The influence of sterols on the sensitivity of lipid bilayers to melittin

The sensitivity of planar lipid bilayers to the permeabalizing effect of melittin was evaluated when sterols of varying structure were incorporated into the membrane. The addition of increasing amount of cholesterol (0-50 mole %) decreased the sensitivity of membranes formed from negatively charged phospholipids to melittin but did not (in amount of up to 66 mole %) change the sensitivity of membranes formed from zwitterionic lipids. 7-Dehydrocholesterol, stigmasterol and ergosterol had the same ability as that of cholesterol to decrease the membrane sensitivity to melittin, while lanosterol had no effect on the sensitivity of membranes to melittin. The results suggest that the effect of sterols is complex and cannot be explained only by a direct interaction of melittin with cholesterol, by a decrease of membrane fluidity, or by changes in distribution of surface charge.     

Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990

Information on the incidence of progressive supranuclear palsy (PSP) is limited; incidence rates for multiple system atrophy (MSA) are not available. We studied the incidence of PSP and MSA in Olmsted County, Minnesota, for the years 1976 to 1990. This study was part of a larger investigation of all forms of parkinsonism. We used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects whose records contained documentation of any from of parkinsonism, related neurodegenerative diseases, or tremor of any type. A nurse abstractor screened the records and, when applicable, a neurologist reviewed them to determine the presence or absence of parkinsonism. Cases of parkinsonism were classified using specified diagnostic criteria. Population denominators were derived from census data and were corrected by removing prevalent cases of parkinsonism. Over the 15 years of the study, we found 16 incident cases of PSP and nine incident cases of MSA. No cases of PSP or MSA had onset before age 50 years. The average annual incidence rate (new cases per 100,000 person-years) for ages 50 to 99 years was 5.3 for PSP and 3.0 for MSA. The incidence of PSP increased steeply with age from 1.7 at 50 to 59 years to 14.7 at 80 to 99 years, and was consistently higher in men. Median survival time from symptom onset was 5.3 years for PSP and 8.5 years for MSA. The incidence of PSP increases with age and is consistently higher in men at all ages. PSP and MSA are more common than previously recognized.     

Closed-chest cardiopulmonary bypass and cardioplegia: basis for less invasive cardiac surgery

BACKGROUND: We developed a method of closed-chest cardiopulmonary bypass to arrest and protect the heart with cardioplegic solution. This method was used in 54 dogs and the results were retrospectively analyzed. METHODS: Bypass cannulas were placed in the right femoral vessels. A balloon occlusion catheter was passed via the left femoral artery and positioned in the ascending aorta. A pulmonary artery vent was placed via the jugular vein. In 17 of the dogs retrograde cardioplegia was provided with a percutaneous coronary sinus catheter. RESULTS: Cardiopulmonary bypass time was 111 +/- 27 minutes (mean +/- standard deviation) and cardiac arrest time was 66 +/- 21 minutes. Preoperative cardiac outputs were 2.9 +/- 0.70 L/min and postoperative outputs were 2.9 +/- 0.65 L/min (p = not significant). Twenty-one-French and 23F femoral arterial cannulas that allowed coaxial placement of the ascending aortic balloon catheter were tested in 3 male calves. Line pressures were higher, but not clinically limiting, with the balloon catheter placed coaxially. CONCLUSIONS: Adequate cardiopulmonary bypass and cardioplegia can be achieved in the dog without opening the chest, facilitating less invasive cardiac operations. A human clinical trial is in progress.     

Tissue factor expression in mesothelial cells: induction both in vivo and in vitro

Docking algorithms play an important role in the process of rational drug design and in understanding the mechanism of molecular recognition. An important determinant for successful docking is the extent to which the configurational space (including conformational changes) of the ligand/receptor system is searched. Here we describe a new, combinatorial method for flexible docking of peptides to proteins that allows full rotation around all single bonds of the peptide ligand and around those of a large set of receptor side chains. We have simulated the binding of several viral peptides to murine major histocompatibility complex class I H-2Kb. In addition, we have explored the limits of our method by simulating a complex between calmodulin and an 18-residue long helical peptide from calmodulin-dependent protein kinase IIalpha. The calculated peptide conformations generally matched well with the X-ray structures. Essential information about local flexibility and about residues that are responsible for strong binding was obtained. We have frequently observed considerable side-chain flexibility during the simulations, showing the need for a flexible treatment of the receptor. Our method may also be useful whenever the receptor side-chain conformation is not available or uncertain, as illustrated by the docking of an H-2Kb binding nonapeptide to the receptor structure taken from an octapeptide/H-2Kb complex.     

Blastomycotic osteomyelitis of the pelvis: a case report

Blastomycosis dermatitis is an unusual fungal infection that can become a diagnostic dilemma if a high index of suspicion is not maintained in patients who present with a chronic granulomatous infection of bone and soft tissue. We present a patient with a long history of pain, systemic manifestations of chronic infection, a draining sinus, and lytic changes on plain films to illustrate the difficulty in establishing the diagnosis. Appropriate staging studies and a bone biopsy led to the correct diagnosis in the patient.