Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions

BACKGROUND: Previous work from our laboratory demonstrated that interleukin (IL)-6 plays a potentially critical role in postreperfusion myocardial injury and is the major cytokine responsible for induction of intracellular adhesion molecule (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICAM-1 induction is necessary for neutrophil-associated myocyte injury. We have previously demonstrated the induction of IL-6 in the ischemic myocardium, and the current study addresses the cells of origin of IL-6. METHODS AND RESULTS: In the present study, we combined Northern blot analysis and in situ hybridization to demonstrate IL-6 gene expression in cardiac myocytes. Isolated ventricular myocytes were stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, preischemic lymph, and postischemic lymph. Unstimulated myocytes showed no significant IL-6 mRNA expression. Myocytes stimulated with preischemic lymph showed minimal or no IL-6 mRNA expression, whereas myocytes stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, or postischemic lymph showed a strong IL-6 mRNA induction. Northern blot with ICAM-1 probe revealed ICAM-1 expression under every condition that demonstrated IL-6 induction. We then investigated the expression of IL-6 mRNA in our canine model of ischemia and reperfusion. Cardiac myocytes in the viable border zone of a myocardial infarction exhibited reperfusion-dependent expression of IL-6 mRNA within 1 hour after reperfusion. Mononuclear cells infiltrate the border zone and express IL-6 mRNA. CONCLUSIONS: Isolated cardiac myocytes produce IL-6 mRNA in response to several cytokines as well as postischemic cardiac lymph. In addition to its production by inflammatory cells, we demonstrate that IL-6 mRNA is induced in myocytes in the viable border zone of a myocardial infarct. The potential roles of IL-6 in cardiac myocytes in an infarct border are discussed.     

Myelolipoma of the adrenal gland

We report the 14th case of myelolipoma of the adrenal gland. Recommendations for appropriate diagnostic and therapeutic methods are made. Myelolipoma of the adrenal gland is a rare non-functioning tumor composed of lipoid and hematopoietic elements. The most consistent complaint is abdominal pain caused by hemorrhage within the tumor. We identified an association with obesity and hypertension. Ultrasound combined with computed tomography is useful in diagnosis. With expanded use of these studies, myelolipoma will be recognized more frequently. Definitive diagnosis and treatment are accomplished by simple excision; radical surgery is unnecessary.     

Structure-based design of a lysozyme with altered catalytic activity

Here we show that the substitution Thr 26-->His in the active site of T4 lysozyme causes the product to change from the alpha- to the beta-anomer. This implies an alteration in the catalytic mechanism of the enzyme. From the change in product, together with inspection of relevant crystal structures, it is inferred that wild-type T4 lysozyme is an anomer-inverting enzyme with a single displacement mechanism in which water attacks from the alpha-side of the substrate. In contrast, the mutant T26H is an anomer-retaining enzyme with an apparently double displacement mechanism in which a water molecule attacks from the opposite side of the substrate. The results also show that the mechanism of wild-type T4 lysozyme differs from that of hen egg-white lysozyme even though both enzymes are presumed to have evolved from a common precursor.     

Alar fold resection in horses: 24 cases (1979-1992)

Between 1979 and 1992, the alar folds were resected bilaterally in 22 horses and unilaterally in 2 horses. Abnormal respiratory tract noise and exercise intolerance were the primary complaints prior to surgery. Significantly (P = 0.01) more Standardbreds underwent resection of the alar folds, compared with the number of Standardbreds in the hospital population during the same period. The alar folds palpated abnormally thick in 13 horses and normal in 11 horses. Temporary dilatation of the nares with mattress sutures or clips lessened the respiratory tract noise and improved exercise tolerance in all 8 horses in which the diagnostic test was performed. Manual elevation of the alar folds reduced respiratory noise in the 11 horses evaluated. Long-term follow-up evaluation by telephone was available for 14 horses. All surgical incisions had healed cosmetically. Respiratory tract noise was decreased, and exercise tolerance improved in 10 of 14 (71%) horses. Complete charted racing information was obtained for 16 horses. Fourteen horses started their first race a mean of 118 days (range, 13 to 321 days) after surgery. The mean number of starts after surgery was 51, with 14 of 16 (88%) horses starting more than 6 times after surgery. Of the 16 horses, 8 horses raced at least 3 times before and after surgery; 4 had improved racing performance, 2 had similar performance, and 2 had decreased performance. Five Standardbreds never raced, and 1 Standardbred raced once before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)