Michael A. Kjelsberg

Leukocyte recruitment and expression of chemokines following different forms of vascular injury

Inflammation plays a central role in restenosis following coronary intervention. Recent human and animal data suggest important differences between the inflammatory responses to simple balloon angioplasty compared with stent implantation. To investigate the mechanisms of these differences, New Zealand white rabbits underwent bilateral iliac artery balloon denudation. Half received intravascular stents. Arteries were harvested at three, seven and 14 days for immunohistochemistry, and 4 hours, 8 hours and 14 days for chemokine mRNA analysis. Leukocyte content was quantifi ed utilizing immunohistochemistry (RPN357, monoclonal antibody (mAb) against rabbit neutrophil; RAM-11, mAb against rabbit macrophage). We analyzed the mRNA levels of the chemokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) through semi-quantitative polymerase chain reaction. We demonstrated the spatial pattern of MCP-1 mRNA levels through in situ mRNA hybridization. In balloon-injured arteries, leukocyte recruitment was confi ned to early neutrophil infi ltration. IL-8 and MCP-1 mRNA levels peaked within hours and were undetectable at 14 days. In contrast, in stented arteries, early neutrophil recruitment was followed by prolonged macrophage accumulation. IL-8 and MCP-1 mRNA levels peaked within hours but were still detectable 14 days post injury. Conclusions: In contrast to balloon injury, stent-induced injury results in sustained chemokine expression and leukocyte recruitment. These data may have important implications for antirestenotic strategies.

Synthesis and protonation reactions of trimethylphosphine-substituted carbyne complexes of molybdenum and tungsten. The tungsten alkylidene complexes [(W=CHR)Cl2(CO)(PMe3)2] as precursors for carbyne complexes containing weakly coordinated ligands

Synthese des complexes [(W≡CR)Cl(CO)(PMe 3 ) 3 ] et [M≡CPh)Br(PMe 3 ) 4 ]. Reactions avec HBr. Structure cristalline de [(W=CHPh)Cl 2 (CO)(PMe 3 ) 2 ]

Synthesis, structure, and dynamic behavior of dichloro alkylidene alkyne bis(trimethylphosphine)tungsten complexes.

The mechanism of alkyne polymerization by molybdenumand tungsten-based catalysts has been proposed to propagate via metal alkylidene intermediates (Scheme I).I For mononuclear systems each mechanistic cycle involves coordination of an alkyne to the transition-metal center, formation of a metallacyclobutene, and regeneration of the metal carbene by ring opening. Fischer-type carbyne complexes are among the best catalyst precursors and transformation of the carbyne ligand into a carbene ligand for catalytic activity has been post~lated.~ We have developed simple methods for the synthesis of group 6 transition-metal carbyne complexes3 and we have begun to investigate the reactions of these compounds with unsaturated hydrocarbons. Reactions of pyridine-substituted tungsten carbyne complexes [(W=CR)CI( c O ) , ( p ~ ) ~ ] with activated olefins leading to stable tungsten alkene carbyne complexes have already been d e ~ c r i b e d . ~ Analogous reactions of [(W=LR)CI(CO),(py),] with alkynes did not afford isolable tungsten alkyne carbyne complexes; rather, polymerization of alkynes was observed. More recently, we have developed routes to trimethylphosphine-stabilized metal carbyne complexes and we have shown that deprotonation of the tungsten alkylidene complex [(W==CHPh)(Cl),(CO)(PMe3)2] (1) provides an anionic tungsten carbyne complex, [ ( WSCP~)(CI)~(CO)( PMeJ2]-, containing a labile chloride ligand.5 Dehydrochlorination of 1 in the presence of ligands L thus provides good access to substituted tungsten carbyne complexes [(W=tPh)Cl(CO)L(PMe,),], and we hoped this method might allow the synthesis of stable tungsten carbyne complexes containing alkyne ligands. Here we report about reactions of 1 with acetylenes in the presence of base which afford stable transition-metal alkyne alkylidene complexes,6 possibly via labile tungsten alkyne carbyne complexes. The products exhibit the elements of the first intermediate in Masudas mechanism for acetylene polymerization and they serve as precursors for moderately active alkyne polymerization catalysts. An equimolar mixture of 1, diphenylacetylene, and 1,8-bis(dimethy1amino)naphthalene is allowed to react for 30 min at 0

Vasoconstriction After Coronary Stenting

An 83-year-old woman was transferred to Brigham and Women’s Hospital with postinfarction angina and cardiogenic shock 24 hours after thrombolytic therapy for an inferior myocardial infarction. Coronary angiography showed a 90% stenosis in a dominant right coronary artery (Figure⇓). She underwent successful percutaneous coronary angioplasty, including deployment of an articulated Palmaz-Schatz stent, leaving …