Wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross-react with virus and cardiac myosin

The pyruvate dehydrogenase complex (PDC) plays a key role in the anaerobic metabolism of the parasitic nematode Ascaris suum. Two isoforms of the alpha-subunit of pyruvate dehydrogenase (E1) have been identified: alpha I is most abundant in anaerobic adult muscle and alpha II in aerobic larvae. Both isoforms have been expressed as alpha 2 beta 2 tetramers with a muscle-specific beta-subunit, purified to apparent homogeneity, reconstituted with E1-deficient adult A. suum muscle PDC, and assayed for PDC and E1 kinase activity. Recombinant alpha II is a poor substrate for the adult E1 kinase, but its stoichiometry of phosphorylation/inactivation is similar to that reported for the human E1. Initially, inactivation parallels the incorporation of about 1 mol 32P/mol E1 and at maximal phosphorylation about 2.4 32P/mol E1 is incorporated. In contrast, recombinant alpha I (r alpha I) is phosphorylated rapidly, and substantially more phosphorylation accompanies inactivation. To examine this altered pattern of phosphorylation, the two phosphorylation sites in each E1 alpha subunit of the r alpha I (site 1 and site 2) were changed either individually or together from Ser to Ala by site-directed mutagenesis. Site 1 was phosphorylated more rapidly than site 2, but the phosphorylation of either site resulted in inactivation, and the phosphorylation of only a single E1 alpha subunit of the tetramer was necessary for inactivation. However, both E1 alpha subunits of the tetramer were phosphorylated, based on the incorporation of about 3.5 mol 32P/mol E1 at maximal phosphorylation and the altered mobility of most of the E1 alpha subunits during SDS-PAGE. These observations suggest that the regulation of both E1 isoforms is modified to maintain PDC activity during the transition to anaerobiosis.     

Day hospital/crisis respite care versus inpatient care, Part II: Service utilization and costs

OBJECTIVE: The authors compared service utilization and costs for acutely ill psychiatric patients treated in a day hospital/crisis respite program or in a hospital inpatient program. METHOD: The patients (N = 197) were randomly assigned to one of the two programs and followed for 10 months after discharge. Both programs were provided by a community mental health center (CMHC) in a poor urban community. Data were collected for developing service utilization profiles and estimates of per-unit costs of the inpatient, day hospital, and outpatient services provided by the CMHC. RESULTS: On average, the day hospital/crisis respite program cost less than inpatient hospitalization. The average saving per patient was +7,100, or roughly 20% of the total direct costs. There were no significant differences between programs in service utilization or costs during the follow-up phase. Cost savings accrued in the index episode because per-unit costs were lower for day hospital/crisis respite and the average stay was shorter. Significant differences in cost were found among patient groups with psychosis, affective disorders, and dual diagnoses; psychotic patients had the highest costs in both programs. The two programs had roughly equal direct service staff and capital costs but significantly different operating costs (day hospital/crisis respite operating costs were 51% of inpatient hospital costs). CONCLUSIONS: The programs were equally effective, but day hospital/crisis respite treatment was less expensive for some patients. Potential cost savings are higher for nonpsychotic patients. Cost differences between the programs are driven by the hospital's relatively higher overhead costs. The roughly equal expenditures for direct service staff costs in the two programs may be an important clue for understanding why these programs provided equally effective acute care.     

Mandibular forces during simulated tooth clenching

Differential, functional loading of the mandibular condyles has been suggested by several human morphologic studies and by animal strain experiments. To describe articular loading and the simultaneous forces on the dental arch, static bites on a three-dimensional finite element model of the human mandible were simulated. Five clenching tasks were modeled: in the intercuspal position; during left lateral group effort; during left lateral group effort with balancing contact; during incisal clenching; and during right molar clenching. The model's predictions confirmed that the human mandibular condyles are load-bearing, with greater force magnitudes being transmitted bilaterally during intercuspal and incisal clenching, as well as through the balancing-side articulation during unilateral biting. Differential condylar loading depended on the clenching task. Whereas higher forces were found on the lateral and lateroposterior regions of the condyles during intercuspal clenching, the model predicted higher loads on the medial condylar regions during incisal clenching. The inclusion of a balancing-side occlusal contact seemed to decrease the forces on the balancing-side condyle. Whereas the predicted occlusal reaction forces confirmed the lever action of the mandible, the simulated force gradients along the tooth row suggest a complex bending behavior of the jaw.     

Biodegradation of poly(ethylene adipate) microcapsules in physiological media

Spherical reservoir-type microcapsules fabricated using a water/oil/water (W/O/W) double emulsion technique with solvent evaporation and composed of poly(ethylene adipate) (PEAD) blended with 20% poly-epsilon-caprolactone (PCL II) containing a range of bovine serum albumin (BSA) loadings were incubated in Hank's buffer, pH 7.4, newborn calf serum, 1.5% pancreatin and synthetic gastric juice containing 10% pepsin A over 30 days and their percentage weight loss (PWL) and changes in ultrastructural morphology monitored by gravimetry and stereoscan electron microscopy (SEM) respectively. The greatest PWL from microcapsules was observed after incubation in newborn calf serum (NCS) and pancreatin and decreased in the order NCS > pancreatin > synthetic gastric juice > Hank's buffer. Only microcapsules theoretically loaded with 5-20% BSA and incubated in synthetic gastric juice showed a significant increase in PWL with increasing percentage BSA loading. The structural biodegradation of PEAD microcapsules in both Hank's buffer and synthetic gastric juice was minimal whilst the morphological changes observed during incubation in NCS involved pitting of the membrane, some surface erosion and reduction in diameter, followed by microcapsule membrane disruption and loss of reservoir contents. Biodegradation in pancreatin was associated with surface flaking and loss of large fragments of the microcapsule membrane. Only in NCS and pancreatin, where one would expect to see the effects of enzyme activity in addition to simple ester hydrolysis, did biodegradation proceed to the stage where there was a loss of spherical shape and almost total disruption of the microcapsule structure within 30 days.     

Plasma sprayed hydroxyapatite coatings on titanium substrates. Part 1: Mechanical properties and residual stress levels

Heat treatment and the introduction of a Ti bond coat have been applied to hydroxyapatite (HA) coatings sprayed using different plasma powers and gas mixtures. Attempts were made in this way to achieve optimal coating properties for orthopaedic implants. In particular, the effects on the degree of crystallinity, the adhesion, the OH ion content and the purity were evaluated. Heat treatment at 700 C for 1 h in air proved to be effective in increasing the crystallinity, regaining the OH- ion and removing other non-HA compounds, although it caused a significant decrease in the degree of adhesion (interfacial fracture toughness) for those specimens sprayed at high powers. This heat treatment was found to induce significant transformation of amorphous HA to the crystalline form, while not detrimentally changing the properties of the underlying Ti-6Al-4V substrates. Precoating with a 100 microm Ti layer increased the adhesion of the HA coatings on Ti-6Al-4V substrates, primarily by providing a rougher surface and promoting better mechanical interlocking. Changes in coating properties during immersion in biological fluids were also studied and were found to depend critically on the chemical composition of the fluids. Small precipitates formed on the coating surfaces when immersed in Ringers solution. These might account for the apparent drop in the degree of crystallinity when measured using X-ray diffraction. A significant drop in the interfacial adhesion was found for those coatings sprayed at high powers. This could be offset by prior precoating with a titanium bond coat and suitable heat treatment. In summary, the following processing sequence is suggested in order to achieve optimum coating properties: precoating the substrate with a layer of Ti (approximately 100 microm), spraying HA at a sufficiently high-power level (depending on particle size and gas mixture) and heat treatment at 700 degrees C for 1 h in air.