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Biomedical subjects

M Shannon

Publications and source records attributed to M Shannon.

At least 73 records · Page 4Linked to original sources
PubMed1996

The effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation.

What determines the degree of cell-resistance or sensitivity to ionizing radiation is not yet known. As a corollary to the ability of ceramide to induce apoptosis, some questions arise as to whether malignant cells escape apoptosis because of their inability to mount a ceramide response to inducers of apoptosis. To shed more light on the molecular mechanisms of tumor cell response to radiation, we tested whether exposure to ionizing radiation (of 200-1000 cGy) is associated with changes in ceramide levels in A431 tumor epithelial cells and whether the ability of ceramide to induce apoptosis is inhibited by protein kinase C (PKC) activation. Our studies demonstrate an immediate decrease in cellular levels of ceramide in response to radiation, while sphingosine levels increase. Under the same conditions the cellular 1,2-diacylglycerol (DAG) levels decrease as well, being accompanied by the translocation of PKC alpha from the membrane to the cytoplasm. Elevation of membrane PKC levels by 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment had no effect on cell survival after irradiation, while treatment with EGF during and after irradiation augmented cell survival. Moreover, monoclonal antibodies to the EGF receptor (EGFR) sensitize cells to radiation by facilitating radiation-induced apoptosis. It is thus plausible that in human Squamous carcinoma cells, radiation activates predominantly the EGFR to induce resistance, while both sphingomyelin and PKC signal transduction pathways are deactivated and demonstrate no significant role in the modulation of the sensitivity or the resistance of A431 cells to ionizing radiation.

Antibodies↗
PubMed1996

Comparative analysis of a conserved zinc finger gene cluster on human chromosome 19q and mouse chromosome 7.

Several lines of evidence now suggest that many of the zinc-finger-containing (ZNF) genes in the human genome are arranged in clusters. However, little is known about the structure or function of the clusters or about their conservation throughout evolution. Here, we report the analysis of a conserved ZNF gene cluster located in human chromosome 19q13.2 and mouse chromosome 7. Our results indicate that the human cluster consists of at least 10 related Kruppel-associated box (KRAB)-containing ZNF genes organized in tandem over a distance of 350-450 kb. Two cDNA clones representing genes in the murine cluster have been studied in detail. The KRAB A domains of these genes are nearly identical and are highly similar to human 19q13.2-derived KRAB sequences, but DNA-binding ZNF domains and other portions of the genes differ considerably. The two murine genes display distinct expression patterns, but are coexpressed in some adult tissues. These studies pave the way for a systematic analysis of the evolution of structure and function of genes within the numerous clustered ZNF families located on human chromosome 19 and elsewhere in the human and mouse genomes.

Amino Acid Sequence↗
PubMed1996

Mouse ret finger protein (rfp) proto-oncogene is expressed at specific stages of mouse spermatogenesis.

Many proteins involved in the regulation of cell growth and differentiation possess structural motifs that participate in specific molecular interactions. The human rfp (ret finger protein) has a tripartite motif, consisting of two novel zinc fingers (the RING linger and the B box) and a coiled-coil domain, and belongs to the B box zinc finger protein family. Rfp becomes oncogenic when its tripartite motif is recombined with the tyrosine kinase domain from the c-ret proto-oncogene. To further understand the function of rfp during normal development and cellular differentiation, we cloned the mouse rfp cDNA and analyzed its pattern of expression and subcellular distribution. We found that the mouse rfp cDNA shared a 98.4% homology with the human sequence. The gene mapped to human chromosome 6 and mouse chromosome 13 indicating that it was linked to a several other genes encoding proteins that possess common domains. rfp transcripts and protein were ubiquitous in day 10.5-13.5 mouse embryos, however, they were restricted in adult mice, with the highest level of expression in pachytene spermatocytes and round spermatids of differentiating sperm. The rfp protein was detected within cell nuclei as nuclear bodies similar to the PODs (PML oncogenic domains) observed with another B box family member, PML (promyelocytic leukemia protein). These results suggest that rfp may function in the regulation of cell growth and differentiation during mouse embryogenesis and sperm differentiation.

Amino Acid Sequence↗
PubMed1996

Lead intoxication in children with pervasive developmental disorders.

OBJECTIVE: To investigate the observation that children with pervasive developmental disorders have later and more prolonged lead exposure and are more likely to be reexposed when compared to lead-poisoned children without pervasive developmental disorders. DESIGN: Retrospective chart review. SETTING: A large, urban lead treatment program. RESULTS: Over a six year period 17 children with pervasive developmental disorders (including autism) were treated. Compared to a randomly selected group of 30 children without pervasive developmental disorders who were treated for plumbism over the sam interval, those with pervasive developmental delay were significantly older at diagnosis (46.5 vs 30.3 months, p = .03) and had a longer period of elevated blood lead levels (39.1 vs 14.1 months, p = .013) during management. Despite close monitoring, state-mandated environmental inspection and prompt lead hazard reduction or alternative housing, 75% of children with pervasive developmental disorders were reexposed to lead during medical management compared with 23% of children without pervasive developmental disorders (p = .001). CONCLUSIONS: 1) lead intoxication among children with pervasive developmental disorders may appear de novo beyond the third year of life and is associated with a high rate of reexposure; 2) the provision of deleaded housing (by current techniques) may not be sufficient to protect these children from repeated lead exposure; 3) these data support recommendations by the Centers for Disease Control that children with developmental delays be closely monitored for the appearance of lead intoxication. This monitoring should continue beyond the third year of life.

Chelating Agents↗
PubMed1995

Anticonvulsant effects of intracerebroventricular adenocard in theophylline-induced seizures.

STUDY OBJECTIVE: To evaluate the potential anticonvulsant effects of Adenocard in theophylline-induced seizures, we developed a rodent model of theophylline neurotoxicity with resultant convulsions. We used this model to investigate the actions of intracerebroventricular (ICV) Adenocard on seizure onset. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTIONS: Surgical cannulation of the jugular veins of the rats was followed by stereotaxic placement of a catheter in the right lateral ventricle. The rats then received 15 micrograms (5 microL) ICV Adenocard or an equivalent. Ten seconds later, continuous infusion of IV aminophylline was begun at a rate of 75 mg/minute until the appearance of generalized convulsions with maximal hindlimb extension. RESULTS: Compared with vehicle-injected controls, rats that received ICV Adenocard had a significant delay in mean time to seizure (162.1 seconds versus 107.4 seconds; P < .001). There was a corresponding increase in the weight-adjusted convulsant dose of aminophylline after the ICV administration of Adenocard (311.4 mg/kg versus 470.4 mg/kg; P < .003). CONCLUSION: Our data indicate that ICV Adenocard ameliorates theophylline-induced seizures. Potential anticonvulsant benefits of Adenocard and other adenosinergic compounds for victims of severe theophylline poisoning should be investigated further.

Adenosine↗
PubMed1995

Environmental toxins: cutting the risks.

From pesticides to PCBs, the chemical residues of modern life are all around us--and children are at high risk of harm. The authors describe some of the major culprits and suggest ways to reduce your patients' exposure.

Child↗
PubMed1994

Efficacy of oral meso-2,3-dimercaptosuccinic acid therapy for low-level childhood plumbism.

OBJECTIVE: To compare the response to oral meso-2,3-dimercaptosuccinic acid (DMSA) treatment in children with an initial blood lead (BPb) concentration less than versus more than 2.17 mumol/L (45 micrograms/dl). DESIGN: Retrospective cohort study. SETTING: Regional referral lead treatment program in an urban children's hospital. PATIENTS: Thirty consecutive children, median age 34 months (range, 5 to 161 months), with an initial BPb concentration 0.97 to 2.90 mumol/L (20 to 60 micrograms/dl) selected for DMSA use. Reasons for DMSA use included BPb concentration > 2.17 mumol/L (11 children), complications with penicillamine therapy (11), chronic renal failure (1), and compassionate use (7). All patients received required environmental hazard reductions before drug administration. RESULTS: Group 1 (n = 23) had a mean BPb concentration of 1.50 mumol/L (31 micrograms/dl), and group 2 (n = 7) had a mean BPb concentration of 2.41 (51 micrograms/dl). Sixteen patients (70%) in group 1 and five patients (71%) in group 2 had had previous chelation therapy (p value not significant). No significant difference was found in the mean percentage of the reduction of BPb concentration during treatment of group 1 (60%) versus group 2 (58%). The mean BPb concentration in group 1 rebounded to 70% of pretreatment values by mean day 41; the BPb concentration in group 2 rebounded to 69% by day 37 (p value not significant). Prior chelation therapy did not result in a significant difference in either the percentage reduction of BPb concentration or the percentage of rebound BPb. CONCLUSION: DMSA is equally effective in acutely lowering BPb concentration in children with BPb concentrations less than and greater than 2.17 mumol/L.

Adolescent↗
PubMed1994

Efficacy of magnesium citrate cathartic in pediatric toxic ingestions.

STUDY OBJECTIVE: To investigate the efficacy of magnesium citrate in reducing gastrointestinal transit time of activated charcoal in children. DESIGN: A prospective, randomized, clinical comparison of four magnesium doses. SETTING: Urban children's hospital emergency department. PARTICIPANTS: Children aged 1 month to 6 years who presented for management of an acute toxic ingestion. INTERVENTION: Each child received 1 g/kg activated charcoal combined with a randomly assigned dose of a 6% solution of magnesium citrate: 0 mL/kg, 4 mL/kg (standard recommended dose), 6 mL/kg, or 8 mL/kg. The primary outcome measure was the interval to first activated charcoal-containing stool, which was determined by follow-up telephone call or review of the medical record. RESULTS: Sixty-four children were enrolled. Median times to first charcoal stool were 19.5 hours (0 mL/kg), 13.0 hours (4 mL/kg), 14.0 hours (6 mL/kg), and 12.0 hours (8 mL/kg). Intergroup differences were significant by Kruskal-Wallis analysis of variance (P = .0035). CONCLUSION: Magnesium citrate reduces gastrointestinal transit times of activated charcoal stools when administered to children who receive activated charcoal for a toxic ingestion. Further study is needed to determine the clinical value of this reduction.

Antacids↗
PubMed1994

Clinical issues and therapeutic interventions in the care of pregnant women infected with the human immunodeficiency virus.

As the incidence of human immunodeficiency virus (HIV) infection increases in women of reproductive age in the United States, clinical issues and therapeutic interventions specifically addressing the needs of HIV-positive pregnant women will continue to evolve and be incorporated into their obstetric care. This article provides perinatal nurse clinicians with an overview to the epidemiology and clinical manifestations of HIV infection in pregnant women, as well as the therapeutic modalities and psychosocial components included in their plan of care. Data regarding perinatal transmission rates and maternal factors possibly facilitating vertical transmission are also presented.

Female↗
PubMed1994

Hypokalemia, hyperglycemia and plasma catecholamine activity after severe theophylline intoxication.

To determine if differences in the rate of hypokalemia and hyperglycemia between victims of acute versus chronic theophylline intoxication relate to alterations in plasma catecholamine activity, we evaluated plasma catechols in three groups of patients: victims of acute theophylline intoxication (n = 10), chronic theophylline overmedication (n = 3), and healthy controls (n = 6). There were no differences in peak serum theophylline concentration between acute and chronic groups (86.6 vs 73.0 mcg/mL, p = NS). Among those with acute intoxication mean (+/- SEM) serum potassium was 2.80 +/- .16 mEq/L while mean serum glucose was 208 +/- 26 mg/dL. In contrast, those with chronic intoxication had a mean serum potassium of 4.10 +/- .70 mEq/L with a mean serum glucose of 139 mg/dL (p < .0001 and p < .04 for between-group potassium and glucose, respectively). Potassium and glucose concentrations of those with chronic theophylline intoxication were similar to those of controls. Plasma epinephrine was higher in those with acute theophylline intoxication than in victims of chronic overmedication and controls (282 vs 133 vs 58 pg/mL, p < .003). Plasma norepinephrine and dopamine in contrast were significantly higher in those with chronic overmedication than in those with acute intoxication and controls (norepinephrine 1395 vs 965 vs 268 pg/mL, p < .008; dopamine 198 vs 148 vs 39 pg/mL, p < .009). These data suggest that the pattern of glucose and potassium disturbances after acute theophylline intoxication parallel differences in plasma epinephrine concentrations. This supports theories that hypokalemia is the result of enhanced beta-2 receptor stimulation.

Adolescent↗
PubMed1993

Predictors of major toxicity after theophylline overdose.

OBJECTIVE: To identify patients at high risk for major toxicity after theophylline intoxication who might benefit from early charcoal hemoperfusion. DESIGN: A 67-month prospective study. SETTING: Massachusetts Poison Control System. PATIENTS: 249 consecutive patients referred after theophylline intoxication (defined by a peak serum theophylline concentration > or = 167 mumol/L [30 mg/L]). INTERVENTIONS: Uniform, protocol-directed management recommendations. MAIN OUTCOME MEASURES: Identification of risk factors for major toxicity. RESULTS: 119 patients (48%) not receiving theophylline therapy had acute intoxication; among those receiving such therapy, 92 (37%) had theophylline intoxication because of chronic overmedication and 38 (15%) had acute intoxication. Major toxicity developed in 62 patients (25%); 13 patients (5%) died. Major toxicity was more common in patients with intoxication due to chronic overmedication than in those with acute intoxication who were not receiving theophylline therapy (49% compared with 10%, risk ratio, 4.85; 95% CI, 2.96 to 7.94), even though the former group had lower peak serum theophylline concentrations (283 mumol/L compared with 777 mumol/L, P = 0.001). Logistic regression analysis identified two major factors associated with the development of major toxicity: 1) peak serum theophylline concentrations in cases of acute intoxication and 2) patient age in cases of chronic overmedication. Receiver-operating characteristic curve analysis indicated that major toxicity occurred in patients with a peak serum theophylline concentration of greater than 555 mumol/L (100 mg/L) after acute intoxication and in patients older than 60 years (regardless of peak serum theophylline concentration) after chronic overmedication. CONCLUSIONS: Predictors for major toxicity after theophylline intoxication differ by type of overdose.

Acute Disease↗
PubMed1993

Expression of the Hprt gene during spermatogenesis: implications for sex-chromosome inactivation.

The goal of this study was to determine the developmental pattern of expression of the X-linked gene for hypoxanthine phosphoribosyltransferase (Hprt) during spermatogenesis and the relevance of this expression to X-chromosome inactivation during meiotic prophase. The results demonstrated that HPRT activity is maintained in mouse spermatogenic cells throughout development in spite of X-chromosome inactivation; however, specific activities of HPRT in meiotic and postmeiotic germ cells were significantly lower than in premeiotic ones. Maintenance of Hprt transcripts at all stages was also demonstrated. Interestingly, the highest level of Hprt transcripts was found in leptotene/zygotene spermatocytes, suggesting a hyperactivation of the Hprt gene and/or stabilization of Hprt transcripts in these cells. Hprt transcripts were present at very low levels in pachytene spermatocytes, and at slightly elevated levels in round spermatids. It was also found that the relative abundance of Hprt transcripts in the somatic cells of germ-cell-deficient testes was much greater than that in meiotic and postmeiotic germ cells, even though their activities of HPRT were similar. Examination of the translational status of Hprt transcripts in testicular cells revealed that while most of the transcript was translationally active in somatic cells of testes, less than half of the transcript was on polysomes in pachytene spermatocytes and round spermatids. Since no functional autosomal Hprt gene exists in the mouse, these data suggest that the germ cell maintains both transcript and protein product of the Hprt gene in spite of apparent X-chromosome inactivation.

Animals↗