Correlation of cyclosporine and metabolite binding to cyclophilin and a 50 kDa binding protein with in vitro immunosuppression: a preliminary report

Seven purified cyclosporine (CsA) metabolites were analyzed for binding to cyclophilin and to a 50 kDa protein purified from a JURKAT cell line. In addition, the potency of the seven metabolites, relative to CsA, was obtained using a primary mixed lymphocyte culture (MLC) suppression assay. CsA, M1, 17, and 21 were found to be immunosuppressive in the concentration range used (0-500 ng/mL). These results were then compared to protein binding. CsA and metabolite 17 (M17) bound to both proteins. Conversely, M1, 13, 21, and 26 bound only to cyclophilin, while M8 and M18 bound only to the 50 kDa protein.     

A Modification to the Fascia-Bone-Fascia Technique for Repair of the Middle Fossa Floor

A commonly used method for resurfacing of the middle fossa floor is the fascia-bone-fascia technique. One disadvantage of this technique however is the occasional migration of the bone graft. To prevent this, we have modified the technique to include securing of the graft using simple craniotomy fixation materials. We have now used this method in five patients, all of whom have had satisfactory clinical outcomes. Follow-up imaging has demonstrated the grafts to have remained in their original position.     

Genetic control of myeloproliferation in BXH-2 mice

While studying the unique Nramp1 (Slc11a1)-independent susceptibility to Mycobacterium bovis (BCG) infection of BXH-2 mice, we noted that these mice develop important splenomegaly and enlargement of lymph nodes. Segregation analyses in several F2 crosses showed that splenomegaly segregates as a single recessive trait caused by a novel mutation in BXH-2, independent of the infection. Histologic and fluorescence-activated cell sorter (FACS) analyses indicated that splenomegaly is associated with a large increase in Mac1+/GR1+ (macrophage antigen-1+/granulocyte differentiation antigen 1+) granulocyte precursors in spleen, lymph nodes, and bone marrow, resembling a myeloproliferative syndrome. This is concomitant to extramedullary erythropoiesis in the spleen, as measured by proportion of Ter119+ erythroid cells. The locus controlling this myeloproliferative syndrome and splenomegaly was designated Myls and maps to an 18 centimorgan (cM) region of chromosome 8, which also contains an integrated copy of an N-ecotropic murine leukemia virus (MuLV) provirus (Emv2). The relationship between Myls, expansion of Mac1+/GR1+ cells, and Emv2 was investigated. Homozygosity at Myls is necessary but not sufficient for B-ecotropic virus replication in splenocytes, the extent of which appears to be under separate genetic control. Our results suggest a model in which Myls-dependent myeloproliferation in BXH-2 acts as a predisposing factor for the subsequent development of virally induced myeloid leukemia characteristic of this strain.     

EPZ011989, A Potent,Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

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Estimation tools for reducing the impact of sampling and nonresponse errors in dual-frame RDD telephone surveys

We discuss alternative estimators of the population total given a dual-frame random-digit-dial (RDD) telephone survey in which samples are selected from landline and cell phone sampling frames. The estimators are subject to sampling and nonsampling errors. To reduce sampling variability when an optimum balance of landline and cell phone samples is not feasible, we develop an application of shrinkage estimation. We demonstrate the implications for survey weighting of a differential nonresponse mechanism by telephone status. We illustrate these ideas using data from the National Immunization Survey-Child, a large dual-frame RDD telephone survey sponsored by the Centers for Disease Control and Prevention and conducted to measure the vaccination status of American children aged 19 to 35 months.     

CONCEPTUALIZING FAMILY MEMBERS OF VIOLENT MENTALLY ILL INDIVIDUALS AS A VULNERABLE POPULATION

A review of literature concerning familial violence and mental illness using the Vulnerable Populations Conceptual Model (VPCM) as an organizing framework is presented. Since family members are most likely to be targets if a person who is mentally ill becomes violent, this review emphasizes the VPCM concepts of resource availability (including capital, stigma, and access to healthcare), risk, and health status of those family members. The population-based VPCM was used in an attempt to move the examination of this phenomenon from a focus on the individual to a conceptualization of it as family violence occurring within a broader, social context.