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M Shannon

Publications and source records attributed to M Shannon.

At least 55 records · Page 3Linked to original sources
PubMed1998

Analysis of homologous XRCC1-linked zinc-finger gene families in human and mouse: evidence for orthologous genes.

Genetic and physical mapping studies indicate that hundreds of zinc-finger (ZNF)-containing genes populate the human genome and that many of these genes are arranged in familial clusters. However, the extent to which these tandemly arrayed families are conserved among mammalian species is largely unknown. In a previous study, we identified a conserved cluster of Kruppel-associated box (KRAB)-containing ZNF genes located near the XRCC1 gene in human chromosome 19q13.2 and mouse chromosome 7 and analyzed two members of the murine gene family, Zfp93 and Zfp94, in detail. Here we report the identification and characterization of putative human orthologs of these murine genes. The human genes ZFP93 and ZNF45 are substantially similar to their murine counterparts in overall structure, but two notable differences exist between the sets of genes. First, the human genes encode more ZNF repeats than their murine counterparts. Second, the ZNF repeats that are common to orthologs exhibit varying degrees of conservation. Expression studies indicate that the human genes, like their mouse equivalents, are expressed widely and are coexpressed at similar levels in most adult tissues. These comparative gene sequence and expression studies therefore suggest that at least two members of the mammalian XRCC1-linked KRAB-ZNF gene family were elaborated prior to the divergence of primate and rodent lineages and were well conserved in human and mouse.

Adult↗
PubMed1998

CD1.1 expression by mouse antigen-presenting cells and marginal zone B cells.

Mouse CD1.1 is an MHC class I-like, non-MHC-encoded, surface glycoprotein that can be recognized by T cells, in particular NK1.1+ T cells, a subset of alphabeta T cells with semiinvariant TCRs that promptly releases potent cytokines such as IL-4 and IFN-gamma upon stimulation. To gain insight into the function of CD1.1, a panel of nine mAbs was generated and used to biochemically characterize and monitor the surface expression of CD1.1 on different cell types. CD1.1 is a heavily glycosylated, beta2-microglobulin-associated surface protein. Its recognition by a panel of 12 V alpha14-positive and -negative CD1-specific alphabeta T cell hybridomas was blocked by two groups of mAbs that bound to adjacent clusters of epitopes, indicating that different alphabeta TCRs bind to the same region of CD1.1, presumably above the groove. Remarkably, CD1.1 was mainly expressed by dendritic cells, B cells, and macrophages, suggesting a function in Ag presentation to Th cells. Furthermore, the cell type that expressed the highest levels of CD1.1 was the splenic marginal zone B cell, a distinct subset of B cells that also expresses CD21 (the C3d receptor) and may be involved in natural responses to bacterial Ags. Altogether, the results support the idea that CD1.1 may function in recruiting a form of innate help from specialized cytokine producer alphabeta T cells to APCs, a role that might be important at the preadaptive phase of immune responses to some microbial pathogens.

Animals↗
PubMed1998

Fixing mismatches.

Explore the source record for details and available documents.

Adenosine Triphosphatases↗
PubMed1998

H2O2 acts on cellular membranes to generate ceramide signaling and initiate apoptosis in tracheobronchial epithelial cells.

Hydrogen peroxide (H2O2) is an inflammatory oxidant which contributes to the pathogenesis of chronic diseases such as lung injury of the respiratory tract, atherosclerosis and cancer. The mechanisms and target sites of this reactive oxidant are mainly unknown. So far there are opposing reports as to whether reactive oxidants inhibit or promote apoptosis. We activated the death pathway in primary tracheobronchial epithelial (TBE) cells with H2O2 (20-200 microM) and observed the morphological changes, DNA laddering patterns, and DNA fragmentation associated with apoptosis. Elevation of ceramide with exogenous ceramide analogs was sufficient for apoptosis induction with the same characteristics and in the same time frame. H2O2 induced rapid sphingomyelin hydrolysis to ceramide, the elevation of which paralleled the induction of apoptosis. Furthermore, H2O2 acted directly on TBE cells membrane preparations devoid of nuclei, stimulating sphingomyelin hydrolysis through a neutral Mg2+ dependent sphingomyelinase (SMase). These data suggest that the formation of ceramide from sphingomyelin in the plasma membrane is a key event in H2O2-induced apoptosis in tracheobronchial epithelial cells.

Animals↗
PubMed1998

Lead poisoning from an unexpected source in a 4-month-old infant.

Childhood lead poisoning is characteristically a disease that occurs between the second and third years of life, generally resulting from the child's ingestion of lead-based paint or dust. However, lead poisoning may also appear in the first year of life. The case of a 4-month-old infant is reported in which the preparation of infant formula in a lead-soldered samovar (urn) resulted in venous blood lead levels as high as 46 microg/dl. The samovar had been brought into the United States by the parents while on a visit to Iran. The infant was placed on chelation therapy with parenteral CaNa2EDTA followed by oral meso-2,3-dimercaptosuccinic acid (DMSA) and d-penicillamine. This resulted in a rapid and substantial reduction in the blood lead level. Lead poisoning in infancy may have unusual etiologies such as in utero transmission of lead by lead-poisoned women. Because sources of lead poisoning in infancy may be unusual, a detailed environmental investigation may be necessary to identify the exact source. Children exposed to lead in the first 2 years of life have a special vulnerability to the neurotoxicity of lead, with the risk of enduring developmental handicaps. Continued public health initiatives to remove lead from the environment, in conjunction with routine lead screening of young children, will be key in meeting the goal of the Centers for Disease Control and Prevention to eliminate childhood lead poisoning by the year 2011.

Cooking and Eating Utensils↗
PubMed1998

Tandem zinc-finger gene families in mammals: insights and unanswered questions.

Evidence for the remarkable conservation of mammalian genomes, in both content and organization of resident genes, is rapidly emerging from comparative mapping studies. The frequent occurrence of familial gene clustering, presumably reflecting a history of tandem in situ duplications starting from a single ancestral gene, is also apparent from these analyses. Genes encoding Kruppel-type zinc-finger (ZNF) proteins, including those containing Kruppel-associated box (KRAB) motifs, are particularly prone to such clustered organization. Existing data suggest that genes in KRAB-ZNF gene clusters have diverged in sequence and expression patterns, possibly yielding families of proteins with distinct, yet related, functions. Comparative mapping studies indicate that at least some of the genes within these clusters in mammals were elaborated prior to the divergence of mammalian orders and, subsequently, have been conserved. These data suggest a possible role for these tandem KRAB-ZNF gene families in mammalian evolution.

Amino Acid Sequence↗
PubMed1997

EGF receptor phosphorylation is affected by ionizing radiation.

Eukaryotic cells respond to ionizing radiation with cell cycle arrest, activation of DNA repair mechanisms, and lethality. However, little is known about the molecular mechanisms that constitute these responses. Here we report that ionizing radiation enhances epidermal growth factor (EGF) receptor tyrosine phosphorylation in intact cells as well as in isolated membranes of A431 cells. Phosphoamino acid analysis revealed that ionizing radiation preferentially enhances tyrosine phosphorylation, while EGF enhances the phosphorylation of all three phosphoamino acids (serine, threonine and tyrosine) of the EGF receptor. In addition, radiation reduces the turnover rate of the EGF receptor, while EGF increases the rate of the receptor turnover and down-regulation. Moreover, the confined radiation-induced phosphorylation of tyrosine residues is inhibited by genistein, indicating that this phosphorylation of EGF receptor is due to protein tyrosine kinase activation. These studies provide novel insights into the capacity of radiation to modulate EGF receptor phosphorylation and function. The radiation-induced elevation in the EGF receptor tyrosine phosphorylation and the receptor's slower rate of turnover are discussed in terms of their possible role in cell growth and apoptosis modulation.

Adenosine Triphosphate↗
PubMed1997

Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation. The Flumazenil Pediatric Study Group.

OBJECTIVE: To determine the safety and efficacy of flumazenil when given for reversal of benzodiazepine-induced conscious sedation in children. DESIGN: Multicenter study conducted in emergency departments and pediatric endoscopy, bronchoscopy, or oncology suites. PATIENTS: One hundred seven children (median age, 6 years; range, 1 to 17 years) who received intravenous benzodiazepine for an invasive procedure. INTERVENTIONS: Flumazenil was given in increments of 0.01 mg/kg (0.2 mg maximum) at 1-minute intervals to a maximum total dose of 0.05 mg/kg (1.0 mg maximum). MEASUREMENTS: Clinical efficacy was assessed by the Clinical Global Impression Scale and Observer's Assessment of Alertness/Sedation Scale. The OAA/S, vital signs, lead II electrocardiogram, and clinical assessments were recorded at 0, 10, 30, 60, 90, and 120 minutes after flumazenil was given. RESULTS: All children received midazolam (mean total dose, 0.18 mg/kg) for sedation. One hundred (96%) patients achieved a complete or partial response to flumazenil by 10 minutes after its administration, on the basis of their CGIS scores (the mean dose of flumazenil administered at the time of the first complete response was 0.017 +/- 0.010 mg/kg). Seventy-one of 93 (76%) patients with a baseline OAA/S score < or = 3 (1 = deep sleep, 5 = alert) experienced an increase of > or = 2 points at 10 minutes after flumazenil administration, and 81 of 93 (87%) had a score of 4 or 5 after flumazenil administration. Seven patients, all within the 1- to 5-year age range, experienced resedation after initially responding to flumazenil. Thirty-seven of 107 patients (35%) experienced a total of 56 adverse events, most of which were considered to be unrelated to flumazenil administration. The most frequently occurring adverse events were abnormal crying, dizziness, nausea, fever, and headache. There were no clinically significant changes in vital signs or ECG tracings. No adverse events resulted in premature termination of drug administration. CONCLUSIONS: Flumazenil promptly and effectively reverses the central nervous system depressant effects of midazolam in children undergoing conscious sedation, with no significant adverse effects. Because of the potential for resedation, children who receive flumazenil should be monitored for 1 to 2 hours after its administration.

Adolescent↗