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E M Allen

Publications and source records attributed to E M Allen.

At least 19 recordsLinked to original sources
PubMed2001

Base-pairing between untranslated regions facilitates translation of uncapped, nonpolyadenylated viral RNA.

Translationally competent mRNAs form a closed loop via interaction of initiation factors with the 5' cap and poly(A) tail. However, many viral mRNAs lack a cap and/or a poly(A) tail. We show that an uncapped, nonpolyadenylated plant viral mRNA forms a closed loop by direct base-pairing (kissing) of a stem loop in the 3' untranslated region (UTR) with a stem loop in the 5' UTR. This allows a sequence in the 3' UTR to confer translation initiation at the 5'-proximal AUG. This base-pairing is also required for replication. Unlike other cap-independent translation mechanisms, the ribosome enters at the 5' end of the mRNA. This remarkably long-distance base-pairing reveals a novel mechanism of cap-independent translation and means by which mRNA UTRs can communicate.

3' Untranslated Regions↗
PubMed2000

Liver transplantation improves cirrhosis-associated impaired oral glucose tolerance.

BACKGROUND: Thirty-five percent to 80% of cirrhotic patients have impaired glucose tolerance (IGT) or diabetes mellitus (DM). Diabetic cirrhotics have higher morbidity and mortality than nondiabetics. Therefore, it would be worthwhile to determine whether liver transplantation improves glucose homeostasis in these patients. METHOD: A total of 26 patients awaiting liver transplantation were evaluated for impaired glucose homeostasis by fasting blood glucose and/or oral glucose tolerance tests (OGTT). Five patients underwent transplant surgery within 1 year of OGTT and had a repeat OGTT 3-6 months after transplantation. RESULTS: Sixty-five percent (17/26) of the patients had abnormal glucose homeostasis. Twenty-three percent (6/26) met American Diabetes Association criteria for DM, and another 42.3% (11/26) had IGT. All patients had normal HbA1C levels. After transplantation, the 2-hr blood glucose improved in four patients and the mean 2-hr glucose level was reduced (204 +/- 94 vs. 132 +/- 53 mg/dl [mean +/- SD, P=0.051]). CONCLUSION: Liver transplantation can reverse cirrhosis-associated impaired glucose tolerance.

Adult↗
PubMed2000

IL-10 kinetics in thyroiditis-prone BB/Wor rats.

UNLABELLED: Cytokines modulate the course of autoimmunity, but their role in the evolution of spontaneous disease is unclear. This study compared the cytokine kinetics of T cell cultures from thyroiditis (LT)-prone NB line BB/Wor rats with those of Wistar (Wis) rat controls following activation with the thyroid-specific antigen thyroglobulin (Tg) or Concanavalin A (Con A). DESIGN: T cell enhanced splenocytes from 60 day old Wis and NB rats were activated with 0.5 microg/ml rat thyroglobulin (Tg) or Con A in the presence of homologous irradiated splenocytes as antigen presenting cells (APC's). In addition, the effect of APC's was determined in a crisscross experiment which examined NB T cell responses to Con A in the presence of Wis APC's. ELISA and RT-PCR were used to examine IL-2, IL-4, IL-10, TNFalpha, IFNgamma, IL-I0 concentrations and mRNA expression in the supernatant and cells from parallel cultures harvested at specific intervals. Frozen thyroids from 60 day old NB, Wis and Fisher rats were examined for the presence of IL-10 by immunohistochemistry. T cell proliferation was measured by 3H thymidine uptake. RESULTS: Following activation with either Tg or Con A, IL-10 concentrations exceeded IFNgamma in NB rat cultures, but IFNgamma exceeded IL-10 in Wis cultures. Wis splenocytes significantly enhanced NB T cell proliferation and cytokine responses to Con A. Thyroids from 60 day NB rats contained IL-10, but no IFNgamma. There was no IL-10 in thyroids from Wistar or Fisher rats. CONCLUSION: Splenocyte responses in LT-prone BB/Wor rats favor IL-10 production. Future investigations will examine the source of intrathyroidal IL-10 and its role in LT.

Animals↗
PubMed1999

Water fluoridation and the sudden infant death syndrome.

AIMS: To determine whether exposure to fluoridated water supplies prenatally or postnatally at the time of death increases the risk of sudden infant death syndrome (SIDS). METHODS: A nationwide, case-control study, with infant's water fluoridation status determined from census area unit information for mother's usual address at the time of the infant's birth, infant's usual address at the time of death / nominated sleep and address where infant died / was at nominated sleep. SIDS risk associated with fluoride exposure postnatally was assessed according to method of infant feeding (breast or reconstituted formula), for the two days prior to infant's death / nominated sleep. RESULTS: Infants exposed to fluoridated water supplies during pregnancy were not at increased risk for SIDS, adjusted odds ratio (OR) 1.19 (95% confidence interval (CI) 0.82, 1.74). For breast-fed infants at the time of death / nominated sleep, fluoridated water exposure was not associated with an increased risk for SIDS, adjusted OR 1.09 (95% CI 0.66, 1.79). Similarly, 'fluoridated' formula feeding, when compared with 'unfluoridated' formula feeding, showed no increased risk of SIDS, adjusted OR 1.25 (95% CI 0.73, 2.13). There was no evidence of an interaction between fluoridation and infant feeding for the last two days (chi2 = 0.171, df = 1, p = 0.68). CONCLUSION: Exposure to a fluoridated water supply prenatally or postnatally at the time of death did not affect the relative risk for SIDS.

Analysis of Variance↗
PubMed1999

The effect of methimazole, iodine and splenocytes on thyroid transplants in BB/Wor rats.

BACKGROUND: BB/Wor rats develop spontaneous autoimmune insulin-requiring diabetes mellitus and lymphocytic thyroiditis (LT). Our investigations examined the effect of the thyroid-specific agents, iodine and methimazole (MMI) on thyroid graft survival in BB/Wor rats, compared the intrathyroidal cytokine mRNA expression of endogenous and engrafted thyroids, and ascertained whether unfractionated splenocytes could protect thyroid grafts from lymphocytic infiltration. METHODS: In study 1, 0.025% iodine water-treated LT-prone NB line BB/Wor rats were randomized to receive one of the following treatments: (1) 1.0 x 10(8) splenocytes, IV from LT-resistant WA line BB/Wor rats, (2) WA rat thyroid transplants, (3) both, or (4) neither (controls). In study 2, after thyroid transplantation, LT-prone BB/Wor rats were randomized to receive (1) WA splenocytes, (2) 0.025% iodine water, (3) 0.05% MMI water or, (4) tap water (controls). The incidence of LT was determined by microscopic inspection after hematoxylin and eosin staining. Lymphocytic infiltrates were characterized by immunohistochemistry. Cytokine mRNA was detected by RT-PCR. RESULTS: Grafts from MMI-treated rats had a significantly lower incidence of lymphocytic infiltration (MMI: 2/5; Tap: 5/5; I 5/5, P<0.05, chi2). IL-10 mRNA was expressed in 77% (7/9) endogenous thyroids and 20% (1/5) of the transplanted WA thyroids (P<0.05, chi2) from iodine-treated rats with LT. There was no difference in IL-12 mRNA expression. Lymphocytic infiltration occurred in 100% of the splenocyte-treated graft recipients. Both endogenous and engrafted thyroids contained CD4 and C8 T cells with scattered IgG staining. CONCLUSION: Target organ-specific interventions that suppress antigen presentation may have an adjunctive role in transplantation tolerance. The differential expression of IL-10 may indicate preferential Th2 lymphocyte activation in the endogenous tissues.

Analysis of Variance↗
PubMed1997

A randomized, controlled study of the 1-hour and 24-hour effects of inhaled nitric oxide therapy in children with acute hypoxemic respiratory failure.

STUDY OBJECTIVE: To determine whether 24 h of inhaled nitric oxide improves oxygenation greater than conventional therapy alone in children with acute hypoxemic respiratory failure. DESIGN: Prospective, randomized, controlled study. SETTING: Twenty-six-bed pediatric ICU in a tertiary children's hospital. PATIENTS: Twenty-four patients with acute bilateral lung disease requiring a positive-end expiratory pressure >6 cm H2O and a fraction of inspired oxygen >0.5 for >12 h. INTERVENTIONS: Twelve patients were treated with 10 ppm inhaled nitric oxide from the onset of randomization and 12 control patients were initially maintained on a regimen of conventional therapy alone. After a period of 24 h, control patients were also treated with 10 ppm inhaled nitric oxide. Hemodynamic and blood gas measurements were performed at baseline, at 1 h after randomization, and at 24-h intervals for 2 days. MEASUREMENTS AND RESULTS: Inhaled nitric oxide decreased the ratio of pulmonary to systemic vascular resistance and improved oxygenation indexes during the initial hour following randomization. However, 24 h after randomization, the oxygenation indexes of 11 surviving treated patients were not improved in comparison to baseline or the oxygenation indexes of 10 surviving control patients. Oxygenation indexes acutely improved in control patients when inhaled nitric oxide was started after 24 h of conventional therapy. Oxygenation indexes remained improved in the initial control patients after 24 h of inhaled nitric oxide. CONCLUSIONS: Pulmonary vascular resistance and systemic oxygenation are acutely improved by 10 ppm inhaled nitric oxide in some children with severe lung disease. However, a sustained improvement in oxygenation may not occur during prolonged therapy. Thus, inhaled nitric oxide may have a limited therapeutic role in children with acute hypoxemic respiratory failure.

Acute Disease↗
PubMed1996

Life events, social support and the risk of sudden infant death syndrome.

The effects of a lack of maternal social support and stressful life events on the risk of Sudden Infant Death Syndrome (SIDS) were examined by case-control design: 390 cases and 1592 control infants. A seven item index of mother's social support was used. A possible 21 life events experienced by each family were summed and then put into one of three categories: 0-2, 3-5, and 6 or more life events. Similar levels of maternal social support were found for both groups. SIDS families experienced significantly more stressful life events than control families, but once social factors had been taken into account this association was lost.

Analysis of Variance↗
PubMed1996

The pathogenicity of spontaneously-occurring thyroglobulin-reactive T lymphocytes from BB/WOR rats.

Autoantigen-reactive T lymphocytes have been implicated in the pathogenesis organ-specific autoimmune disease. Thyroglobulin (Tg) is one of the primary autoantigens associated with autoimmune lymphocytic thyroiditis (LT). These experiments investigated the pathogenicity of a lymphocyte line derived from spontaneously-occurring Tg-reactive T lymphocytes isolated from unprimed NB line BB/Wor rats which have nearly a 100% incidence of spontaneous LT. Adoptive transfer of LT was accomplished by injecting 1.0 x 10(5) Tg-reactive lymphocytes into the tail vein of MHC compatible, non LT-prone BB line BB/Wor rats. All of the Tg-reactive cell line recipients (5/5) developed LT compared to only 20% (1/5) of the control rats given a parallel tetanus toxoid-reactive T cell line (p < 0.05, Fisher's exact test). Furthermore, despite the presence of LT, only one Tg-reactive cell line recipient developed insulitis. When Tg-reactive lymphocytes were incubated with an MHC compatible Wistar rat thyrocyte line at increasing effector: target ratios, the T cell line lysed thyrocytes in a dose-response fashion (r = 0.99, p < 0.05, linear regression), but did not lyse smooth muscle cell targets. FACS analysis established that this cell line is CD8 predominant. This is the first study to demonstrate that spontaneously-occurring Tg-reactive T lymphocytes from a nonimmunized animal model for LT are pathogenic. Further investigations into the repertoire of Tg-reactive lymphocytes in BB/Wor rats should provide insight into the pathogenesis of autoimmune thyroid disease and provide a basis for targeted immunotherapy.

Adoptive Transfer↗
PubMed1996

HPLC micromethod for amrinone and metabolites in patients receiving concurrent cephalosporin therapy.

Amrinone (AMR), a bipyridine derivative, is receiving increasing use in postoperative cardiac patients as an inotrope and vasodilator. The hemodynamic response to amrinone in adults is linearly related to AMR concentrations, warranting therapeutic drug monitoring. We report a rapid microsample HPLC method for monitoring AMR and its principal metabolites, N-acetyl (N-ac) and N-glycolyl (N-gly) AMR. Serum was precipitated with acetonitrile, and the supernatant fluid was then injected into a C18 narrow-bore column. The mobile phase consisted of a 0.1 mol/L sodium phosphate buffer (pH 6) with a gradient of acetonitrile going from 50 to 100 mL/L of eluent. Detection with a diode-array detector (DAD) concurrently monitored the absorbances at 320 and 345 nm. Monitoring 320 nm allows optimal quantification of AMR, N-gly, and N-ac. Patients often receive concurrent cephalosporin therapy, which is detectable at 320 nm but not 345 nm. Because cephalosporins coelute with AMR or metabolites, monitoring at 345 nm allows separation of these antibiotics from AMR and metabolites while retaining a detection limit of 0.5 mg/L.

Acetonitriles↗
PubMed1996

Hemodynamic effects of N-acetylamrinone in a porcine model of group B streptococcal sepsis.

High plasma concentrations of N-acetylamrinone, a primary metabolite of amrinone, are measured in some children during prolonged amrinone infusion. The purpose of this investigation was to determine if N-acetylamrinone has direct hemodynamic effects independent of amrinone. Twenty neonatal piglets received an infusion of 6 x 10(9) colony-forming units/kg of group B Streptococcus to induce sepsis. Subsequently, they were divided into 1 of 3 groups and received a 1-hr infusion of either normal saline (N = 4); 8 mg/kg amrinone, followed by 20 micrograms/kg/min (N = 9); or 8 mg/kg N-acetylamrinone, followed by 20 micrograms/kg/min (N = 7). Hemodynamic measurements and arterial/venous blood-gas determinations were obtained every 30 min during the study. Systemic vascular resistance and pulmonary vascular resistance were calculated. One milliliter of blood was obtained every 30 min during drug administration to determine plasma amrinone and N-acetylamrinone concentrations. The mean amrinone plasma concentrations measured at 30 and 60 min during the infusion time in the group receiving amrinone were 8.8 +/- 1.1 and 6.9 +/- 0.7 micrograms/ml, respectively. These animals experienced a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance, compared with saline controls after a 30-min infusion of amrinone. The mean N-acetylamrinone plasma concentrations measured at 30 and 60 min during the N-acetylamrinone infusion were 7.3 +/- 0.8 and 5.7 +/- 0.6 micrograms/ml, respectively. There was no difference between any hemodynamic parameter measured in these animals, compared with saline controls at any time during the infusion. We conclude that amrinone, but not N-acetylamrinone, causes pulmonary vasodilation in a porcine model of sepsis and that the parent drug is the sole active component in amrinone.

Amrinone↗
PubMed1995

Oral dimercaptosuccinic acid and ongoing exposure to lead: effects on heme synthesis and lead distribution in a rat model.

Lead (Pb) exposure and subsequent toxicity continues to be a significant problem in the United States. Treatment with meso-2,3-dimercaptosuccinic acid (DMSA) has been reported to be effective in reducing the body's Pb burden, with fewer adverse side effects than other chelating agents. The oral availability and relative safety of DMSA presents the controversial option of treating patients with Pb poisoning on an outpatient basis. Despite recommendations that children be removed from the Pb contaminated environment, some children will inevitably be exposed to environmental Pb while receiving oral DMSA therapy. The study hypothesized that oral DMSA chelation therapy is beneficial even when faced with continued dietary Pb. Sprague-Dawley rats were exposed to Pb in water for 35 days and then placed in various treatment groups, including groups administered oral DMSA with and without concurrent Pb exposure. The concentration of Pb in blood and critical organs and Pb diuresis were measured. The effect of Pb on heme synthesis was determined by assaying the urinary delta-aminolevulinic acid (delta-ALA), and blood zinc protoporphyrin (ZPP). DMSA reversed the hematological effects of Pb, decreased the blood, brain, bone, kidney, and liver Pb concentration, and produced a marked Pb diuresis, even when challenged with ongoing Pb exposure. In conclusion, even though DMSA treatment without exposure to Pb is optimal, oral DMSA could be beneficial even when challenged with ongoing Pb exposure.

Administration, Oral↗
PubMed1995

Thyroglobulin-reactive T lymphocytes in thyroiditis-prone BB/Wor rats.

Autoimmune lymphocytic thyroiditis (LT) is a common cause of primary hypothyroidism. Autoreactive T lymphocytes are clearly associated with this disorder, but their pathogenic role in spontaneously occurring LT remains to be established. In the present study, thyroglobulin-reactive T lymphocytes were cultured from young, unprimed LT-prone BB/Wor rats before the age of spontaneously-occurring LT. Although similar investigations have been conducted in animal models for experimental autoimmune thyroiditis (EAT), this study is unique because it examines a mammalian model for spontaneous LT. Splenic T lymphocytes were isolated from unprimed 30 to 45-day-old Fisher and LT-prone BB/Wor rats before the onset of LT, then tested for activation by normal (NL), iodine-poor (LI), and iodine-rich (HI) rat thyroglobulin (Tg) in bulk proliferation assay. BB/Wor rat lymphocytes were activated by all three Tg preparations, but Fisher lymphocytes were unresponsive (BB/Wor vs Fisher; p < 0.0001, Student's t-test). There was no difference between BB/Wor rat responses to the three preparations (p > 0.05, ANOVA). Based on these results, we conclude that Tg-responsive T lymphocytes can be cultured from young, unprimed LT-prone BB/Wor rats. Isolating such lymphocytes before the onset of histologically demonstrable LT strengthens the argument that antigen-specific T cells have a pathogenic role in the development of spontaneous autoimmune thyroid disease. The fact that these lymphocytes recognized normal, iodine-rich and iodine poor preparations of rat Tg equally well suggest that unlike the EAT model, spontaneously-occurring Tg-reactive T cells are not influenced by thyroglobulin's iodine content.

Animals↗
PubMed1995

Antenatal and intrapartum factors associated with sudden infant death syndrome in the New Zealand Cot Death Study.

OBJECTIVE: To describe the relationship between antenatal and intrapartum factors and sudden infant death syndrome (SIDS). METHODOLOGY: The New Zealand Cot Death Study was a 3 year case-control study, with 485 infants who died from SIDS in the postneonatal period and 1800 randomly selected control infants. Data were obtained from obstetric records, parental interview and community nursing records. RESULTS: This study confirms many of the antenatal and intrapartum risk factors for SIDS noted in studies from both the southern and northern hemispheres. After controlling for potential confounders, such as occupational group and marital status, significant inverse effects were noted for interpregnancy interval, birthweight and gestation. Other factors that retained a significantly increased risk of SIDS were: increasing parity, bacteriological evidence of urinary tract infection (UTI) (adjusted odds ratio 1.73, 95% CI 1.10-2.73); smoking antenatally (AdjOR 2.14, 95% CI 1.61-2.84); less than six antenatal checks attended (AdjOR 1.84, 95% CI 1.19-2.84); second stage of labour less than 16 min (AdjOR 2.06, 95% CI 1.35-3.14) and multiple birth (AdjOR 3.23, 95% CI 1.70-6.02). No interaction was observed between maternal haemoglobin and antenatal smoking. Interactions were tested for and not found between antenatal smoking and three antenatal risk factors (UTI, short second stage of labour and number of antenatal appointments). The only significant interaction between these three factors and three modifiable postnatal risk factors (prone sleeping, bed sharing and bottle feeding) was between bed sharing and fewer antenatal appointments. The risk of SIDS associated with bed sharing was greater among those whose mothers had fewer antenatal appointments. CONCLUSIONS: Although many of the previously identified antenatal and intrapartum risk factors for SIDS are confirmed, the risks of SIDS associated with obstetric factors are in general considerably lower than the risks associated with the four modifiable postnatal risk factors.

Case-Control Studies↗
PubMed1995

Difference between the measured and ordered dose of catecholamine infusions.

OBJECTIVE: To measure the actual concentrations of dopamine, dobutamine, and epinephrine in infusates prepared for patients, and to compare these concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl infusates that had been prescribed to evaluate drug preparation accuracy. DESIGN: Prospective, unblind study. SETTING: Pediatric intensive care unit in a tertiary-care teaching hospital. PARTICIPANTS: All dopamine, dobutamine, and epinephrine infusions ordered for patients during the 2-month study period were eligible for inclusion in the study. MEASUREMENTS: Daily samples of dopamine, dobutamine, and epinephrine infusates that were prepared for 41 pediatric patients were obtained; the infusate catecholamine concentration was measured by HPLC and compared with the ordered concentration. The concentration than was multiplied by the rate of infusion to determine the catecholamine dose. MAIN RESULTS: There were significant differences between the measured doses of dopamine, dobutamine, and epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p = 0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of preparation inaccuracies. Failure to account for the HCl salt in the stock drug accounted for some, but not all, of the inaccuracy of the dopamine HCl and epinephrine HCl infusates. There was a wide interday variability in the measured catecholamine dosage in patients receiving the same dose for 3 days or more. CONCLUSIONS: There are daily fluctuations in the preparation of dopamine, dobutamine, and epinephrine infusates that could alter the amount of drug actually delivered to critically ill patients and potentially contribute to their hemodynamic instability.

Adolescent↗
PubMed1994

Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study.

Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted.

Adult↗