苄基四氢巴马汀对表达于非洲爪蟾卵母细胞及中华大蟾蜍卵母细胞的延迟整流钾电流的抑制作用

苄基四氢巴马汀对表达于非洲爪蟾卵母细胞及中华大蟾蜍卵母细胞的延迟整流钾电流的抑制作用童秋生，夏国瑾，姚伟星，江明性，白小川，包永德（同济医科大学基础医学院药理学教研室，武汉４３００３０；中国科学院上海生理学研究所，上海２０００３１）苄基四氢巴马汀（ｂ...     

CD40 ligand triggered interleukin-6 secretion in multiple myeloma

Previous studies have suggested that interleukin-6 (IL-6) may mediate growth of multiple myeloma (MM) in either an autocrine or paracrine growth mechanism. However, those molecules which can trigger IL-6 secretion either by tumor cells or non-MM marrow cells are not well characterized. In the present study, we have examined the expression and functional significance of CD40 on MM and plasma cell leukemia (PCL) cells and derived cell lines, as well as long-term bone marrow stromal cells (BMSCs) and derived cell lines. CD40 was expressed on the majority of MM cells (> 90%) and BMSCs (> 70%). Triggering via CD40 using NIH3T3 CD40 ligand transfectant (CD40LT) cells increased (> 30%) cell surface CD80, CD18, CD11a, CD11b, and CD11c expression on MM cell lines. Culture with either fresh or paraformaldehyde fixed NIH3T3 CD40LT cells upregulates IL-6 secretion in MM cells and MM-derived cell lines, as well as normal and MM bone marrow mononuclear cells (BMMCs), BMSCs, and BMSC lines; this effect can be specifically blocked by anti- CD40 monoclonal antibody (MoAb). BMMCs and BMSCs from patients with MM secreted significantly more IL-6 than those from healthy donors (n = 3, P < .001); moreover, after stimulation using CD40L, IL-6 secretion was fourfold greater (n = 3, P < .001) from MM BMMCs and BMSCs than from normal BMMCs and BMSCs. Myeloma (CD38+CD45RA-) cells and non-MM (CD38+CD45RA+, CD38-CD45RA+, and CD38-CD45RA-) BMMCs were separated by dual fluorescence cell sorting. The latter secreted fourfold more IL-6 than the former (n = 2, P < .001). Increased IL-6 secretion (up to 28- fold) and proliferation (Stimulation index 10) by CD38+CD45RA-MM cells was triggered by culture with NIH3T3 CD40LT cells. Finally, anti- CD40MoAb partially (30%) blocked tumor cell to BMSC adhesion-induced IL- 6 secretion. These studies support the view that CD40L may trigger IL-6 secretion by both MM cells and BMSCs and that IL-6-mediated autocrine and paracrine growth mechanisms may be possible in MM.     

Clinical outcomes and maternal perceptions of an updated model of perinatal care

BACKGROUND: Postpartum hospital stays seem likely to remain limited even under new laws which mandate that insurers cover 48-hour hospitalization after uncomplicated delivery. Clinicians, who are increasingly practicing in capitated arrangements, need better information to maximize clinical benefit to mothers and newborns using finite resources. OBJECTIVE AND INTERVENTIONS: This study's aim was to evaluate the clinical outcomes, patient perceptions, and costs of a revised model of perinatal care services. In this model, a new postpartum care center was established for routine follow-up of newborns within 48 hours after hospital discharge, educational efforts were shifted from the postpartum hospitalization to the prenatal period, and lactation consultant hours were increased. DESIGN AND PARTICIPANTS: Controlled, nonrandomized (double cohort) study that compared mothers and newborns with hospital stays of 48 hours or less during the Baseline Care (preintervention) study period (N = 344) with those under the Revised Care (postintervention) study period (N = 456). SETTING: The Hayward, California, medical center of Kaiser Permanente, a nonprofit health maintenance organization. DATA COLLECTION: Telephone interviews were attempted with all mothers 3 weeks after delivery. Data on rehospitalizations, emergency department (ED) and clinic visits, and costs during the first 14 postpartum days were collected from computerized databases and chart review. OUTCOME MEASURES: The combined clinical outcome was defined as any undesirable health event, including rehospitalization, an ED visit, or an urgent clinic visit by either the mother or newborn within the first 14 days postpartum, or breastfeeding discontinuation within the first 21 days postpartum. Maternal satisfaction and costs were also studied. RESULTS: Of 876 attempted interviews, 800 were completed (91%). Analyses were adjusted for age, race, education, parity, breastfeeding experience, and other relevant variables. Among the interviewed mother-newborn pairs, 45% in the Revised Care group experienced the combined clinical outcome, compared with 52% in the Baseline Care group. Newborns in the Revised Care group (29%) were significantly less likely to make urgent clinic visits during the first 14 days of life than those in the Baseline Care group (36%). There were no differences between groups in newborn ED visits or rehospitalizations, maternal clinical outcomes, or breastfeeding continuation. Mothers in the Revised Care group expressed higher satisfaction with the newborn's care, the amount of information they received about newborn care and breastfeeding, and the amount of help they received with breastfeeding. Planned hospital care, planned follow-up visits, and unplanned care costs decreased by $149 per delivery, while the new prenatal class and increased lactation consultant services cost $58 per delivery, for an estimated overall reduction in cost. CONCLUSIONS: We conclude that the revised model of perinatal care in this health maintenance organization medical center improved clinical outcomes and maternal satisfaction for low-risk mothers and newborns without increasing costs.     

INDIVIDUALISATION OF HIV THERAPY: THE CLINICIAN'S PERSPECTIVE

SUMMARY Assessment of clinical and laboratory markers of HIV infection may be used to individualise antiretroviral therapy. Data suggest that measures of viral load may be of considerable value as both a baseline and dynamic therapy marker, making these tools particularly useful in driving therapeutic decisions. Similarly, in-vitro data regarding intracellular pharmacokinetics and activity, resistance patterns and potential synergy of antiretroviral agents may be used to guide selection of optimal treatment regimens in clinical practice.     

The number of receptors for factor VII correlates with the ability of cultured cells to initiate coagulation

Previously, we showed that cells derived from nonvascular tissues initiate clotting primarily by markedly increasing the activity of coagulation factor VII. Cells derived from vascular tissue do not normally exhibit this property (tissue factor activity). In this study, we have characterized the relationship between the tissue factor activity of cultured cells derived from normal tissues and the number of receptors they possess for coagulation factor VII. Only cultured nonvascular cells expressed tissue factor activity or possessed receptors for 125I-factor VII. Fetal lung cells, the nonvascular tissue with the largest amount of procoagulant and tissue factor activity, possessed the most receptors for 125I-factor VII (880,000/cell). Bovine corneal endothelial cells, the nonvascular tissue possessing the fewest number of receptors (2,400/cell), had the least amount of procoagulant or tissue factor activity. The affinity of nonvascular cells for 125I- factor VII varied for the cells studied (Kd congruent to 1.3-90 X 10(- 10) M). Vascular cells expressed no tissue factor activity, nor did they bind 125I-factor VII. 125I-factor VII and unlabeled factor VII bound to cells had identical procoagulant activities. These results indicate that the ability of cultured cells to initiate coagulation may be regulated in part by the number of receptors they possess for factor VII.