Phospholamban reduces cardiac Ca-ATPase sensitivity to thapsigargin and cyclopiazonic acid.
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Biomedical subjects
Publications and source records attributed to A Barlow.
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The development of the vertebrate face is a dynamic multi-step process which starts with the formation of neural crest cells in the developing brain and their subsequent migration to form, together with mesodermal cells, the facial primordia. Signalling interactions co-ordinate the outgrowth of the facial primordia from buds of undifferentiated mesenchyme into the intricate series of bones and cartilage structures that, together with muscle and other tissues, form the adult face. Some of the molecules that are thought to be involved have been identified through the use of mouse mutants, data from human craniofacial syndromes and by expression studies of signalling molecules during facial development. However, the way that these molecules control the epithelial-mesenchymal interactions which mediate facial outgrowth and morphogenesis is unclear. The role of neural crest cells in these processes has also not yet been well defined. In this review we discuss the complex interaction of all these processes during face development and describe the candidate signalling molecules and their possible target genes.
Important cultural, linguistic, traditional, and spiritual differences among Native American reservations are likely to go unrecognized to the detriment of children in need of mental health intervention. The authors discuss the impact of these factors on the expressions of psychiatric distress of Native American children, their care-seeking behaviors, and the acceptability of the forms taken by mental health systems that serve them. They suggest new, innovative models of care that can be developed within the context of contemporary Native American culture. Although the roles envisioned for child psychiatrists include the provision of direct clinical service, the authors posit that a model in which child psychiatrists provide consultation and supervision to native outreach and other mental health workers is a more acceptable and potentially more effective use of scarce resources.
Every cell contains many families of protein kinases, and may express several structurally related yet genetically distinct kinases of each family. The activity of the serine/threonine protein kinase C (PKC) enzymes has long been implicated in T-cell activation, but it is not known which members of the PKC family regulate the T-cell response to foreign antigens. The activation of T cells by antigen-presenting cells (APCs) is spatially restricted to their site of contact, where receptors on the T cells engage their counter-receptors on the APCs. We used this localized engagement to identify, at the single-cell level, intracellular proteins involved in the activation process. By digital immunofluorescence microscopy, we localized six isoforms of PKC in antigen-specific T-cell clones activated by APCs. Surprisingly, only PKC-theta translocated to the site of cell contact. Accordingly, in vitro kinase activity assays of PKC immunoprecipitates from the conjugates of T cells and APCs showed a selective increase in the activity of PKC-theta, indicating that the translocated enzyme is active. Several modes of partial T-cell activation that failed to cause PKC-theta translocation also failed to cause T-cell proliferation, further suggesting the involvement of PKC-theta in T-cell activation.
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BACKGROUND: Controversies in nomenclature, especially of hearts with "single ventricle," have clouded discussion and understanding of the anatomy. Many patients with such malformations are submitted to the Fontan procedure as definitive surgical palliation. The spectrum of anatomy among these patients is wide and deserves analysis in an effort to provide a simple framework for description and to eliminate confusion. METHODS: We reviewed 138 successive patients undergoing the Fontan operation at one institution to demonstrate the variability in pathology. RESULTS: Only 89 patients (65%) had a univentricular type of atrioventricular connection. All but 5 patients had two ventricular chambers. Among the 49 patients with biventricular atrioventricular connections, 43 had a hypoplastic ventricle that precluded a biventricular repair. CONCLUSIONS: Full understanding of the malformations that may preclude a "biventricular" repair and hence necessitate a Fontan procedure requires knowledge of the different forms of univentricular atrioventricular connection that, although usually associated with two ventricular chambers, are seldom amenable to a "two-pump repair." Understanding of those types of "biventricular heart" that preclude a two-pump repair (eg, severe hypoplasia of the left ventricle or the right ventricle) or are associated with high risks (eg, straddling atrioventricular valve) is also important.
The non-obese diabetic (NOD) mouse spontaneously develops an insulin-dependent diabetes mellitus that resembles human type I diabetes. This disease can be transferred by purified T cells or cloned T cell lines, implicating an autoimmune T cell attack on the pancreatic beta cells of the islets of Langerhans. As all T cell responses involve recognition of peptides bound to MHC molecules displayed at the cell surface, we have examined self peptides binding to the MHC molecules on spleen cells of the NOD mouse. Peptides eluted from the MHC class I molecule Kd have sequences that conform to known motifs for peptides binding this molecule in other strains of mice. The NOD mouse expresses the unique MHC class II molecule I-Ag7. Peptides eluted from I-Ag7 have sequences that implicate an acidic residue in the C terminus of the peptide as important for binding. The role of this residue in binding has been confirmed by direct peptide-binding analysis. This C-terminal acidic amino acid may interact with an arginine residue in the MHC class II alpha-chain that is exposed when beta-chain residue 57 is mutated to serine, or to the unique beta-chain residue histidine 56. These data may provide valuable insights into the nature of autoantigenic peptides presented by NOD mouse MHC molecules by defining the nature of I-Ag7-peptide binding.
CD4 T cells recognize peptide fragments of foreign proteins bound to self class II molecules of the major histocompatibility complex (MHC). Naturally processed peptide fragments bound to MHC class II molecules are peptides of 13-17 amino acids which appear to be precessively truncated from the carboxy terminus, perhaps after binding to the MHC class II molecule. The finding of predominant self peptides has interesting implications for antigen processing and self-non-self discrimination.
Schatzki's ring is a distinct anatomical entity associated with hiatal hernia; however, its significance is unclear. Thirty-two patients with a radiologically demonstrated Schatzki's ring were compared with 32 patients with hiatal hernia and no Schatzki's ring. Schatzki's ring was confirmed on endoscopy in 59 percent of patients. Seventy-five percent of patients with Schatzki's ring presented with dysphagia compared with 41 percent of control patients (p less than 0.01). Heartburn and regurgitation were less frequent than in control subjects (38 percent versus 91 percent, p less than 0.0001). Schatzki's ring patients were found to have a lower incidence of proven gastroesophageal reflux on 24-hour pH monitoring. Those with proven reflux were found to have a more efficient lower esophageal sphincter than control patients. Sixty-two percent of Schatzki's ring patients without proven reflux had a history of chronic ingestion of drugs known to be damaging to the esophageal mucosa, whereas only 26 percent of patients with reflux had this history. This was found in 16 percent of controls. Sixty-two percent of Schatzki's ring patients without reflux responded to a single dilatation compared with 37 percent of those with reflux. These findings suggest an etiologic relationship between pill lodgement and Schatzki's ring in patients without reflux and indicate that different therapy should be employed in these patients.
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Nonsense-defective auxotrophic strains of Escherichia coli B/r were used to study mutation frequency decline (MFD) after mutagenesis with ethyl methanesulfonate (EMS). The mutation frequencies for prototrophic revertants that were either converted or de novo glutamine tRNA suppressor mutations declined as treated auxotrophic parental cells were incubated with glucose but without required amino acids (a condition typically producing MFD). The decline for converted suppressor mutations was more rapid than the decline for de novo suppressor mutations after low or moderate EMS treatment, but both suppressor mutation types showed the same slow decline after extensive treatment. The declines for both types of suppressor mutation were eliminated in uvrA-defective cells, and the rapid decline seen for converted suppressor mutations appeared as a slow decline in mfd-defective cells. The results are interpreted that true MFD (the rapid process) affects only the EMS-induced converted glutamine tRNA suppressor mutations. This would account for the rapid decline that is blocked in cells with an mfd defect and in cells with deficient excision repair activity (uvrA or excessive DNA damage). In addition, a second non-specific antimutation mechanism is proposed that is dependent on excision repair only and accounts for the slow decline seen with converted suppressor mutations in some instances and with de novo suppressor mutations at all times. The true MFD mechanism may consist of a physiologically dependent facilitated excision repair specifically for premutational residues located in the transcribed strand of the target DNA sequence (for O6-ethylguanine in cells treated with ethyl methanesulfonate or pyrimidine-pyrimidine photoproducts after UV irradiation).
With the advent of RFLPs, genetic linkage maps are now being assembled for a number of organisms including both inbred experimental populations such as maize and outbred natural populations such as humans. Accurate construction of such genetic maps requires multipoint linkage analysis of particular types of pedigrees. We describe here a computer package, called MAPMAKER, designed specifically for this purpose. The program uses an efficient algorithm that allows simultaneous multipoint analysis of any number of loci. MAPMAKER also includes an interactive command language that makes it easy for a geneticist to explore linkage data. MAPMAKER has been applied to the construction of linkage maps in a number of organisms, including the human and several plants, and we outline the mapping strategies that have been used.
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Twenty-seven patients sensitive to ragweed pollen were treated with topical imipramine 0.05% in one eye and vehicle in the other in a double-masked fashion. The eyes treated with imipramine showed significantly less redness, tearing, and discomfort after exposure to pollen extract. Imipramine, a tricyclic antidepressant, appears to be an effective antihistamine in the eye.
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The use of radiolabeled antibodies may play a major role in future treatment of cancer patients, affecting procedural operations throughout both radiology and radiation therapy departments. Because of the number of different radioisotopes that may be used, education of medical personnel will be of critical importance. Adaptation of current radiology procedures may enhance this therapeutic modality.
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