Global structure of four-way RNA junctions studied using fluorescence resonance energy transfer

The diagnosis and treatment of Sj?gren's syndrome, which poses many severe complications, should be of critical interest to dentists, who are often the first practitioners to detect symptoms. Dentistry is an integral part of health care delivery for patients with this condition. Management of Sj?gren's syndrome can be seen as a model for the expanded scope of dental care in the future.     

Ligaments and articular contact guide passive knee flexion

The aim of this study was to test the hypothesis that the coupled features of passive knee flexion are guided by articular contact and by the isometric fascicles of the ACL, PCL and MCL. A three-dimensional mathematical model of the knee was developed, in which the articular surfaces in the lateral and medial compartments and the isometric fascicles in the ACL, PCL and MCL were represented as five constraints in a one degree-of-freedom parallel spatial mechanism. Mechanism analysis techniques were used to predict the path of motion of the tibia relative to the femur. Using a set of anatomical parameters obtained from a cadaver specimen, the model predicts coupled internal rotation and ab/adduction with flexion. These predictions correspond well to measurements of the cadaver specimen's motion. The model also predicts posterior translation of contact on the tibia with flexion. Although this is a well-known feature of passive knee flexion, the model predicts more translation than has been reported from experiments in the literature. Modelling of uncertainty in the anatomical parameters demonstrated that the discrepancy between theoretical predictions and experimental measurement can be attributed to parameter sensitivity of the model. This study shows that the ligaments and articular surfaces work together to guide passive knee motion. A principal implication of the work is that both articular surface geometry and ligament geometry must be preserved or replicated by surgical reconstruction and replacement procedures to ensure normal knee kinematics and by extension, mechanics.     

Hemispheric control of motor function: a whole brain echo planar fMRI study

A sample of 130 patients with vertical maxillary hyperplasia; mandibular hypoplasia with a high mandibular plane angle; narrow, tapered maxillary dental arch form; and anterior vertical open bite were collected from three different institutions to evaluate the stability of transverse maxillary arch dimensions after correction of the open bite. Surgical treatment consisted of Le Fort I or bimaxillary osteotomies. Intermolar, interpremolar, and anterior arch widths were measured three-dimensionally on dental casts using a Reflex microscope, and transverse stability after orthodontic or surgical maxillary expansion was analyzed. Orthodontic expansion followed by a one-piece Le Fort I intrusion osteotomy was performed in 77 patients, and surgical maxillary expansion by a multisegment Le Fort I intrusion osteotomy was performed in 53 patients. The increase of transverse arch width and the relapse after orthodontic or surgical expansion were not significantly different. The transverse arch width in these two groups did not relapse in 20% of the patients after a mean follow-up of 69 months. An additional bilateral sagittal split osteotomy had no detectable effect on stability. Patients who underwent a multisegment Le Fort I osteotomy stabilized with rigid internal fixation showed better transverse stability than those with intraosseous wire fixation and maxillomandibular fixation. Maxillary intermolar and interpremolar arch width relapses were not correlated with tongue interposition or loss of interdigitation. The relapse of these arch widths showed significant correlations with clockwise rotation of the mandible but not with changes of overbite or overjet.     

Mitochondria and apoptosis

A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins. The different signals that converge on mitochondria to trigger or inhibit these events and their downstream effects delineate several major pathways in physiological cell death.     

Anti-CD36 autoantibodies in thrombotic thrombocytopenic purpura and other thrombotic disorders: identification of an 85 kD form of CD36 as a target antigen

The presence of anti-CD36 antibodies in plasma of patients with thrombotic thrombocytopenic purpura (TTP), idiopathic thrombocytopenic purpura (ITP), and heparin-induced thrombocytopenia without/with thrombosis (HIT/HITT) has been examined by immunoblots, and a monoclonal antibody capture assay, the platelet-associated IgG characterization assay (PAICA). Results with PAICA showed that 73% (8/11) of patients with TTP were positive, and 71% (10/14) by immunoblots. With ITP, 20% (6/30) were positive by PAICA and 19% (3/16) by immunoblots; HIT, 30% (3/10) were positive by PAICA and 60% (6/10) by immunoblot; HITT, 50% (2/4) by PAICA and 100% (4/4) by immunoblot. Purification of CD36 by fast protein liquid chromatography (FPLC) from Triton X-100 extracts of normal platelet membranes resulted in the isolation of two different forms: the classic 88 kD form, and a second, lighter 85 kD form. Our data indicated that the patients' plasma autoantibodies reacted strongly with the 85 kD form. Conventional monoclonal and polyclonal antisera produced to the 88 kD form reacted strongly with the 88 kD form but weakly with the 85 kD form. These results confirm the possible importance of anti-CD36 antibodies in the pathophysiology of TTP and other thrombocytopenias and demonstrate the presence of a previously unrecognized target antigen for these antibodies.     

The glio-toxic mechanism of alpha-aminoadipic acid on cultured astrocytes

Porcine pancreatic phospholipase A2 (PLA2) hydrolyses phosphatidylcholine when in the lamellar state as well as in the micellar state. We have found that alpha-tocopherol, the most active form of vitamin E, is able to inhibit PLA2 activity only toward lamellar fluid membranes, thus protecting phospholipids toward this lytic enzyme. This compound decreases both the initial rate and the extent of hydrolysis. The inhibition is of the non-competitive type and the evidence strongly suggests that it is due to an effect of alpha-tocopherol on the substrate, i.e. the membrane, and not on the enzyme itself. Other tocopherols, such as the isomers beta-, gamma- and delta-tocopherol also display PLA2 inhibition but consecutively to a lower extent. The grade of inhibition of PLA2 activity by tocopherols correlates well with their biological activity and with their location in the bilayer as shown by fluorescence quenching. Cholesterol does not inhibit PLA2 activity at concentrations even higher than those of tocopherols, indicating that the effect of tocopherols is not due to alteration of membrane fluidity. The possible mechanisms underlying the different behaviour of tocopherol isomers as PLA2 inhibitors are discussed considering its biological significance as membrane stabilizers, suggesting biological actions of compounds with vitamin E activity other than their classical roles as antioxidants.     

TrfA dimers play a role in copy-number control of RK2 replication

Heat stress pretreatment of the heart is known to protect this organ against an ischemic/reperfusion insult 24 h later. Degradation of membrane phospholipids resulting in tissue accumulation of polyunsaturated fatty acids, such as arachidonic acid, is thought to play an important role in the multifactorial process of ischemia/reperfusion-induced damage. The present study was conducted to test the hypothesis that heat stress mitigates the postischemic accumulation of arachidonic acid in myocardial tissue, as a sign of enhanced membrane phospholipid degradation. The experiments were performed on hearts isolated from rats either 24 h after total body heat treatment (42 degrees C for 15 min) or 24 h after sham treatment (control). Hearts were made ischemic for 45 min and reperfused for another 45 min. Heat pretreatment resulted in a significant improvement of postischemic hemodynamic performance of the isolated rat hearts. The release of creatine kinase was reduced from 30 +/- 14 (control group) to 17 +/- 5 units/g wet wt per 45 min (heat-pretreated group) (p < or = 0.05). Moreover, the tissue content of the inducible heat stress protein HSP70 was found to be increased 3-fold 24 h after heat treatment. Preischemic tissue levels of arachidonic acid did not differ between heat-pretreated and control hearts. The postischemic ventricular content of arachidonic acid was found to be significantly reduced in heat-pretreated hearts compared to sham-treated controls (6.6 +/- 3.3. vs. 17.8 +/- 12.0 nmol/g wet wt). The findings suggest that mitigation of membrane phospholipid degradation is a potential mechanism of heat stress-mediated protection against the deleterious effects of ischemia and reperfusion on cardiac cells.     

Treatment of infection with débridement and retention of the components following hip arthroplasty

Forty-two patients (forty-two hips) who had an infection following a hip arthroplasty were managed with open débridement, retention of the prosthetic components, and antibiotic therapy. After a mean duration of follow-up of 6.3 years (range, 0.14 to twenty-two years), only six patients (14 per cent) -- four of nineteen who had had an early postoperative infection and two of four who had had an acute hematogenous infection -- had been managed successfully. Of the remaining thirty-six patients, three (7 per cent of the entire group) were being managed with chronic suppression with oral administration of antibiotics and thirty-three (79 per cent of the entire group) had had a failure of treatment. All nineteen patients who had a late chronic infection were deemed to have had a failure of treatment. Débridement had been performed at a mean of six days (range, two to fourteen days) after the onset of symptoms in the patients who had been managed successfully and at a mean of twenty-three days (range, three to ninety-three days) in those for whom treatment had failed. Débridement with retention of the prosthesis is a potentially successful treatment for early postoperative infection or acute hematogenous infection, provided that it is performed in the first two weeks after the onset of symptoms and that the prosthesis previously had been functioning well. In our experience, this procedure has not been successful when it has been performed more than two weeks after the onset of symptoms. Retention of the prosthesis should not be attempted in patients who have a chronic infection at the site of a hip arthroplasty as this approach universally fails.     

Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour

Reduction or loss of the intercellular junctions known as desmosomes may contribute to the invasive and metastatic behaviour of various carcinomas. Previous studies have shown that metastasis of oral squamous cell carcinomas of the head and neck correlates with a reduction in immunohistochemical staining for desmoplakin and desmoglein at the invasion front. The primary aim of the present study was to extend these observations to include a third component of desmosomes, the glycoprotein desmocollin. An additional aim was to determine whether the differentiation status of tumours is reflected in their staining for cytokeratins 1, 13, and 19, and, if so, whether these parameters correlate with desmosomal staining and/or metastasis. The study included 54 primary tumours of which 28 showed lymph node metastases. The results of this investigation show that tumours can be divided into three groups according to whether they have lost staining for no, one or more than one desmosomal component. A statistically significant correlation was found between the number of desmosomal components lost and metastasis. Tumours could also be divided into five groups according to their staining for different combinations of cytokeratins. Furthermore, differentiation status as indicated both histologically and by cytokeratin staining correlated with reduced desmosomal staining and metastasis. Tumours were also examined for intensity of staining for the adhesion molecule E-cadherin. Reduction in E-cadherin staining was correlated with mode of invasion and with reduction in desmosomal staining, but not with poor differentiation as indicated by cytokeratin staining. The results of this extensive study reinforce the view that adhesive junctions and adhesion molecules contribute to the suppression of tumour invasion and metastasis.     

Study of molecular flow inside a test dome connected to the same diameter diffusion pump

The paper presents a study of molecular flow inside a test dome connected to the same diameter diffusion pump. The theoretical analysis of the problem connected with the tubulated as well as the orifice type pressure gauges has been briefly reviewed by introducing the new factors J_t and J_orf for the tubulated and the orifice gauges respectively. The values of these factors for different gauge positions inside the test domes of different sizes (L = R to L = 8R) are determined. The mathematical relationships for determining the measured pressure for different orientations of the gauge inlet at the different positions are also derived. The improved values of the gauge position ‘Y_o/R’ to measure the intrinsic speed) for a tubulated gauge are determined by using the correct value of wall flux distribution. To verify the theoretical analysis for tubulated gauge, an experimental study using a 104 mm diameter pump connected to the same diameter dome of effective length 6 R is made by measuring the pressures at the four different positions. The analysis of the experimental results obtained shows a good agreement with the theory. A new approach to intrinsic speed measurement, by measuring the pressure at the different positions of the test dome, has been presented in which the measurement of throughput is not required. By measuring the pressures in different directions of the inlet of the gauge, the number of molecules s^?1 crossing the dome at any position is determined and is compared with the number of molecules s^?1 actually introduced inside the test dome by the gas throughput.