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Biomedical subjects

S M Wells

Publications and source records attributed to S M Wells.

9 recordsLinked to original sources

In vivo and in vitro mechanical properties of the sheep thoracic aorta in the perinatal period and adulthood.

The mammalian aorta undergoes rapid remodeling during the perinatal period and more gradual remodeling during subsequent development, but the implications of this remodeling for arterial mechanics are poorly understood. In this study in vivo and in vitro techniques were used to determine the static and viscoelastic properties of the thoracic aortas of 119-day-gestation fetal sheep (full term = 145 days), 21-day-old lambs, and adult sheep at control distending pressures and after 70% increases or 30% decreases in pressure. In the weeks surrounding birth, aortic wall tissue became substantially stiffer (static elastic modulus in vitro increased by 28%, and pressure wave velocity in vivo increased by 61%) but less viscous (pressure wave attenuation in vivo decreased by 46%, and viscoelastic phase angle in vitro decreased by 15%), whereas the wall thickness-to-radius ratio was unchanged. By contrast, modest changes in tissue viscoelasticity from neonatal to adult life were accompanied by a halving of the wall thickness-to-radius ratio from 0.19 +/- 0.01 to 0.10 +/- 0.01. The relative thinning of the vessel wall, combined with a doubling of blood pressure after birth, resulted in a 265% increase in aortic wall tensile stress over the period of study. We concluded that rapid remodeling in the perinatal period primarily alters the viscoelastic properties of aortic wall tissues, whereas more gradual postnatal remodeling largely affects vessel geometry.

Aging

B-1 cells: unique origins and functions.

B-1 cells represent a distinct population of B lymphocytes with unique phenotypic, developmental and functional characteristics. We present evidence that the expression of MHC class II antigens differentiates two distinct developmental pathways which define the fetal-type (FT) and adult-type B-cell lineages. Further in-vivo and in-vitro analyses suggest that B-1 cells are derived primarily if not exclusively from the FT lineage. Combining these results with other studies suggesting that signalling plays a role in the development of B-1 cells, we propose a modified dual lineage model for the generation of B-1 cells. In this model fetal-type B cells are uniquely 'born' with the capacity to be B-1 cells, however, they must be properly educated (i.e. receive the appropriate signals) before they can be 'made' functional, phenotypic B-1 cells. With respect to the function of B-1 cells, we have used PerC/BM allotype chimeric animals to investigate the capacity of B-1 cells to participate in the formation of germinal centers. In these mice we were unable to detect any significant involvement of B-1 cells in the generation of germinal centers. These results are discussed in the context of the known characteristics of B-1 responses including the low frequency of hypermutation and isotype class switching.

Animals

CD43 (S7) expression identifies peripheral B cell subsets.

CD43 (leukosialin) expression has previously been demonstrated on the surface of developing B cells in mouse bone marrow and on plasma cells induced in vitro, but not on peripheral B cells in spleen. Here we show that CD43, as recognized by mAb S7, is indeed expressed on a small population of splenic B cells. Flow cytometric phenotyping of normal mice and radiation chimeras reveals that CD43/S7 is expressed on virtually all (> 90 to 95%) splenic B-1 cells and the majority of peritoneal B-1 cells, but not on conventional B cells. The expression of CD43/S7, in conjunction with other cell surface markers, clearly distinguishes B-1 cells from follicular, marginal zone, and immature B cells in the unstimulated adult spleen and permits further phenotyping of these subsets. The phenotype of splenic and peritoneal B-1 cells in normal BALB/c and BAB/25 mice is essentially identical with the exception that all peritoneal B-1 cells express CD11b (Mac-1) and some lack CD43/S7 and heat stable Ag (as detected by the mAb 53-10) expression. Although splenic B-1, marginal zone, and immature B cells share many phenotypic characteristics, these studies show that, in addition to CD43, they differ with respect to the expression levels of a variety of Ags including heat stable Ag, B220, and the B cell activation Ag B7.

Aging

Reaction of germinal centers in the T-cell-independent response to the bacterial polysaccharide alpha(1-->6)dextran.

Primary immunization of BALB/c mice with alpha(1-->6)dextran (DEX), a native bacterial polysaccharide, induces an unexpected pattern of splenic B-cell responses. After a peak of antibody-secreting B-cell response at day 4, deposition of dextran-anti-dextran immune complexes, as revealed by staining with both dextran and antibodies to dextran, occurs and persists in splenic follicles until at least the fourth week after immunization. Antigen-specific B cells appear and proliferate in such follicles, leading by day 11 to development of DEX-specific germinal centers as characterized by the presence of distinct regions of DEX+ peanut agglutinin-positive (PNA+) cells. At this time, fluorescence-activated cell sorter analysis also reveals the appearance of a distinct population of DEX+ PNA+ splenic B cells. In contrast, DEX+ PNA- cells, characterized by intense cytoplasmic staining, are present outside of splenic follicles, peak at day 4 to day 5, and persist until at least day 28. The frequency of these cells correlates with DEX-specific antibody-secreting cells, as detected by the ELISA-spot assay. Thus, in addition to the expected plasma cellular response, the typical T-cell-independent type II antigen, DEX, surprisingly also elicits the formation of antigen-specific germinal centers. These observations raise fundamental questions about the roles of germinal centers in T-cell-independent immune responses.

Animals

Inpatient hospital utilization in three prepaid comprehensive health care plans compared with a regular Blue Cross plan.

The evidence is substantial that comprehensive, HMO-type prepayment plans can significiantly reduce hospitalization rates. Yet it remains unclear which factors contribute to this phenomenon. This study focuses on organizational characteristics of four plans with different hospitalization experiences. Regular medical staff review and frequent use of second opinions and economies of scale achieved by providing care at one well-equipped, large health center appear to have the largest impact. However, such organizational advantages can easily be wiped out by adverse self-selection of patients during open-enrollment periods. Evidence of selection based on predictable high obstetrical and newborn care costs is presented.

Blue Cross Blue Shield Insurance Plans