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Biomedical subjects

Richard J Jackson

Publications and source records attributed to Richard J Jackson.

18 recordsLinked to original sources
PubMed2004

Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population.

We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S. residents 6-59 years of age during 1999 and 2000 as a part of the ongoing National Health and Nutrition Examination Survey (NHANES). We detected each DAP metabolite in more than 50% of the samples, with DEP being detected most frequently (71%) at a limit of detection of 0.2 microg/L. The geometric means for the metabolites detected in more than 60% of the samples were 1.85 microg/L for DMTP and 1.04 microg/L for DEP. The 95th percentiles for each metabolite were DMP, 13 microg/L; DMTP, 46 microg/L; DMDTP, 19 micro g/L; DEP, 13 microg/L; DETP, 2.2 microg/L; and DEDTP, 0.87 microg/L. We determined the molar sums of the dimethyl-containing and diethyl-containing metabolites; their geometric mean concentrations were 49.4 and 10.5 nmol/L, respectively, and their 95th percentiles were 583 and 108 nmol/L, respectively. These data are also presented as creatinine-adjusted concentrations. Multivariate analyses showed concentrations of DAPs in children 6-11 years of age that were consistently significantly higher than in adults and often higher than in adolescents. Although the concentrations between sexes and among racial/ethnic groups varied, no significant differences were observed. These data will be important in evaluating the impact of organophosphorus pesticide exposure in the U.S. population and the effectiveness of regulatory actions.

Adolescent↗
PubMed2003

What determines whether mammalian ribosomes resume scanning after translation of a short upstream open reading frame?

If the 5'-proximal AUG triplet in a mammalian mRNA is followed by a short open reading frame (sORF), a significant fraction of ribosomes resume scanning after termination of sORF translation, and reinitiate at a downstream AUG. To examine the underlying mechanism, we examined reinitiation in vitro using a series of mRNAs that differed only in the 5'-untranslated region (UTR). Efficient reinitiation was found to occur only if the eIF4F complex, or at a minimum the central one-third fragment of eIF4G, participated in the primary initiation event at the sORF initiation codon. It did not occur, however, when sORF translation was driven by the classical swine fever virus or cricket paralysis virus internal ribosome entry sites (IRESs), which do not use eIF4A, 4B, 4E, or 4G. A critical test was provided by an mRNA with an unstructured 5'-UTR, which is translated by scanning but does not absolutely need eIF4G and eIF4A: There was efficient reinitiation in a standard reticulocyte lysate, when initiation would be largely driven by eIF4F, but no reinitiation in an eIF4G-depleted lysate. These results suggest that resumption of scanning may depend on the interaction between eIF4F (or the eIF4G central domain) and the ribosome being maintained while the ribosome translates the sORF.

Animals↗
PubMed2003

The Apaf-1 internal ribosome entry segment attains the correct structural conformation for function via interactions with PTB and unr.

We have shown previously that polypyrimidine tract binding protein 1 (PTB) binds and activates the Apaf-1 internal ribosome entry segment (IRES) when the protein upstream of N-ras (unr) is prebound. Here we show that the Apaf-1 IRES is highly active in neuronal-derived cell lines due to the presence of the neuronal-enhanced version of PTB, nPTB. The unr and PTB/nPTB binding sites have been located on the Apaf-1 IRES RNA, and a structural model for the IRES bound to these proteins has been derived. The ribosome landing site has been located to a single-stranded region, and this is generated by the binding of the nPTB and unr to the RNA. These data suggest that unr and nPTB act as RNA chaperones by changing the structure of the IRES into one that permits translation initiation.

Apoptotic Protease-Activating Factor 1↗
PubMed2003

Evolution of staged versus primary closure of gastroschisis.

OBJECTIVE: Since the introduction of a preformed silo to the authors' practice in 1997, there has been a decrease in primary closure of gastroschisis. To clarify the impact of this change, the authors reviewed their results over the past 10 years. METHODS: From patient records, the authors abstracted the closure method, mechanical ventilation days, time to full feeds, mechanical and infectious complications, and length of stay. The authors compared groups using the Student t test and the Mann-Whitney test, as appropriate. RESULTS: Between 1993 and the present, 124 patients were identified. Between 1993 and 1997, 38 children presented with gastroschisis. Thirty-two (84.2%) closures were primary and six (18.8%) were staged. After 1997, the authors treated 80 children with gastroschisis. There were 27 (33.8%) primary and 53 (66.2%) staged closures. Six patients with other lethal anomalies were excluded. Length of stay and ventilator days were higher for the staged closure group, but infection and mechanical complications were less common in the staged closure group. The time to full feeds did not differ. CONCLUSIONS: A lower incidence of infection and complications related to abdominal compartment syndrome has made staged closure of gastroschisis more common in the authors' practice. While it has resulted in a longer hospital stay, staged closure decreases the risk of long-term bowel dysfunction and need for reoperation.

Child↗
PubMed2003

The impact of community design and land-use choices on public health: a scientific research agenda.

The design of a community's built environment influences the physical and mental health of its residents. Because few studies have investigated this relationship, the Centers for Disease Control and Prevention hosted a workshop in May 2002 to help develop a scientific research agenda on these issues. Workshop participants' areas of expertise included physical activity, injury prevention, air pollution, water quality, urban planning, transportation, architecture, epidemiology, land use, mental health, social capital, housing, and social marketing. This report describes the 37 questions in the resulting research agenda. The next steps are to define priorities and obtain resources. The proposed research will help identify the best practices for designing new communities and revitalizing old ones in ways that promote physical and mental health.

Centers for Disease Control and Prevention, U.S.↗
PubMed2003

Public health effects of inadequately managed stormwater runoff.

OBJECTIVES: This study investigated the scale of the public health risk from stormwater runoff caused by urbanization. METHODS: We compiled turbidity data for municipal treated drinking water as an indication of potential risk in selected US cities and compared estimated costs of waterborne disease and preventive measures. RESULTS: Turbidity levels in other US cities were similar to those linked to illnesses in Milwaukee, Wis, and Philadelphia, Pa. The estimated annual cost of waterborne illness is comparable to the long-term capital investment needed for improved drinking water treatment and stormwater management. CONCLUSIONS: Although additional data on cost and effectiveness are needed, stormwater management to minimize runoff and associated pollution appears to make sense for protecting public health at the least cost.

Cost of Illness↗
PubMed2002

Enteral feeding tubes are a reservoir for nosocomial antibiotic-resistant pathogens.

BACKGROUND: Patients and their surroundings are known reservoirs for nosocomial pathogens. Enteral feeding tubes and formula are not thought of as reservoirs for nosocomial organisms. METHODS: A prospective observation study was conducted comparing methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) cultured from nosocomial infections and MRSA/VRE cultured from enteral feeding tubes used in the same neonatal intensive care unit during the same time period but in different babies. DNA fingerprinting then was used to compare MRSA and VRE cultured from feeding tubes with MRSA/VRE isolates cultured from clinical infections. RESULTS: There were 23 S aureus isolates; 12 of 23 were methicillin resistant (MRSA). There were 4 MRSA infections in patients without feeding tubes. DNA fingerprinting showed that the MRSA species causing each of the clinical infections also was found in the feeding tubes of other babies. There were no vancomycin-resistant Enterococcus infections during the study period. CONCLUSION: Feeding tubes are a reservoir for antibioticresistant pathogens that can be transmitted to other infants.

Cross Infection↗
PubMed2002

Management of typical and atypical intestinal malrotation.

BACKGROUND: "Atypical Malrotation" has been increasingly diagnosed at the authors' institution. METHODS: The authors reviewed retrospectively 201 consecutive operations for malrotation over 5 years to anatomically classify, and describe results of operation for, atypical malrotation. The ligament of Treitz (LOT) was classified as high if left of midline and above the 12th thoracic vertebra, low if left of midline and below the 12th thoracic vertebra, and typical if absent or right of midline. RESULTS: A total of 201 patients underwent operation for malrotation, in 176 there were adequate radiologic studies to allow classification of the LOT. Typical malrotation was present in 75 patients, low LOT in 56, and a high LOT in 45. Volvulus was more common in the Typical group compared with the other 2 groups (12 of 75 v 1 of 56 low; 1 of 45 high; P <.05) as were internal hernias (18 of 75 v 6 of 56 low, 1 of 45 high; P <.05). Complications occurred in 13% of typical versus 22% low and 21% of high patients (P =.10). Low and high LOT patients had 13% and 11% incidence of persistent symptoms postoperatively versus 0% of typical patients. CONCLUSION: Atypical malrotation patients are at significantly lower risk of volvulus and internal hernia compared with typical malrotation patients, and operation appears to come with increased morbidity.

Adolescent↗
PubMed2002

Prospective study of the incidence and complications of bacterial contamination of enteral feeding in neonates.

PURPOSE: The goal of this study was to determine incidence of, and complications resulting from, bacterial contamination of enteral feedings in neonates. METHODS: A prospective study of 50 tube-fed neonates was conducted. Infants were bolus fed via an open gravity drained system; demographic and clinical data were gathered. The lumen of the tube was cultured quantitatively after 7 days. All organisms were isolated, identified, frozen, and stored to correlate with clinical cultures. RESULTS: The 50 neonates were fed for a mean of 17.6 days each and represent 125 patient weeks (1 tube per patient per week). A total of 71 of 125 tubes were "contaminated" (>1,000 colony forming units [CFU]/mL), with a mean 908,173 CFU and 3 different bacteria types. Among formula-fed infants, feeding intolerance occurred in 24 of 32 weeks with contaminated tubes versus 0 of 44 weeks with noncontaminated tubes (P <.05). Contamination occurred in 41 of 48 weeks in patients on H2 antagonists versus 32 of 66 weeks in patients with normal gastric acidity (P <.05). Necrotizing enterocolitis developed in 7 patients; all were fed formula contaminated with greater than 100,000 CFU/mL of Gram-negative bacteria. Four required operation; intraoperative cultures found the same organism as cultured previously in the tube in all 4 infants. CONCLUSION: Bacterial contamination of enteral feeding occurs frequently, causes significant feeding intolerance, and may contribute to NEC.

Bacterial Infections↗
PubMed2002

Fibrin sheath enhances central venous catheter infection.

OBJECTIVE: To determine whether fibrin-coated central venous catheters have a higher infection rate, and spawn more septic emboli, than uncoated catheters after exposure to bacteremia. DESIGN: Animal study comparing catheter infection and blood cultures of fibrin-coated and uncoated catheters exposed to bacteremia. SETTING: Animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: A total of 210 rats had catheters placed with the proximal end buried subcutaneously. Rats were divided into three groups: tail vein bacterial injection on day 0 (no fibrin group) or on day 10 (fibrin group), or no injection/saline injection (control, n = 40). Bacterial injections were 1 x 108 colony forming units of either Staphylococcus epidermidis (n = 100) or Enterobacter cloacae (n = 60). Animals were killed 3 days after injection. Blood cultures were obtained via cardiac puncture, and catheters were removed via the chest. Half of the catheter was rolled onto agar and the other half was placed in trypticase soy broth. Plates and broth were incubated at 37 degrees C for 48 hrs. The presence of >15 colonies on roll plates, or growth in broth, was accepted as a positive sign of infection. Microscopy was performed on day 20-10 catheters. Thirty animals without catheters had bacterial injections and underwent blood culture 3 days after injection. MEASUREMENTS AND MAIN RESULTS: Catheter infection with S. epidermidis occurred in 32% of roll plates and 80% of broth from the fibrin group vs. 4% and 20% from the no fibrin group (p <.01 for each). Catheter infection with E. cloacae occurred in 50% of roll plates and 80% of broth from the fibrin group vs. 0% and 12% from the no fibrin group (p <.01 for each). Positive blood cultures occurred in 47 of 68 animals from the fibrin group vs. 8 of 68 from the no fibrin group (p <.01). Microscopy showed a fibrin sheath on 20 of 20 catheters. Without catheters, 30 of 30 blood cultures were negative. CONCLUSION: The fibrin sheath significantly enhanced catheter-related infection and persistent bacteremia.

Animals↗
PubMed2002

Acidification of formula with citric acid is equally effective and better tolerated than acidification with hydrochloric acid.

OBJECTIVE: To determine whether acidification of formula with citric acid is equally protective against bacterial translocation and gut colonization but better tolerated than acidification with hydrochloric acid in neonatal rabbits. DESIGN: Paired animal model with control. SETTING: Animal laboratory. SUBJECTS: Premature neonatal New Zealand rabbit pups. INTERVENTIONS: A standard neonatal rabbit model in two versions, a bacterial challenge and a no bacterial challenge model, was used to assess bacterial translocation and gut colonization. Two hundred forty-six rabbit pups were delivered by cesarean section 1 day premature and randomly placed into two groups sorted by type of formula acidification (hydrochloric acid or citric acid). Pups were gavage fed pH 3 kitten formula every 12 hrs. Ranitidine hydrochloride at 20 mg x kg(-1) x day(-1) was added to all formula. Bacterial challenge animals were given 1 x 10(6) colony-forming units/mL of Enterobacter cloacae with the third feeding. Animals in the no bacterial challenge group received no bacterial challenge. Animals were killed on day of life 3, and the liver, spleen, mesenteric lymph nodes, and cecum were sequentially harvested and cultured. Organs were qualitatively judged for growth, whereas cecal cultures were quantified as colony-forming units/gram. Stomach biopsies were performed to look for mucosal damage. Long-term tolerance was assessed in 48 pups fed formula acidified to pH 3 with either hydrochloric acid or citric acid and 20 animals fed pH 7 formula without ranitidine. Weight gain and mortality rate were followed for 14 days. MEASUREMENTS AND MAIN RESULTS: Gut colonization and bacterial translocation to liver, spleen, and mesenteric lymph nodes were equivalent between citric acid and hydrochloric acid in both bacterial challenge and no bacterial challenge models. Long term, citric acid animals exceeded hydrochloric acid animals in daily weight gain and survival (p <.05 for both) and equaled pH 7 animals in these measurements. CONCLUSION: Acidification of formula with citric acid is equally protective against bacteria but better tolerated than acidification with hydrochloric acid.

Animals↗
PubMed2002

Pestivirus internal ribosome entry site (IRES) structure and function: elements in the 5' untranslated region important for IRES function.

The importance of certain structural features of the 5' untranslated region of classical swine fever virus (CSFV) RNA for the function of the internal ribosome entry site (IRES) was investigated by mutagenesis followed by in vitro transcription and translation. Deletions made from the 5' end of the CSFV genome sequence showed that the IRES boundary was close to nucleotide 65: thus, the IRES includes the whole of domain II but no sequences upstream of this domain. Deletions which invaded domain II even to a small extent reduced activity to about 20% that of the full-length structure, and this 20% residual activity persisted with more extensive deletions until the whole of domain II had been removed and the deletions invaded the pseudoknot, whereupon IRES activity fell to zero. The importance of both stems of the pseudoknot was verified by making mutations in both sides of each stem; this severely reduced IRES activity, but the compensating mutations which restored base pairing caused almost full IRES function to be regained. The importance of the length of the loop linking the two stems of the pseudoknot was demonstrated by the finding that a reduction in length from the wild-type AUAAAAUU to AUU almost completely abrogated IRES activity. Random A-->U substitutions in the wild-type sequence showed that IRES activity was fairly proportional to the number of A residues retained in this pseudoknot loop, with a preference for clustered neighboring A residues rather than dispersed As. Finally, it was found that the sequence of the highly conserved domain IIIa loop is, rather surprisingly, not important for the maintenance of full IRES activity, although amputation of the entire domain IIIa stem and loop was highly debilitating. These results are interpreted in the light of recent models, derived from cryo-electron microscopy, of the interaction of the closely related hepatitis C virus IRES with 40S ribosomal subunits.

5' Untranslated Regions↗
PubMed2002

Poliovirus internal ribosome entry segment structure alterations that specifically affect function in neuronal cells: molecular genetic analysis.

Translation of poliovirus RNA is driven by an internal ribosome entry segment (IRES) present in the 5' noncoding region of the genomic RNA. This IRES is structured into several domains, including domain V, which contains a large lateral bulge-loop whose predicted secondary structure is unclear. The primary sequence of this bulge-loop is strongly conserved within enteroviruses and rhinoviruses: it encompasses two GNAA motifs which could participate in intrabulge base pairing or (in one case) could be presented as a GNRA tetraloop. We have begun to address the question of the significance of the sequence conservation observed among enterovirus reference strains and field isolates by using a comprehensive site-directed mutagenesis program targeted to these two GNAA motifs. Mutants were analyzed functionally in terms of (i) viability and growth kinetics in both HeLa and neuronal cell lines, (ii) structural analyses by biochemical probing of the RNA, and (iii) translation initiation efficiencies in vitro in rabbit reticulocyte lysates supplemented with HeLa or neuronal cell extracts. Phenotypic analyses showed that only viruses with both GNAA motifs destroyed were significantly affected in their growth capacities, which correlated with in vitro translation defects. The phenotypic defects were strongly exacerbated in neuronal cells, where a temperature-sensitive phenotype could be revealed at between 37 and 39.5 degrees C. Biochemical probing of mutated domain V, compared to the wild type, demonstrated that such mutations lead to significant structural perturbations. Interestingly, revertant viruses possessed compensatory mutations which were distant from the primary mutations in terms of sequence and secondary structure, suggesting that intradomain tertiary interactions could exist within domain V of the IRES.

Amino Acid Motifs↗
PubMed2002

Economic gains resulting from the reduction in children's exposure to lead in the United States.

In this study we quantify economic benefits from projected improvements in worker productivity resulting from the reduction in children's exposure to lead in the United States since 1976. We calculated the decline in blood lead levels (BLLs) from 1976 to 1999 on the basis of nationally representative National Health and Nutrition Examination Survey (NHANES) data collected during 1976 through 1980, 1991 through 1994, and 1999. The decline in mean BLL in 1- to 5-year-old U.S. children from 1976-1980 to 1991-1994 was 12.3 microg/dL, and the estimated decline from 1976 to 1999 was 15.1 microg/dL. We assumed the change in cognitive ability resulting from declines in BLLs, on the basis of published meta-analyses, to be between 0.185 and 0.323 IQ points for each 1 g/dL blood lead concentration. These calculations imply that, because of falling BLLs, U.S. preschool-aged children in the late 1990s had IQs that were, on average, 2.2-4.7 points higher than they would have been if they had the blood lead distribution observed among U.S. preschool-aged children in the late 1970s. We estimated that each IQ point raises worker productivity 1.76-2.38%. With discounted lifetime earnings of $723,300 for each 2-year-old in 2000 dollars, the estimated economic benefit for each year's cohort of 3.8 million 2-year-old children ranges from $110 billion to $319 billion.

Child↗
PubMed2002

The influence of viral coding sequences on pestivirus IRES activity reveals further parallels with translation initiation in prokaryotes.

Classical swine fever virus (CSFV) is a member of the pestivirus family, which shares many features in common with hepatitis C virus (HCV). It is shown here that CSFV has an exceptionally efficient cis-acting internal ribosome entry segment (IRES), which, like that of HCV, is strongly influenced by the sequences immediately downstream of the initiation codon, and is optimal with viral coding sequences in this position. Constructs that retained 17 or more codons of viral coding sequence exhibited full IRES activity, but with only 12 codons, activity was approximately 66% of maximum in vitro (though close to maximum in transfected BHK cells), whereas with just 3 codons or fewer, the activity was only approximately 15% of maximum. The minimal coding region elements required for high activity were exchanged between HCV and CSFV. Although maximum activity was observed in each case with the homologous combination of coding region and 5' UTR, the heterologous combinations were sufficiently active to rule out a highly specific functional interplay between the 5' UTR and coding sequences. On the other hand, inversion of the coding sequences resulted in low IRES activity, particularly with the HCV coding sequences. RNA structure probing showed that the efficiency of internal initiation of these chimeric constructs correlated most closely with the degree of single-strandedness of the region around and immediately downstream of the initiation codon. The low activity IRESs could not be rescued by addition of supplementary eIF4A (the initiation factor with ATP-dependent RNA helicase activity). The extreme sensitivity to secondary structure around the initiation codon is likely to be due to the fact that the eIF4F complex (which has eIF4A as one of its subunits) is not required for and does not participate in initiation on these IRESs.

5' Untranslated Regions↗
PubMed2002

Chernobyl and iodine deficiency in the Russian Federation: an environmental disaster leading to a public health opportunity.

The Chernobyl nuclear disaster of April 26, 1986, triggered a chain of devastating events that later included an unexpected increase in childhood thyroid cancer and evidence of iodine deficiency (ID) in Russia. For the Russian people the Chernobyl event had profound psychological impacts, provoking anxiety about nuclear technology and mistrust of governmental control efforts. Frequently in public health a crisis is required to create the political will to manage longstanding problems, and public health officials must rapidly mobilize to take advantage of the opportunity. In this case, ID, previously not seen as a problem in Russia, was recognized to be potentially serious, and the Russian Federation, assisted by the catalytic bi-national effort of the U.S.-Russian Joint Commission on Economic and Technological Cooperation (Gore-Chernomyrdin Commission (GCC)) established a model salt iodization policy, developed a planning process, and implemented a program to prevent ID through a systematic approach that included the people, government, and private groups using open communication, dissemination of the findings, and action plans. By 1999, political will had been mobilized and over 20% of the nation's salt was being iodized, up from about 1% in 1996. Universal iodization of salt was not a specific objective of the GCC; however, the increasing availability of iodized salt is leading to the elimination of ID, which is now a political goal in Russia. The full realization of this goal will require more time for education, marketing, and possibly legislative action.

Adolescent↗