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Biomedical subjects

Richard J Jackson

Publications and source records attributed to Richard J Jackson.

At least 19 recordsLinked to original sources
PubMed2007

How do microRNAs regulate gene expression?

Several thousand human genes, amounting to about one-third of the whole genome, are potential targets for regulation by the several hundred microRNAs (miRNAs) encoded in the genome. The regulation occurs posttranscriptionally and involves the approximately 21-nucleotide miRNA interacting with a target site in the mRNA that generally has imperfect complementarity to the miRNA. The target sites are almost invariably in the 3'-untranslated region of the messenger RNA (mRNA), often in multiple copies. Metazoan miRNAs were previously thought to down-regulate protein expression by inhibiting target mRNA translation at some stage after the translation initiation step, without much effect on mRNA abundance. However, recent studies have questioned these suppositions. With some targets, an increase in the rate of mRNA degradation by the normal decay pathway contributes to the decrease in protein expression. miRNAs can also inhibit translation initiation, specifically the function of the cap-binding initiation factor, eIF4E. Repressed target mRNAs as well as miRNAs themselves accumulate in cytoplasmic foci known as P-bodies, where many enzymes involved in mRNA degradation are concentrated. However, P-bodies may also serve as repositories for the temporary and reversible storage of untranslated mRNA, and reducing the expression (knockdown) of several distinct P-body protein components can alleviate miRNA-mediated repression of gene expression.

Animals↗
PubMed2006

Surgical management of lipoblastoma.

BACKGROUND/PURPOSE: Lipoblastoma/lipoblastomatosis, a rare benign pediatric tumor composed of embryonic fat, most often presents as a rapidly growing mass in children younger than 3 years. This benign tumor locally recurs up to 25% of the time. This retrospective review was done to emphasize problems with diagnosis, management, and the approach to follow-up care. METHODS: Sixteen cases of pathologically proven lipoblastoma presenting to a single institution over a 16-year period (1988-2004) were reviewed retrospectively for clinical features and outcome. RESULTS: There were 11 males and 5 females ranging in age from 18 days to 12.75 years. Preoperative diagnoses were accurate in only 3 cases. Two lesions recurred locally over a period of 10 months and 5 years. One lesion presented with local infiltration. Six lesions were right-sided, 5 were left-sided, and 5 were midline. CONCLUSIONS: It is important to consider lipoblastoma in the diagnosis of a rapidly enlarging fatty mass in children. Complete resection is the only definitive treatment and should not be delayed when impingement on surrounding structures is imminent. There is a tendency for these lesions to recur despite presumed complete excision. Therefore, follow-up for a minimum of 5 years is recommended.

Child↗
PubMed2006

Delayed manifestation of abdominal aortic stenosis in a child presenting 10 years after blunt abdominal trauma.

We report the case of a 13-year-old boy who, at 3 years of age, was a rear seat-restrained passenger in a high-speed motor vehicle crash necessitating segmental small-bowel resection. The patient remained well for 10 years; then he began to have exercise-induced fatigue in his lower extremities. Routine physical examination revealed a bruit and thrill in the mid abdomen and diminished femoral pulses. Aortic stenosis was diagnosed and treated surgically. We discuss the pathophysiology of the lesion and review the literature. This is the first report of abdominal aortic stenosis 10 years after blunt abdominal trauma in a child.

Abdominal Injuries↗
PubMed2005

Malignant triton tumor presenting as a rectal mass in an 11-month-old.

We report the case of an 11-month-old white male who had a family history of neurofibromatosis, had multiple café-au-lait spots on the trunk and extremities, and was diagnosed with a malignant triton tumor of the rectum. To our knowledge, this is the first report of a malignant triton tumor of the rectum and one of the youngest patients reported with the tumor.

Diagnosis, Differential↗
PubMed2004

All five cold-shock domains of unr (upstream of N-ras) are required for stimulation of human rhinovirus RNA translation.

Efficient translation of human rhinovirus-2 (HRV-2) RNA from its internal ribosome entry site (IRES) depends on the presence of cellular trans-acting factors upstream of N-ras (unr) and polypyrimidine-tract-binding protein. unr contains five cold-shock domains (CSDs) and is predicted to act as an RNA chaperone, allowing the HRV-2 IRES to attain the correct conformation for ribosome binding. To investigate the role of each of the CSDs in IRES-dependent translation, five unr mutants, each harbouring a point mutation in a different CSD, were generated. All five mutants were severely impaired in their ability to bind to the IRES and to stimulate translation from it. This showed that the ability of unr to function as an activator of HRV-2 RNA translation requires the RNA-binding activity of all five CSDs.

5' Untranslated Regions↗
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↗
PubMed2004

Air-gun injuries: initial evaluation and resultant morbidity.

Severity of injuries from air-powered weapons can be underappreciated. Transformation of these weapons into toys makes them available to children. Our experience reveals the underestimated injury severity and emphasizes need for prompt trauma evaluation. Retrospective chart review of children sustaining air-gun injuries and evaluated at a single, pediatric hospital from 1991 to 2002 was performed. Medical record numbers were retrieved from a trauma data base. Data included age, weapon type, firing distance, injury site, radiographic studies, operative intervention, length of stay, and long-term disability. Ocular injuries were excluded secondary to known severity. All other injuries and treatments are described. Thirty-four children, average age 10 years +/- 3.3 years, sustained 35 injuries from 1991 through 2002. Twenty-one children required admission, 19 children required surgery, and 5 children experienced long-term disability. Average time to definitive care was 3 hours 12 minutes. Sites of injury included head, neck, chest, abdomen, and extremities. Average hospital stay was 4.3 days. In the pediatric population, air-gun injuries can be underestimated. Lack of collateral tissue damage makes wounds appear innocuous to unsuspecting medical personnel resulting in delayed care. During initial evaluation, injuries from air guns deserve the same respect as those caused by conventional firearms.

Child↗
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↗