These results suggest that a subset of ALK-negative IMTs have rearrangement of ROS1, ETV6 or NTRK3 as a possible oncogenic mechanism, and that the detection of these alterations may be of diagnostic value and helpful for determining promising therapeutic strategies.

To clarify the mechanism of cartilage degradation induced by mechanical stress, we investigated the influence of cyclic tension force (CTF) on the metabolism of cultured chondrocytes. The chondrocytes were exposed to CTF using a Flexercell strain unit. Five or 15 kPa of high frequency CTF significantly inhibited the syntheses of DNA, proteoglycan, collagen, and protein. Fifteen kPa of high frequency CTF induced the expression of interleukin-1 (IL-1), matrix metalloproteinase (MMP)-2 and -9 mRNA, and increased the production of pro- and active-MMP-9. The degradation of proteoglycan was inhibited by and MMP inhibitor, indicating that MMPs are involved in the degradation of proteoglycans induced by high frequency CTF. Moreover, reducing the frequency of CTF from high to low decreased the inhibition of proteoglycan synthesis. These findings suggest that the CTF frequency is one of the key determinants of chondrocyte metabolism. Low magnitude CTF, whether high or low frequency, did not cause the gene expression of cartilage degradation factors, suggesting that this CTF magnitude causes only minor changes in the cartilage matrix. High magnitude and frequency CTF caused the gene expression of IL-1 and MMP-9, followed by increases in the production of MMP-2 and -9 proteins, suggesting that excessive and continuous cyclic mechanical stress induces the production of IL-1 and MMP-9, resulting in cartilage degradation.

This study aimed (1) to investigate the influences of sex, age and number of teeth on biting ability through a descriptive survey, and (2) to compare the biting ability between the subjects with and without mobile teeth in a case-control study. A total of 687 subjects cooperated in the descriptive survey. Each subject bit on a pressure detecting sheet with their maximum biting force. Three indices of biting ability: biting pressure (MPa), biting force (N) and occlusal contact area (mm2) were calculated from the impressed marks on the sheet using a high vision video processor system. These indices were correlated well with the number of teeth according to the multiple regression analysis. In the case-control study, matching procedures with sex, age and number of teeth were performed between the subjects with and without mobile teeth. No differences in the three indices were observed between the two well-balanced groups. The results showed that the number of teeth is most important to maintain biting ability, and that the presence of mobile teeth does not always reduce biting ability.

Single items from a typical clinical examination have proved disappointing in their predictive value for temporomandibular joint (TMJ) disc displacement. Only one criterion (the 12 o'clock) is used to diagnose normal disc position. According to this criterion, the posterior band of the disc should be located at the top of the condyle, at the 12 o'clock position. The purpose of this study was to determine which signs and symptoms provide a valid prediction of the condition of the joint based on 4 magnetic resonance imaging (MRI) criteria used to define normal disc position. Sagittal MRI and clinical findings of 137 temporomandibular disorder patients and 23 normal asymptomatic volunteers were used. Three calibrated and blinded observers interpreted the images. Disc position with the mouth closed was evaluated based on 4 MRI criteria: 12, 11, 10 o'clock, and the intermediate zone. Disc position with the mouth open was determined based on one criterion. It was considered normal if the intermediate zone of the disc was located between the condyle and the articular eminence. Joints were classified as normal or as having disc displacement with or without reduction. The sensitivity and specificity of multiple clinical parameters for predicting the condition of the joint established by each of these 4 gold-standard MRI criteria were then determined. Regarding disc displacement with reduction, significant differences were observed in the sensitivity and specificity of all of the clinical parameters used to predict the imaging diagnosis established by each of the criteria. Concerning disc displacement without reduction, no significant differences were observed. The intermediate zone criterion was the criterion that most accurately reflected the condition of the joint. The clinical predictability of the disorder diagnosed according to this criterion suggests that clinical findings alone are too often nonspecific as predictors of the imaging stage of disc displacement. However, we found that combining the most sensitive clinical items to predict the disorder and using an overall criterion for positivity to interpret the results led to an impressive increase in the specificity of the combination, enabling false-positive diagnoses to be excluded.

Summary.  Background: Thrombus formation through the activation of tissue factor (TF) and factor (F) XI is a critical event in the onset of cardiovascular disease. TF expressed in atherosclerotic plaques and circulating blood is an important determinant of thrombogenicity that contributes to fibrin‐rich thrombus formation after plaque disruption. However, the contribution of FXI to thrombus formation on disrupted plaques remains unclear. Methods: A mouse monoclonal antibody against FXI and activated FXI (FXIa) (XI‐5108) was generated by immunization with activated human FXI. Prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time, and ex vivo platelet aggregation in rabbits were measured before and after an intravenous bolus injection of XI‐5108. We investigated the role of FXI upon arterial thrombus growth in the rabbit iliac artery in the presence of repeated balloon injury. Results: The XI‐5108 antibody reacted to the light chain of human and rabbit FXI/FXIa, and inhibited FXIa‐initiated FXa and FXIa generation. Fibrin‐rich thrombi developed on the injured neointima that was obviously immunopositive for glycoprotein IIb‐IIIa, fibrin, TF, and FXI. Intravenous administration of XI‐5108 (3.0 mg kg−1) remarkably reduced thrombus growth, and the APTT was significantly prolonged. However, PT, bleeding time and platelet aggregation were not affected. Conclusions: These results indicate that plasma FXI plays a potent role in thrombus growth on the injured neointima. Inhibition of plasma FXI activity might help to reduce thrombus growth on ruptured plaques without prolonging bleeding time.