Prolonged bleeding time in patients with lupus anticoagulant.

Platelet adhesion to collagen under flow conditions was studied in 18 patients with lupus anticoagulant, seven of which showed a prolonged bleeding time in the presence of a normal platelet count. The effect of patient plasma, IgG and purified anticardiolipin antibodies on platelet adhesion was also examined. We found a significant reduction of platelet adhesion in patients with lupus anticoagulant, which was more evident in patients with prolonged bleeding time. This platelet adhesion defect could be attributed to a plasma factor. In fact, patients' platelets regained normal adhesion when mixed with normal plasma, whereas controls' platelets showed abnormal adhesion in the presence of patient plasma. A causative role of antiphospholipid antibodies was demonstrated in experiments using purified immunoglobulins and anticardiolipin antibodies.     

Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.     

Computed tomography evaluation of temporomandibular joint alterations in patients with class II division 1 subdivision malocclusions: condyle-fossa relationship.

Thirty persons with Class II Division 1 subdivision malocclusions, ranging in age from 12 years 8 months to 42 years, underwent computed tomography of the temporomandibular joints. The images obtained from sagittal slices were used to assess the depth of the mandibular fossa, the angulation of the posterior wall of the articular tubercle, the condyle-fossa relationship, and the concentric position of the condyles associated with this malocclusion. Paired Student t tests were applied, and Pearson product moment correlations (r) were determined after measurements on both Class I and Class II sides were obtained. No statistically significant asymmetries were found in the depth of the mandibular fossa, the angulation of the posterior wall of the articular tubercle, or the condyle-fossa relationship. However, a statistically significant (P <.05) anterior positioning of the condyles was observed.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Preliminary investigation of respiratory self-gating for free-breathing segmented cine MRI.

Segmented cine MRI generally requires breath-holding, which can be problematic for many patients. Navigator echo techniques, particularly successful for free-breathing coronary MRA, are incompatible with the acquisition strategies and SSFP pulse sequences commonly used for cine MRI. The purpose of this work is to introduce a new self-gating technique deriving respiratory gating information directly from the raw imaging data acquired for segmented cine MRI. The respiratory self-gating technique uses interleaved radial k-space sampling to provide low-resolution images in real time during the free-breathing acquisition that are compared to target expiration images. Only the raw data-producing images with high correlation to the target images are included in the final high-resolution reconstruction. The self-gating technique produced cine series with no significant differences in quantitative image sharpness to series produced using comparable breath-held techniques. Because of the difficulties associated with breath-holding, the respiratory self-gating technique represents an important practical advance for cardiac MRI. , Inc.     

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.     

Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration

Because of its similarity to ageing in impaired immune efficiency 48 h after surgical procedures on young partially hepatectomised mice, partial hepatectomy/liver regeneration (pHx) provides a good model for the study of inflammation in ageing. In old age, high metallothionein (I+II) (MT) sequesters a substantial number of intracellular zinc ions consequently leading to low zinc ion bioavailability for an adequate immune response. Corticosterone and IL-6 affect MTmRNA induction in inflammation and after pHx against oxidative damage. The aim of this study was to investigate the role played by MT in conferring immune plasticity in ageing and in very old age using the pHx model. 48 h after their partial hepatectomy, the crude zinc balance was negative in young, old and very old mice coupled with increased MT, corticosterone, sIL-6R and IL-6. Concomitantly, Natural Killer (NK) cell activity and IL-2 production decreased. Complete restoration of the nutritional-endocrine-immune parameters occurred 15 days from the surgical procedures in young and very old mice, but not in old or transgenic mice overexpressing MT. A significant positive or inverse correlation among nutritional-endocrine-immune parameters exists in young and very old mice, but not in old mice during liver regeneration. Since MT also affects c-myc, the gene expression of c-myc declines from 48 h to days 7 and 15 after pHx in young and very old mice, but remains constantly high in old pHx mice for the same days. This circumstance leads to the appearance of tumours in the long run in old pHx mice and survival times that are shorter than old sham controls. Because complete remodelling also occurs in IL-6 and in sIL-6R in very old mice during liver regeneration, the pre-existing inflammation is not detrimental in very old age. As such, very old mice are still responsive to large inflammation, such as pHx, thanks to correct MT homeostasis. Correct MT homeostasis, via c-myc, is therefore pivotal in both suitable liver regeneration and in conferring immune plasticity with subsequent successful ageing. High MT plays an extremely harmful role in ageing: on one hand it lowers zinc ion bioavailability levels required for immune efficiency and on the other hand it increases c-myc expression. The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases.