SummaryCD4 + T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed T helper function. The surface structures on activated CD4 + T cells that mediate this function are not fully known. We previously reported the isolation of a functionally unique subclone of the Jurkat leukemic T cell line (D1.1) that constitutively expressed contact-dependent helper effector function. To identify T cell surface molecules that mediate contact-dependent T helper function, a monoclonal antibody (mAb), designated 5c8, was generated that inhibits Dl.l-mediated B cell activation and immunoprecipitates a novel 30-kD protein structure from surface-iodinated D1.1 cells. Normal CD4 + T cells express 5c8 antigen (Ag) transiently after activation by phorbol myristate acetate and phytohemagglutinin with maximal expression 5-6 h after activation and absence of expression by 24 h. In contrast, neither resting nor activated CD8 § T cells express 5c8 Ag. In functional studies, mAb 5c8 inhibits the ability of fixed, activated CD4 § T cells to induce B cell surface CD23 expression. In addition, mAb 5c8 inhibits the ability of CD4 + T cells to direct terminal B cell differentiation driven by pokeweed mitogen. Taken together, these data suggest that 5c8 Ag is a novel, activation-induced surface T cell protein that is involved in mediating a contactdependent element of the helper effector function of CD4 § T lymphocytes.I n a contact-dependent process, termed T helper (Th) function, CD4 + T lymphocytes direct the activation and differentiation of B lymphocytes and thereby regulate the humoral immune response by modulating the specificity, secretion and isotype-encoded effector functions of antibody molecules (1-7). The T cell surface molecules that mediate the contact-dependent elements of Th cell function are not fully known.The process by which T cells help B cells to differentiate has been divided into two distinct phases: the inductive and the effector (8, 9). In the inductive phase, resting T cells contact antigen-primed B cells and this association allows clonotypic TCR-CD4 complexes to interact with Ia/Ag complexes on B cells (5, 10-16). TCP,/CD4 recognition of Ia/Ag results in the formation of stable T-B cognate pairs and bidirectional T and B cell activation (17-22). In the effector phase, activated T cells drive B cell differentiation by secreting lymphokines (23, 24) and by contact-dependent stimuli (20,(25)(26)(27)(28)(29)(30)(31)(32), both of which are required for T cells to drive small, resting B cells to terminally differentiate into Ig-secreting cells (25, 33, 34).Although the inductive phase of T cell help is Ag dependent and MHC restricted (5, 10-15, 34, 35), the effector phase of Th function can be Ag independent and MHC nonrestricted (25, 28, 30, 34,(36)(37)(38)(39)(40)(41)(42)(43)). An additional contrasting feature is that the inductive phase of T cell help often requires CD4 molecules and is inhibited by anti-CD4 mAb (16), whereas help...

To succeed, health care reform must slow spending growth while improving quality. We propose a new approach to help achieve more integrated and efficient care by fostering local organizational accountability for quality and costs through performance measurement and “shared savings” payment reform. The approach is practical and feasible: it is voluntary for providers, builds on current referral patterns, requires no change in benefits or lock-in for beneficiaries, and offers the possibility of sustained provider incomes even as total costs are constrained. We simulate the potential expenditure impact and show that significant Medicare savings are possible.

Posterior parietal cortex (PPC) has been implicated in navigation, in the control of movement, and in visually-guided decisions. To relate these views, we measured activity in PPC while mice performed a virtual navigation task driven by visual decisions. PPC neurons were selective for specific combinations of the animal's spatial position and heading angle. This selectivity closely predicted both the activity of individual PPC neurons, and the arrangement of their collective firing patterns in choice-selective sequences. These sequences reflected PPC encoding of the animal’s navigation trajectory. Using decision as a predictor instead of heading yielded worse fits, and using it in addition to heading only slightly improved the fits. Alternative models based on visual or motor variables were inferior. We conclude that when mice use vision to choose their trajectories, a large fraction of parietal cortex activity can be predicted from simple attributes such as spatial position and heading.

Background Previous studies have reported an association between the timing of menarche and cardiovascular disease ( CVD ). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events ( MACE ). Methods and Results A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the WISE (Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse CVD outcomes. MACE was defined as the first occurrence of all‐cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self‐reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra–total estrogen time were calculated. Cox regression analysis was performed adjusting for CVD risk factors. Baseline age was 57.9 ± 12 years (mean ± SD ), body mass index was 29.5 ± 6.5 kg/m 2 , total estrogen time was 32.2 ± 8.9 years, and supra–total estrogen time was 41.4 ± 8.8 years. MACE occurred in 172 (27%), and its adjusted regression model was J‐shaped. Compared with women with menarche at age 12 years, the adjusted MACE hazard ratio for menarche at ≤10 years was 4.53 (95% CI 2.13‐9.63); and at ≥15 years risk for MACE was 2.58 (95% CI , 1.28‐5.21). Conclusions History of early or late menarche was associated with a higher risk for adverse CVD outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse CVD events. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00000554.