The mouse homologue to human fetal antigen 1 (hFA1) was purified from mouse amniotic fluid by cation exchange chromatography and immunospecific affinity chromatography. Mouse FA1 (mFA1) is a single chain glycoprotein with an M(r) of 42-50 kDa (SDS-PAGE). The N-terminal amino acid sequence (39 residues) revealed 74% identity to hFA1 and 100% identity to the translated cDNAs referred to as mouse dlk, pref-1 and SCP-1. mFA1 is the secreted processed molecule encoded by the mRNA defined by these identical mouse cDNAs. Monospecific rabbit anti-mFA1 antibodies, purified by ammonium sulfate precipitation and immunospecific affinity chromatography, were used for immunohistochemical and quantitative ELISA techniques. The indirect immunoperoxidase technique demonstrated mFA1 within the endocrine structures of adult mouse pancreas, whereas the exocrine tissue remained unstained. FA1-positive staining was also seen in the pituitary gland and the mouse adrenal gland. The concentration of mFA1 in a pool of amniotic fluid was assessed at 25 micrograms ml-1 and the serum concentration in normal nonpregnant adult mice (n = 28) was 11.3 +/- 5.0 ng ml-1 (2 SD). During pregnancy the concentration of mFA1 in maternal serum increased above the nonpregnant reference value at midpregnancy, reaching a maximum concentration (> 0.35 microgram ml-1) 2 days prepartum. The maternal serum concentration was positively correlated with the number of fetuses. After delivery the rate of disappearance of mFA1 in maternal serum was very fast with a t1/2 < 1 h. The concentration of mFA1 in newborn mice was about 15 micrograms ml-1 and did not reach normal adult values until the age of > 50 days.

Shoulders with rotator cuff tears (RCT) tears are associated with significantly larger critical shoulder angles (CSA) (RCT CSA ¼ 38.2˚) than shoulders without RCT (CSA ¼ 32.9˚). We hypothesized that larger CSAs increase the ratio of glenohumeral joint shear to joint compression forces, requiring substantially increased compensatory supraspinatus loads to stabilize the arm in abduction. A previously established three dimensional (3D) finite element (FE) model was used. Two acromion shapes mimicked the mean CSA of 38.2˚found in patients with RCT and that of a normal CSA (32.9˚). In a first step, the moment arms for each muscle segment were obtained for 21 different thoracohumeral abduction angles to simulate a quasi-static abduction in the scapular plane. In a second step, the muscle forces were calculated by minimizing the range of muscle stresses able to compensate an external joint moment caused by the arm weight. If the joint became unstable, additional force was applied by the rotator cuff muscles to restore joint stability. The model showed a higher joint shear to joint compressive force for the RCT CSA (38.2˚) for thoracohumeral abduction angles between 40å nd 90˚with a peak difference of 23% at 50˚of abduction. To achieve stability in this case additional rotator cuff forces exceeding physiological values were required. Our results document that a higher CSA tends to destabilize the glenohumeral joint such that higher than normal supraspinatus forces are required to maintain modeled stability during active abduction. This lends strong support to the concept that a high CSA can induce supraspinatus (SSP) overload. The etiology of rotator cuff tears (RCT) is considered multifactorial and the contribution of an excessive load on the rotator cuff (RC) is a subject of ongoing debate. Recent clinical studies have reported a correlation between scapular geometry and the prevalence of RCT 1-4 indicating that anatomy related biomechanical factors may play an important role in the development of RCT. The lateral extension of the acromion (acromion index 2 ), and the inclination of the glenoid 1 have both emerged as important factors of interest. The critical shoulder angle (CSA) considers both the lateral extension of the acromion and the inclination of the glenoid, and is defined as the angle between the glenoid surface and a line connecting the inferior rim of the glenoid and the lateral tip of the acromion (Fig. 1). It has recently been identified as the strongest known anatomical predictor for the development of RCT 5 . The intuitive biomechanical basis of this relationship is that the lateral extension of the acromion leads to a more vertical line of action of the deltoid and therefore, promotes the tendency for a superior dislocation of the humeral head.2,3 More recently, this hypothesis has been experimentally supported using a robotic shoulder simulator.6 However, this experimental simulator setup required reduction of the problem to a two dimensional (2D) load case in which potentially important c...

This study of 52 European patients with Hodgkin's disease (HD) expressing the latent membrane protein 1 (LMP1) oncogene within diagnostic Hodgkin and Reed-Sternberg (HRS) cells was performed to detect LMP1 isolates carrying deletions and to characterize them at a molecular and histologic level. Deletions were identified in 5 cases, clustered near the 3′ end of the LMP1 gene, and histologically associated with numerous HRS cells. DNA sequencing showed homology with the deletions seen in the Asian nasopharyngeal carcinoma (NPC) isolates CAO and 1510. Our findings suggest that partial deletions of the LMP1 oncogene, associated with aggressive behavior in NPC CAO and NPC 1510, occur at a particular localization and confer a proliferative phenotype to lymphoid cells in HD.

This study of 52 European patients with Hodgkin's disease (HD) expressing the latent membrane protein 1 (LMP1) oncogene within diagnostic Hodgkin and Reed-Sternberg (HRS) cells was performed to detect LMP1 isolates carrying deletions and to characterize them at a molecular and histologic level. Deletions were identified in 5 cases, clustered near the 3′ end of the LMP1 gene, and histologically associated with numerous HRS cells. DNA sequencing showed homology with the deletions seen in the Asian nasopharyngeal carcinoma (NPC) isolates CAO and 1510. Our findings suggest that partial deletions of the LMP1 oncogene, associated with aggressive behavior in NPC CAO and NPC 1510, occur at a particular localization and confer a proliferative phenotype to lymphoid cells in HD.

Epstein-Barr virus DNA was detected by the polymerase chain reaction (PCR) in five lymph node biopsies from eight patients with diagnosis of angioimmunoblastic lymphadenopathy (AILD). Three pairs of specific primers detected EBV DNA sequences near the 5' end (Bam W region), the middle (BMRF 1 region) and the 3' end (Eco RI D region) of the viral genome with equal accuracy when 1 microgram of DNA and 30 amplification cycles were used. When only 100 ng of DNA were screened with the BMRF 1 set of primers, a specific amplification product was still identifiable. The 593 base pair amplification product obtained using the Eco RI D set of primers was shown to contain an expected Sma I site at position 215, confirming the viral origin of the amplified sequence [corrected]. Our findings indicate that lymph nodes of AILD patients frequently harbour the entire EBV genome at a high percentage of at least 1 viral copy per 15,000 human cells.

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The aim of this study was to quantitatively assess changes in collagen structure using MR T1-and T2*-mapping in a novel controlled ex vivo tendon model setup. MATERIALS AND METHODS Twenty-four cadaveric bovine flexor tendons underwent MRI at 3 T before and after chemical modifications, representing mechanical degeneration and augmentation. Collagen degradation (COL), augmenting collagen fiber cross-linking (CXL), and a control (phosphate-buffered saline [PBS]) were examined in experimental groups, using histopathology as standard of reference. Variable echo-time and variable-flip angle gradient-echo sequences were used for T2*-and T1-mapping, respectively. Standard T1-and T2-weighted spin-echo sequences were acquired for visual assessment of tendon texture. Tendons were assessed subsequently for their biomechanical properties and compared with quantitative MRI analysis. RESULTS T1-and T2*-mapping was feasible and repeatable for untreated (mean, 545 milliseconds, 2.0 milliseconds) and treated tendons. Mean T1 and T2* values of COL, CXL, and PBS tendons were 1459, 934, and 1017 milliseconds, and 5.5, 3.6, and 2.5 milliseconds, respectively. T2* values were significantly different between enzymatically degraded tendons, cross-linked tendons, and controls, and were significantly correlated with mechanical tendon properties (r =-0.74, P < 0.01). T1 values and visual assessment could not differentiate CXL from PBS tendons. Photo-spectroscopy showed increased autofluorescence of cross-linked tendons, whereas histopathology verified degenerative lesions of enzymatically degraded tendons. CONCLUSIONS T2*-mapping has the potential to detect and quantify subtle changes in tendon collagen structure not visible on conventional clinical MRI. Tendon T2* values might serve as a biomarker for biochemical alterations associated with tendon pathology.

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