The changing face of ectopic pregnancy.
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Female↗
Biomedical subjects
S Smith
Publications and source records attributed to S Smith.
House dust mite and cat allergen levels in domestic dwellings in Christchurch.
AIMS: To quantify the levels of Dermatophagoides pteronyssinus allergen (Der p I) and Felis domesticus allergen (Fel d I) in domestic dwellings in Christchurch and to assess possible relationships with housing characteristics. METHODS: Domestic dwellings (n = 93) were randomly selected and housing characteristics documented during the summer of 1994/95. Dust samples were obtained from the floor of the living room (LR) and bedroom (BR) and from the bed by standard vacuuming methods. The predominant mite species were determined and D pteronyssinus and F domesticus levels quantified. RESULTS: D pteronyssinus was the predominant (95%) species. D pteronyssinus allergen levels [geomean (95% confidence intervals) were 3.5(2.5-4.8) micrograms/g in LR, 10.1(7.5-13.7) micrograms/g in BR and 5.7(4.3-7.6) micrograms/g in the bed. F domesticus allergen levels were significantly higher (p < 0.001) in houses with cats than without cats [median (range) 93.2 (3.3-1227.2) micrograms/g and 2.9 (0.4-214.8) micrograms/g respectively]. Higher LR D pteronyssinus allergen levels were found in houses classified as having high indoor humidity and in houses situated in geographically damp locations. CONCLUSIONS: Domestic D pteronyssinus and F domesticus allergen levels in Christchurch are comparable with those found in other climatically similar locations. D pteronyssinus allergen levels are associated with both indoor and outdoor humidity factors.
Adult↗
Improving the quality of outcomes research involving pharmaceutical services.
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Drug Therapy↗
Regulatory elements in the first intron of the rat fatty acid synthase gene.
Sequence elements have been identified within the 1.2 kb-long first intron of the fatty acid synthase (FAS) gene that mediate both positive and negative effects on transcription. The negative regulatory element, when positioned downstream of either the FAS or simian virus 40 promoter, down-regulates the expression of a coupled reporter gene in an orientation-dependent manner. Sequences mediating this effect have been mapped, by deletion mutagenesis, to two regions approximately within nucleotides +405 to +768 and +924 to +1083. Both regions contain sequence elements that are strongly protected from DNase I digestion by nuclear extracts prepared from liver, but not by those prepared from spleen. The results of run-on assays performed with nuclei derived from tissues that express FAS at either high or low levels indicate that the different rates of transcription of the endogenous FAS gene result from differences in the extent of initiation, so it is unlikely that the negative effect is caused by transcriptional pausing in the first intron. The positive element maps to nt +292 to +297 and corresponds to an authentic binding site for upstream stimulatory factor (USF). This USF-binding element can up-regulate transcription from a heterologous promoter in a position- and orientation-independent manner. However, in the context of the entire FAS first intron, the effect of the USF-binding site is masked unless the effect of the negative elements is ablated by mutagenesis. These results suggest that the dominant negative element of the first intron may play a role in determining the tissue-specific expression of the FAS gene.
Alternative Splicing↗
Alteration of the substrate specificity of the malonyl-CoA/acetyl-CoA:acyl carrier protein S-acyltransferase domain of the multifunctional fatty acid synthase by mutation of a single arginine residue.
The structural basis for the dual specificity of the malonyl-CoA/acetyl-CoA:acyl carrier protein S-acyltransferase associated with the multifunctional animal fatty acid synthase has been investigated by mutagenesis. Arginine 606, which is positionally conserved in the transacylase domains of all multifunctional fatty acid and polyketide synthases, was replaced by alanine or lysine in the context of the isolated transacylase domain, and the mutant proteins were expressed in Escherichia coli. Malonyl transacylase activity of the Arg-606 --> Ala and Arg-606 --> Lys mutant enzymes was reduced by 100- and 10-fold, respectively. In contrast, acetyl transacylase activity was increased 6.6-fold in the Arg-606 --> Ala mutant and 1.7-fold in the Arg-606 --> Lys mutant. Kinetic studies revealed that selectivity of the enzyme for acetyl-CoA was increased >16,000-fold by the Ala mutation and 16-fold by the Lys mutation. Activity toward medium chain length acyl thioesters was also increased >3 orders of magnitude by mutation of Arg-606, so that the Ala-606 enzyme is an effective medium chain length fatty acyl transacylase. These results indicate that Arg-606 plays an important role in the binding of malonyl moieties to the transacylase domain but is not required for binding of acetyl moieties; these results are also consistent with a mechanism whereby interaction between the positively charged guanidinium group of Arg-606 and the free carboxylate anion of the malonyl moiety serves to position this substrate in the active site of the enzyme.
Acetyl Coenzyme A↗
Gene therapy for cystic fibrosis.
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Animals↗
F-18-fluorodeoxyglucose PET imaging alters clinical decision making in patients with impaired ventricular function.
The effect of F-18-fluorodeoxyglucose positron emission tomography imaging on decision making in the selection of patients with impaired ventricular function for revascularization was determined in 87 patients. In 57% of patients, positron emission tomography data influenced management decisions, indicating an important effect of myocardial viability determination on difficult therapy decisions in these patients.
Aged↗
TRF1 is a dimer and bends telomeric DNA.
TRF1 is a mammalian telomeric protein that binds to the duplex array of TTAGGG repeats at chromosome ends. TRF1 has homology to the DNA-binding domain of the Myb family of transcription factors but, unlike most Myb-related proteins, TRF1 carries one rather than multiple Myb-type DNA-binding motifs. Here we show that TRF1 binds DNA as a dimer using a large conserved domain near the N-terminus of the protein for TRF1-TRF1 interactions. Dimerization was observed both in a complex with DNA and in the yeast two-hybrid assay. TRF1 dimers were found to require both Myb repeats for the formation of a stable complex with DNA, indicating a parallel between the DNA-binding mode of TRF1 and other Myb-related proteins. TRF1 was found to have a number of biochemical similarities to Rap1p, a distantly related DNA-binding protein that functions at telomeres in yeast. Rap1p and TRF1 both require two Myb motifs for DNA binding and both factors bind along their cognate telomeric sequences without showing strong cooperative interactions between adjacent proteins. Furthermore, TRF1 was found to bend its telomeric site to an angle of -120 degrees. Since Rap1p similarly distorts telomeric DNA, we propose that DNA bending is important for the function of telomeres in yeast and mammals.
Amino Acid Sequence↗
Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency.
Interleukin-4 (IL-4) is an important cytokine for B and T lymphocyte function and mediates its effects via a receptor that contains gammac. B cells derived from patients with X-linked severe combined immunodeficiency (X-SCID) are deficient in gammac and provide a useful model in which to dissect the role of this subunit in IL-4-mediated signaling. We found that although IL-4 stimulation of X-SCID B cells did not result in Janus tyrosine kinase-3 (JAK3) phosphorylation, other IL-4 substrates including JAK1 and IRS-1 were phosphorylated. Additionally, we detected signal transducers and activators of transcription 6 (STAT6) tyrosine phosphorylation and DNA binding activity in X-SCID B cells with a wide range of gammac mutations. However, reconstitution of these X-SCID B cells with gammac enhanced IL-4-mediated responses including STAT6 phosphorylation and DNA binding activity and resulted in increased CD23 expression. Thus, gammac is not necessary to trigger IL-4-mediated responses in B cells, but its presence is important for optimal IL-4-signaling. These results suggest that two distinct IL-4 signaling pathways exist.
B-Lymphocytes↗
Mapping of functional interactions between domains of the animal fatty acid synthase by mutant complementation in vitro.
Polypeptides of the animal fatty acid synthase (FAS) consist of three amino-terminal catalytic domains, beta-ketoacyl synthase, malonyl/acetyltransacylase, and dehydrase, separated by a 600-residue structural core from four carboxyl-terminal catalytic domains, enoyl reductase, beta-ketoacyl reductase, acyl carrier protein, and thioesterase. In the active dimeric form of the protein the two identical multifunctional polypeptides are oriented head-to-tail such that two sites for palmitate synthesis are formed at the subunit interface. In order to map the functional interactions between domains of the two subunits that contribute to the two sites of synthesis, we have utilized a strategy based on complementation analysis in vitro of modified FASs carrying mutations in specific catalytic domains. Homodimeric mutant FASs lacking functional beta-ketoacyl synthase (KS-), dehydrase (DH-), acyl carrier protein (ACP-), or thioesterase (TE-) domains, as well as heterodimers formed between ACP- and TE- subunits, between ACP- and DH- subunits, and between DH- and TE- subunits, were unable to synthesize fatty acids. However, heterodimers formed between KS- and either DH-, ACP-, or TE- subunits regained partial FAS activity. These data indicate that the dehydrase domain, although located in the amino-terminal half of the polypeptide, should be assigned to the complementation group located in the carboxy-terminal half that includes the acyl carrier protein and thioesterase domains. Thus, the current model for the animal FAS must be revised to reflect the finding that the two constituent polypeptides are not simply positioned side-by-side in a fully extended conformation but are coiled in a manner that allows the dehydrase domain to access the beta-hydroxyacyl-ACP located more than 1100 residues distant on the same subunit.
Animals↗
Differential activation of the tyrosine kinases ZAP-70 and Syk after Fc gamma RI stimulation.
Engagement of the high-affinity IgG Fc receptor (Fc gamma RI) activates a signal transduction pathway involving tyrosine phosphorylation of associated kinases. We compared the activation of the related protein tyrosine kinases (PTKs), Syk and ZAP-70, in Fc gamma RI-mediated signaling. Cross-linking of the Fc gamma RI multimeric receptor in monocytic cells results in tyrosine phosphorylation of the Fc epsilon RI gamma subunit and association of Syk with this complex. We stably introduced ZAP-70 via a retroviral vector into two monocytic cell lines, U937 and THP-1, which normally do not express ZAP-70. Neither Syk nor MAP kinase activation was affected by the presence of ZAP-70. Although transduced ZAP-70 had in vitro kinase activity and associated with Fc epsilon RI gamma after receptor aggregation, it was not tyrosine phosphorylated. In contrast, both ZAP-70 and Syk were phosphorylated in a T-cell line in which their respective levels of expression were similar to those detected in U937/ZAP-70 cells. Therefore, these results suggest that requirements for Syk and ZAP-70 phosphorylation are distinct in a monocytic cell context.
Cell Line↗
Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption.
OBJECTIVE: To examine eyes from mice with targeted adenomatous polyposis coli (APC) gene disruption to determine if retinal pigment epithelium (RPE) abnormalities replicate the human counterpart. METHODS: Thirty-two eyes from 16 mice heterozygous for APC gene disruption (chain-termination mutation in codon 1638 of exon 15) and 12 control eyes were examined by light microscopy. RESULTS: Fifteen of 32 eyes from 12 of 16 APC-disrupted mice demonstrated abnormalities of the RPE and retina. The RPE abnormalities included RPE coloboma, unifocal and multifocal RPE hypertrophy, RPE hyperplasia, and RPE duplication with invasion in the areas of outer and inner segments. Retinal abnormalities included outer nuclear layer duplication and outer nuclear layer atrophy. There were no RPE and retinal abnormalities seen in the control eyes. CONCLUSIONS: This study is consistent with the hypothesis that the APC gene is critical in the regulation of RPE proliferation and development. These findings also demonstrate that mutation of the APC gene in codon 1638, a location beyond the previously described critical region for human RPE abnormalities, leads to perturbation in the mouse RPE and retina. Further study of this murine model and the APC/RPE relationship may provide insight into regulatory mechanisms for RPE proliferation.
Adenomatous Polyposis Coli↗
Differential inhibitory effect of regular inhaled corticosteroid on airway responsiveness to adenosine 5' monophosphate, methacholine, and bradykinin in symptomatic children with recurrent wheeze.
Indirect tests of bronchial responsiveness to agents such as adenosine 5'-monophosphate (AMP) or bradykinin might be more specific markers of a therapeutic responses to anti-inflammatory treatment than a test of direct responsiveness to agents such as methacholine. In children selected from the community on the basis of mildly symptomatic wheeze, we compared in a randomized, double-blind study design the effect of 400 micrograms/day of beclomethasone dipropionate (BDP) or placebo on three separate ways of provoking bronchial responsiveness, using methacholine, bradykinin, and AMP as the provoking agents. Following pretreatment bronchial challenges, 29 children received paired monthly methacholine and AMP challenges for 3 months, while for the same period another 33 children received paired monthly methacholine and bradykinin challenges. Compared with placebo-treated subjects, FEV1 increased significantly in the children receiving BDP. This improvement was observed in those randomized to either the AMP challenge or the bradykinin challenge. In children challenged with AMP, the PD20 AMP increased significantly after 1 month and 2 months of BDP therapy when compared with placebo, while under similar conditions the PD20 methacholine was not significantly affected. In children challenged with bradykinin, BDP therapy did not significantly alter either the PD20 bradykinin or PD20 methacholine. We conclude that a bronchial challenge with AMP appears to be a more sensitive predictor of response to anti-inflammatory treatment than either methacholine or bradykinin.
Adenosine Monophosphate↗
Inhibitory control during sentence comprehension in individuals with dementia of the Alzheimer type.
In two experiments we investigated the extent to which individuals with dementia of the Alzheimer type (DAT) manage the activation of contextually appropriate and inappropriate meanings of ambiguous words during sentence comprehension. DAT individuals and healthy older individuals read sentences that ended in ambiguous words and then determined if a test word fit the overall meaning of the sentence. Analysis of response latencies indicated that DAT individuals were less efficient than healthy older individuals at suppressing inappropriate meanings of ambiguous words not implied by sentence context, but enhanced appropriate meanings to the same extent, if not more, than healthy older adults. DAT individuals were also more likely to allow inappropriate information to actually drive responses (i.e., increased intrusion errors). Overall, the results are consistent with a growing number of studies demonstrating impairments in inhibitory control, with relative preservation of facilitatory processes, in DAT.
Aged↗
Teenage truancy, part-time working and wages.
"Although the determinants of teenager participation in the labour market have been studied previously (both in the United States and the United Kingdom), there remain a number of neglected questions. We address some of these in this paper, basing our analysis on data taken from the UK National Child Development Study. We first examine how teenagers divide their time between working and studying. We further analyse what explains teenage wages and labour supply. We utilize a rich set of variables describing parental background, as well as parents' labour force status and draw on information on physical stature to explain variations in wages."
Adolescent↗
Helicobacter pylori infection is related to atheroma in patients undergoing coronary angiography.
OBJECTIVES: Helicobacter pylori infection has been related to an increased risk of ischaemic heart disease (IHD) possibly by raising plasma fibrinogen. The evidence for this association is conflicting. Furthermore, no attempt has been made to distinguish between an effect on atheroma and thrombosis. We have determined the association of H. pylori status with IHD assessed by coronary angiography. We have also evaluated the influence of H. pylori infection on haemostatic factors. METHODS: Caucasian patients undergoing coronary angiography for suspected IHD were recruited. H. pylori status was determined by serology (Helico G). Plasma fibrinogen was measured by the Clauss assay. Coronary angiograms were assessed and significant atheroma defined as > or = 50% stenosis. A history of myocardial infarction was ascertained by WHO criteria. RESULTS: 292 patients were recruited (median age 59, 95 female); 204 (70%) patients had IHD and 185 (64%) of all patients were H. pylori-positive; 68% patients with IHD were H. pylori-positive compared with 50% without IHD (P = 0.003). When adjusted for other risk factors by logistic regression, H. pylori remained significantly associated with IHD (odds ratio = 2.4, 95% CI = 1.2-5.1, P = 0.02). H. pylori status was not related to a history of myocardial infarction. Circulating levels of PAI-1, vWF, Factor VII and fibrinogen were not related to H. pylori status. CONCLUSION: This study suggests that infection with H. pylori is associated with coronary atheroma, but that this relationship is unlikely to be mediated through raised plasma fibrinogen.
Adult↗
Mouse in vitro fertilization, embryo development and viability, and human sperm motility in substances used for human sperm preparation for assisted reproduction.
OBJECTIVE: To investigate the endotoxin content and effects on mouse IVF and embryo development and human sperm motility of human sperm separation substances. DESIGN: One-cell and zona-free two-cell mouse embryo bioassays and Limulus Amoebocyte Lysate endotoxin tests and mouse oocyte parthenogenetic activation, IVF, preimplantation and postimplantation embryo development, and human sperm motility were performed in control medium or medium containing Percoll, Nicodenz, or the washings from Sperm Prep sephadex columns. SETTING: Research Laboratories, Sinai Hospital of Baltimore, Baltimore, Maryland. MAIN OUTCOME MEASURE(S): Endotoxin levels, embryo development, and sperm motility. RESULT(S): Mouse embryo bioassays indicated negative endotoxin levels in Percoll and Nicodenz but Limulus Amoebocyte Lysate assays had positive gel formation. Mouse IVF and preimplantation development was equivalent in control and Percoll- and Nicodenz-containing medium; none had parthenogenetic properties but postimplantation development was reduced for embryos grown in the presence of Percoll or Nicodenz. Human sperm remained motile in the presence of Percoll or Nicodenz. Sperm Prep column washes were toxic to mouse gametes and embryos and human sperm and had gel formation with the Limulus Amoebocyte Lysate assay. CONCLUSION(S): Percoll and Nicodenz, but not Sperm Prep sephadex column washes, were compatible with mouse preimplantation and postimplantation embryo development and human sperm motility.
Animals↗
Immunobiology of childhood tuberculosis: a window on the ontogeny of cellular immunity.
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Age Factors↗