Association between CARD15/NOD2 gene polymorphisms and paratuberculosis infection in cattle

Paratuberculosis represents a major problem in farmed ruminants and at the present is considered a potential zoonosis. The disease is caused by Mycobacterium avium subsp. paratuberculosis, and susceptibility to infection is suspected to have a genetic component. Caspase recruitment domain 15 (CARD15) gene encodes for a cytosolic protein implicated in bacterial recognition during innate immunity. Crohn's disease (CD) is an idiopathic inflammatory bowel disease in humans comparable in many features to bovine paratuberculosis involving an abnormal mucosal immune response. The association between mutations in the CARD15 gene and increased risk of Crohn's disease has been described. The objective of this candidate gene case-control study was to characterize the distribution of three polymorphisms in the bovine CARD15 gene and test their association with paratuberculosis infection in cattle. Three previously reported single nucleotide polymorphisms (E2[-32] intron 1; 2197/C733R and 3020/Q1007L) were screened for the study population (431 adult cows). The statistical analysis resulted in significant differences in allelic frequencies between cases and controls for SNP2197/C733R (P<0.001), indicating a significant association between infection and variant allele. In the analysis of genotypes, a significant association was also found between SNP2197/C733R and infection status (P<0.0001); cows with the heterozygous genotype were 3.35 times more likely to be infected than cows with the reference genotype (P=0.01). Results suggest a role for CARD15 gene in the susceptibility of cattle to paratuberculosis infection. These data contribute to the understanding of paratuberculosis, suggest new similarities with Crohn's disease and provide new information for the control of bovine paratuberculosis.     

Malignant peripheral nerve sheath tumour of the urinary bladder in a cat

A 14-year-old domestic shorthair cat presented with a 5-month history of urinary incontinence and inappro-priate elimination. Ultrasonography revealed a well-marginated, vascular mass of mixed echogenicity ex-tending from the dorsal wall of the urinary bladder into the lumen. Partial cystectomy was performed for re-moval of the urinary bladder mass; histopathological evaluation revealed a spindle cell neoplasm with a prominent palisading pattern. Histomorphologic features and immunohistochemical demonstration of vimentin, glial fibrillary acidic protein and S-100 protein, combined with negativity for smooth muscle actin and desmin were consistent with malignant peripheral nerve sheath tumour. This case report describes a novel location of malignant peripheral nerve sheath tumour; to the authors' knowledge, the bladder has not been described as a site of origin in the cat or any other domestic species.     

The role of acidogenic diets and beta-hydroxybutyate on lymphocyte proliferation and serum antibody response against bovine respiratory viruses in Holstein steers

Acidogenic diets were evaluated for their effects on lymphocyte proliferation in response to Staphylococcus aureus exotoxin B (SEB), and specific lymphocyte proliferation and serum-neutralizing antibody titers to four bovine respiratory viruses in vitro. Four Holstein steer calves, with an average weight of 213 +/- 42 kg, were fed a basal (control) diet consisting of 49% forage and 51% concentrate (DM basis), with 15% CP (on a DM basis). Three additional treatment diets were used: 1) the basal diet supplemented with 700 mL/d of butylene glycol (BG) to induce ketoacidosis by increasing blood beta-hydroxybutyate (BHBA); 2) the basal diet supplemented with 1.2 +/- 0.1 kg/d of anionic salts (AS; Soychor 16.7, West Central Soy, Ralston, IA) to induce a metabolic acidosis; and 3) the basal diet with all forage replaced by finely ground corn and soybean meal blended to provide 15% CP (HG), to induce lactic acidosis. The calves were fed each diet for 21 d in a 4 x 4 Latin square design. Blood samples were collected on d 18, 19, and 20 of each 21-d period and analyzed for pH; concentrations of BHBA; in vitro lymphocyte proliferation to SEB, bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza-3 (PI-3), and bovine herpesvirus-1 (BHV-1); and titers of serum-neutralizing antibodies against the four viruses. Following treatment, the average pH of the serum samples was 7.38 for calves fed the control diet, 7.37 for the BG treatment, and 7.36 for the HG treatment, and was decreased (P < 0.05) to 7.33 for the AS treatment. All acidogenic diets decreased lymphocyte response to SEB (P < 0.05). The lymphocyte proliferative response, however, of each virus showed a different pattern of interaction with the three acidogenic diets tested. The AS diet was associated with increased lymphocyte proliferative response to BVDV and BRSV (P < 0.01) and increased serum neutralization titers to BHV-1 (P < 0.05). In calves fed the BHBA-inducing diet (BG), an increase in lymphocyte proliferation to BRSV was observed (P < 0.05). A similar relationship to blood BHBA concentration was not observed with the lymphocyte proliferation to BVDV, PI-3, or BHV-1. Titers of serum-neutralizing antibody against PI3 (P < 0.05) and BHV-1 (P < 0.01) were negatively correlated with blood pH, and titers of serum neutralizing antibodies to BHV-1 were negatively correlated to elevated circulating concentrations of BHBA (P < 0.05).     

Focal premature physeal closure (hyena disease) in calves.

Focal premature closure of long-bone physes was the cause of conformational abnormalities that affected about 1% of a herd of dairy replacement calves. Affected calves were noticed to "bunny hop" by 3 months of age, and by 6 months of age, they developed abnormal conformation characterized by short pelvic limbs. This condition resembled "hyena disease," which has been described in dairy calves in Europe and Japan. With the exception of the aforementioned abnormalities and femoropatellar joint distention, a group of 5 affected calves examined were clinically normal. At necropsy, focal to almost complete closure of physes was found in the humeri, tibias, and femurs. Cause was not established for the condition; however, it was discovered that the calves had been given supplemental vitamin A/D3 in amounts greater than 10 times those recommended.     

Transfer of maternal colostral leukocytes promotes development of the neonatal immune system I. Effects on monocyte lineage cells

Although it has been established that maternal leukocytes traffic from colostrum into the neonatal circulation, the effects of these cells on neonatal immunity are only beginning to be understood. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal antigen presenting cells. At birth, groups of neonatal calves received whole or cell-free colostrum (CFC) from their respective dams. Peripheral blood samples were obtained over the first 4 weeks of life, and expression of surface markers associated with cellular activation and physiological stress were monitored on monocyte lineage cells. Calves receiving cell-free colostrum at birth expressed elevated levels of CD11a, CD11c, and CD14, compared to calves receiving whole colostrum (C). Calves receiving cell-free colostrum had an elevated number of monocytes in the peripheral blood during the first 2 weeks of life, however, these cells expressed lower levels of expression of CD25 and MHC class I compared to calves receiving whole colostrum. The most significant differences in marker expression occurred within the first 7 days of life.     

Transfer of maternal colostral leukocytes promotes development of the neonatal immune system Part II. Effects on neonatal lymphocytes

It has been established that maternal leukocytes, conditioned by the mammary environment, cross the neonatal gut and circulate in the newborn calf. However, the impact of these cells on the development of neonatal immunity remains to be determined. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal adaptive immunity by examining the expression of surface markers on neonatal lymphocytes. At birth, neonatal calves were fed whole colostrum, or colostrum that had the maternal cells removed (cell-free colostrum), from their respective dams. Peripheral blood samples were collected at regular intervals over the first 4 weeks of life and lymphocytes were evaluated for surface expression of cellular markers. The results of these studies demonstrated that calves receiving whole colostrum had fewer CD11a positive lymphocytes in circulation during the first 2 weeks of life and this marker was expressed at a lower density than calves receiving cell-free colostrum. In addition, calves receiving whole colostrum also had a higher percentage of lymphocytes expressing the activation markers CD25 and CD26 by 7 days after birth. During the first week of life, lymphocytes from calves receiving whole colostrum had a higher density of MHC class I expression on their surfaces than cells from calves receiving cell-free colostrum. In general, these results indicate that transfer of maternal cells with colostrum allows for more rapid development of lymphocytes and maternal cells appeared to enhance their activation.