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The synthesis of a series of NHC building blocks that can then be incorporated into more complicated structures by palladium catalysis is reported. This approach is used for the synthesis of three amino acids containing NHC side chains. The ability to use the amino acids in solid-phase peptide synthesis to make NHC-containing peptides is also demonstrated. Additionally, the NHC side chain can be deprotected and coordinated to a catalytically active transition metal. Finally, it is illustrated that the building blocks participate in Suzuki coupling to provide access to substituted NHC ligands.

Work toward the development of a bisphosphine ligand system for the palladium-catalyzed addition to cyclic allyl acetates is reported. A parallel approach using phosphine-containing amino acids in conjunction with natural amino acids was used to develop a selective ligand system. The ligand system was examined while attached to the polymer support as well as in solution. Selectivites with the difficult substrate 3-acetoxycyclopentene of up to 95% ee are reported.

Work toward the development of a bis-phosphine ligand system for the palladium-catalyzed desymmetrization of meso-diols is reported. A parallel approach using phosphine-containing amino acids and a “representational search” was taken to find a polymer-supported catalyst system. The selectivities reported are comparable to many other polymer-bound asymmetric catalysts.

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.

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.

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.

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.

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.

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.

Cells enriched for NK activity (poly I:C induced, x-ray resistant, and nonadherent), include two phenotypically and functionally different populations. Both populations of NK cells are AGM1+, Ly-1.1-, Ly-2.1-, Ia-, and have the morphology of large granular lymphocytes. One population, however, is Thy-1+ while the second population is Thy-1-. Thy-1+ NK cells lyse YAC-1 and P815 target cells; Thy-1- NK cells lyse YAC-1 but not P815 target cells. The FACS was used to obtain homogeneous populations of Thy-1+ and Thy-1- NK cells, which retain high cytotoxicity. While Thy-1- NK cells suppress the antibody response in vitro by suppressing or eliminating DC, Thy-1+ NK cells do not suppress antibody responses in vitro.