An overview of types of aggressive behaviour in dogs and methods of treatment

In 223 cases of dogs presented to a specialist behavioural clinic in Brisbane, Australia, 87 (39%) were for severe aggression. The classes of aggression included dominance (31.6%), territorial (29%), predatory (12.3%), intermale (12.3%), sibling rivalry (7.9%), fear biting (6%) and idiopathic rage (0.9%). The breeds most represented which attacked humans were the Bull Terrier (16%), German Shepherd and crosses (15%), Cattle dog breeds (Blue Heeler and crosses, 9.2%), Terrier breeds (9.2%), Labrador (8%), Poodle and Cocker Spaniel (both 5.7%) and Rottweiler (4.6%). The dangerous dog list put out by the local Brisbane City Council includes the first three breeds mentioned and the Rottweiler as the top four breeds causing aggression problems.

Hospital records in Victoria and Queensland confirm that most damage is caused to humans by Bull Terriers and German Shepherds. Many breeds similar to those in our study are also represented in American data on aggressive breeds.

Treatments included obedience training only, restraint only, obedience and restraint, synthetic progestins and obedience, castration, progestins and obedience, castration and obedience, use of chlorpromazine and as a last resort, euthanasia (12.6%). Entire males formed the largest group (44%), followed by castrated males and females (both 21%) and spayed females (15%).

Several breeds (Boxer, Briand, Samoyed and St. Bernard) only attacked other animals and birds.

This study reinforces evidence that social disruption is caused by aggressive dogs, but it also indicates that many responsible clients seek advice on how to deal with this behavioural problem.     

Transgenic animals as a tool for studying the effect of the c-myc proto-oncogene on cardiac development

Transgenic animals provide a model system to elucidate the role of specific proteins in development. This model is now being used increasingly in the cardiovascular system to study cardiac growth and differentiation. During cardiac myocyte development a transition occurs from hyperplastic to hypertrophic growth. In the heart the switch from myocyte proliferation to terminal differentiation is synchronous with a decrease in c-myc mRNA abundance. To determine whether c-myc functions to regulate myocyte proliferation and/or differentiation, we examined the in vivo effect of increasing c-myc expression during fetal development and of preventing the decrease in c-myc mRNA expression that normally occurs during myocyte development. The model system used was a strain of transgenic mice exhibiting constitutive expression of c-myc mRNA in cardiac myocytes throughout development. Increased c-myc mRNA expression is associated with both atrial and ventricular enlargement in the transgenic mice. This increase in cardiac mass is secondary to myocyte hyperplasia, with the transgenic hearts containing greater than twice as many myocytes as nontransgenic hearts. The results of this study indicate that constitutive expression of c-myc mRNA in the heart during development results in enhanced hyperplastic growth, and suggest a regulatory role for the c-myc protooncogene in cardiac myogenesis.     

A molecular genetic approach to the identification of isochromosomes of chromosome 21

Summary The largest class of de novo chromosomal rearrangements in Down syndrome are rea(21q21q). Classically, these rearrangements have been termed Robertsonian translocations, implying an attachment of two different chromosome 21 homologues. Additionally, a Robertsonian translocation between two chromosomes 21 cannot be distinguished from an isochromosome composed of genetically identical arms by cytogenetic analyses. Therefore, we have used molecular techniques to differentiate between true Robertsonian translocations and isochromosomes. Samples were obtained from 12 probands, ascertained for de novo rearrangements between homologous chromosomes 21 [11 rea(21q21q) and 1 rea (21;21)(q22;q22)], their parents (n = 24) and available siblings (n = 7). The parental origins of the de novo rearrangements were assigned using molecular and cytogenetic analyses. Although not statistically significant, there was a two-fold increase in the number of paternally derived de novo rearrangements (n = 8) as compared with maternally derived rearrangements (n = 4). To distinguish between rob(21q21q) and i(21q), we used restriction fragment length polymorphisms (RFLPs) spanning the length of chromosome 21. Using all informative and partially informative RFLPs, we used the method of maximum likelihood to assign the most likely rearrangement definition (i or rob) and parental origin in each family. The maximum likelihood estimates indicated that all rearrangements tested (n = 8) were isochromosomes. C-banding revealed two centromeres in three cases indicating that a U-type exchange occurred between sister chromatids in these rearrangements. Our results suggest that the majority of de novo rea(21q21q) are isochromosomes derived from a single parental chromosome 21.     

Cirrhosis with atypia. A potential pitfall in the interpretation of liver aspirates

Needle aspirations of the liver yielding highly atypical hepatocytes present a diagnostic challenge, with the differential diagnosis lying between hepatocellular carcinoma and benign reactive atypia. A case of a healing liver abscess in a patient with cirrhosis, mistakenly diagnosed as an hepatocellular carcinoma, is presented. Criteria for the avoidance of false-positive diagnoses of hepatocellular carcinoma on needle aspirates are presented, and the concept of "liver cell dysplasia" as a cytodiagnostic entity is discussed.     

Design and synthesis of metabolically stable atrial natriuretic factor analogs. Amino- and carboxy-terminal stabilization

Two analogs of rat atrial natriuretic factor, rANF7-28-NH2 and [Mpr7,Ala20,D-Arg27]rANF7-27-NH2, were prepared by the solid-phase method. These peptides had 2-fold and 7-fold less affinity, respectively, than rANF1-28 in binding to membranes prepared from cultured aortic smooth muscle cells, and both peptides were 5-fold less potent than rANF1-28 in relaxing serotonin-contracted rabbit aortic rings. rANF7-28-NH2 was rapidly degraded by rat kidney homogenates but [Mpr7,Ala20,D-Arg27]rANF7-27-NH2 had enhanced stability against rat kidney homogenate degradation. However, this in vitro stability did not translate into an extended duration of action in vivo.     

Agalinis (Scrophulariaceae) in Peru and Bolivia

Chromosome numbers determined for ten species ofAgalinis from Peru and Bolivia are alln=16. Field observations have provided morphological data about habit, leaves, inflorescences, and flowers. A key to species in Peru and Bolivia is provided.     

Calcium dependence during single-cycle catalysis of the sarcoplasmic reticulum ATPase

We have investigated the kinetic and thermodynamic properties of the Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum under conditions that result in a single transport cycle. Simultaneous addition of ATP and EGTA to sarcoplasmic reticulum vesicles, preincubated with calcium, resulted in a transient of intermediate species. In the presence of saturating Ca2+ levels, total E-P species reached a maximum of 2.3 nmol/mg at 100 ms, followed by a monoexponential decay with kobs = 3.6 s-1. The data are interpreted in terms of Ca2+ sequestration, either by occlusion as Ca2+ in the phosphorylated enzyme or chelation by EGTA. Maximum Ca2+ uptake was 8.3 nmol/mg with the release of 4.4 nmol/mg Pi. The ratio of Ca2+ uptake to Pi release approached 1.9 over a wide [Ca2+] range. Equilibrium Ca2+ binding, in the absence of ATP, showed a K0.5 of 0.88 microM with a Hill coefficient of 1.9. The Ca2+ concentration dependence of Ca2+ uptake during single-cycle catalysis showed a 10-fold enhanced affinity (K0.5 = 0.06 microM) and was noncooperative (nH = 0.9). Quench with excess EGTA (greater than 2 mM) decreased Ca2+ uptake to 1 nmol/mg, indicating an "off" rate of Ca2+ from high affinity sites that exceeds 100 s-1. The ATP concentration dependence for a single-cycle catalysis showed an apparent K0.5 of 1.1 microM, similar to that for ATP equilibrium binding. It is proposed that enzyme phosphorylation proceeds only following binding of a second calcium ion to externally oriented sites whose intrinsic affinity is in the same range as the calcium dependence of a single-cycle turnover.     

Human cytotoxic T cell clones directed against herpes simplex virus-infected cells. IV. Recognition and activation by cloned glycoproteins gB and gD

Results of studies in mice and clinical observations in man indicate that T cell-mediated immunity is important in resistance to herpes simplex virus (HSV) infections. This study was undertaken to elucidate the viral antigen specificity of human HSV-immune T cells. Purified HSV-1 glycoproteins gB-1 and gD-1, cloned and expressed in mammalian cells, were found to stimulate proliferation of, and interleukin 2 (IL 2) production by, peripheral blood lymphocytes (PBL) of HSV seropositive individuals, indicating the presence of memory T cells to gB-1 and gD-1 in individuals with serologic evidence of immunity to HSV. Second, T cell clones, generated by stimulation of PBL with HSV-1, were found to recognize gB-1 or gD-1, as evidenced by the ability of the clones to proliferate in response to stimulation with gB-1 or gD-1 in the absence of exogenous IL 2. Third, HSV-specific T cell clones, lytic for HSV-1 or both HSV-1- and HSV-2-infected autologous target cells, were generated after stimulation of PBL with purified cloned gB-1 or gD-1. Our findings, that human HSV-specific T cells can recognize and be activated by HSV subunit antigens gB-1 or gD-1, imply that these glycoproteins play a role in human T cell-mediated immunity to HSV and support the contention that a gB-1 or gD-1 subunit vaccine may be protective in man.     

Binding of C-reactive protein to nucleated cells leads to complement activation without cytolysis

C-reactive protein (CRP) is an acute-phase reactant that is found bound to cells at sites of inflammation. We have passively sensitized HEp-2 cells for CRP binding and examined the effect of this treatment on complement activation and cell lysis. When cells were treated with protamine sulfate and CRP and were incubated with normal human serum in a 4-hr 51Cr-release assay, no significant lysis was noted. In contrast, HEp-2 cells treated with antibody and normal human serum were lysed. The consumption of complement components in normal human serum after incubation with cells treated with protamine and CRP was measured by hemolytic assays. CRP-treated cells consumed over 80% of C1, C4, and C2 and about 40% of C3 present. No significant consumption of C5 through C9 components was observed. Cells treated with antibody and complement showed consumption of C1 through C9. Cells were also sensitized for CRP binding by using diazophenylphosphocholine. This treatment also led to CRP binding and activation of the early classical pathway (C1, C4, C2, and to a lesser extent C3). The components of the membrane attack complex (C5 through C9) were not activated. Both a mouse monoclonal IgM and a human IgG antibody to phosphocholine activated the entire classical pathway. These results indicate that CRP activation of the classical complement pathway is restricted to the early part of the pathway. In the absence of activation of the membrane attack complex, complement-mediated cell lysis cannot occur.     

Absorbance and fluorescence properties of 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate bound to coupled and uncoupled Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum

Preincubation of skeletal muscle sarcoplasmic reticulum vesicles in the presence of the calcium chelator, [ethylenebis(oxyethylenenitrilo)tetraacetic acid] (EGTA), irreversibly uncouples calcium transport from ATP hydrolysis. Uncoupling cannot be explained by increased membrane permeability, but is associated with decreased capacity of the Ca2+-ATPase to bind noncatalytic, tightly bound ATP and ADP (Berman, M. C. (1982) Biochim. Biophys. Acta 694, 95-121). The effects of EGTA-induced uncoupling on absorbance and fluorescence properties of the bound ATP analog, 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP), have been studied under static and turnover conditions. Binding of 4.5-4.9 nmol of TNP-ATP/mg, as determined by absorbance difference titration, was relatively unaffected in the uncoupled state. TNP-ATP, bound to coupled vesicles during turnover, showed 6-8-fold enhanced fluorescence and a shift in the difference absorbance maximum from 510 to 493 nm, indicating increased hydrophobicity of the noncatalytic site. Turnover-dependent fluorescence enhancement was diminished by 60-70% in the uncoupled state, while the absorbance maximum wavelength shift was abolished. These data, correlating changes in the environment of the noncatalytic or regulatory nucleotide binding site on the Ca2+-ATPase with coupling activity, indicate that uncoupling is an intramolecular process, involving a ligand binding site on the ATPase, and that exclusion of H2O from the site occupied by noncatalytic nucleotides, during at least part of the catalytic cycle, is an event associated with energy transduction.