No abstract

Cyanoformates and cyanoformamides are found to add across alkynes by nickel/Lewis acid (LA) cooperative catalysis to give beta-cyano-substituted acrylates and acrylamides, respectively, in highly stereoselective and regioselective manners. The resulting adducts serve as versatile synthetic building blocks through chemoselective transformations of the ester, amide, and cyano groups as demonstrated by the synthesis of typical structures of beta-cyano ester, beta-amino nitrile, gamma-lactam, disubstituted maleic anhydride, and gamma-aminobutyric acid. The related reactions of cyanoformate thioester and benzoyl cyanide, on the other hand, are found to add across alkynes with decarbonylation in the presence of a palladium/LA catalyst.

Ultrasonography was used to evaluate spleen size in patients with various clinical conditions including those of the liver, blood, collagen, or autoimmune disease. To express spleen size, a spleen index (SI), the product of the transverse diameter and its perpendicular diameter measured on the maximum cross-sectional image of the spleen, was used. SI correlated well with the volumes of resected spleens. Splenomegaly was present in high percentages of patients with liver, blood, collagen, and autoimmune disease, even though a majority of these spleens were not large enough to palpate. By grading the SI, characteristic distributions of SI were obtained for patients with different types of diseases. Obtaining and grading the SI by the use of ultrasound appears to be a significant supplemental aid for evaluating spleen size, especially in patients whose spleens are not palpable.

Allyl cyanides are found to add across alkynes in the presence of a nickel catalyst prepared from Ni(cod)2 and P(4-CF3-C6H4)3 in situ to give variously functionalized di- or trisubstituted acrylonitriles in highly stereoselective manners possibly via a pi-allylnickel species as an intermediate. alpha-Siloxyallyl cyanides also react at the gamma-position of a cyano group with both internal and terminal alkynes having various functional groups to give silyl enol ethers, which give the corresponding aldehydes or ketones upon hydrolysis.

Whereas immobility is a common cause of muscle atrophy, the mechanism underlying this causality is unclear. We here show that KLF15 and IL-6 are up-regulated in skeletal muscle of limb-immobilized mice and that mice with KLF15 deficiency in skeletal muscle or with systemic IL-6 deficiency are protected from immobility-induced muscle atrophy. A newly developed Ca 2+ bioimaging revealed that the Ca 2+ concentration ([Ca 2+ ]i) of skeletal muscle is reduced to below the basal level by immobilization, which is associated with the down-regulation of Piezo1. Acute disruption of Piezo1 in skeletal muscle induced Klf15 and Il6 expression as well as muscle atrophy, which was prevented by antibodies to IL-6. A role for the Piezo1/KLF15/IL-6 axis in immobilityinduced muscle atrophy was validated by human samples. Our results thus uncover a paradigm for Ca 2+ signaling in that a decrease in [Ca 2+ ]i from the basal level triggers a defined biological event.

Cyanoformate esters add across 1,2-dienes in the presence of a nickel/PMe(2)Ph catalyst to afford beta-cyano-alpha-methylenealkanoates regioselectively, which are kinetically favored and readily isomerize to thermodynamically favored alpha-cyanomethyl-alpha,beta-unsaturated carboxylates at high temperature under the nickel catalysis, possibly through oxidative addition of the C-CN bond. Similar cyanoesterification products are produced from chloroformate esters, trimethylsilyl cyanide, and 1,2-dienes in the presence of a nickel/dppp catalyst. The resulting cyanoesterification products have a structure of allylic cyanide and thus undergo further allyl cyanation reaction across alkynes with the aid of a nickel/P(4-CF(3)-C(6)H(4))(3) catalyst to afford highly substituted acrylonitrile derivatives.

Visceral larva migrans (VLM) is a disease characterized by chronic eosinophilia, hepatomegaly, and hypergl~bulinemia.l-~ The parasite Toxocara canis and its near relative Toxocara cati are the most common organisms of the disease. After infective-stage eggs are ingested by humans, the second-stage larvae of T. canis and T. cati wander widely in the tissues, reach many organs including the lung, eye, heart, liver, and brain, and form eosinophilic granulomas. As a consequence, it sometimes causes serious complicat i o n s . '~~ Ultrasonographic and other diagnostic imaging features of hepatic granuloma of toxocariasis have not yet been fully described. Here we describe 2 cases with hypereosinophilia associated with VLM by T . canis or T . cati in which several imaging studies were applied. Sonography was useful as a screening method in the identification of hepatic eosinophilic granuloma and in evaluating the effect of the treatment. CASE REPORT Case 1A 52-year-old Japanese man, a farmer, was referred to the Kyushu University Hospital in July 1989 because of eosinophilia. When he had consulted a local physician because of trauma, leukocytosis (27,6OO/kL) with eosinophilia (61%) was disclosed. He had had neither symptoms nor eruptions. He had been keeping 15 dogs, 7 cats, 12 chickens, and 110 cows. He had had a food habit of eating raw meat or liver of wild birds, chickens, and wild boars. 204On admission the patient was well nourished with no symptoms. Anemia, jaundice, or lymphadenopathy were not evident. A stool test was negative for parasite ova. Peripheral blood count revealed leukocytosis (2 1 ,OOO/p,L) with 64% eosinophils. The slight elevation of serum glutamic-oxaloacetic transaminase (SCOT), serum glutamic-pyruvic transaminase (sGPT), alkaline phosphatase, and gamma-glutamyl transpeptidase were seen. Alpha-fetoprotein was negative. The serum immunoglobulin E (IgE) level was increased to 7500 IU/mL, but other immunoglobulin levels were normal.A bone marrow tap revealed eosinophilic hyperplasia but abnormal cells were not observed. Upper and lower gastrointestinal series were negative. Immunological tests for causative agents gave a precipitin arc against T. canis by Ouchterlony's method as well as immunoelectrophoresis, and showed a high titer of anti-T. canis antibody by enzyme-linked immunosorbent assay.Case 2 A 63-year-old Japanese farmer was referred to the Kyushu University Hospital in April 1990 because of eosinophilia. When he had consulted a local physician because of hypertension, leukocytosis with hypereosinophilia was disclosed. He had neither symptoms nor eruptions on the skin. He had been keeping dogs and had a food habit of eating raw meat and liver of chickens, wild boars, and horses.On admission, the patient was a well-nourished, apparently healthy man. A stool examination was negative for parasite ova. Peripheral blood white blood cell count was 16,9OO/pL with 62% eosinophils. The serum IgE level was as high as 18,000 IU/mL. SGOT (32 IU/mL) and sGPT (20 IU/mL) levels were normal, but the a...

A Ni/PMe2Ph catalyst is found to effect regioselective addition of cyanoformate esters across 1,2-dienes, giving rise to 3-alkoxycarbonyl-3-butenenitriles. Functional groups such as cyano, protected hydroxyl, and amino groups in the 1,2-diene substrates are tolerated. Isomerization of the initial products to thermodynamically more stable isomers takes place possibly through further oxidative addition of the C-CN bond of 3-alkoxycarbonyl-3-butenenitriles to Ni(0) followed by reductive elimination. The cyanoesterification products undergo further addition across alkynes in the presence of a Ni/P(4-CF3-C6H4)3 catalyst.