Christine Y. Yeh

Atherosclerosis causes most acute coronary syndromes and strokes.The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells.CD44 is an adhesion protein expressed on inflammatory and vascular cells.CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells.Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells.To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice.We found a 50-70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates.We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions.Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic" state as measured by expression of VCAM-1.Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation.We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms.

Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50-70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic" state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms.

Hepatitis C virus (HCV) has been associated with several extrahepatic conditions. To date, most studies assessing these associations involved small numbers of patients and lacked a control group. Using the computerized databases of the Department of Veterans Affairs, we carried out a hospital-based case-control study that examined all cases of HCV-infected patients hospitalized during 1992 to 1999 (n = 34,204) and randomly chosen control subjects without HCV (n = 136,816) matched with cases on the year of admission. The inpatient and outpatient files were searched for several disorders involving the skin (porphyria cutanea tarda [PCT], vitiligo, and lichen planus); renal (membranous glomerulonephritis [GN] and membranoproliferative glomerulonephritis); hematologic (cryoglobulin, Hodgkin’s and non-Hodgkin’s lymphoma [NHL]); endocrine (diabetes, thyroiditis); and rheumatologic (Sjögren’s syndrome). The association between HCV and these disorders was examined in multivariate analyses that controlled for age, gender, ethnicity, and period of military service. Patients in the case group were younger in age (45 vs. 57 years), were more frequently nonwhite (39.6% vs. 26.3%), and were more frequently male (98.1% vs. 97.0%). A significantly greater proportion of HCV-infected patients had PCT, vitiligo, lichen planus, and cryoglobulinemia. There was a greater prevalence of membranoproliferative GN among patients with HCV but not membranous GN. There was no significant difference in the prevalence of thyroiditis, Sjögren’s syndrome, or Hodgkin’s or NHL. However, NHL became significant after age adjustment. Diabetes was more prevalent in controls than cases, but no statistically significant association was found after adjustment for age. In conclusion, we found a significant association between HCV infection and PCT, lichen planus, vitiligo, cryoglobulinemia, membranoproliferative GN, and NHL. Patients presenting with these disorders should be tested for HCV infection. (Hepatology2002;36:1439-1445).

Current prosthetic hands, although functional, have the potential of being improved significantly. We report here the design and development of a novel prosthetic hand that is lighter in weight, less expensive, and more functional than current hands. The new prosthesis features an endoskeleton embedded in self-skinning foam that provides a realistic look and feel and obviates the need for a separate cosmetic glove. The voluntary-closing mechanism offers variable grip strength. Placement of joints at three locations (metacarpophalangeal and proximal and distal interphalangeal) within each of four fingers affords realistic finger movement. High-strength synthetic cable attached to the distal phalanx of each finger is used to effect flexion. A multiposition passive thumb provides both precision and power grips. The new prosthesis can securely grasp objects with various shapes and sizes. Compared to current hands, weight has been reduced by approximately 50%, and cable excursion required for full finger flexion by more than 50%. The new endoskeletal prosthesis requires approximately 12-24% less force input to grasp a variety of everyday objects, largely due to its adaptive grip. Production cost estimates reveal the new prosthesis to be significantly less expensive than current prosthetic hands.