Increase in Regulatory T Cells in Dogs with Cancer Undergoing Chemotherapy

Introduction:  Regulatory T cells (Treg) are a naturally occurring population of T cells phenotypically identified by co‐expression of CD4 and the IL‐2 receptor (CD25). Theyplay a critical role in the control of tolerance and autoimmunity and have also been implicated in impairment of anti‐tumor responses. We hypothesized that levels of Treg would be higher in cancer‐bearing dogs than in normal dogs and that they would decrease with chemotherapy.
Methods:  Serial PBMC were isolated from twenty cancer‐bearing dogs receiving either single‐agent doxorubicin or the Madison‐Wisconsin protocol. The following time points were studied: pre‐treatment, day 2, week 1, week 3, 3 months and 6 months after initial treatment. Ten age‐matched, normal dogs were also studied. PBMC were immunostained with directly conjugated antibodies to CD4, CD8, CD44 and IL‐2 receptor and then evaluated by flow cytometry.
Results:  Low numbers of lymphocytes with the CD4+/IL‐2R+ phenotype were detectable in both normal and cancer‐bearing dogs. A statistically significant increase in the percentage of IL2‐R+/CD4+ T cells was observed in the cancer‐bearing dogs beginning two days after chemotherapy and persisting throughout treatment. The percentage of IL‐2R+/CD4+ T cells was also increased in pre‐treated cancer‐bearing dogs compared to control dogs.
Conclusion:  The percentage of IL‐2R+/CD4+ T cells was generally higher in dogs with cancer than in healthy dogs. Unexpectedly, the percentage of IL‐2R+/CD4+ cells increased during chemotherapy which suggests that chemotherapy may exert immunosuppressive effects through a previously undescribed mechanism. The identity of these CD4+/IL‐2R+ T cells as true Treg awaits additional characterization studies.     

Oxidative stress during acute FIV infection in cats

Oxidative stress is thought to contribute to the pathogenesis of HIV infection in humans. For example, CD4(+) T cells are particularly affected in HIV patients and oxidative stress may also contribute to impairment of neutrophil function in HIV/AIDS patients. Since cats infected with FIV develop many of the same immunological abnormalites as HIV-infected humans, we investigated effects of acute FIV infection on oxidative stress in cats. Cats were infected with a pathogenic strain of FIV and viral load, changes in neutrophil number, total blood glutathione, malondiadehye, antioxidant enzyme concentrations, and reduced glutathione (GSH) concentration in leukocytes were measured sequentially during the first 16 weeks of infection. We found that superoxide dismutase and glutathione peroxidase concentrations in whole blood increased significantly during acute FIV infection. In addition, neutrophil numbers increased significantly during this time period, though their intracellular GSH concentrations did not change. In contrast, the numbers of CD4(+) T cells decreased significantly and their intracellular GSH concentration increased significantly, while intracellular GSH concentrations were unchanged in CD8(+) T cells. However, by 16 weeks of infection, many of the abnormalities in oxidative balance had stabilized or returned to pre-inoculation values. These results suggest that acute infection with FIV causes oxidative stress in cats and that CD4(+) T cells appear to be preferentially affected. Further studies are required to determine whether early treatment with anti-oxidants may help ameliorate the decline in CD4(+) T cell number and function associated with acute FIV infection in cats.     

Cyclic and geographic trends in seawater temperature and abundance of american lobster

In Maine, fluctuations in the abundance of American lobster (Homarus americanus) and in seawater temperature have correlated well during the years since the first temperature measurements were made in 1905. Recent record catches in chronological sequence from the northern limit of range in Newfoundland to New York, while temperatures measured in Maine declined from higher to lower than optimum, suggest that at the present rate optimum conditions should reach the southern limit of the lobster's range by the mid-1970's.     

Studies on immunisation of pigs with the Bartha strain of Aujeszky's disease virus.

The K strain of Aujeszky's disease virus (ADV) grown in Vero cells was used to vaccinate pigs. Following intramuscular inoculation, the pigs remained healthy, no vaccine virus was excreted and virus could be detected only at the inoculation site. One inoculation gave good protection against challenge with a virulent strain of ADV, and the amount of virulent ADV excreted was geatly curtailed. Following vaccination only low leads of serum neutralizing antibody were detected (geometric mean titre 1/2), but three weeks after challenge very high levels were found (GMT 1/1773). Intranasal vaccination gave similar results. There was minimal excretion of vaccine virus. The clinical reaction on challenge was less severe than in the intramuscularly challenged group, although lower antibody levels were detected three wekks following challenge (GMT 1/483). A field trial, using this strain given subcutaneously, indicated that one inoculation of this vaccine is effective.     

Ethanol neurotoxicity: effects on neurite formation and neurotrophic factor production in vitro

The effects of ethanol on chick embryo sensory and spinal cord neurons growing on one of several biological substrates (poly-D-lysine, laminin, or neuron-produced neurite-promoting materials) were examined. Ethanol inhibited process formation by the neurons in a dose-dependent manner and inhibited the production of neurotrophic factors. Neuronal attachment to the substrates, survival of attached neurons, and receptor interactions of sensory neurons with nerve growth factor were not influenced by ethanol. It appears that ethanol alters certain metabolic characteristics of developing neurons.     

Strange magnetism and the anapole structure of the proton

The violation of mirror symmetry in the weak force provides a powerful tool to study the internal structure of the proton. Experimental results have been obtained that address the role of strange quarks in generating nuclear magnetism. The measurement reported here provides an unambiguous constraint on strange quark contributions to the proton's magnetic moment through the electron-proton weak interaction. We also report evidence for the existence of a parity-violating electromagnetic effect known as the anapole moment of the proton. The proton's anapole moment is not yet well understood theoretically, but it could have important implications for precision weak interaction studies in atomic systems such as cesium.     

Mesenchymal stem cells for treatment of musculoskeletal disease in horses: Relative merits of allogeneic versus autologous stem cells

Mesenchymal stem cells (MSCs) are widely used for treatment of musculoskeletal diseases in horses, but there is ongoing debate regarding the relative safety and efficacy of allogeneic MSCs, compared with autologous equine MSCs. This review summarises the currently available published data regarding the therapeutic use of autologous and allogeneic MSCs in horses. Arguments that have been advanced against the use of allogeneic MSCs include higher risk of immunological reactions and shorter cell survival times following injection. Arguments favouring the use of allogeneic MSCs include the ability to bank cells and reduce the time to treatment, to collect MSCs from younger donor animals and the ability to manipulate banked cells prior to administration. In vitro studies and a limited set of experimental in vivo studies have indicated that adverse immunological reactions may occur when allogeneic MSCs are administered to horses. However, newer studies lack evidence of inflammatory reactions or adverse clinical responses when allogeneic MSCs are administered and compared with autologous MSCs. Thus, while the relative merits of allogeneic vs autologous MSCs for treatment of musculoskeletal injuries in horses have not been fully established, accumulating evidence from studies in horses suggests that allogeneic MSCs maybe a safe alternative to autologous MSCs. Large, properly designed, randomised trials in addition to careful immunological evaluation of short-term and long-term, local and systemic immune responses are needed to more fully resolve the issue.     

Hypercalcemia associated with blastomycosis in dogs

Hypercalcemia that could not be explained by previously recognized causes was detected in 4 dogs with systemic blastomycosis. A variety of malignancies and certain endocrine, metabolic, and renal disorders may cause hypercalcemia, but to our knowledge, no infectious diseases have been associated with hypercalcemia in dogs. Increased production of calcitriol by mononuclear cells was thought to be the mechanism of hypercalcemia in granulomatous disease.