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Biomedical subjects

Wendy Smith

Publications and source records attributed to Wendy Smith.

9 recordsLinked to original sources

Borrelia burgdorferi-induced expression of matrix metalloproteinases from human chondrocytes requires mitogen-activated protein kinase and Janus kinase/signal transducer and activator of transcription signaling pathways.

Elevations in matrix metalloproteinase 1 (MMP-1) and MMP-3 have been found in patients with Lyme arthritis and in in vitro models of Lyme arthritis using cartilage explants and chondrocytes. The pathways by which B. burgdorferi, the causative agent of Lyme disease, induces the production of MMP-1 and MMP-3 have not been elucidated. We examined the role of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways in MMP induction by B. burgdorferi. Infection with B. burgdorferi results in rapid phosphorylation of p38 and JNK within 15 to 30 min. Inhibition of JNK and p38 MAPK significantly reduced B. burgdorferi-induced MMP-1 and MMP-3 expression. Inhibition of ERK1/2 completely inhibited the expression of MMP-3 in human chondrocytes following B. burgdorferi infection but had little effect on the expression of MMP-1. B. burgdorferi infection also induced phosphorylation and nuclear translocation of STAT-3 and STAT-6 in primary human chondrocytes. Expression of MMP-1 and MMP-3 was significantly inhibited by inhibition of JAK3 activity. Induction of MMP-1 and -3 following MAPK and JAK/STAT activation was cycloheximide sensitive, suggesting synthesis of intermediary proteins is required. Inhibition of tumor necrosis factor alpha (TNF-alpha) significantly reduced MMP-1 but not MMP-3 expression from B. burgdorferi-infected cells; inhibition of interleukin-1beta (IL-1beta) had no effect. Treatment of B. burgdorferi-infected cells with JAK and MAPK inhibitors significantly inhibited TNF-alpha induction, consistent with at least a partial role for TNF-alpha in B. burgdorferi-induced MMP-1 expression in chondrocytes.

Borrelia burgdorferi↗

Swallowed partial dentures.

Swallowed or inhaled partial dentures can present a diagnostic challenge. Three new cases are described, one of them near-fatal because of vascular erosion and haemorrhage. The published work points to the importance of good design and proper maintenance. The key to early recognition is awareness of the hazard by denture-wearers, carers and clinicians.

Deglutition↗

PTTH-stimulated ecdysone secretion is dependent upon tyrosine phosphorylation in the prothoracic glands of Manduca sexta.

PTTH stimulates ecdysteroid secretion by the insect prothoracic glands. The peptide activates cAMP synthesis in a calcium-dependent manner, ultimately enhancing ecdysteroid synthesis. We have found that PTTH stimulates a rapid increase in tyrosine phosphorylation of at least four proteins in the prothoracic glands of larval Manduca sexta, as seen on Western blots of glandular lysates probed with antibody directed against phosphotyrosine. PTTH-stimulated tyrosine phosphorylation is blocked by an inhibitor of Src family tyrosine kinases, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1). The inhibitor also blocks PTTH-stimulated ecdysone secretion, as well as PTTH-stimulated cAMP synthesis. Direct activation of the catalytic subunit of adenylyl cyclase by forskolin is not affected by PP1. In addition, ecdysteroid secretion stimulated by the cAMP analog dbcAMP is not blocked by PP1. These findings point to an important role for a Src-family tyrosine kinase at a very early step in the PTTH signaling pathway, prior to the activation of adenylyl cyclase.

Animals↗

Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification.

Idiopathic infantile arterial calcification (IIAC; OMIM 208000) is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. We analyzed affected individuals from 11 unrelated kindreds and found that IIAC was associated with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This cell surface enzyme generates inorganic pyrophosphate (PP(i)), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification.

Arteries↗

Fetal fibronectin: the impact of a rapid test on the treatment of women with preterm labor symptoms.

OBJECTIVE: The purpose of this study was to determine whether knowledge of the results of a rapid fetal fibronectin test affects treatment decisions during the evaluation and treatment of possible preterm labor. Previous observational studies have suggested that a negative test might help to avoid unnecessary intervention. STUDY DESIGN: This was a randomized study of women who were between 24 weeks and 34 weeks 6 days of gestation with symptoms of preterm labor and who were seen in three community hospitals. A rapid fetal fibronectin test was performed on all subjects. Patients were assigned randomly to a group whose results were known to physician or to a group whose results were not known. Treatment decisions were at the discretion of the physician. RESULTS: One hundred eight samples were collected between September 2000 and December 2001. There were 10 positive fetal fibronectin tests. The overall prevalence of delivery within 2 weeks for the study population was 2.8%. For women who had negative fetal fibronectin test results, the hospital stay was not significantly shorter when the result was known (6.8 hours) than when it was not known (8.1 hours, P =.35). However, when the physician knew the fetal fibronectin status of women with a negative test result who were observed for >6 hours, the hospital stay was shortened 40%, to 22.7 hours from 37.8 hours (P =.04). CONCLUSION: Fetal fibronectin testing may be able to supplement clinical judgment in the evaluation of the condition of patients with symptoms of preterm labor. The greatest benefit of fetal fibronectin testing might be for the patient whom the physician judges to be at high risk for imminent delivery. In such patients, the knowledge of a negative fetal fibronectin may shorten the hospital stay.

Adult↗

Statistical analysis of decorrelation-based transducer tracking for three-dimensional ultrasound.

The use of speckle decorrelation techniques to calculate the displacement of a moving transducer has shown promise. We describe a technique to estimate displacement between pairs of parallel planes without assuming that plane separation in the scan is uniform. We perform theoretical and empirical analyses of the bias and uncertainty in plane spacing estimates as a function of speckle size, patch size, and the number of planes used for normalization. Practically, only the central, linear region of the autocovariance curves can be used in this decorrelation method, which implies that distance between acquired image planes should be approximately half the speckle size. In this region, the uncertainty in estimated plane spacing was less than 15% for a 8.1 mm (axial) by 9.1 mm (lateral) patch and increased to 33% for an 8.1 mm (axial) by 1.5 mm (lateral) patch. The number of planes, Nz, used to calculate the normalization factors (averages of brightness and- squared brightness) was a major source of bias. Optimum Nz was found to be five to ten planes, depending on distance between acquired image planes, with a poor choice of Nz resulting in a bias of 10% or greater. A second source of bias is brightness gradients which, although they appear very slight on intensity images, can cause a large bias is the plane spacing estimates made using linearized data.

Algorithms↗

Second-trimester sonographic diagnosis of diastrophic dysplasia: report of 2 index cases.

OBJECTIVE: To describe the sonographic features of diastrophic dysplasia in 2 second-trimester index offspring. METHODS: Real-time sonography was performed on 2 second-trimester fetuses with no risk factors for skeletal dysplasia. RESULTS: Each fetus had severe bilateral upper and lower extremity long bone shortening, hitchhiker thumbs and great toes, and clubbed feet, indicating a diagnosis of diastrophic dysplasia. CONCLUSIONS: Index cases of diastrophic dysplasia may be correctly diagnosed on the basis of second-trimester sonography.

Adult↗

Preferential use of sonographically guided biopsy to minimize patient discomfort and procedure time in a percutaneous image-guided breast biopsy program.

OBJECTIVE: To determine whether preferential use of sonographic guidance for percutaneous biopsy of breast masses results in a subset of patients with a shorter procedure time and less discomfort compared with patients undergoing stereotactic biopsy. METHODS: A prospective observational study was performed on 193 women undergoing percutaneous image-guided breast biopsy between 1997 and 1999. Data were collected on room time, physician time, and patient comfort levels for 122 stereotactic and 71 sonographically guided biopsies. Differences between stereotactic and sonographically guided biopsy for all lesions and for masses were analyzed for statistical significance. RESULTS: Mean room times were 62.2 minutes for stereotactic biopsy and 39.4 minutes for sonographically guided biopsy (P < .0001). Mean physician times were 23.0 minutes for stereotactic biopsy and 15.8 minutes for sonographically guided biopsy (P < .0001). When we limited our analyses to women undergoing biopsy for masses, the difference in physician time largely disappeared, but the difference in room time remained (P < .0001). Women undergoing stereotactic biopsy were more likely to report discomfort due to body positioning than were women undergoing sonographically guided biopsy (P < .001). These differences existed whether we included all lesions or restricted our analyses to masses. CONCLUSIONS: Preferential use of sonographically guided breast biopsy for masses results in shorter procedure times and less patient discomfort compared with prone stereotactic biopsy.

Aged↗