ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE : STRUCTURAL REQUIREMENTS IN THE SIDE CHAIN OF TYROSINE FOR IMMUNOGENICITY OF L-TYROSINE-AZOBENZENEARSONATE

The low molecular weight compound L-tyrosine-azobenzenearsonate (RAT) induces a cellular immune response in guinea pigs. The contribution of the side chain of tyrosine to the immunogenicity of RAT and the structural requirements at that position for immunogenicity were assessed by synthesizing a series of analogs of RAT containing modifications in the side chain of tyrosine and employing them as immunogens. Removal of either the carboxyl or amino group did not markedly affect immunogenicity, measured by the induction of delayed cutaneous sensitivity, whereas deletion of both completely abolished it. However, a charged group was not required since side chains containing a polar hydroxyl group could substitute for chains bearing an amino or carboxyl group. The size of the side chain exerted a pronounced influence; the charged or polar substituent had to be extended from the phenolic ring by at least two carbon atoms in order to confer immunogenicity

Inflammatory abdominal aortic aneurysms: A case-control study

AbstractPurpose: This study was designed to identify significant differences in the clinical and radiologic characteristics and outcome between patients with inflammatory and noninflammatory abdominal aortic aneurysms (AAAs).Methods: We reviewed 29 consecutive patients who underwent repair of an inflammatory AAA between 1985 and 1994. This group was matched in a case-control fashion by date of surgery and by the performing surgeon to a group of 58 patients who underwent repair of noninflammatory AAAs.Results: The two groups had comparable characteristics of age, gender, and cardiovascular risk factors. Patients with inflammatory AAAs were significantly more symptomatic than those with noninflammatory AAAs (93% vs 9%, p < 0.001), were more likely to have a family history of aneurysms (17% vs 1.5%, p = 0.007), and tended to be current smokers (45% vs 24%, p = 0.049). Thi most significant laboratory difference was an elevated sedimentation rate in patients with inflammatory AAAs (mean, 53 mm/hr vs 12 mm/hr, p < 0.00001). Inflammatory AAAs also were significantly larger than noninflammatory AAAs at presentation (6.8 cm vs 5.9 cm, p < 0.05). Although operative mortality was low in both groups, patients with an inflammatory AAA tended to have higher morbidity, including sepsis ( p < 0.01) and renal failure ( p = 0.04). Five-year survival rates, however, were similar for the two groups (79% for inflammatory and 83% for noninflammatory AAAs). On follow-up computed tomographic scans, the retroperitoneal inflammatory process resolved completely in 53% of the patients, but 47% of patients had persistent inflammation that involved the ureters in 32% and resulted in long-term solitary or bilateral renal atrophy in 47%.Conclusions: This case-control study provides preliminary evidence that inflammatory AAAs may have a relatively strong familial connection and that current smoking may play an important role in the inflammatory response. The study also documents that persistent retroperitoneal inflammation may be more prevalent than has been previously reported, and stresses the need for an improved understanding of the pathogenesis and long-term management of inflammatory AAAs. (J Vasc Surg 1996;23:860-9.

Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model

BACKGROUND: Angiogenic therapy with vascular endothelial growth factor (VEGF) has been proposed as a treatment paradigm for patients suffering from an insufficiency of collateral vessels. Diabetes is associated with increase in the production of VEGF and therefore additional VEGF may not be beneficial. Accordingly, we sought to determine the efficacy of VEGF therapy to augment collateral formation and tissue perfusion in a diabetic mouse ischemic hindlimb model. METHODS: Diabetic and non-diabetic mice were studied in parallel for the efficacy of VEGF administration. Diabetes was induced with streptozotocin. Hindlimb ischemia was produced by severing the left iliac artery. An outlet tube from an osmotic infusion pump with placebo/ 500 micrograms of plasmid-DNA encoding VEGF was fenestrated and tunneled into the left quadriceps muscle. RESULTS: VEGF induced more rapid and complete restoration of blood flow in normal mice. However, in the setting of diabetes there was no difference between VEGF Vs. placebo in the rate or adequacy of flow restoration. There was a significant increase in smooth muscle actin and Factor-VIII antigen densities in diabetic animals and in animals which received VEGF. CONCLUSIONS: Angiogenic therapy with VEGF in the setting of diabetes does not appear to have the beneficial effects seen in the absence of diabetes

The Stratified Structure of Spaces of Smooth Orbifold Mappings

We consider four notions of maps between smooth C^r orbifolds O, P with O compact (without boundary). We show that one of these notions is natural and necessary in order to uniquely define the notion of orbibundle pullback. For the notion of complete orbifold map, we show that the corresponding set of C^r maps between O and P with the C^r topology carries the structure of a smooth C^\infty Banach (r finite)/Frechet (r=infty) manifold. For the notion of complete reduced orbifold map, the corresponding set of C^r maps between O and P with the C^r topology carries the structure of a smooth C^\infty Banach (r finite)/Frechet (r=infty) orbifold. The remaining two notions carry a stratified structure: The C^r orbifold maps between O and P is locally a stratified space with strata modeled on smooth C^\infty Banach (r finite)/Frechet (r=infty) manifolds while the set of C^r reduced orbifold maps between O and P locally has the structure of a stratified space with strata modeled on smooth C^\infty Banach (r finite)/Frechet (r=infty) orbifolds. Furthermore, we give the explicit relationship between these notions of orbifold map. Applying our results to the special case of orbifold diffeomorphism groups, we show they inherit the structure of C^\infty Banach (r finite)/Frechet (r=infty) manifolds. In fact, for r finite they are topological groups, and for r=infty they are convenient Frechet Lie groups.Comment: 31 pages, 2 figures; corrected and expande

A striking correspondence between the dynamics generated by the vector fields and by the scalar parabolic equations

The purpose of this paper is to enhance a correspondence between the dynamics of the differential equations $\dot y(t)=g(y(t))$ on $\mathbb{R}^d$ and those of the parabolic equations $\dot u=\Delta u +f(x,u,\nabla u)$ on a bounded domain $\Omega$. We give details on the similarities of these dynamics in the cases $d=1$, $d=2$ and $d\geq 3$ and in the corresponding cases $\Omega=(0,1)$, $\Omega=\mathbb{T}^1$ and dim($\Omega$)$\geq 2$ respectively. In addition to the beauty of such a correspondence, this could serve as a guideline for future research on the dynamics of parabolic equations