Src activation in the induction of long-term potentiation in CA1 hippocampal neurons

Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation producing LTP. Directly activating Src in the postsynaptic neuron enhanced excitatory synaptic responses, occluding LTP. Src-induced enhancement of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor-mediated synaptic responses required raised intracellular Ca2+ and N-methyl-D-aspartate (NMDA) receptors. Thus, Src activation is necessary and sufficient for inducing LTP and may function by up-regulating NMDA receptors.     

Risk factors for rifampin-monoresistant tuberculosis: A case-control study

Rifampin is the cornerstone of short-course chemotherapy for the treatment of tuberculosis (TB). Rifampin monoresistance (RMR) is less common than resistance to isoniazid alone or in combination with other antituberculous medications. We conducted a retrospective case-control study to identify risk factors for RMR-TB. Complete records for 21 of a total of 26 RMR patients from 1990 to 1997 were available for review, and were compared with those of 48 patients with drug-susceptible TB, controlling for year of diagnosis. Cases more frequently had a history of TB than did controls (61% versus 22%, p < 0.01), and were more often human immunodeficiency virus (HIV) positive (81% versus 46%, p = 0.02). With control for HIV status, cases were more likely to have extrapulmonary involvement (47.6% versus 11.6%, p = 0.05). Four cases (19%) and one control (2. 1%) died (p = 0.02) during hospitalization. Cases more often had a history of incarceration (71.4% versus 37.5%, p = 0.09). Among the 13 cases with a history of TB, five had evidence of malabsorption (vomiting and/or diarrhea), versus none of the 11 controls with prior TB. These data support the hypothesis that RMR is seen primarily in individuals with a history of TB and who are HIV positive. Cases were frequently noncompliant with previous treatment for TB, had a history of incarceration, and had poor outcomes.     

Immunolocalization of ion transport proteins in human autosomal dominant polycystic kidney epithelial cells

The kidneys of patients with autosomal dominant polycystic kidney disease become massively enlarged due to the progressive expansion of myriad fluid-filled cysts. The epithelial cells that line the cyst walls are responsible for secreting the cyst fluid, but the mechanism through which this secretion occurs is not well established. Recent studies suggest that renal cyst epithelial cells actively secrete Cl across their apical membranes, which in turn drives the transepithelial movement of Na and water. The characteristics of this secretory flux suggest that it is dependent upon the participation of an apical cystic fibrosis transmembrane conductance regulator (CFTR)-like Cl channel and basolateral Na,K-ATPase. To test this hypothesis, we have immunolocalized the CFTR and Na,K-ATPase proteins in intact cysts and in cyst epithelial cells cultured in vitro on permeable filter supports. In both settings, cyst epithelial cells were found to possess Na,K-ATPase exclusively at their basolateral surfaces; apical labeling was not detected. The CFTR protein was present at the apical surfaces of cyst epithelial cells that had been stimulated to secrete through incubation in forskolin. CFTR was detected in intracellular structures in cultured cyst epithelial cells that had not received the forskolin treatment. These results demonstrate that the renal epithelial cells that line cysts in autosomal dominant polycystic kidney disease express transport systems with the appropriate polarity to mediate active Cl and fluid secretion.     

Development of perceptual completion originates in information acquisition.

Adults have little difficulty perceiving objects as complete despite occlusion, but newborn infants perceive moving partly occluded objects solely in terms of visible surfaces. The developmental mechanisms leading to perceptual completion have never been adequately explained. Here, the authors examine the potential contributions of oculomotor behavior and motion sensitivity to perceptual completion performance in individual infants. Young infants were presented with a center-occluded rod, moving back and forth against a textured background, to assess perceptual completion. Infants also participated in tasks to assess oculomotor scanning patterns and motion direction discrimination. Individual differences in perceptual completion performance were strongly correlated with scanning patterns but were unrelated to motion direction discrimination. The authors present a new model of development of perceptual completion that posits a critical role for targeted visual scanning, an early developing oculomotor action system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physicians taking the lead to improve patient care

BACKGROUND: "Quality: putting clinicians in the Cockpit"--a conference about producing measurable, clinically important improvement in the quality and cost of health care--was sponsored by the Institute for Clinical Systems Integration, based in Minneapolis, and the Institute for Healthcare Improvement, in Boston. More than 200 persons, including clinicians engaged in clinical improvement activities, medical directors, medical group administrators, and quality improvement staff and researchers, attended the Minneapolis meeting, held October 1-3, 1997. PHYSICIANS AS LEADERS: According to James Reinertsen, MD, who described the strategies that physician leaders can use, the leader's main role is to "establish an environment in which quality can thrive" by removing obstacles to quality improvement. DATA: IMPROVING CESAREAN SECTION RATES: Robert DeMott, MD, reported an initiative conducted in a region in which physicians had strongly held beliefs and long-held approaches to obstetric care. DATA LEADS TO DECISION SUPPORT TOOLS FOR CARDIAC CARE: William Nugent, MD, described the impact of the Northern New England Cardiovascular Disease Study Group, a voluntary regional initiative to improve outcomes in patients undergoing coronary bypass grafting. EVIDENCE-BASED IMPROVEMENT--THE GROUP HEALTH EXPERIENCE: Michael Stuart, MD, commented on Group Health's efforts to develop clinical guidelines so that clinical decisions are based on the best available evidence. SHARING INFORMATION IN A COMPETITIVE ENVIRONMENT: Gordon Mosser, MD, and Donald Berwick, MD, discussed the challenges clinicians face in sharing information in a competitive environment. In a session on making sense of information, Paul Batalden, MD, noted, "There is lots of information; if it were only clear who to send it to for the improvement of health care."     

Observations on health care issues in the former Soviet Union

Bacteriologic samples from 31 young men were cultured quantitatively for aerobes and anaerobes; these samples included 31 specimens of tonsils (16 infected and 15 healthy), 16 specimens from pericoronal pockets of lower third molars (11 infected and 5 symptom-free), and 6 postoperative specimens from lower-third-molar extraction sockets. Anaerobes were isolated more often from infected third molars than from infected tonsils (14.5 isolates vs. 8.4 isolates, respectively; P < .001). Infected tonsil samples contained significantly more anaerobic species if an adjacent partly erupted lower third molar was present rather than absent (10.3 isolates vs. 6.9 isolates, respectively; P < .05). Eubacterium aerofaciens, Clostridium species, Peptostreptococcus micros, and Prevotella oris were frequently isolated. Streptococcus salivarius was found more frequently in tonsillar specimens, whereas Corynebacterium species, Prevotella denticola, Capnocytophaga species, Peptostreptococcus anaerobius, and Lactobacillus species were more common in pericoronal pocket samples. Thus, partial eruption of lower third molars increases the number of anaerobic bacterial species on tonsils and many species can be isolated simultaneously from both tonsils and lower third molars.     

A Comparison Between the Mechanical and Thermoelectric Properties of Three Highly Efficient p-Type GeTe-Rich Compositions: TAGS-80, TAGS-85, and 3% Bi2Te3-Doped Ge0.87Pb0.13Te

Since the 1960s, the TAGS system, namely (GeTe) _x (AgSbTe₂)_1?x , with two specific compositions x = 0.8 and 0.85, known as TAGS-80 and TAGS-85, respectively, was identified as containing highly efficient p-type thermoelectric materials. Recently, another highly efficient p-type GeTe-rich composition, namely 3% Bi₂Te₃-doped Ge_0.87Pb_0.13Te, achieving thermoelectric properties comparable to TAGS-based solid solutions, was also reported. Since all of these compositions were obtained by different manufacturing approaches, a comparison between the transport and mechanical properties of these alloys, prepared by the same manufacturing techniques, is required to identify the advantages and disadvantages of these compositions for practical thermoelectric applications. In the current research, the thermoelectric and mechanical properties of three highly efficient GeTe-rich alloys, TAGS-80, TAGS-85, and 3% Bi₂Te₃-doped Ge_0.87Pb_0.13Te, following hot pressing, were investigated and compared. Maximal ZT values of ～1.75, ～1.4, and ～1.6 at 500°C were found for these compositions, respectively. Improvement of the mechanical properties was observed by increasing the GeTe content. The influence of the GeTe relative amount on the transport and mechanical properties was interpreted by means of the phase-transition temperatures from the low-temperature rhombohedral to the high-temperature cubic phases.     

Determination of morphine by electron capture gas-liquid chromatography

We describe a micromethod for determining as little as 0.1 microgram of morphine per liter of human urine. The procedure is about 20-fold more sensitive than are currently used gas-liquid chromatographic methods. It is particularly suitable for use as a confirmatory method for large-scale radioimmunoassay screening tests. The procedure involves extraction of morphine from urine and analysis of its heptafluorobutyryl derivative by gas-liquid chromatography with electron capture detection. Morphine can be determined by this procedure over a range of 0.1-200 microgram/liter of urine, 2 pg of the pure derivative being the lowest amount detectable. Urine samples from patients receiving methadone were analyzed by thin-layer chromatography, radioimmunoassay, and our procedure. The results by our procedure agreed well with those obtained by radioimmunoassay.     

Mutations affecting the activity of urokinase-type plasminogen activator

Mutagenesis throughout the single-chain urokinase-type plasminogenactivator (scu-PA) cDNA molecule, followed by expression ofthe mutant genes and secretion of the resulting mutant proteinsfrom yeast, has been used to determine the amino acid residuesimportant for activity of scu-PA molecules. Twelve out of 13colonies secreting variant scu-PA molecules with decreased abilityto form a zone of fibrinolysis had mutant genes with a singlecodon alteration in the serine protease encoding domain (B-chain).Many of these changes are of highly conserved residues in theserine proteases and are consequently of considerable interest.A model three-dimensional structure of the protease domain ofurokinase was used to explain the basis for the effects of thesedown mutations. The model showed that the strongest down mutationsresult from either interference of the mutated side chain withsubstrate binding at the active site or the introduction ofbulky or charged groups at structurally sensitive internal positionsin the molecule. Attempts to find second site revertants offive down mutants, altered either at the plasmin activationsite or near the serine at the active site, only resulted insame-site revertants, with the original or closely related aminoacids restored.