The biomechanical and morphological changes in the medial collateral ligament of the rabbit after immobilization and remobilization

The effects of immobilization and remobilization on the biomechanical and morphological properties of the femur-medial collateral ligament-tibia complex and each of its components were investigated in the rabbit. Specimens that had been obtained after periods of unilateral immobilization of the knee and remobilization were evaluated for structural properties. In addition, the mechanical properties of the substance of the medial collateral ligament and the histological characteristics of both the substance of the ligament and its sites of insertion were evaluated. After immobilization, there were significant reductions in the ultimate load and energy-absorbing capabilities of the bone-ligament complex, and an increased number of failures occurred by tibial avulsion. The tissue of the medial collateral ligament also became less stiff as a result of immobilization. Histologically, the femoral and tibial insertion sites showed increased osteoclastic activity, resorption of bone, and disruption of the normal attachment of the bone to the ligament. With remobilization, the ultimate load and energy-absorbing capabilities of the bone-ligament complex improved but did not return to normal. Failure by tibial avulsion became less frequent, and the stress-strain characteristics of the medial collateral ligament returned to normal. Histologically, the sites of insertion of the ligament also showed evidence of recovery.     

MR imaging of pineal cysts

Identification of pineal cysts with imaging modalities other than magnetic resonance (MR) has been infrequent, despite a reported autopsy incidence of as high a 40%. We recently identified 15 patients in whom pineal cysts were seen on MR. These cysts ranged from 5 to 15 mm in maximum diameter. The cyst walls were thin, usually measuring less than 2 mm. The signal characteristics of the fluid within the cysts paralleled that of CSF, although it differed somewhat in signal intensity from CSF collections in which there was pulsatile motion. All lesions were midline in location. There was no significant mass effect, although mild flattening of the superior colliculi could be seen. Two cases were operated on; at operation, typical pineal cysts were found, with one containing hemosiderin-laden proteinaceous material, which accounted for its markedly higher signal intensity. It is important that this entity be recognized so that these lesions are not confused with pineal tumors.     

Development of OASYS-2: a system for the analysis of serial measurement of peak expiratory flow in workers with suspected occupational asthma.

BACKGROUND: Serial peak expiratory flow (PEF) measurement is usually the most appropriate first step in the confirmation of occupational asthma. Visual assessment of the plotted record is more sensitive and specific than statistical methods so far reported. The use of visual analysis is limited by lack of widespread expertise in the methods. A computer assisted diagnostic aid (OASYS-2) has been developed which is based on a scoring system developed from visual analysis. This removes the requirement for an experienced interpreter and should lead to the more widespread use of the technique. METHODS: PEF records were collected from workers attending an occupational lung disease clinic for investigation of suspected occupational asthma and from workers participating in a study of respiratory symptoms in a postal sorting office. PEF records were divided into two development sets and two gold standard sets. The latter consisted of records from workers in which a final diagnosis had been reached by a method other than PEF recording. An experienced observer scored individual work and rest periods for the two development set PEF records; linear discriminant analysis was used to compare measurements taken from development set 1 records with visual scores. Two equations were produced which allowed prediction of scores for individual work or rest periods. The development set 2 was used to determine how these scores should be used to produce a whole record score. The first gold standard set was used to determine the whole record score which best separated those with and without occupational asthma. The second set determined the sensitivity and specificity of the chosen score. RESULTS: Two hundred and sixty eight PEF records were collected from 169 workers and divided into two development sets (81 and 60 records) and two gold standard sets (60 and 67 records). Linear discriminant analysis produced equations predicting the score for work periods incorporating five indices of PEF change and one for rest periods using seven indices. These equations correctly predicted the score for development set 1 work and rest periods on 61% of occasions (kappa = 0.47). The whole record score for development set 2 records, after weighting for definite or definitely no occupational effect, correlated with the visual score (correlation coefficient 0.86). Comparison with gold standard set 1 identified a cut off which proved to have a sensitivity of 75% and a specificity of 94% for an independent diagnosis of occupational asthma when applied to gold standard set 2. CONCLUSIONS: These results suggest that the sensitivity and specificity of analysing PEF records for occupational asthma using OASYS-2 approaches that of visual analysis, but it should be absolutely reproducible. The performance of OASYS-2 is more specific and approaches the sensitivity of other statistical methods of analysis. The evaluation of a large number of PEF records from workers exposed to different sensitising agents suggests that these results should be robust and should be repeatable in clinical practice.     

Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites

Among 404 patients with primary tumors of extremity-trunk sites entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972 to 1984), 154 were placed in clinical group IIa, ie, with negative nodes but with "microscopic residual" (MR) disease, following the initial excisional (not biopsy) procedure. An elective reexcision of the area of the primary tumor (PRE) was performed in 41 of these patients within 35 days (mean interval, 14 days; SE, 0.9) with no intervening therapy. These procedures consisted of wider excision of the tumor "bed," resulting in a technical transfer of these patients from group IIa to group I, ie, complete excision. This reduced intensity of nonsurgical therapy (irradiation and chemotherapy). Among the 41 patients who underwent PRE, the 3-year survival estimate (Kaplan-Meier) was 91% (SE, 4%). This may be compared with the results in 113 patients who remained in group IIa, in which the 3-year survival estimate was 74% (SE, 4%). A second group for comparison consisted of the 73 patients with trunk/extremity tumors who were placed in group I after a single excisional procedure, ie, no PRE, in whom the 3-year survival estimate was 74% (SE, 5%). Recognized prognostic factors influencing survival in these groups were comparable, with the exception of tumor size, ie, the largest tumors (greater than or equal to 10 cm in diameter) were concentrated in groups I and IIa. When patients with tumors greater than or equal to 10 cm in diameter (9.7% of the total) were removed from all three study groups, patients undergoing PRE had longer survival duration estimates than patients in the control groups.     

Real-time imaging of Rab3a and Rab5a reveals differential roles in presynaptic function

We investigated the roles of two Rab-family proteins, Rab3a and Rab5a, in hippocampal synaptic transmission using real-time fluorescence imaging. During synaptic activity, Rab3a dissociated from synaptic vesicles and dispersed into neighbouring axonal regions. Dispersion required calcium-dependent exocytosis and was complete before the entire vesicle pool turned over. In contrast, even prolonged synaptic activity produced limited dispersion of Rab5a. A GTPase-deficient mutant, Rab3a (Q81L), dispersed more slowly than wild-type Rab3a, and decreased the rate of exocytosis and the size of the recycling pool of vesicles. While overexpression of Rab3a did not affect vesicle recycling, overexpression of Rab5a reduced the recycling pool size by 50%. We propose that while Rab3a preferentially associates with recycling synaptic vesicles and modulates their trafficking, Rab5a is largely excluded from recycling vesicles.     

Large-scale identification of mammalian proteins localized to nuclear sub-compartments

Many nuclear components participating in related pathways appear concentrated in specific areas of the mammalian nucleus. The importance of this organization is attested to by the dysfunction that correlates with mis-localization of nuclear proteins in human disease and cancer. Determining the sub-nuclear localization of proteins is therefore important for understanding genome regulation and function, and it also provides clues to function for novel proteins. However, the complexity of proteins in the mammalian nucleus is too large to tackle this on a protein by protein basis. Large-scale approaches to determining protein function and sub-cellular localization are required. We have used a visual gene trap screen to identify more than 100 proteins, many of which are normal, located within compartments of the mouse nucleus. The most common discrete localizations detected are at the nucleolus and the splicing speckles and on chromosomes. Proteins at the nuclear periphery, or in other nuclear foci, have also been identified. Several of the proteins have been implicated in human disease or cancer, e.g. ATRX, HMGI-C, NBS1 and EWS, and the gene-trapped proteins provide a route into further understanding their function. We find that sequence motifs are often shared amongst proteins co-localized within the same sub-nuclear compartment. Conversely, some generally abundant motifs are lacking from the proteins concentrated in specific areas of the nucleus. This suggests that we may be able to predict sub-nuclear localization for proteins in databases based on their sequence.     

Oculoauriculovertebral anomaly: Segregation analysis

Seventy-four families of probands with oculoauriculovertebral anomaly were evaluated, including 116 parents and 195 off-spring. Relatives were examined to identify ear malformations, mandibular anomalies, and other craniofacial abnormalities. For segregation analysis using POINTER, selection of the sample was consistent with single as-certainment. Different population liabilities were used for probands and relatives, because affection was narrowly defined for probands and broadly defined for relatives. The hypothesis of no genetic transmission was rejected. The evidence favored autosomal dominant inheritance; recessive and polygenic models were not distinguishable. © 1992 Wiley-Liss, Inc.     

Pathologic features of extraosseous Ewing's sarcoma: a report from the Intergroup Rhabdomyosarcoma Study

Eighty-four cases of extraosseous Ewing's sarcoma (EOE) were found during the pathology review of the Intergroup Rhabdomyosarcoma Study I and II. Patients commonly presented during or after adolescence with the most common primary sites including the trunk, extremities, and retroperitoneum. Males were slightly more affected. Histologic sections of 74 tumors in the pathology repository were re-reviewed with attention to rosette formation (positive in 18 cases) and glycogen deposition (++ in 21, + in 36, +/- in 11, and - in 2 of 70 cases examined). Fourteen tumors (7 with rosettes and 7 without) were selected for immunohistochemical and ultrastructural studies, and 13 showed single or multiple neural markers (neuron-specific enolase in 8, S-100 protein in 6, and neurosecretory-type granules in 9). These possible cases of neural EOE could be divided into three subgroups: tumor with bidirectional neuroblastic and schwannian differentiation (5 cases), tumor with monodirectional neuroblastic differentiation (7 cases), and tumor with monodirectional schwannian differentiation (1 case). EOE with a neural nature may be categorized into a spectrum of peripheral primitive neuroectodermal tumors. Clinical, histopathologic, and biologic differences between this disease and conventional sympathetic neuroblastoma are discussed.