Hyperhomocysteinemia, MTHFR 677C-->T polymorphism, and stroke.
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Adult↗
Biomedical subjects
M Barron
Publications and source records attributed to M Barron.
Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2.
Expression patterns of Tbx2, -3, and -5 genes were analyzed during chick embryonic heart development. Transcripts of these three cTbx genes were detected in overlapping patterns in the early cardiac crescent. cTbx2 and cTbx3 expression patterns closely overlapped with that of bmp2. cTbx5 expression diverged from cTbx2 and bmp2 during the elaboration and folding of the heart tube. In comparison, cTbx2 expression overlapped significantly with that of bmp2 and bmp4 during all stages of heart development and during later embryonic stages, suggestive of a specialized role for Tbx2 in septation. Coexpression of cTbx 2 and cTbx3 genes with bmp2 transcripts raised the possibility that these cTbx genes might be downstream bmp2 targets. Application of bmp2 selectively induced cTbx2 and cTbx3 expression in noncardiogenic embryonic tissue, and the bmp antagonist Noggin down-regulated cTbx2 gene activity. Moreover, the appearance of murine mTbx2 was blocked in bmp2 null mouse embryos. cTbx2 and to a lesser extent cTbx3 gene activity appears to be directed by BMPs during early cardiogenesis.
Animals↗
Requirement for BMP and FGF signaling during cardiogenic induction in non-precardiac mesoderm is specific, transient, and cooperative.
We previously reported that combined treatment with bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-4 (FGF-4) induces cardiogenic events culminating in full cardiac differentiation of non-precardiac mesoderm explanted from stage 6 avian embryos (Lough et al. [1996] Dev. Biol. 178:198-202.). To elucidate the respective functions of BMP and FGF in initiating and maintaining the cardiogenic process, we have used these ectopic cells as a cardiac specification model to ascertain requirements for growth factor specificity and extent of application, as well as induction of cardiac transcription factors. The inability of some BMP isoforms to replace the inductive activity of BMPs-2/4 indicated a specific requirement for this signaling pathway; moreover, neither activin-A nor insulin, which support terminal differentiation of precardiac mesoderm, nor leukocyte inhibitory factor (LIF), which promotes hypertrophy in cardiac myocytes, could replace BMP's cardiogenic activity. A similarly specific requirement for FGF-2/4 signaling was revealed since neither FGF-7, activin-A nor insulin could replace this activity. The effect of both factors was concentration-dependent; maximal incidence of explant differentiation for each occurred at 50 ng/ml. Surprisingly, the majority of explants treated with high BMP levels (250 ng/ml) exhibited a non-cardiac phenotype that was characterized by intense expression of alkaline phosphatase, suggesting differentiation toward an alternative mesodermal phenotype. Experiments to assess the duration of exposure to each factor that was required revealed that while exposure to BMP and FGF during only the initial 30 min of a 48-hr culture period was sufficient to induce cardiogenesis in a significant percentage of explants, 100% incidence of explant differentiation was obtained only when FGF treatment was restricted to the first 30 min and BMP was continuously present during the 48-hr culture period. Treatment with both growth factors was required to induce the cardiac transcription factors cNkx-2.5 and SRF; neither mRNA was induced by BMP or FGF alone. These findings indicate that: (1) specific members of the BMP and FGF families are required to induce cardiogenesis in non-precardiac mesoderm; (2) BMPs-2/4 may function as a morphogen; (3) brief application of both factors can induce cardiogenesis in a modest number of explants whereas (4) 100% incidence of explant differentiation can only be attained by brief FGF treatment combined with continuous BMP treatment and (5) both factors are necessary to induce downstream cardiac transcription factors. These findings are interpreted in terms of these factors' possible roles during cardiac specification and differentiation.
Bone Morphogenetic Protein 2↗
Fluorescence in situ hybridization analysis of the fos/jun ratio in the ageing brain.
We have examined the expression of the fos and jun genes in the cerebellum of the rat brain during ageing, by use of a semi-quantitative fluorescence in situ hybridization (FISH) method. In these experiments we have utilised the digital imaging capabilities of a cooled CCD camera system to store the fluorescence intensities of individual cells and to compare the data from each target (fos or jun) gene with that of a control (beta-actin) gene. In this way we have been able to obtain a relative quantitation of fos and jun mRNA levels. Purkinje cells were analysed in brain from Sprague-Dawley rats of 6, 13 and 23 months of age. Data obtained in this way demonstrated that the level of fos expression decreased significantly during ageing but, in contrast, that of jun increased between 6 and 13 months and thereafter remained constant. We subsequently carried out a further comparison of fos/jun ratios in purkinje cells in Wistar rats and also observed a highly significant fall in the ratio between 6 and 23 months. This change in the fos/jun ratio has important implications for the composition of the AP-1 transcription factor and for the expression of genes that it regulates.
Aging↗
Controlled ventilation enhances catheter stability during radiofrequency ablation.
Variations in the amplitude of the atrial and ventricular depolarization waves of the intracardiac electrogram occur during different phases of respiration. Therefore, we tested whether controlled ventilation would reduce ablation attempts and increase the rate of success in patients undergoing radiofrequency ablation with general anesthesia. Thirty-eight children were divided into two groups: (1) controlled and (2) noncontrolled or cyclic ventilation. In the controlled ventilation group, the mapping electrogram was recorded during sustained inspiration, sustained expiration, and cyclic ventilation. Ablation was done in the phase of ventilation that had the least variability in atrial and ventricular amplitudes. Seventeen patients in the controlled ventilation group had tracings adequate for review. In eight patients, ablation was done during sustained inspiration with the percentage change of atrial and ventricular amplitudes (15% +/- 16% and 13% +/- 16%, respectively) being < that during sustained expiration (38% +/- 27%, P = 0.04 and 20% +/- 21%) or during cyclic ventilation (57% +/- 27%, P < 0.01 and 54% +/- 26%, P = 0.003). In nine patients, ablation was done during sustained expiration with the percentage change of atrial and ventricular amplitudes (5% +/- 5% and 5% +/- 2%) being less than that during sustained inspiration (21% +/- 14%, P = 0.01 and 11% +/- 6%, P = 0.01) or during cyclic ventilation (68% +/- 23%, P < 0.001 and 48 +/- 26%, P = 0.001). We achieved success with each patient in both groups, but the number of ablation attempts were less in the controlled ventilation group 1 (3 +/- 2), as compared to the cyclic ventilation group 2 (8 +/- 8; P < 0.02). We concluded that controlled ventilation reduced the number of ablation attempts and facilitated the ablation procedure.
Adolescent↗
Tardive dyskinesia.
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Antipsychotic Agents↗
Expression of retinol binding protein and transthyretin during early embryogenesis.
Previous studies have shown that anterior lateral plate endoderm from stage 6 chicken embryos is necessary and sufficient to enable precardiac mesoderm to complete its cardiogenic program in vitro, culminating in a rhythmically contractile multicellular vesicle (Sugi and Lough [1994] Dev. Dyn. 200:155-162). To identify cardiogenic factors, we have begun to characterize proteins that are secreted by endoderm cell explants. Fluorography of proteins from endoderm-conditioned medium revealed 1-2 dozen bands, the most prominent of which migrated at approximately 17 and 25 kD. The bulk of the 17-kD band, which migrates near FGFs and subunits of the transforming growth factor-beta family, was identified by N-terminal sequencing as transthyretin (TTR). A component of the 25-kD band was identified by Western blotting as retinol binding protein (RBP). RT/PCR analysis revealed that mRNAs for both proteins are in the embryo as early as stage 3. In situ hybridization localized these mRNAs to the extraembryonic endoderm at stage 6, after which they were detected in endoderm overlying the embryo proper, including the developing heart. Later, RBP and TTR mRNA and protein were detected in cells associated with the developing heart. Western blotting of whole embryo proteins revealed the presence of RBP by stage 7, followed by sequential increases to stage 25; by contrast, content of RBP in isolated hearts peaked at stage 14, then declined. Immunohistochemistry revealed the presence of RBP protein in the extracellular matrix subjacent to lateral plate endoderm beginning at stage 8; upon formation of the definitive heart, intense staining was observed in the cardiac "jelly." By contrast TTR was intracellular, first detected as subtle deposits in stage 6 embryonic endoderm, which by stage 8 were prominent in the dorsally invaginated endoderm subjacent to the precardiac splanchnic mesoderm. At stages 11-14, TTR was detected only in myocardial cells. Such localization of RBP and TTR may indicate a role in the transport and distribution of retinol and thyroid hormone, respectively, from yolk to embryo prior to establishment of the circulatory system, and is suggestive of a subsequent role in heart development.
Amino Acid Sequence↗
Disease surveillance in the ED: factors leading to the underreporting of gonorrhea.
Emergency departments (EDs) are potentially important surveillance sites. This study assessed reporting completeness for gonorrhea by hospital and gender and explored reasons for underreporting. A retrospective review was conducted of ED charts from three hospitals for 2 months. Potential gonorrhea cases were identified by history, physical examination, testing, treatment, and diagnostic practices. Cases were divided into those tested only, those treated with or without testing, and those with positive tests. Reporting completeness was assessed for each. Of 936 cases included, 29.0% were tested without treatment and 71% received treatment. One third of treated patients were not tested, and none of these were reported. Two EDs reported cases themselves and reported 75.9% of confirmed cases. There were significant differences in testing and reporting between hospitals and genders. Underreporting of suspected and confirmed gonorrhea cases was common from these EDs. A major cause was physicians treating without testing for confirmation.
Anti-Bacterial Agents↗
Cardiopulmonary bypass in a patient with moyamoya disease.
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Anesthesia, General↗
Combined BMP-2 and FGF-4, but neither factor alone, induces cardiogenesis in non-precardiac embryonic mesoderm.
Previous work in this laboratory has shown that endoderm cells in the heart forming region (HFR endoderm) of the chicken embryo induce terminal cardiac differentiation in explanted precardiac mesoderm cells. Immunostaining patterns indicating that HFR endoderm cells express Drosophila decapentaplegic (dpp)-like antigens prompted a degenerate polymerase chain reaction (PCR) screen to identify cDNAs in the dpp subgroup of the transforming growth factor-beta (TGF-beta) family. Among 50 clones of PCR products that have been sequenced, over half have identity with bone morphogenetic protein-2 (BMP-2). No other TGF-beta cDNAs have been detected, suggesting that BMP-2 is the major dpp subgroup protein synthesized by HFR endoderm cells. However, BMP-2 protein did not promote survival of either precardiac or non-precardiac mesoderm cells in culture. Whereas FGF-4 supports cardiogenesis in precardiac mesoderm, it did not induce cardiogenesis in nonprecardiac mesoderm, although explant viability was maintained. In contrast to the isolated effects of these growth factors, treatment of non-precardiac mesoderm with combined BMP-2 and FGF-4 induced cardiogenesis in the majority of explants, as revealed by the formation of a rhythmically contractile multicellular vesicle that expresses sarcomeric alpha-actin. These findings suggest that BMP-2 and FGF-4 possess respective differentiative and proliferative activities, the combination of which specifies cells to the cardiac lineage.
Animals↗
Developmental expression of fibroblast growth factor receptor-1 (cek-1; flg) during heart development.
Previous work in this laboratory has indicated that fibroblast growth factor-2 (FGF-2; bFGF) regulates the initial stages of avian heart development in paracrine and autocrine fashion (Parlow et al. [1991] Dev. Biol. 146:139-147; Sugi et al. [1993] Dev. Biol. 157:28-37). Because these findings inferred the presence of a functional receptor for fibroblast growth factor (FGFR), we have immunochemically assessed the appearance of FGFR-1 (cek-1; flg) during development. Using a peptide-generated antibody, Western blots of total embryonic proteins revealed that FGFR-1 was barely detectable at pre-heart stages, followed by sequential increases in relative abundance that peaked at stage 24, followed by a decline at days 7-14. Western blots of proteins from isolated embryonic hearts demonstrated a similar developmental pattern, except that FGFR-1 expression was not decreased at later stages. The presence of FGFR-1 mRNA was verified by reverse transcription/polymerase chain reaction (RT/PCR) amplification. Immunohistochemical examination revealed punctate deposits of FGFR-1 in the precardiac endoderm at stage 6, followed by detection in the endoderm, foregut, and pre-cardiac splanchnic mesoderm at stage 8 and in the newly formed myocardium at the heart tube stage (9/10). By stage 13, FGFR-1 staining was observed only in the myocardium, a pattern which persisted at least until stage 30 (day 7), after which only isolated hearts were examined. After stage 30, staining was diminished in the ventricle, but not in the atrium. Staining of cardiac endothelial cells was not observed at any stage. A functional role for FGFR-1 was indicated by experiments in which anti-FGFR-1, but not pre-absorbed antiserum, retarded proliferation and multilayering of cardiogenic cells in an in vitro model of cardiac morphogenesis.
Animals↗
Symmetry of cerebral blood flow and cognitive responses to hypoglycaemia in humans.
A low blood glucose level is associated with impairment of higher cerebral function and an increase in cerebral blood flow. This study examined whether there are differences in the physiological responses to hypoglycaemia between the cerebral hemispheres. Eight healthy men participated in two hyperinsulinaemic glucose clamp studies: after 60 min at 4.5 mmol/l, blood glucose was either lowered to 2.0 mmol/l and "clamped" there for 60 min (hypoglycaemia) or continuously maintained at 4.5 mmol/l (euglycaemia). Cardiac output, middle cerebral artery velocity (transcranial Doppler) and cerebral blood flow (133-xenon inhalation) were measured during the studies. Neuropsychological tests were used to determine whether hypoglycaemia caused differential impairment of hemispheric cognitive function. Hypoglycaemia was associated with symmetrical impairment of cognitive function in both cerebral hemispheres and a rise in cardiac output (from 5.5 [0.2] to 8.7 [0.2] l.min-1, p < 0.0001, mean [standard error]), middle cerebral artery velocity (from 55 [2.6] to 64 [2.8] cm.s-1, p < 0.002), and global cerebral blood flow (from 56 [2.6] to 69 [2.9] ml.100 g-1.min-1, p < 0.005 compared to pre-insulin values). There were no differences in the blood flow response during hypoglycaemia between hemispheres and the increase in blood flow did not correlate with either the change in cardiac output or rise in plasma catecholamine levels. After 120 min of hyperinsulinaemic, euglycaemia, global cerebral blood flow rose significantly above baseline (from 58 [2.4] to 63 [2.2] ml.100 g-1.min-1, p < 0.05). In conclusion, using the techniques described, the physiological and cognitive responses of each cerebral hemisphere to hypoglycaemia were symmetrical.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Staghorn calculi: analysis of treatment results between initial percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy monotherapy with reference to surface area.
Treatment recommendations and results reported for the management of staghorn calculi are highly variable. In an attempt to provide a more objective means to compare treatment results for staghorn renal calculi, stone burden as measured by stone surface area was used. Stone surface area was determined by computer analysis. A total of 380 cases of staghorn calculi treated at the same institution was evaluated. Treatment consisted of initial percutaneous nephrostolithotomy with or without extracorporeal shock wave lithotripsy (ESWL*) in 298 cases and ESWL monotherapy in 82. When considered as a group, the overall stone-free rate for initial percutaneous nephrostolithotomy (mean surface area 1,378.3 mm.2) was 84.2% compared to 51.2% (p less than 0.0001) for ESWL monotherapy (mean surface area 693.4 mm.2). For staghorn calculi smaller than 500 mm.2 a stone-free rate of 94.4% was achieved in the percutaneous nephrostolithotomy with or without ESWL group compared to 63.2% for ESWL monotherapy (p = 0.0214). For calculi of 501 to 1,000 mm.2 the stone-free rates were 86% and 45.7%, respectively (p less than 0.0001). When stone surface area exceeded 1,000 mm.2 the stone-free rate for percutaneous nephrostolithotomy with or without ESWL was 82.4% but it was only 22.2% for ESWL monotherapy (p = 0.0002). Overall, when adjusted for stone surface area the odds of being stone-free were more than 8 times higher for initial percutaneous nephrostolithotomy versus ESWL monotherapy (odds ratio = 8.36, p less than 0.0001). While percutaneous nephrostolithotomy with or without ESWL appears to be the procedure of choice for most staghorn stones, ESWL monotherapy may have a role for some stones smaller than 500 mm.2. In 12 such cases associated with a nondilated renal collecting system (mean surface area 380.5 mm.2) a stone-free rate of 91.7% was achieved. The number of procedures required to complete therapy was higher in the initial percutaneous nephrostolithotomy group (2.8 versus 2.1, p less than 0.0001). Although complications were more common in the ESWL monotherapy group (manifested as obstruction in 30.5%), bleeding requiring blood transfusion was more frequent in the initial percutaneous nephrostolithotomy group (9.4%).
Adolescent↗
Geographic variation in lumbar diskectomy: a protocol for evaluation.
In 1989 the Maryland Hospital Association (MHA) began developing a protocol related to lumbar diskectomy, a procedure with widely reported geographic variation in its use. The MHA's Laminectomy Advisory Committee drafted three criteria for performance of lumbar diskectomy and also developed a data-collection instrument with which the eight hospitals participating in a pilot study could abstract the necessary data from medical records. Both individual hospital and aggregate results showed wide variation in compliance with the criteria. These findings suggest research and development activities such as refinement of the data-collection instrument, use of the protocol for bench-marking, further investigation of clinical and other determinants of rate variation, and study of the effect of new diagnostic technology on utilization rates for this procedure.
Catchment Area, Health↗
Dystrophin or a "related protein" in Duchenne muscular dystrophy?
Previously we have shown low levels of dystrophin immunoreactivity in muscle from patients with DMD. According to the "frame-shift hypothesis" DMD muscle should not synthesize any dystrophin through to the C-terminus and it has been suggested that the protein detected is not dystrophin, but a related autosomal homologue. We have labelled serial sections of DMD muscle with specific monoclonal antibodies to the amino, rod and C-terminal domains of dystrophin and find labelling on the same individual fibres, allowing us to conclude that the protein detected is Xp21-encoded dystrophin. This has an impact on the interpretation of myoblast transfer experiments. The abundance (on blots) of "C-terminal dystrophin" appears lower than "rod dystrophin" in both BMD and DMD.
Antibodies, Monoclonal↗
Regional anesthesia of the eye and orbit.
The principles and techniques of providing topical and regional anesthesia to the eye are presented in this article. Potential complications and their treatments are outlined, with special emphasis placed on the characteristics of the oculocardiac reflex.
Anesthesia, Conduction↗
An improved technique for changing endotracheal tubes.
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Bronchoscopes↗
The primary care physician's role in management of the patient with myelomeningocele.
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Child↗