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Biomedical subjects

T M Jenkins

Publications and source records attributed to T M Jenkins.

At least 19 recordsLinked to original sources
PubMed2006

Genetic diversity of Crotalaria germplasm assessed through phylogenetic analysis of EST-SSR markers.

The genetic diversity of the genus Crotalaria is unknown even though many species in this genus are economically valuable. We report the first study in which polymorphic expressed sequence tag-simple sequence repeat (EST-SSR) markers derived from Medicago and soybean were used to assess the genetic diversity of the Crotalaria germplasm collection. This collection consisted of 26 accessions representing 4 morphologically characterized species. Phylogenetic analysis partitioned accessions into 4 main groups generally along species lines and revealed that 2 accessions were incorrectly identified as Crotalaria juncea and Crotalaria spectabilis instead of Crotalaria retusa. Morphological re-examination confirmed that these 2 accessions were misclassified during curation or conservation and were indeed C. retusa. Some amplicons from Crotalaria were sequenced and their sequences showed a high similarity (89% sequence identity) to Medicago truncatula from which the EST-SSR primers were designed; however, the SSRs were completely deleted in Crotalaria. Highly distinguishing markers or more sequences are required to further classify accessions within C. juncea.

Base Sequence↗
PubMed2004

Assessment of virulence-factor activity relationships (VFARs) for waterborne diseases.

Virulence-factor activity relationship (VFAR) is a concept that was developed as a way to relate the architectural and biochemical components of a microorganism to its potential to cause human disease. Development of these relationships requires specialised bioinformatics databases that do not exist at present. A pilot-scale VFAR database was designed for three different waterborne organisms: Escherichia coli, Norovirus and Cryptosporidium, to evaluate VFAR relationships. For the web-based database, each organism has separate pages containing virulence genes, occurrence genes, primer sets and probes, taxonomy, outbreaks, and serotype/species/genogroup/genotype. As the database continues to grow, it will be possible to relate the occurrence and prevalence of certain genes in various microorganisms to outbreak data and, subsequently, to establish the utility of using a combination of specific genes as markers of virulence and in establishing virulence-factor activity relationships (VFARs). The database and the VFARs established will be of use to the regulatory community as a way to assist with prioritising those organisms, which need to be regulated.

Animals↗
PubMed2003

Measurements of accelerator-produced leakage neutron and photon transmission through concrete.

Optimum shielding of the radiation from particle accelerators requires knowledge of the attenuation characteristics of the shielding material. The most common material for shielding this radiation is concrete, which can be made using various materials of different densities as aggregates. These different concrete mixes can have very different attenuation characteristics. Information about the attenuation of leakage photons and neutrons in ordinary and heavy concrete is, however, very limited. To increase our knowledge and understanding of the radiation attenuation in concrete of various compositions, we have performed measurements of the transmission of leakage radiation, photons and neutrons, from a Varian Clinac 2100C medical linear accelerator operating at maximum electron energies of 6 and 18 MeV. We have also calculated, using Monte Carlo techniques, the leakage neutron spectra and its transmission through concrete. The results of these measurements and calculations extend the information currently available for designing shielding for medical electron accelerators. Photon transmission characteristics depend more on the manufacturer of the concrete than on the atomic composition. A possible cause for this effect is a non-uniform distribution of the high-density aggregate, typically iron, in the concrete matrix. Errors in estimated transmission of photons can exceed a factor of three, depending on barrier thickness, if attenuation in high-density concrete is simply scaled from that of normal density concrete. We found that neutron transmission through the high-density concretes can be estimated most reasonably and conservatively by using the linear tenth-value layer of normal concrete if specific values of the tenth-value layer of the high-density concrete are not known. The reason for this is that the neutron transmission depends primarily on the hydrogen content of the concrete, which does not significantly depend on concrete density. Errors of factors of two to more than ten, depending on barrier thickness, in the estimated transmission of neutrons through high-density concrete can be made if the attenuation is scaled by density from normal concrete.

Air Pollutants, Radioactive↗
PubMed2001

Prenatal diagnosis of congenital nephrosis by in utero kidney biopsy.

The diagnosis of congenital nephrosis is difficult during the antepartum period. The combination of an elevated amniotic fluid alpha-fetoprotein, a negative acetylcholinesterase, and a negative ultrasound examination is highly indicative of congenital nephrosis; however, these findings can also be associated with a normal gestation. This is the first report of pathologic confirmation of congenital nephrosis from an in utero fetal kidney biopsy.

Acetylcholinesterase↗
PubMed2001

Phylogenetic analyses of two mitochondrial genes and one nuclear intron region illuminate European subterranean termite (Isoptera: Rhinotermitidae) gene flow, taxonomy, and introduction dynamics.

Phylogenetic analyses of multiple DNA sequences were conducted to elucidate gene flow, evolutionary patterns, taxonomy, and the dynamics of two accidental introductions: Reticulitermes lucifugus grassei into Devon, United Kingdom and R. flavipes into Europe. Two mitochondrial DNA genes totaling 1495 bp and a 380-bp ribosomal intergenic transcribed spacer were sequenced. Neighbor-joining and parsimony analyses revealed that multiple female lineages of R. lucifugus grassei were introduced into Devon possibly from southwestern France, where the species was indigenous. The taxonomic status of the European R. santonensis as a species separate from the North American R. flavipes has been questioned since it was described in 1924. Phylogenetic analyses revealed a close genetic relationship between R. flavipes from the United States and R. santonensis from France. These analyses, coupled with morphological and chemotaxonomic data, provide strong support for R. santonensis and R. flavipes being the same species. They also suggested that R. santonensis infestations likely resulted from R. flavipes being introduced into Europe.

Animals↗
PubMed2001

Transcervical Foley catheter for preinduction cervical ripening in an outpatient versus inpatient setting.

OBJECTIVE: To compare use of the Foley catheter for preinduction cervical ripening in an inpatient versus outpatient setting. METHODS: A randomized trial was conducted from May 1998 to December 1999. Women with a term gestation in the vertex presentation, a reactive nonstress test, an amniotic fluid index above the fifth percentile, and a Bishop score of no more than 5 were included. The primary outcome variable was a change in Bishop score. A Foley catheter with a 30-mL balloon was placed through the cervix on gentle traction in each group. The outpatient group was then discharged home with written instructions and returned in the morning for induction. The inpatient group was admitted to labor and delivery, with induction started upon extrusion of the Foley. RESULTS: Sixty-one women were randomized into the outpatient group, and 50 women into the inpatient group. Maternal age, gravidity, previous cesarean delivery, and gestational age did not differ between the groups. The median Bishop score at entry was 3.0 for each group (P =.97). The mean change in Bishop scores after catheter placement was not different between the inpatient and outpatient groups (3.0 versus 3.0; P =.74). The maximum dose of oxytocin, time of oxytocin, epidural rate, induction time, 1-minute and 5-minute Apgar scores, and cord pH were not significantly different. The outpatient group on average avoided 9.6 hours of hospitalization. There were no adverse events or maternal morbidity in either group. CONCLUSIONS: The Foley bulb is as effective in the outpatient as the inpatient setting for preinduction cervical ripening.

Adult↗
PubMed2000

Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling.

Adult hematopoietic differentiation is a developmental process that employs many of the same molecular mechanisms as embryogenesis. To explore the possibility that hedgehog signaling is involved in the control of hematopoietic differentiation, we screened a panel of human leukemia cell lines for the expression of Patched1 and Smoothened, the receptor and coreceptor for hedgehog ligands. Expression was found in multiple cell lines, and Patched1 expression was detected in normal marrow. Induction of myeloid differentiation in cell lines downregulated expression of both genes. When normal marrow mononuclear cells were grown in semisolid medium in the presence of 10 microM cyclopamine, development of colonies of granulocytic/monocytic lineage was unaffected in terms of both number and morphology. The number of erythroid colonies, however, was significantly reduced (P < 0.01). Furthermore, hemoglobinization was substantially delayed relative to controls in those erythroid colonies that did form. Incubation of hematopoietic progenitors with Shh-N and GM-CSF resulted in increased granulocyte/monocyte colonies (P < 0.01); the increase was blocked by cyclopamine. Incubation of hematopoietic progenitors with Shh-N and stem cell factor resulted in larger erythroid colonies. These results suggest that elements of the hedgehog signaling pathway are involved in the control of hematopoietic differentiation.

Cell Differentiation↗
PubMed2000

Timing of cerclage removal after preterm premature rupture of membranes: maternal and neonatal outcomes.

OBJECTIVE: Our aim was to evaluate immediate versus delayed removal of cerclage for women with preterm premature rupture of membranes with respect to maternal and neonatal outcomes. STUDY DESIGN: We retrospectively analyzed women with preterm premature rupture of membranes at <34 weeks' gestation with prior cerclage placement. Exclusion criteria included presentation with chorioamnionitis, active labor, or nonreassuring fetal status. Timing of cerclage removal, immediate (<24 hours) or delayed (>24 hours), was compared. RESULTS: There were 25 women in the delayed-removal group and 37 in the immediate-removal group. Average times to removal were 206.8 +/- 7.4 and 5.4 +/- 0.2 hours, respectively. Use of betamethasone was similar for both groups; however, antenatal antibiotic use (100% vs 80%; P =.03) and short-term tocolytic use (20% vs 3%; P =.04) were higher in the delayed-removal group. Duration of latency was significantly longer with delayed removal (10.1 vs 5.0 days; P <. 001). Delivery occurred >48 hours from preterm premature rupture of membranes in 96% (24/25) versus 54% (20/37; P <.001) and >7 days from rupture in 56% (14/25) versus 24% (9/37; P =.02), respectively. Rates of neonatal sepsis (at <10 days) and maternal infection were not statistically different. Neonatal outcomes did not significantly differ regarding mortality, respiratory distress syndrome, birth weight, or duration of stay in the intensive care nursery. CONCLUSION: With the current management scheme for preterm premature rupture of membranes, cerclage retention significantly increases duration of latency without significantly altering maternal or neonatal outcomes.

Delivery, Obstetric↗
PubMed2000

The challenge of prenatal diagnosis in twin pregnancies.

Prenatal diagnosis in multiple gestations poses unique problems. The use of screening modalities is limited, diagnostic procedures are more complicated, and the management of discordant results may be required. This article reviews work, both past and present, regarding these issues.

Amniocentesis↗
PubMed1999

First trimester prenatal diagnosis: chorionic villus sampling.

Chorionic villus sampling has been used successfully for first trimester diagnosis of genetic disorders for over 14 years. When performed between 10 and 14 weeks' gestation, it is both safe and effective in the diagnosis of fetal chromosomal, biochemical, and molecular disorders, with risks comparable to those of second trimester amniocentesis. Cytogenetic results have been confirmed to be reliable and accurate. Although confined placental mosaicism occurs in approximately 1% of cases requiring interpretation, and occasionally additional invasive testing, its finding adds additional information about perinatal outcome and can alert the practitioner to fetal genetic disorders. Earlier concerns about procedure-induced limb defects have been reduced with the accumulation of additional data, showing minimal to no risk when chorionic villus sampling is performed after 70 days of gestation. In experienced hands, it may be the procedure of choice for sampling multiple gestations. Secondary to the advantage of safe, early diagnosis, chorionic villus sampling appears to be the optimal choice for first trimester testing.

Abortion, Spontaneous↗
PubMed1998

Three new structures of the core domain of HIV-1 integrase: an active site that binds magnesium.

HIV-1 integrase is an essential enzyme in the life cycle of the virus, responsible for catalyzing the insertion of the viral genome into the host cell chromosome; it provides an attractive target for antiviral drug design. The previously reported crystal structure of the HIV-1 integrase core domain revealed that this domain belongs to the superfamily of polynucleotidyltransferases. However, the position of the conserved catalytic carboxylic acids differed from those observed in other enzymes of the class, and attempts to crystallize in the presence of the cofactor, Mg2+, were unsuccessful. We report here three additional crystal structures of the core domain of HIV-1 integrase mutants, crystallized in the presence and absence of cacodylate, as well as complexed with Mg2+. These three crystal forms, containing between them seven independent core domain structures, demonstrate the unambiguous extension of the previously disordered helix alpha4 toward the amino terminus from residue M154 and show that the catalytic E152 points in the general direction of the two catalytic aspartates, D64 and D116. In the vicinity of the active site, the structure of the protein in the absence of cacodylate exhibits significant deviations from the previously reported structures. These differences can be attributed to the modification of C65 and C130 by cacodylate, which was an essential component of the original crystallization mixture. We also demonstrate that in the absence of cacodylate this protein will bind to Mg2+, and could provide a satisfactory platform for binding of inhibitors.

Binding Sites↗
PubMed1997

Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking.

Analysis of the crystal structure of HIV-1 integrase reveals a cluster of lysine residues near the active site. Using site-directed mutagenesis and photo-crosslinking we find that Lys156 and Lys159 are critical for the functional interaction of integrase with viral DNA. Mutation of Lys156 or Lys159 to glutamate led to a loss of both 3' processing and strand transfer activities in vitro while maintaining the ability to interact with nonspecific DNA and support disintegration. However, mutation of both residues to glutamate produced a synergistic effect eliminating nearly all nonspecific DNA interaction and disintegration activity. In addition, virus containing either of these changes was replication-defective at the step of integration. Photo-crosslinking, using 5-iododeoxyuracil-substituted oligonucleotides, suggests that Lys159 interacts at the N7 position of the conserved deoxyadenosine adjacent to the scissile phosphodiester bond of viral DNA. Sequence conservation throughout retroviral integrases and certain bacterial transposases (e.g. Tn10/IS10) supports the premise that within those families of polynucleotidyl transferases, these residues are strategic for DNA interaction.

Amino Acid Sequence↗
PubMed1996

Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity.

The N-terminal domain of HIV-1 integrase contains a pair of His and Cys residues (the HHCC motif) that are conserved among retroviral integrases. Although His and Cys residues are often involved in binding zinc, the HHCC motif does not correspond to any recognized class of zinc binding domain. We have investigated the binding of zinc to HIV-1 integrase protein and find that it binds zinc with a stoichiometry of one zinc per integrase monomer. Analysis of zinc binding to deletion derivatives of integrase locates the binding site to the N-terminal domain. Integrase with a mutation in the HHCC motif does not bind zinc, consistent with coordination of zinc by these residues. The isolated N-terminal domain is disordered in the absence of zinc but, in the presence of zinc, it adopts a secondary structure with a high alpha helical content. Integrase bound by zinc tetramerizes more readily than the apoenzyme and is also more active than the apoenzyme in in vitro integration assays. We conclude that binding of zinc to the HHCC motif stabilizes the folded state of the N-terminal domain of integrase and bound zinc is required for optimal enzymatic activity.

Amino Acid Sequence↗
PubMed1996

DNA polymerases alpha and beta are required for DNA repair in an efficient nuclear extract from Xenopus oocytes.

Xenopus oocytes and an oocyte nuclear extract efficiently repair the bulky DNA lesions cyclobutane pyrimidine dimers,(6-4) photoproducts, and N-acetoxy-2-aminofluorene (AAF) adducts by an excision repair mechanism. Nearly all (>95%) of the input damaged DNA was repaired within 5 h in both injected cells and extracts with no significant incorporation of label into control undamaged DNA. Remarkably, more than 10(10) cyclobutane pyrimidine dimers or(6-4) photoproducts are repaired/nuclei. The extracts are free from nuclease activity, and repair is independent of exogenous light. Both the high efficiency and DNA polymerase requirements of this system appear to be different from extracts derived from human cells. We demonstrated a requirement for DNA polymerases alpha and beta in repair of both photoproducts and AAF by inhibiting repair with several independent antibodies specific to either DNA polymerases alpha or beta and then restoring repair by adding the appropriate purified polymerase. Repair is inhibited by aphidicolin at concentrations specific for blocking DNA polymerase alpha and dideoxynucleotide triphosphates at concentrations specific for inhibiting DNA polymerase beta.

Animals↗
PubMed1996

A soluble active mutant of HIV-1 integrase: involvement of both the core and carboxyl-terminal domains in multimerization.

Structural studies of human immunodeficiency virus type 1 (HIV-1) integrase have been impeded by the low solubility of the protein. By systematic replacement of hydrophobic residues, we previously identified a single amino acid change (F185K) that dramatically improved the solubility of the catalytic domain of HIV-1 integrase and enabled the structure to be determined by x-ray crystallography. We have introduced the same mutation into full-length HIV-1 integrase. The resulting recombinant protein is soluble and fully active in vitro, whereas, HIV-1 carrying the mutation is replication-defective due to improper virus assembly. Analysis of the recombinant protein by gel filtration and sedimentation equilibrium demonstrate a dimer-tetramer self-association. We find that the regions involved in multimerization map to both the catalytic core and carboxyl-terminal domains. The dramatically improved solubility of this protein make it a good candidate for structural studies.

Amino Acid Sequence↗