Unique ζ‐chain motifs mediate a direct TCR‐actin linkage critical for immunological synapse formation and T‐cell activation

TCR‐mediated activation induces receptor microclusters that evolve to a defined immune synapse (IS). Many studies showed that actin polymerization and remodeling, which create a scaffold critical to IS formation and stabilization, are TCR mediated. However, the mechanisms controlling simultaneous TCR and actin dynamic rearrangement in the IS are yet not fully understood. Herein, we identify two novel TCR ζ‐chain motifs, mediating the TCR's direct interaction with actin and inducing actin bundling. While T cells expressing the ζ‐chain mutated in these motifs lack cytoskeleton (actin) associated (cska)‐TCRs, they express normal levels of non‐cska and surface TCRs as cells expressing wild‐type ζ‐chain. However, such mutant cells are unable to display activation‐dependent TCR clustering, IS formation, expression of CD25/CD69 activation markers, or produce/secrete cytokine, effects also seen in the corresponding APCs. We are the first to show a direct TCR‐actin linkage, providing the missing gap linking between TCR‐mediated Ag recognition, specific cytoskeleton orientation toward the T‐cell–APC interacting pole and long‐lived IS maintenance.     

Childhood and adolescent ovarian malignant tumors in Israel. A nationwide study.

OBJECTIVES: To determine the incidence of ovarian malignant tumors in childhood and adolescence, to ascertain the frequency distribution of the various tumor types and to assess time trends in Israel on a nationwide basis. METHODS: The study group included all Israeli Jewish patients < or = 19 years old with histologically confirmed ovarian malignancies, diagnosed in Israel from 1970 to 1994. Data were obtained from the Israel Cancer Registry. The effects of age at diagnosis and period of diagnosis were analyzed using the Poisson regression. RESULTS: Among the 82 patients identified, the most frequent tumors (72.0%) were of germ cell origin and among those about one third were dysgerminomas. Epithelial tumors were diagnosed in 26.6% of the patients and most of these were borderline malignancies. The incidence rate (IR) for the total group of ovarian malignancies in the 0-19 age group was 0.52 and for ages 5-19 it was 0.71 per 100,000. After adjustment for age, a significant linear trend for a decrease of germ cell tumors over time was found, stemming from a decrease of dysgerminomas. A significant trend for increase in the IRs with age was also found. In addition, a steep rise in the age specific IRs of epithelial borderline tumors was noted in the last 5 year period. CONCLUSIONS: The IRs of ovarian malignancies in childhood and adolescence in Israel, as in other countries, is very low as compared to adults and the most common tumors are of germ cell origin while malignant epithelial tumors are very rare. A time period effect in the germ cell tumors that resulted from an inexplicable significant decrease in the age specific IRs of dysgerminomas, was observed. A significant increase in borderline tumors was also noted and may be attributed to greater awareness of pathologists to this entity.     

Psychomotor skills for endoscopic manipulations: differing abilities between right and left-handed individuals.

OBJECTIVE: The objective of this study was to compare the psychomotor aptitudes relevant to endoscopic manipulations between right-handed and left-handed subjects. SUMMARY BACKGROUND DATA: There has been little research on the psychomotor performance in relation to minimal access surgery and there are no psychomotor tests to evaluate aspects of psychomotor abilities relevant to endoscopic manipulations. METHODS: A microprocessor-controlled psychomotor tester was developed for objective evaluation of endoscopic performance. The task involved negotiating ten target holes with a probe under videoscopic imaging. Subjects consisted of two groups of 10 medical students: right- and left-handed. After a prestudy familiarization session, each subject performed two test runs with one hand, followed by two runs with the other hand. These test runs were repeated 1 week later. The outcome measures were the total execution time, force on backplate, angular deviations, error rate, and first-time accuracy. RESULTS: A significant difference in the error rate and first time accuracy was observed between subjects (p < 0.001 and p < 0.001, respectively) and between the dominant and nondominant hands (p < 0.001 and p < 0.025, respectively), with no significant change with practice. Right-handed subjects performed better with either hand in terms of error rate (p < 0.001) and first time accuracy (p < 0.001). Practice improved the execution time (p < 0.001) and the degree of angular deviations (p < 0.02). CONCLUSIONS: Right-handed subjects perform less errors and exhibit better first time accuracy. The parameters that improve with practice reflect the positive effect of training, whereas others, such as errors rate and first time accuracy which do not, reflect innate abilities.     

Backbone metal cyclization: novel 99mTc labeled GnRH analog as potential SPECT molecular imaging agent in cancer

Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted to the pituitary where it binds to specific receptors on the gonadotropes to regulate gonadotropic hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) synthesis and secretion. Specific GnRH receptors are overexpressed in breast, prostatic, ovarian, and other tumors. The aim of this study was to synthesize a cyclic GnRH analog with high affinity to GnRH receptors that can be radiolabeled with 99mTc. A precyclic GnRH analog, [Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH (Gn-2), containing two hemi-chelator groups was synthesized. It was cyclized applying the recently reported backbone metal cyclization (BMC) approach, to obtain cyclo(Re(O)1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH (cyclo[Re(O)-Gn-2]). For comparative evaluations, Gn-2 was oxidized on-resin to yield cyclo(S-S,1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH, (cyclo[S-S-Gn-2]). The binding affinity of cyclo[Re(O)-Gn-2] to rat pituitary membranes showed IC50 of 50 nM, compared to IC50 = 10 nM in the native GnRH. Cyclo(99mTc(O)1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH (cyclo[99mTc(O)-Gn-2]) was synthesized from Gn-2 and showed similar chromatographic behavior to its rhenium surrogate.     

Séparation traumatique axiale de la médiocarpienne à déplacement palmaire. À propos d’un cas avec revue de la littérature

We report a case of traumatic axial disruption of the radial mid carpal joint. This unusual type of scaphotrapezo-trapezoïdal dislocation occurred after falling from a height. We performed open reduction and wire fixation. At 12 months follow-up, functional outcome was satisfactory with good muscle strength (clamping force, grip strength and pinch grip: 90% compared to the opposite side) and good range of motion was preserved. Work was resumed at the tenth week. Radial midcarpal disruption is uncommon. It includes the separation of the trapezium, trapezoïdal, first and second and third metacarpal bones from the remaining wrist. This pattern of carpal derangement has not been previously described in the literature. Mechanism of the injury and treatment are discussed.     

Acrométastase du pied révélant un cancer bronchique: à propos d’un cas

Foot bone acrometastasis, as the first manifestation of an occult primary malignant tumor, is rarely reported in the literature, and delayed or inappropriate diagnosis is frequent. We report a case of arcometastasis at the head of the first metatarsus revealing an occult lung adenocarcinoma.