗
PubMed1992

C-ets-1 protooncogene expression alters the growth properties of immortalized rat fibroblasts.

Ets family genes have been cloned and characterized from a variety of species ranging from human to Drosophila. The ets proteins encode transcription factors that activate transcription via specific binding to GGAA core sequence present in various promoter/enhancers. To investigate the role of ets protooncogene expression on the growth properties of rat embryo fibroblasts (REF), we constructed and introduced ets expression vectors into primary, as well as immortalized REF cells. The transfected cells contained multiple copies of the vector DNA, and the Northern blot analysis demonstrated overexpression of the c-ets-1-specific mRNA. Although the expression of the ets genes was unable to immortalize primary rat embryo fibroblasts, the expression of ets-1 in REF-1 cells enabled their growth in serum-free medium and effected tumorigenic activity in nude mice.

Animals↗
PubMed1992

The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors.

All cellular ets proteins contain a region of high amino acid identity to those found in the last two exons of the ets-1 gene (C domain). We have identified and characterized a new member of the human ETS gene family, ERGB. The ERGB gene shows extensive amino acid identity to the human ERG and the mouse Fli-1 genes. The ERGB gene is found to be transcriptionally active in a variety of human cell lines and tissues, in contrast to the more restrictive expression pattern of the ERG gene. The ERGB gene encodes for a 3.2-kilobase mRNA containing an open reading frame of 451 amino acids. The ERGB gene, like human ETS1, is located on chromosome 11 and is transposed to chromosome 4 as a result of the translocation t(4;11) associated with leukemia. Pulse-field gel analysis suggests that ETS1 and ERGB are more than 200 kilobases apart. Similar to the other members of the ets family (ets 1, ets 2), this new member is also able to trans-activate transcription of a reporter gene linked to the ETS-binding sequences derived from either the GATA-1 promoter or an optimal Ets-binding site.

Amino Acid Sequence↗
PubMed1991

A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression.

The c-myc gene encodes a sequence-specific DNA-binding protein (c-Myc) that forms leucine zipper complexes and can act as a transcription factor. Growth factor stimulation of cells causes the phosphorylation of the c-Myc transcriptional activation domain at Ser62 within a proline-rich region that is highly conserved among members of the Myc family (Alvarez, E., Northwood, I.C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) J. Biol. Chem. 266, 15277-15285). This phosphorylation site is a substrate for growth factor-regulated MAP kinases and for the cell cycle-dependent protein kinase p34cdc2. We report that serum treatment of cells results in a marked increase in the transactivation of gene expression mediated by the c-Myc transcriptional activation domain. A point mutation at the site of growth factor-stimulated phosphorylation (Ser62) decreases the serum induction of transactivation. These data indicate that the c-Myc transcriptional activation domain may be a direct target of signal transduction pathways.

Amino Acid Sequence↗