Myeloma-related disorders in cats commonly present as extramedullary neoplasms in contrast to myeloma in human patients: 24 cases with clinical follow-up

BACKGROUND: Myeloma-related disorders (MRD) are rare neoplasms of plasma cells. Published case reports describe a diversity of clinical presentations with confusing terminology and diagnostic criteria as a consequence of the assumption that MRD in cats are analogous to those in dogs or humans. OBJECTIVE: The aim of the study was to describe clinical, clinicopathologic and imaging findings, response to treatment, survival and possible associations with other diseases or vaccination in a large case series. A priori hypotheses were that cats with MRD commonly present with extramedullary involvement and uncommonly have radiographic bone lesions, in contrast to human patients. ANIMALS: Twenty-four cats with MRD confirmed by cytology or histopathology and immunohistochemistry. METHOD: A multicenter retrospective study was performed. RESULTS: Two types of clinical presentation were observed. The first group (n = 17) had neoplasia involving abdominal organs, bone marrow, or both. All developed systemic clinical signs and paraproteinemia. Five of 7 cats that received chemotherapy improved clinically or had decreased serum globulin concentration (median survival, 12.3 months; range, 8.5-22 months). The second group comprised 7 cats with skin masses, 2 of which were paraproteinemic and developed rapidly worsening systemic signs. In cats without systemic signs, excision of the skin masses appeared to be associated with prolonged survival (up to 2.4 years). Cats with MRD commonly presented with extramedullary involvement (67%), versus humans with MRD (5%) (P < .001), and uncommonly presented with radiographic bone lesions (8%) versus humans with MRD (80%) (P < .001). CONCLUSIONS: Radiographic bone lesions are uncommon in cats with MRD and extramedullary presentation is common, relative to human myeloma.     

Use of 3-nitrooxypropanol in a commercial feedlot to decrease enteric methane emissions from cattle fed a corn-based finishing diet

The present study evaluated enteric CH₄ production, dry matter (DM) intake (DMI), and rumen fermentation in feedlot cattle supplemented with increasing concentrations of 3-nitrooxypropanol (3-NOP). A total of 100 crossbred steers (body weight, 421 ± 11 kg) was randomly assigned to one of four treatments (n = 25/treatment): control (no 3-NOP) or low (100 mg/kg DM), medium (125 mg/kg DM), and high (150 mg/kg DM) doses of 3-NOP. The study was comprised of 28 d of adaptation followed by three 28-d periods, with CH₄ measured for 7 d per period and cattle remaining on their respective diets throughout the 112-d study. Each treatment group was assigned to a pen, with the cattle and diets rotated among pens weekly to allow the animals to access the GreenFeed emission monitoring (GEM) system stationed in one of the pens for CH₄ measurement. Measured concentration (mg/kg DM) of 3-NOP in the total diet consumed (basal diet + GEM pellet) was 85.6 for low, 107.6 for medium, and 124.5 for high doses of 3-NOP. There was a treatment × period interaction (P < 0.001) for DMI; compared with control, the DMI was less for the low and high doses in period 1, with no differences thereafter. Compared with control (10.78 g/kg DMI), CH₄ yield (g/kg DMI) was decreased (P < 0.001) by 52%, 76%, and 63% for low, medium, and high doses of 3-NOP, respectively. A treatment × period effect (P = 0.048) for CH₄ yield indicated that the low dose decreased in efficacy from 59% decrease in periods 1 and 2 to 37% decrease in period 3, while the efficacy of the medium and high doses remained consistent over time. Irrespective of dose, hydrogen emissions increased by 4.9-fold (P < 0.001), and acetate:propionate ratio in rumen fluid decreased (P = 0.045) with 3-NOP supplementation, confirming that other hydrogen-utilizing pathways become more important in the CH₄-inhibited rumen. The study indicates that supplementation of corn-based finishing diets with 3-NOP using a medium dose is an effective CH₄ mitigation strategy for commercial beef feedlots with a 76% decrease in CH₄ yield. Further research is needed to determine the effects of 3-NOP dose on weight gain, feed conversion efficiency, and carcass characteristics of feedlot cattle at a commercial scale.     

Evolution and functional impact of rare coding variation from deep sequencing of human exomes

As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111× in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.     

Melanesian blond hair is caused by an amino acid change in TYRP1

Naturally blond hair is rare in humans and found almost exclusively in Europe and Oceania. Here, we identify an arginine-to-cysteine change at a highly conserved residue in tyrosinase-related protein 1 (TYRP1) as a major determinant of blond hair in Solomon Islanders. This missense mutation is predicted to affect catalytic activity of TYRP1 and causes blond hair through a recessive mode of inheritance. The mutation is at a frequency of 26% in the Solomon Islands, is absent outside of Oceania, represents a strong common genetic effect on a complex human phenotype, and highlights the importance of examining genetic associations worldwide.     

Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti

Streptococcus suis serotypes have traditionally been identified by morphology, biochemical profiling and serotyping. Analysis of the sequences of 16S rRNA and cpn60 genes of the 35 characterized serotypes of S. suis led to the observation that two serotypes 32 and 34, are significantly distinct from other S. suis serotypes and may represent a distinct species. Here we present DNA sequence data and biochemical profiles which indicate that S. suis serotypes 32 and 34, isolated from pigs, are clustered with Streptococcus orisratti, a Voges-Proskauer negative, alpha-haemolytic, aesculin-hydrolytic, Lancefield group A streptococcus isolated from the teeth of rats.     

In vivo CXCR4 expression, lymphoid cell phenotype, and feline immunodeficiency virus infection

Primary isolates of feline immunodeficiency virus (FIV) appear to require binding to CD134 in conjunction with CXCR4(X4) to infect IL-2-dependent T-cell-derived cells in culture. However, much less is known about the role of X4 for the infection of cells in vivo. To investigate the correlation between X4 expression and FIV infection in cats acutely infected with FIV-C-Pgmr we used high-speed fluorescence-activated cell sorting and realtime PCR to co-analyze cell phenotypes from lymph node, thymus, bone marrow and blood for FIV infection and X4 expression. X4 expression was greatest in lymph node, both in frequency and in mean fluorescence intensity. The thymus demonstrated a higher proviral burden in X4+ thymic T cells (14% in X4+ thymic T cells and 7% in X4− cells) whereas, proviral loads were similar between X4+ and X4− cell populations in all other tissues examined. Assuming a minimum of one proviral copy per cell, a maximum of 50% of FIV-positive cells were X4+. The highest fraction of FIV-infected X4− cells was present in bone marrow. Regardless of X4 status, proviral loads were higher in lymph node and blood T cells than in B cells. These studies provide both a positive association between X4 expression and FIV infection and introduce the probability that X4-independent infection occurs in other target cells in vivo.     

The importance of functional connectivity in the conservation of a ground-dwelling mammal in an urban Australian landscape

The distribution of the northern brown bandicoot (Isoodon macrourus), a medium-sized ground-dwelling marsupial, was examined in habitat fragments within the urban landscape of the city of Brisbane, Australia. From surveys conducted in 68 fragments, bandicoots were found to be present in 33 (49%) despite widespread habitat loss and fragmentation. Logistic regression analysis revealed that of 13 measured independent variables, functional connectivity was the only factor that significantly predicted the presence of bandicoots within fragments, with connectivity positively correlated with the likelihood of occupation. Functional connectivity was equated to the likelihood of bandicoot immigration into the focal fragment from the nearest occupied fragment, based on the estimated resistance to movement offered by the intervening matrix. Within Brisbane, riparian habitat fragments typically have a relatively high level of functional connectivity, as thin strips of vegetation fringing waterways serve as corridors between larger riparian areas and facilitate the movement of bandicoots between patches. Analyses based on the Akaike Information Criterion revealed that the optimal model based on landscape context variables was convincingly better supported by the data than the optimal model produced from fragment characteristics. However, it is important to examine both internal attributes of habitat fragments and external features of the surrounding landscape when modelling the distribution of ground-dwelling fauna in urban environments, or other landscapes with a highly variable matrix. As urban centres throughout the world expand, it is crucial that the ecology of local wildlife be considered to ensure functional connection is maintained between habitat patches, especially for the conservation of species that are highly susceptible to fragmentation.     

Recombinant single-chain canine interleukin 12 induces interferon gamma mRNA expression in peripheral blood mononuclear cells of dogs with visceral leishmaniasis

Canine visceral leishmaniasis poses important concerns for public health and veterinary medicine in many areas of the world. Resistance to it seems to be associated with cellular specific immune responses of the so-called Th1 type. Interleukin-12 (IL-12) is one of the most potent inducers of Th1 type of immune responses to co-administered antigens. Herein, the cloning of canine IL-12, as a single-chain fusion protein (sccaIL-12), and its expression in biologically active form in COS-7 cells is reported. Supernatants from these cells stimulated the expression of comparable amounts of interferon gamma mRNA in peripheral blood mononuclear cells from dogs with natural visceral leishmaniasis. In addition, after stimulation with sccaIL-12, there was no difference between interferon gamma mRNA expressions in peripheral blood mononuclear cells of dogs with visceral leishmaniasis and from normal healthy control animals.