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Biomedical subjects

L Simpson

Publications and source records attributed to L Simpson.

At least 19 recordsLinked to original sources
PubMed2003

Rhesus rhadinovirus infection in healthy and SIV-infected macaques at Tulane National Primate Research Center.

Rhesus rhadinovirus (RRV) infection was quantified in peripheral blood mononuclear cells (PBMC) from healthy and simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) at the Tulane National Primate Research Center and in a large collection of simian acquired immunodeficiency syndrome--(SAIDS)-associated lymphomas. Quantification of RRV load was performed by real-time PCR using amplification primers specific for the RRV interleukin-6 homologue (RRV vIL-6). RRV infection was detected infrequently and at low levels in PBMC of randomly selected healthy animals. Examination of longitudinally collected PBMC from 22 SIV-infected animals throughout progression to SAIDS revealed similarly low RRV loads that sometimes increased with advancing disease. RRV infection was detected more frequently in the peripheral blood of SIV-infected animals than in healthy animals. Examination of SAIDS-associated lymphomas showed that RRV is rare within the tumor mass, likely representing infection in an occasional tumor-infiltrating cell or contaminating blood. The results indicate that RRV infection in PBMC is not predictive of, and is apparently not required for, development of lymphoma or hyperplastic lymphadenopathy in SIV-infected animals at TNPRC.

Animals↗
PubMed2003

Study of erythrocyte shape changes in schistosomiasis.

The aim of this work was to study the red cell morphology in different stages of schistosomiasis. Patients were divided into three groups according to the stage of the disease. For each patient, complete clinical examination, liver function tests, renal function tests, complete blood picture, scanning electron microscopy for erythrocytes (SEM) and abdominal ultrasonography were done. Abnormal morphologic changes of a total discoid flat cells of 70.14%, margin changes of 12.34% and 3.55% of cup forms were found. To our knowledge, these marked changes were not reported in any other disease. No statistical differences were found between red cell shape changes and stage of liver disease. There was a positive correlation between portal vein diameter and percentage of flat discoid forms and a negative correlation between surface changes and clinical stage of liver disease. These changes are known to be accompanied by reduction of red cell deformability and impaired capillary flow.

Adult↗
PubMed2003

Pleural effusion in complicated Salmonella paratyphi A infection.

Enteric fever can present with unusual manifestations. We observed a rare case of Salmonella paratyphi A infection in which multiple organs were involved and the organism was isolated from pleural fluid and blood. In the present era of antimicrobial drug resistance, awareness about such atypical presentations is essential to initiate a prompt treatment.

Child, Preschool↗
PubMed2001

Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial.

CONTEXT: The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice. OBJECTIVES: To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000. PARTICIPANTS: A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery. INTERVENTION: All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246). MAIN OUTCOME MEASURE: Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death). RESULTS: Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity. CONCLUSIONS: Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.

Betamethasone↗
PubMed2001

Isolation and characterization of a U-specific 3'-5'-exonuclease from mitochondria of Leishmania tarentolae.

We have purified a 3'-5'-exoribonuclease from mitochondrial extract of Leishmania tarentolae over 4000-fold through six column fractionations. This enzyme digested RNA in a distributive manner, showed a high level of specificity for 3'-terminal Us, and was blocked by a terminal dU; there was slight exonucleolytic activity on a 3'-terminal A or C but no activity on a 3'-terminal G residue. The enzyme preferred single-stranded 3'-oligo(U) overhangs and did not digest duplex RNA. Two other 3'-5'-exoribonuclease activities were also detected in the mitochondrial extract, one of which was stimulated by a 3'-phosphate and the other of which degraded RNAs with a 3'-OH to mononucleotides in a processive manner. The properties of the distributive U-specific 3'-5'-exoribonuclease suggest an involvement in the U-deletion RNA editing reaction that occurs in the mitochondrion of these cells.

Animals↗
PubMed2001

PTEN: life as a tumor suppressor.

PTEN, a tumor suppressor located at chromosome 10q23, is mutated in a variety of sporadic cancers and in two autosomal dominant hamartoma syndromes. PTEN is a phosphatase which dephosphorylates phosphatidylinositol (3,4,5)-triphosphate (PtdIns-3,4,5-P3), an important intracellular second messenger, lowering its level within the cell. By dephosphorylating PtdIns-3,4,5-P3, PTEN acts in opposition to phosphatidylinositol 3-kinase (PI3K), which has a pivotal role in the creation of PtdIns-3,4,5-P3. PtdIns-3,4,5-P3 is necessary for the activation of Akt, a serine/threonine kinase involved in cell growth and survival. By blocking the activation of Akt, PTEN regulates cellular processes such as cell cycling, translation, and apoptosis. In this review, we will discuss the identification of PTEN, its mutational status in cancer, its role as a regulator of PI3K, and its domain structure.

Animals↗
PubMed2001

Guide RNAs of the recently isolated LEM125 strain of Leishmania tarentolae: an unexpected complexity.

Guide RNAs (gRNAs) are encoded both in the maxicircle and minicircle components of the mitochondrial DNA of trypanosomatid protozoa. These RNAs mediate the precise insertion and deletion of U residues in transcripts of the maxicircle DNA. We showed previously that the old UC laboratory strain of Leishmania tarentolae apparently lost more than 40 minicircle-encoded gRNAs that are present in the recently isolated LEM125 strain (Thiemann et al., EMBO J, 1994, 13:5689-5700]. We have further analyzed the population of minicircle-encoded gRNAs in the LEM125 strain. Sau3AI and MspI minicircle libraries were constructed and screened for novel gRNAs by negative colony hybridization. This search yielded 20 minicircles encoding new gRNAs that covered most of the remaining gaps in the editing cascades of the ND8, ND9, G4, and G5 genes, and in addition, more than 30 minicircles containing either unassigned or undetectable gRNA genes. We also completely sequenced 34 of the 45 minicircle sequence classes encoding previously identified gRNAs. A total of 19 pairs of redundant gRNAs, which are gRNAs of different sequences covering the same editing blocks, were identified. The gRNAs in each redundant pair generally had different relative abundances and different extents of mismatches with edited sequences. Alignments of the minicircles encoding redundant gRNAs yielded 59 to 93% matching nucleotides, suggesting an origin from duplication of ancestral minicircles and subsequent genetic drift. We propose a functional explanation for the existence of redundant gRNAs in this strain.

Amino Acid Sequence↗
PubMed2001

PTEN expression causes feedback upregulation of insulin receptor substrate 2.

PTEN is a tumor suppressor that antagonizes phosphatidylinositol-3 kinase (PI3K) by dephosphorylating the D3 position of phosphatidylinositol (3,4,5)-triphosphate (PtdIns-3,4,5-P3). Given the importance of PTEN in regulating PtdIns-3,4,5-P3 levels, we used Affymetrix GeneChip arrays to identify genes regulated by PTEN. PTEN expression rapidly reduced the activity of Akt, which was followed by a G(1) arrest and eventually apoptosis. The gene encoding insulin receptor substrate 2 (IRS-2), a mediator of insulin signaling, was found to be the most induced gene at all time points. A PI3K-specific inhibitor, LY294002, also upregulated IRS-2, providing evidence that it was the suppression of the PI3K pathway that was responsible for the message upregulation. In addition, PTEN, LY294002, and rapamycin, an inhibitor of mammalian target of rapamycin, caused a reduction in the molecular weight of IRS-2 and an increase in the association of IRS-2 with PI3K. Apparently, PTEN inhibits a negative regulator of IRS-2 to upregulate the IRS-2-PI3K interaction. These studies suggest that PtdIns-3,4,5-P3 levels regulate the specific activity and amount of IRS-2 available for insulin signaling.

Apoptosis↗
PubMed2001

Promoting education, mentorship, and support for pediatric research.

Pediatricians have an important role to play in the advancement of child health research and should be encouraged and supported to pursue research activities. Education and training in child health research should be part of every level of pediatric training. Continuing education and access to research advisors should be available to practitioners and academic faculty. Recommendations to promote additional research education and support at all levels of pediatric training, from premedical to continuing medical education, as well as suggestions for means to increase support and mentorship for research activities, are outlined in this statement.

Career Choice↗
PubMed2001

Low dependency residents in private nursing homes in Glasgow.

OBJECTIVES: To investigate why nursing home care had been recommended for elderly people who were assessed subsequently as being of low dependency. DESIGN: Examination of community care assessment documentation for low dependency residents to assess reasons for recommending nursing home care; comparison of these with data from a subsequent SCRUGs (Scottish Care Resource Utilisation Groups) assessment. SETTING AND SUBJECTS: Three hundred and four residents within eight private nursing homes in Glasgow. RESULTS: Twenty six percent of the residents were described as being of low dependency. Of these, 44% had dementia and 6% personal care needs alone; 29% had medical problems which required nursing input, but not necessarily to a level requiring nursing home care. Information in the community care assessment often described a higher level of need than that identified subsequently. From the information given in the medical component of the community care assessment it was often unclear why the decision to recommend nursing home care was made. CONCLUSION: Admission to nursing homes may be encouraged by over-emphasiZing care requirements, by placing emphasis on safety rather than independence and by inadequate recording of information. Elderly people who cannot remain at home need improved assessment procedures, better understanding of their needs and a wider range of accommodation options.

Activities of Daily Living↗
PubMed2000

End processing precedes mitochondrial importation and editing of tRNAs in Leishmania tarentolae.

All mitochondrial tRNAs in Leishmania tarentolae are encoded in the nuclear genome and imported into the mitochondrion from the cytosol. One imported tRNA (tRNA(Trp)) is edited by a C to U modification at the first position of the anticodon. To determine the in vivo substrates for mitochondrial tRNA importation as well as tRNA editing, we examined the subcellular localization and extent of 5'- and 3'-end maturation of tRNA(Trp)(CCA), tRNA(Ile)(UAU), tRNA(Gln)(CUG), tRNA(Lys)(UUU), and tRNA(Val)(CAC). Nuclear, cytosolic, and mitochondrial fractions were obtained with little cross-contamination, as determined by Northern analysis of specific marker RNAs. tRNA(Gln) was mainly cytosolic in localization; tRNA(Ile) and tRNA(Lys) were mainly mitochondrial; and tRNA(Trp) and tRNA(Val) were shared between the two compartments. 5'- and 3'-extended precursors of all five tRNAs were present only in the nuclear fraction, suggesting that the mature tRNAs represent the in vivo substrates for importation into the mitochondrion. Consistent with this model, T7-transcribed mature tRNA(Ile) underwent importation in vitro into isolated mitochondria more efficiently than 5'-extended precursor tRNA(Ile). 5'-Extended precursor tRNA(Trp) was found to be unedited, which is consistent with a mitochondrial localization of this editing reaction. T7-transcribed unedited tRNA(Trp) was imported in vitro more efficiently than edited tRNA(Trp), suggesting the presence of importation determinants in the anticodon.

Animals↗
PubMed2000

Effect of mycobacterial infection on virus loads and disease progression in simian immunodeficiency virus-infected rhesus monkeys.

The effect of a mycobacterial infection on AIDS disease was studied in the simian model. Monkeys were infected with the primary virulent isolate SIV/DeltaB670 and inoculated 90 days later with BCG, an attenuated strain of Mycobacterium bovis. All monkeys experienced a dramatic transient increase in plasma viremia and CCR5 expression on T lymphocytes after BCG inoculation. Only two of the four SIV+ animals had substantial proliferative responses to PPD, with poor responders developing disseminated BCG during the course of the experiment. BCG inoculation of SIV-infected long-term nonprogressor (LTNP) monkeys was also performed. Similar to the acutely infected animals, two of three LTNPs experienced increases in plasma viral levels and CCR5 expression. In the majority of animals studied, there was no accelerated progression to AIDS despite the concomitant transient stimulation of virus replication and CCR5 expression on T lymphocytes.

AIDS-Related Opportunistic Infections↗
PubMed2000

Evolution of RNA editing in trypanosome mitochondria.

Two different RNA editing systems have been described in the kinetoplast-mitochondrion of trypanosomatid protists. The first involves the precise insertion and deletion of U residues mostly within the coding regions of maxicircle-encoded mRNAs to produce open reading frames. This editing is mediated by short overlapping complementary guide RNAs encoded in both the maxicircle and the minicircle molecules and involves a series of enzymatic cleavage-ligation steps. The second editing system is a C(34) to U(34) modification in the anticodon of the imported tRNA(Trp), thereby permitting the decoding of the UGA stop codon as tryptophan. U-insertion editing probably originated in an ancestor of the kinetoplastid lineage and appears to have evolved in some cases by the replacement of the original pan-edited cryptogene with a partially edited cDNA. The driving force for the evolutionary fixation of these retroposition events was postulated to be the stochastic loss of entire minicircle sequence classes and their encoded guide RNAs upon segregation of the single kinetoplast DNA network into daughter cells at cell division. A large plasticity in the relative abundance of minicircle sequence classes has been observed during cell culture in the laboratory. Computer simulations provide theoretical evidence for this plasticity if a random distribution and segregation model of minicircles is assumed. The possible evolutionary relationship of the C to U and U-insertion editing systems is discussed.

Animals↗