Kinetic Resolution of Diiron Acyl Complexes-An Approach to Asymmetric Bicyclic ß-Lactams.

Kinetic resolution is achieved in the reaction of racemic diiron complexes like 1 with the chiral nitrone (-)-2. Oxidative removal of the metal and reductive cleavage of the N-O bond provides ß-amino acids. This sequence was used in the synthesis of ß-amino acids as well as the corresponding ß-lactams 4 (via 3).

Kinetic resolution in palladium-catalyzed asymmetric allylic alkylations by a P,O ligand system.

[reaction: see text] Through the investigation of peptide-based phosphine oxazoline ligands, a simple P,O ligand system was developed. This system provides palladium complexes that are capable of a very high degree of kinetic resolution of 1,3-diphenylprop-2-enyl acetate. The isolated palladium complex was synthesized, characterized, and determined to be an effective procatalyst.

Chiral P,N-ligands based on ketopinic acid in the asymmetric Heck reaction.

[figure: see text] Novel chiral P,N-ligands were synthesized from (1S)-(+)-ketopinic acid using palladium-catalyzed coupling reaction of a vinyl triflate and either a diarylphosphine or a dialkylphosphine as the key step. Palladium complexes of these ligands are efficient catalysts for asymmetric Heck reaction between aryl or alkenyl triflates and cyclic alkenes. Products were obtained with good to excellent enantioselectivity from arylation and alkenylation of 1,2-dihydrofuran, cyclopentene, and 4,7-dihydro-1,3-dioxepin.

Synthesis of new bicyclic P-N ligands and their application in asymmetric Pd-catalyzed pi-allyl alkylation and Heck reaction.

[structure: see text] The synthesis of phosphine oxazoline ligands based on P-chiral 1-phosphanorbornadienes is reported. The use of these ligands in palladium catalyzed asymmetric allylation and Heck reaction is described.

Clinical, morphologic, and chemical studies on copper toxicosis of Bedlington Terriers.

In a study of 90 Bedlington Terriers, 68 had a defect that resulted in the accumulation of toxic excesses of copper in the liver. Concentrations of copper were 5 to 50 times that of clinically normal mongrel dogs. The bulk of this excess copper was sequestered in lysosomes. When copper concentrations exceeded 2,000 micrograms/g dry liver, progressive signs of functional and morphologic disturbance appeared as focal hepatitis, chronic active hepatitis, and ultimately cirrhosis. The disorder, which appears to be inherited, could only be diagnosed by liver biopsy. It was latent for many years in some dogs but led early in life to acute or chronic hepatic disease and death in others.

Chronic active hepatitis in Doberman pinschers.

Eleven Doberman Pinschers were affected with a disease that had clinical signs, serum biochemical abnormalities, and histologic features of chronic active hepatitis. Intrahepatic cholestasis and accumulations excess hepatic copper were prominent features. Most of the dogs deteriorated within weeks to months, and 6 died within 9 months after the 1st signs of disease were noticed.

Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia.

The plasma cortisol response to exogenous ACTH (ACTH stimulation test) was evaluated in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia. The mean basal cortisol concentration (6.3 microgram/dl) was high, but 7 dogs had basal cortisol concentrations that were within normal range. Administration of exogenous ACTH increased the plasma cortisol concentrations in each dog. Normal post-ACTH cortisol concentrations were found in 9 (41%) of the 22 dogs; 13 (59%) had an exaggerated increase in cortisol concentrations after ACTH administration. In 9 of 13 dogs with carcinoma and in 4 of 9 with adenoma, the cortisol response was exaggerated. The mean post-ACTH cortisol concentration in the dogs with carcinoma was approximately 4 times that of the dogs with adenoma; the 7 dogs with the highest concentrations had carcinoma. Repeat studies were performed in 6 dogs 2 to 8 weeks after initial testing. In 5 of the 6 dogs, repeat testing yielded data of similar diagnostic significance. One dog, however, had an abnormally high post-ACTH cortisol concentration at initial evaluation, but had only a minimal response to ACTH administration, with a normal post-ACTH cortisol concentration, at time of resting. Although ACTH stimulation testing is useful in diagnosing hyperadrenocorticism, it can not reliably separate dogs with hyperfunction adrenocortical tumors from clinically normal dogs or from dogs with pituitary-dependent hyperadrenocorticism (bilateral adrenocortical hyperplasia).

Cutaneous lesion caused by Mycobacterium tuberculosis in a dog.

A 5-month-old female mixed-breed dog was examined because of nonhealing wounds in the right submandibular region. Treatment with antibiotics and surgical excision was ineffective. Specimens of the right mandibular lymph node and surrounding tissues were submitted for bacteriologic culturing, and Mycobacterium tuberculosis was isolated. The dog was euthanatized. The risk of infection of human beings who associate with dogs that have cutaneous wounds caused by mycobacteria is unknown.

Interpretation of canine liver biopsy. A clinician's perspective.

Proper evaluation of hepatic biopsies is essential for the proper management of dogs with liver disease. The clinician must have some basic knowledge of hepatic anatomy and histopathologic nomenclature in order to establish an accurate prognosis and therapeutic plan.

Spontaneous deciduosarcoma in a domestic rabbit (Oryctolagus cuniculus).

Deciduosarcoma is a rare, hormonally dependent neoplasm with features of malignancy, previously reported only in rabbits enrolled in chronic toxicology studies involving estrogens with or without progestins. An exploratory laparotomy was performed on a 6-year-old pet Dutch dwarf rabbit following palpation of a 6-cm-diameter abdominal mass. Grossly, the mass was fleshy and nodular, adhered to but not appearing to originate from the small intestine, with a smaller mass of similar appearance involving the uterus, and an effaced mesenteric lymph node. Histologically, the mass was characterized by spindloid cells and large epithelioid cells with abundant pale eosinophilic vacuolated cytoplasm and an infiltrative pattern of growth. Giant cells with large, bizarre, hyperchromatic nuclei were common. Cells were positive by immunohistochemistry for vimentin and progesterone and estrogen receptors and negative for pancytokeratin (AE1/AE3), cytokeratin 18, desmin, alpha-smooth muscle actin (SMA), and CD10. Based on histologic and immunohistochemical findings, a diagnosis of deciduosarcoma was made.

Proline-based P, N ligands in asymmetric allylation and the Heck reaction.

A series of phosphine-oxazoline ligands based on proline are reported. These ligands are synthesized from commercially available trans-4-hydroxy-L-proline in four steps. The ability of this type of ligand to catalyze allylic alkylation in an asymmetric fashion as well as the asymmetric Heck reaction is reported. The best of these ligands gave a palladium complex, which catalyzed the addition of dimethylmalonate to cyclopentenyl acetate in excellent yield and up to 96% ee. This same system catalyzed the Heck reaction between dihydrofuran and cyclohexene in up to 86% ee. These ligands appear to differ from the traditional phosphine-oxazoline ligands in that the stereochemistry of the stereogenic carbon next to the oxazoline is not necessarily the dominant chiral center in the induction of selectivity.

Cutaneous plasmacytomas in dogs: a morphologic and immunohistochemical study.

Forty-nine cutaneous plasmacytomas in 46 dogs were studied. Tumors occurred at solitary sites in middle-aged to old dogs (mean age, 9.7 years) and most commonly involved the skin of the digits, lips, and ears. Initial diagnosis was made on the basis of light microscopic morphologic findings. Tumors were graded according to the extent of cellular differentiation and immunoreactivity to a panel of immunohistochemical markers (cytokeratins, canine IgG F[ab]2, neurofilament, neuron-specific enolase, S-100 protein, and vimentin). Immunoreactivity was limited to antibodies directed at canine IgG F(ab)2 and vimentin. Vimentin immunoreactivity was usually greater than that of canine IgG F(ab)2, but there was no correlation between immunoreactivity and histologic grade of the tumors. Thirty-six of 39 dogs (92.3%) followed (mean follow-up, 13 months) were cured by surgical excision. The results of this study indicate that canine cutaneous plasmacytomas are benign neoplasms that should be included in the differential diagnosis of cutaneous round cell tumors in dogs.

Distance between phosphine-sulfide sidechains of a disubstituted peptide by DRAMA 31P NMR.

Dipolar restoration at the magic angle (DRAMA) has been used to measure the 31P-31P internuclear distance between phosphine-sulfide substituted sidechanins on the fourth and eighth residues of a 12-residue helical peptide. The 7.4 A distance is the same for the peptide lyophilized in bulk or isolated in a cryo- and lyoprotected matrix of poly(ethylene glycol) and sucrose. However, the 31P linewidth for the undiluted peptide is an order of magnitude greater than for the matrix-isolated peptide indicating charge and hydration heterogeneity in the bulk state.

Cytochemical detection of inherited copper toxicosis of Bedlington terriers.

Sections of paraffin-embedded specimens of liver obtained from Bedlington terriers were stained with rhodanine for copper and examined and graded by two pathologists. Their results correlated well with each other, as well as with the results of quantitative determinations of hepatic copper content. Copper toxicosis was established by cytochemistry in 20 of 21 specimens, indicating a sensitivity of 95%. The method is highly specific--none of the 19 specimens obtained from unaffected dogs displayed copper-containing granules suggestive of copper toxicosis. Copper cytochemistry appears to be a satisfactory substitute for chemical analysis of hepatic copper content.

Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs.

We studied 232 dogs that underwent mastectomy for mammary epithelial neoplasms. The mastectomy specimens were evaluated according to structural parameters found to be prognostically significant in human mammary neoplasms, such as grade of atypia in non-invasive proliferations of duct epithelium, extent of malignant disease, and nuclear differentiation in malignant neoplasms. In this study, the biologic behavior of mammary lesions was assessed according to the frequency of development of de novo or recurrent invasive carcinoma within two years. Our data indicate that we can recognize structural variables which permit classification of mammary neoplasms into categories with distinct patterns of biologic behavior. In addition to normotypic proliferative lesions and invasive malignant neoplasms, we were able to identify precancerous atypic and non-invasive malignant neoplasms that are considered precursor lesions in women. Also, as in women, nuclear differentiation was found to be a prognostically significant variable. Lymphoid cellular reactions, considered to be structural correlates of host-tumor immune responses in women, were noted in 35% of dogs with precancerous or malignant neoplasms. Application of the described parameters should facilitate comparative studies of canine and human mammary carcinogenesis and use of the dog as a model for the development of new therapeutic modalities and immunoprophylaxis of human mammary cancer.

Primary myocardial disease in the cat. A model for human cardiomyopathy.

Thirty-four cats with primary myocardial disease were studied. The cats were divided into two groups, depending on the clinical, hemodynamic, angiocardiographic, and pathologic findings. Group A consisted of those cats with hypertrophic cardiomyopathy and Group B consisted of those cats with congestive cardiomyopathy. Similarity in the characteristics of cardiomyopathy in the human cat was found. Both Group A and Group B consisted predominantly of mature adult male cats. The most common presenting signs were dyspnea and/or thromboembolism, systolic murmurs with gallop rhythms on auscultation, cardiomegaly with (Group A) or without (Group B) pulmonary edema, abnormal electrocardiograms, elevated left ventricular end diastolic pressures, and angiocardiographic evidence of mitral regurgitation with left ventricular concentric hypertrophy (Group A) or left ventricular dilatation (Group B). Some cats in Group A also had evidence of left ventricular outflow obstruction. The principal pathologic findings in these cats were left atrial dilatation, symmetric hypertrophy or asymmetric septal hypertrophy of the left ventricle (Group A), and dilatation of the four cardiac chambers (Group B). Aortic thromboembolism was commonly observed in both groups. These clinical and pathologic findings indicate that cardiomyopathy in the cat is similar to the two most common forms of cardiomyopathy in the human (hypertrophic cardiomyopathy, with and without obstruction, and congestive cardiomyopathy).