Effects of the water content in the sample preparation for MALDI on the mass spectra

Ion abundances in the MALDI TOF mass spectra of the model peptides (bradykinin, alpha-melanocyte stimulating hormone, and melittin) change significantly as water is added to the solution used for dried droplet sample preparation. Changes in the surface tension of the solution can be invoked to explain some of the observed effects on the mass spectra. For example, at low surface tensions, the solution droplet spreads over a larger surface area, resulting in a dilution effect and thereby lowering the [M + H]+ ion yields. Analyte ion yields also have a dependence on matrix crystal morphology. The faster drying samples (low water percentage) promote better inclusion of the analyte into the matrix crystals as compared with the slower drying samples (high water percentage). More efficient inclusion of the analyte in the matrix crystal leads to a better matrix-analyte interaction and hence to higher [M + H]+ ion yields. We present new data that suggest that analyte conformation also influences the MALDI ion yields. The suggestion of conformation affecting MALDI ion yields is based on solvent composition dependence for MALDI H/D exchange data and circular dichroism spectra.     

In vitro long-term potentiation of electrotonic responses of goldfish mauthner cells is accompanied by ultrastructural changes at afferent mixed synapses

The potentiated afferent mixed synapses of the Mauthner cells of fry and adult goldfish in stumps of the medulla oblongata incubated long-term in vitro were studied by electrophysiological and electron microscopic methods. It was shown that brief high-frequency stimulation of posterior branches of the eighth nerve induced a long-term potentiation of electrotonic transmission at large and small mixed club endings. It was about 135% upon subthreshold stimulation and about 200% upon suprathreshold stimulation. The ultrastructural analysis of ultrathin sections of potentiated mixed synaptic endings revealed an increase in the dimensions of desmosome-like contacts which was proportional to the degree of potentiation, about 135% or 200%, depending on the type of stimulation. The dimensions of gap junctions remained unchanged. The dimensions of active zones at potentiated synapses were reduced two-fold as compared with their unpotentiated counterparts, irrespective of the type of stimulation. Considering that desmosome-like contacts consist predominantly of F-actin, a molecule which possesses electroconductivity, it can be assumed that this cytoskeletal protein is involved in the process of potentiation. The increase in the synapse electrical conductivity can be mediated either directly, by shunting the synaptic junction with polymer actin filaments in the region of desmosome-like contacts, or indirectly, via the interaction of actin with gap junction connections situated nearby.     

Characterization of receptors with a new negative image: use in molecular docking and lead optimization

The characterization of receptor binding sites is an important aspect of molecular docking, molecular recognition, and the structure-based design process. This characterization can take several forms: the receptor surface itself can be delineated or described, the space adjacent to the surface can be chemically mapped, or a negative image of the protein binding region can be generated. In this report, we describe a new method of constructing a negative image through generation of a set of spheres. These spheres lie along the receptor surface, and their centers represent possible ligand atom positions. By the method in which they are constructed, these spheres carry a limited amount of energetic and chemical information in addition to their primary geometric information. We test the accuracy of the image by comparing sphere positions to the positions of bound ligand atoms and propose a figure of merit for such tests. Then, we use the spheres to orient ligands in enzyme active sites and show how they can be used to generate low scoring configurations more efficiently than other approaches that search orientation space. In addition, two novel applications of these spheres are described: they are used to help identify structural differences among families of enzymes and to suggest points for ligand modification in analog design.     

Atrial fibrillation after bypass surgery: does the arrhythmia or the characteristics of the patients prolong hospital stay?

STUDY OBJECTIVES: The goal of this study was to determine whether prolonged hospital stay associated with atrial fibrillation or flutter (AF) after coronary artery bypass graft (CABG) surgery is attributable to the characteristics of patients who develop this arrhythmia or to the rhythm disturbance itself. DESIGN: An investigation was conducted through a prospective case series. SETTING: Patients were from a single urban teaching hospital. PARTICIPANTS: Consecutive patients undergoing isolated CABG surgery between December 1994 and May 1996 were included in the study. INTERVENTIONS: No interventions were involved. RESULTS: Of 436 patients undergoing isolated CABG surgery, 101 (23%) developed AF. AF patients were older and more likely to have obstructive lung disease than patients without AF, but both patients with and without AF had similar left ventricular function and extent of coronary disease. ICU and hospital stays were longer in patients with AF. Multivariate analysis, adjusted for age, gender, and race, demonstrated that postoperative hospital stay was 9.2+/-5.3 days in patients with AF and 6.4+/-5.3 days in patients without AF (p<0.001). CONCLUSIONS: Although AF is strongly associated with advanced age, most of the prolonged hospital stay appears to be attributable to the rhythm itself and not to patient characteristics.     

High-Resolution Thermal Expansion of MgB2

The thermal expansion of polycrystalline MgB₂ from 5–300 K is studied using high-resolution capacitance dilatometry. The thermal expansivity exhibits a small jump of –5.8×10^–8 K^–1 at T _c (in accord with expectations from the Ehrenfest relationship and published specific heat and pressure data) and a negative peak-like feature close to 5 K. No indications of any structural instabilities are observed.     

Ca2+-dependent regulation of cGMP-stimulated phosphodiesterase from the soluble fraction of the human brain

Two forms of phosphodiesterase (F1 and F2) with different regulatory properties have been isolated from the soluble fraction of human brain cortex. F1 is the Ca(2+)-calmodulin-dependent phosphodiesterase and its activity is inhibited by calmodulin antagonists (W-7, TFP, tamoxifen) via a mechanism typical for the majority of Ca(2+)-calmodulin-dependent enzymes. F2 is activated by micromolar concentrations of cGMP (7-14-fold) and by Ca2+ ions (1.5-3-fold) in the absence of exogenous calmodulin. F2 contains a tightly bound Ca(2+)-binding component (apparently calmodulin) which does not dissociate from the enzyme in the presence of EGTA. The mechanism of calmodulin antagonists action on F2 is different from that for F1.     

Ross River virus in mosquitoes (Diptera:Culicidae) during the 1994 epidemic around Brisbane, Australia

BACKGROUND: Within a short period of time, video assisted thoracoscopic surgery (VATS) has revolutionised the practice of thoracic surgery. Most of the existing literature, however, is concentrated on the technical aspects. AIMS: We examined the impact of VATS on our practice and its implications. METHODS: We reviewed our thoracic case load two years before and two years after the introduction of VATS in our hospital. RESULTS: We have witnessed a rapid and progressive increase in our thoracic case load since the introduction of VATS. With increased experience, proportionally more cases were performed using VATS compared to conventional surgical access. The increased case load covered a wide range of thoracic diseases with the majority for spontaneous pneumothorax and pleural diseases. CONCLUSIONS: The higher case load is due to increased referrals which at least partly reflect earlier acceptance by both the patients and their physicians for surgical intervention. The changing indications for surgery and the high cost associated with VATS, however, could place extra demand on the healthcare, especially for some countries in Asia. Cost containment is therefore a high priority here. More research is greatly needed in this area.     

Analysis of possible factors influencing PaO2 and (PaO2--PaO2) in patients awaiting operation

Data on arterial oxygen tension (PaO2) and alveolar-arterial PO2 difference (PAO2--PaO2) have been obtained from 337 patients awaiting elective surgery. Statistical analysis of these data has assessed both the individual and the combined influence of various factors on PaO2 and (PAO2-PaO2). The factors of importance in relation to PaO2 include age, smoking habits, body build and PAO2. In relation to (PAO2-PaO2) the significant factors include age, PaCO2, weight and smoking habits.     

Cardiovascular effects of a new inotropic agent, U. K. 14275, in patients with coronary heart disease

1 The chronotropic and inotropic properties of U.K. 14275, a phosphodiesterase inhibitor were assessed in patients with coronary heart disease. 2 Left ventricular function was assessed in eight patients with acute myocardial infarction using the non-invasive measurement of systolic time intervals. 3 Twelve patients with angina pectoris were studied during diagnostic coronary arteriography. Left ventricular function was assessed using a high fidelity catheter tipped transducer in the left ventricle. 4 In both groups of patients U.K. 14275 infused intravenously in doses of 32, 64, 128 and 256 microgram kg-1 bodyweight min-1 enhanced the contractile state of the left ventricle without altering the heart rate.