The discovery of crown ethers

The discovery of the crown ethers stemmed from efforts to control the catalytic activity of vanadium and copper by complexation with multidentate ligands. The first crown ether, 2,3,11,12-dibenzo-1,4,7,10,13,16-hexaoxacyclo-octadeca-2,11-diene, was obtained in 0.4% yield during an attempt to prepare a phenolic ligand from catechol and bis(2-chloroethyl)ether. This compound, which complexed with the sodium cation, was the first compound known to display such activity and became known as dibenzo-18-crown-6, an 18-atom heterocycle containing 6 oxygen atoms. Some 60 related compounds were made involving heterocyclic rings containing 12 to 60 atoms including 4 and 10 oxygen atoms. There are optimum polyether ring sizes for the different alkali metal cations: 15 to 18 for sodium, 18 for potassium, and 18 to 21 for cesium. Complexes having polyether to cation ratios of 1:1, 3:2, and 2:1 were prepared. Solubilization of inorganic salts in aprotic solvents, especially by saturated crown ethers, was demonstrated.     

Comparative efficacy of three commercial feline leukemia virus vaccines against methylprednisolone acetate-augmented oronasal challenge exposure with virulent virus.

Three commercial FeLV vaccines, (A, B, and C) were purchased on the open market and administered to 8- to 20-week-old specific-pathogen-free kittens, according to manufacturers' instructions. A similar group of nonvaccinated kittens served as controls. All kittens were challenge-exposed oronasally with virulent FeLV 4 weeks after the final vaccination. Serum samples were monitored for FeLV-p27 antigenemia using an ELISA at 1- to 2-week intervals for at least 16 weeks after the last day of challenge exposure. Kittens that were either transiently (1 to 4 weeks) or never viremic during this period were counted as recovered, whereas kittens that became viremic and retained viremia for at least 10 weeks were counted as persistently viremic. The 3 vaccines were found to be 39% (vaccine C), 28% (vaccine B), and 17% (vaccine A) efficacious in preventing persistent viremia in immunized, compared with nonimmunized kittens.     

Mitral valve prolapse in 3-year-old healthy Cavalier King Charles Spaniels. An echocardiographic study.

Clinical studies have shown that Cavalier King Charles Spaniels (CKCS) have a high prevalence of mitral valvular insufficiency (MVI). Echocardiography has the potential to disclose early valvular changes, and the present prospective study was designed to investigate the occurrence of mitral valve prolapse (MVP) in young CKCS without heart murmurs, and to correlate the degree of MVP with the clinical status of the dogs by including CKCS with MVI as well. The study was based on blinded evaluations of echocardiographic recordings of mitral valves from 34 CKCS and 30 control dogs. Thirteen (87%) of 15 three-year-old CKCS without heart murmurs had MVP (2 total and 11 partial), as compared with 1 (7%) of 15 three-year-old normal Beagle dogs (P < 0.0001), and none of 15 three-year-old normal Medium Size Poodles (P < 0.0001). Of 19 CKCS with MVI, MVP was found in 84% of the entire group and in 100% of dogs with pulmonary congestion or edema. The occurrence of total MVP tended to be higher in the group with MVI (47%, 9/19), when compared with the younger CKCS without heart murmurs (13%, 2/15, P = 0.06). MVP was positively associated with excessive heart rate variability (P = 0.003). The radius of curvature of the anterior mitral valve leaflet in systole was significantly reduced in dogs with MVP when compared with those without (P < 0.0001). In conclusion, this study shows that CKCS at an early age have a high occurrence of MVP. This suggests: 1) A genetic predisposition of CKCS to MVP; and 2) That MVP is a pathogenetic factor in the development of mitral valvular insufficiency. Follow up studies may add further support to these proposals, and clarify whether echocardiography may be an aid in selecting CKCS for future breeding.     

Synthesis and insect growth regulating activity of thiosemicarbazones of methyl 2-pyridyl ketones

Thirty-six thiosemicarbazones of methyl 2-pyridyl ketone and of some other methyl ketones were tested on Dysdercus cingulatus, Drosophila melanogaster, Locusta migratoria, Aedes aegypti, Tenebrio molitor and Musca domestica. Several derivatives were toxic, delaying or preventing ecdysis. The structure-activity relationship is discussed. The mode of action of these compounds appears to be different from that of juvenile hormones, anti-juvenile hormones, or chitin biosynthesis inhibitors.     

Recovery of microorganisms from synovial and pleural fluids of animals using hyperosmolar media

L-phase (CWD) broth and plate media were used in parallel with conventional microbiological media during a 3-year period for culturing synovial and pleural fluids of animals. Two kinds of recoveries were obtained where parallel conventional methods were negative: (1) parent or normal bacteria, in very low numbers; and (2) Type B CWD variants in equally low numbers. Organisms in group 1 were: Streptococcus zooepidemicus from horses (2X); β-hemolytic streptococci, Lancefield Gp. G (2X); Staphylococcus aureus; Actinobacillus, and Actinomyces viscosus. Group 2 consisted of Bacteroides sp., Propionibacterium acnes, and three “Nocardia-like” sp. Catalase + Actinomyces was not recovered equally well on CWD plates as on conventional media with fluids obtained during ampicillin treatment. This occurred in spite of the fact that the CWD media was shown to support growth and reversion of laboratory induced L-phase variants of Nocardia caviae and N. asteroides, and had facilitated recovery of a Bacteroides L-phase variant from a pleural fluid. The nature of this fault in the media is under investigation in this laboratory.     

Course of feline leukemia virus infection and its detection by enzyme-linked immunosorbent assay and monoclonal antibodies

Monoclonal antibodies specific for 3 distinct epitopes of the species-specific determinants of feline leukemia virus (FeLV) p27 were used in an enzyme-linked immunosorbent assay (ELISA) for measurement of serum p27 in cats infected with FeLV. Group-specific antigen (GSA) of FeLV in peripheral blood leukocytes was also determined by an immunofluorescence assay. Antibodies to FeLV and the feline oncornavirus-associated cell membrane antigen (FOCMA) were also measured. Thirty-six cats were surveyed and assigned to 4 categories. Five developed persistent viremia (category 1), characterized by continuous expression of p27, GSA, and low antibody titers to FeLV and FOCMA. Eleven cats with transient viremia (category 2) and 13 cats that were never detectably viremic (category 3), as judged by absence of GSA and p27, developed increased antibody titers to FeLV and FOCMA. Seven cats were never viremic, as judged by the GSA in the peripheral blood leukocytes, but still had detectable serum p27 (category 4). Most category 4 cats developed high antibody titers against FOCMA and/or FeLV. Of 307 field cats examined, 7% of the healthy cats and 10% of the sick cats could be assigned to category 4. However, this difference was not significant (P greater than or equal to 0.05). Of 26 cats with neoplasms 2 (1 of 12 with lymphosarcoma) could be classified as category 4. Because virus could be isolated from 2 category 4 cats, they were considered immune carriers.     

Persistent upregulation of MHC class II antigen expression on T-lymphocytes from cats experimentally infected with feline immunodeficiency virus.

A significant elevation in the percentage of CD4+ and CD8+ T-lymphocytes expressing major histocompatibility complex (MHC) Class II antigens was observed in the blood of cats shortly after they were experimentally infected with feline immunodeficiency virus (FIV). In addition to an increase in the relative proportion of T-lymphocytes expressing Class II antigens, there was an increase in the density of Class II antigens on the cell surface. These elevations were still evident at the completion of the 5 month study. A second group of cats that had been infected with FIV for almost 5 years, and with either normal or abnormally low levels of CD4+ T-lymphocytes, had similar elevations in MHC II expression, suggesting that such abnormalities are lifelong. Cats with chronic (2 year) feline leukemia virus (FeLV) infection or dual FIV/FeLV infections also showed similar alterations in MHC II expression on CD4+ and CD8+ T-lymphocytes, suggesting that these alterations were not FIV specific. Feline T-lymphocytes expressed more MHC II antigen and interleukin-2 (IL-2) receptor following stimulation in vitro with conconavalin A and IL-2, demonstrating that feline T-lymphocytes respond to activation signals in a manner similar to T-lymphocytes of other species. However, changes in MHC II expression on T-cells of FIV infected cats were not explainable by viral induced T-cell activation alone, because FIV infected cats with elevated MHC II expression did not have coincident elevations in IL-2 receptor expression.     

Inflammatory oral cavity diseases of the cat.

There is a great deal of frustration among veterinarians about the diagnosis and treatment of inflammatory diseases of the oral cavity of the cat. This frustration is due to both the high frequency of feline oral inflammatory lesions and our poor understanding of their causes. This poor understanding can be blamed on several things: (1) a rapidly emerging, but still relatively poor, understanding of feline diseases in general and nutrition in particular; (2) a tendency to lump rather than separate specific oral inflammations; (3) a tendency not to use a thorough and systematic approach to diagnosing oral cavity disease; and (4) the reluctance of veterinarians to apply what is already known about human oral cavity diseases to cats. When problems 2 through 4 are adequately addressed, it becomes apparent that we really know more about oral cavity disease in the cat than we thought we knew and that great progress has been made. The task ahead is to define, in precise medical terms, those remaining disease entities of the oral cavity that pose the greatest health risk to cats, to apply what has been already been discovered from human disease counterparts, and to study them systematically.     

Synthesis and insecticidal properties of derivatives of propane-1, 3-dithiol (analogues of the insecticidal derivatives of dithiolane and trithiane from the alga Chara globularis Thuillier)

Functional derivatives of 2-(methylthio)propane-1, 3-dithiol (open chain analogues of the insecticidal 4-methyithio-1, 2-dithiolane and 5-methylthio-1, 2, 3-trithiane from the alga Chara globularis) possess insecticidal properties similar to those of the structurally related nereistoxin. Some derivatives of propane-1, 3-dithiol, bearing 2-substituents different from the methylthio group, have also been shown to have insecticidal pioperties.