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Biomedical subjects

Stuart J Smith

Publications and source records attributed to Stuart J Smith.

5 recordsLinked to original sources
PubMed2005

The MLC1v gene provides a transgenic marker of myocardium formation within developing chambers of the Xenopus heart.

Many details of cardiac chamber morphogenesis could be revealed if muscle fiber development could be visualized directly within the hearts of living vertebrate embryos. To achieve this end, we have used the active promoter of the MLC1v gene to drive expression of green fluorescent protein (GFP) in the developing tadpole heart. By using a line of Xenopus laevis frogs transgenic for the MLC1v-EGFP reporter, we have observed regionalized patterns of muscle formation within the ventricular chamber and maturation of the atrial chambers, from the onset of chamber formation through to the adult frog. In f1 generation MLC1v-EGFP animals, promoter activity is first detected within the looping heart tube and delineates the forming ventricular chamber and proximal outflow tract throughout their development. The 8-kb MLC1v promoter faithfully reproduces the embryonic expression of the endogenous MLC1v mRNA. At later larval stages, weak patches of EGFP fluorescence are found on the atrial side of the atrioventricular boundary. Subsequently, an extensive lattice of MLC1v-expressing fibers extend across the mature atrial chambers of adult frog hearts and the transgene reveals the differing arrangement of muscle fibers in chamber versus outflow myocardium. The complete activity of the promoter resides within the proximal 4.5 kb of the MLC1v DNA fragment, whereas key elements regulating chamber-specific expression are present in the proximal-most 1.5 kb. Finally, we demonstrate how cardiac and craniofacial muscle expression of the MLC1v promoter can be used to diagnose mutant phenotypes in living embryos, using the injection of RNA encoding a Tbx1-engrailed repressor-fusion protein as an example.

Animals↗
PubMed2005

Neuroendocrine profiling of humans receiving cardiac allografts.

BACKGROUND: Several studies have investigated changes in circulating hormones and markers of cardiac status after heart transplantation in humans. As a result, plasma levels of various hormones and autocoids have been associated with cardiac allograft rejection status. However, no clear associations can be defined given the highly contradictory nature of the available literature. METHODS: In this study of 69 consecutive heart transplant patients followed for >2 years we examine the relationship between neurohumors potentially related to allograft rejection and endomyocardial biopsy grade of rejection (according to the ISHLT) and hemodynamic status. Markers assessed include brain natriuretic peptide (BNP), amino-terminal pro-BNP (N-BNP), atrial natriuretic factor (ANF), adrenomedullin, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, troponin C and C-reactive protein. RESULTS: The highest plasma levels for most neurohumors were found shortly after surgery and showed a trend towards normalization with time. BNP and N-BNP were the only significantly elevated plasma analytes for patients with Grade 3 rejection as compared with other ISHLT grades. ANF plasma levels correlated with BNP and N-BNP in Grades 0 to 2, but not in Grade 3, suggesting that in this rejection grade the usual coordinated changes observed in BNP and ANF secretion no longer exist. Cardiac filling pressures were correlated with plasma BNP, N-BNP and ANF levels only for Grades 0 and 1. CONCLUSIONS: The timing of blood sampling after transplantation influences the level of the neurohumors measured, which may help explain the conflicting literature reports on the association between neurohumor levels and rejection grade. The significant increase in circulating levels of BNP and N-BNP observed in most cases of Grade 3 rejection occurred with no apparent relationship to post-transplantation time, which suggests a specific influence of acute rejection on BNP gene expression.

Adolescent↗
PubMed2003

Prognostic use of cardiac troponin T and troponin I in patients with heart failure.

BACKGROUND: Troponin T (cTnT) and troponin I (cTnI) are present in the sera of some heart failure (HF) patients and have potential importance as prognostic markers. OBJECTIVE: To prospectively evaluate the prognostic value of cTnT and cTnI in well-characterized HF patients and clarify their relationship to other clinical markers of HF severity. METHODS: cTnT and cTnI were measured in 78 HF patients (45 inpatients, 33 outpatients) who were followed up prospectively for 12 months. RESULTS: Plasma cTnT (> or =0.02 ng/mL) and cTnI (> or =0.3 ng/mL) were detected in 51% and 46% of patients, respectively. These patients were more likely to be inpatients (70% versus 45% for cTnT, 75% versus 43% for cTnI, P<0.05 for both), have a higher plasma creatinine (153 versus 119 micromol/L for cTnT; 157 versus 118 micromol/L for cTnI, P<0.05) and lower plasma sodium (134 versus 138 mmol/L for both, P<0.05). At 12 months, they were more likely to have died or undergone cardiac transplantation (41% versus 14%, P=0.01 for cTnT; 43% versus 15%, P=0.004 for cTnI). After adjustment for New York Heart Association class, plasma sodium and inpatient status, a significant association with events was still evident for both troponins. CONCLUSIONS: Both cTnT and cTnI are strongly associated with other clinical indicators of HF severity and remain independent predictors of prognosis after adjustment for these factors. These results indicate a potential role for cTnT and cTnI in the clinical management of HF patients.

Aged↗
PubMed2002

XPOX2-peroxidase expression and the XLURP-1 promoter reveal the site of embryonic myeloid cell development in Xenopus.

Phagocytic myeloid cells provide the principle line of immune defence during early embryogenesis in lower vertebrates. They may also have important functions during normal embryo morphogenesis, not least through the phagocytic clearance of cell corpses arising from apoptosis. We have identified two cDNAs that provide sensitive molecular markers of embryonic leukocytes in the early Xenopus embryo. These encode a peroxidase (XPOX2) and a Ly-6/uPAR-related protein (XLURP-1). We show that myeloid progenitors can first be detected at an antero-ventral site in early tailbud stage embryos (a region previously termed the anterior ventral blood island) and transiently express the haematopoetic transcription factors SCL and AML. Phagocytes migrate from this site along consistent routes and proliferate, becoming widely distributed throughout the tadpole long before the circulatory system is established. This migration can be followed in living embryos using a 5 kb portion of the XLURP-1 promoter to drive expression of EGFP specifically in the myeloid cells. Interestingly, whilst much of this migration occurs by movement of individual cells between embryonic germ layers, the rostral-most myeloid cells apparently migrate in an anterior direction along the ventral midline within the mesodermal layer itself. The transient presence of such cells as a strip bisecting the cardiac mesoderm immediately prior to heart tube formation suggests that embryonic myeloid cells may play a role in early cardiac morphogenesis.

Amino Acid Sequence↗