HIV: from molecular recognition to tissue pathogenesis

The hypothalamic-pituitary-adrenal axis and the immune system interact in a bidirectional manner providing the basis for the regulation of the immune response due to a pathogenic stimulus. This interplay is commonly believed to be based on the action of hormones or cytokines, respectively. Since it has been detected that adrenocortical cells offer immunological properties such as expression of MHC class II antigens and/or CD95 (Fas antigen) and its ligand, the question has to be raised whether direct intercellular communication between immune cells and 'immunocompetent' endocrine cells contributes to the complexity of immunoregulation. Here we discuss the possible reciprocal relevance of physiological and pathological adrenal changes, as well as T-cell-mediated immune response for immune and/or adrenal pathology during disease.     

Differential subcellular localization of protein phosphatase-1 alpha, gamma1, and delta isoforms during both interphase and mitosis in mammalian cells

Protein phosphatase-1 (PP-1) is involved in the regulation of numerous metabolic processes in mammalian cells. The major isoforms of PP-1, alpha, gamma1, and delta, have nearly identical catalytic domains, but they vary in sequence at their extreme NH2 and COOH termini. With specific antibodies raised against the unique COOH-terminal sequence of each isoform, we find that the three PP-1 isoforms are each expressed in all mammalian cells tested, but that they localize within these cells in a strikingly distinct and characteristic manner. Each isoform is present both within the cytoplasm and in the nucleus during interphase. Within the nucleus, PP-1 alpha associates with the nuclear matrix, PP-1 gamma1 concentrates in nucleoli in association with RNA, and PP-1 delta localizes to nonnucleolar whole chromatin. During mitosis, PP-1 alpha is localized to the centrosome, PP-1 gamma1 is associated with microtubules of the mitotic spindle, and PP-1 delta strongly associates with chromosomes. We conclude that PP-1 isoforms are targeted to strikingly distinct and independent sites in the cell, permitting unique and independent roles for each of the isoforms in regulating discrete cellular processes.     

Edgard C. Moreno, PhD: a tribute to his major contributions to oral biology research

The seminal contributions of Dr. Edgard C. Moreno to physical chemical aspects of oral biology research are reviewed, with personal insights provided by the author. Dr. Moreno has made major contributions to our understanding of fundamental processes which occur within the oral cavity and which control the formation of mineralized tissues. These contributions include extensive research in the areas of: the chemistry of synthetic calcium phosphates and biominerals, the interaction of salivary proteins and other molecules of biological interest with calcium phosphate surfaces, the mechanism of dental caries formation and the effects of fluoride on this process, the mechanism of dental calculus formation and prevention, and the mechanism of dental enamel formation.     

Methods for measuring the temporal characteristics and filter response of electroacoustic impedance instruments

Methods for determining the temporal response of electroacoustic impedance instruments are presented along with sample measurements from one instrument. The conditions under which reflex artifacts may occur are discussed in light of electrical measurements of filter response characteristics and measurements of the "threshold" of the artifact measured from two subjects with no acoustic reflex.     

Parent comments and instruction during the first four months of supervised driving: An opportunity missed?

The present study examined the nature of the comments and instruction provided by parents during supervised driving. Unlike previous studies which rely on self-report, the data in this study were obtained through direct observation of parents and teens using in-vehicle cameras with audio recording. The cameras were installed in the vehicles of 50 families for the first four months of the learner license stage. The findings show a great deal of conversation takes place while teens are driving with a supervisor, and that much of this conversation concerns driving. Sixty-one percent (61%) of all recorded clips included driving-related conversation. The most common type of comment by parents was instruction about vehicle handling or operation, observed in 53% of those clips with conversation about driving. This was followed by pointing out something about the driving environment (such as when it was clear to enter traffic; 23%), negative comments about the teen's driving (22%), and helping the driver navigate (18%). Other potentially helpful types of instruction, including explanation or insights regarding higher order skills (e.g., hazard anticipation and detection), were noticeably less frequent. Moreover, higher order instruction remained low during the first four months of the learner stage, even as instruction about vehicle handling/operation decreased. These findings suggest parents are not taking full advantage of the opportunity provided by mandatory periods of supervised driving to help their children develop an understanding of important aspects of driving.     

Bailout and corrective use of Gianturco-Roubin flex stents after percutaneous transluminal coronary angioplasty: operator reports and angiographic core laboratory verification from the National Heart, Lung, and Blood Institute/New Approaches to Coronary Intervention Registry

OBJECTIVES: We sought to determine the in-hospital clinical outcome and angiographic results of patients prospectively entered into the National Heart, Lung, and Blood Institute/New Approaches to Coronary Intervention (NHLBI/NACI) Registry who received Gianturco-Roubin stents as an unplanned new device. BACKGROUND: Between August 1990 and March 1994, nine centers implanted Gianturco-Roubin flex stents as an unplanned new device in the initial treatment of 350 patients (389 lesions) who were prospectively enrolled in the NHLBI/NACI Registry. METHODS: Patients undergoing implantation of the Gianturco-Roubin flex stent were prospectively entered into the Gianturco-Roubin stent portion of the NHLBI/NACI Registry. Only subjects receiving the Gianturco-Roubin stent as a new device in an unplanned fashion are included. RESULTS: The mean age of the patient group was 61.8 years, and the majority of the patients were men. A history of percutaneous transluminal coronary angioplasty (PTCA) was present in 35.4% of the group, and 16.9% had previous coronary artery bypass graft surgery. Unstable angina was present in 67.7%. Double- or triple-vessel coronary artery disease was present in 55.4%, and the average ejection fraction was 58%. The presence of thrombus was noted in 7.3%, and 7.2% had moderate to severe tortuosity of the lesion. The angiographic success rate was 92%. Individual clinical sites reported that 66.3% of the stents were placed after suboptimal PTCA, 20.3% for abrupt closure and 13.4% for some other technical PTCA failure. Major in-hospital events occurred in 9.7% of patients, including death in 1.7%, Q wave myocardial infarction in 3.1% and emergency bypass surgery in 6%. Abrupt closure of a stented segment occurred in 3.1% of patients at a mean of 3.9 days. Cerebrovascular accident occurred in 0.3%, and transfusion was required in 10.6%. Vascular events with surgical repair occurred in 8.6% of patients. CONCLUSIONS: Despite these complications, the use of this device for the treatment of a failed or suboptimal PTCA result remains promising given the adverse outcome of abrupt closure with conventional (nonstent) treatment.     

The fibrinogen-like globe of tenascin-C mediates its interactions with neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta

Two nervous tissue-specific chondroitin sulfate proteoglycans, neurocan and phosphacan (the extracellular domain of protein-tyrosine phosphatase-zeta/beta), are high-affinity ligands of tenascin-C. Using portions of tenascin-C expressed as recombinant proteins in human fibrosarcoma cells, we have demonstrated both by direct radioligand binding assays and inhibition studies that phosphacan binding is retained in all deletion variants except those lacking the fibrinogen-like globe and that phosphacan binds to this single domain with nearly the same affinity (Kd approximately 12 nM) as to native or recombinant tenascin-C. However, maximum binding of neurocan requires both the fibrinogen globe and some of the adjacent fibronectin type III repeats. Binding of phosphacan and neurocan to intact tenascin-C, and of phosphacan to the fibrinogen globe, is significantly increased in the presence of calcium. Chondroitinase treatment of the proteoglycans did not affect their binding to either native tenascin-C or to any of the recombinant proteins, demonstrating that these interactions are mediated by the proteoglycan core proteins rather than through the glycosaminoglycan chains. These results are also consistent with rotary shadowing electron micrographs that show phosphacan as a rod terminated at one end by a globular domain that is frequently seen apposed to the fibrinogen globe in mixtures of phosphacan and tenascin-C. C6 glioma cells adhere to and spread on deletion variants of tenascin-C containing only the epidermal growth factor-like domains or the fibronectin type III repeats and the fibrinogen globe. In both cases cell adhesion was inhibited by similar concentrations of phosphacan, demonstrating that the fibrinogen globe is not necessary for this effect, which is apparently mediated by a direct action of phosphacan on the cells rather than by its interaction with the proteoglycan binding site on tenascin-C.     

What Is Conceptual Glue?

Conceptual structures are commonly likened to scientific theories, yet the content and motivation of the theory analogy are rarely discussed. Gregory Murphy and Douglas Medin's The Role of Theories in Conceptual Coherence is a notable exception and has become an authoritative exposition of the utility of the theory analogy. For Murphy and Medin, the theory analogy solves what they call the problem of conceptual coherence or the problem of conceptual glue. I argue that they conflate a number of issues under these rubrics and that in each case either the problem to be solved isn't subject to a general solution or the theory analogy is of little use. The issues I consider are: (1) what makes a concept efficient, useful, and informative, (2) what makes a concept refer to what it does, (3) what makes a set of objects form a single category, and (4) what makes concepts combine in one way rather than another.     

The computer science pipeline in urban high schools: access to what? For whom?

Our research was conceived out of a desire to understand why so few underrepresented students of color are learning computer science at the high school level. High school is a critical time for pre-college preparation and for getting on the right "track" for college and future career opportunities. Yet, by college the number of students of color obtaining bachelors degrees in computer science is remarkably small. In this article, we discuss our research on the high school "computer science pipeline." We define the "computer science pipeline" as the curriculum and opportunities available to students to learn computer science within their schools. Considering the tremendous economic and educational advantages, and the professional opportunities, that are available to students who understand computer science, this is a critical time to understand what factors are influencing African-American and Latino/a students' enrollment decisions.