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R J MacKay

Publications and source records attributed to R J MacKay.

46 records · Page 3Linked to original sources
PubMed1987

Suppressive effect of interferon-beta on development of tumoricidal activity in mouse macrophages.

The suppressive effect of IFN-alpha and IFN-beta on the induction of tumoricidal activity in mouse bone marrow-derived macrophages was investigated. Macrophages incubated for 24 hr with IFN-beta developed lower levels of cytolytic activity when stimulated with IFN-gamma and LPS, in comparison with macrophages pretreated with medium. The suppressive effect was dependent on the pretreatment dose of IFN-beta over a concentration range of 1 to 1,000 U/ml. Analysis of IFN-gamma dose response curves of IFN-beta treated macrophages showed that these cells were less sensitive to IFN-gamma. The suppressive effects were fully neutralized by an antiserum to IFN-alpha/beta. Prostaglandins were apparently not involved in this process since the addition of indomethacin to IFN-beta treated macrophages did not prevent the loss of responsiveness to activating stimuli. In contrast to the results obtained with IFN-alpha and IFN-beta, macrophages pretreated with IFN-gamma did not develop lower levels of cytolytic activity when again stimulated with IFN-gamma and LPS. These observations provide evidence for a potentially important negative regulatory role for IFN-alpha and IFN-beta in macrophage activation for tumor cell killing.

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PubMed1987

Protein phenotypes of mouse macrophages activated in vivo for tumor cell killing.

We have shown previously that the cellular proteins 47b and 71/73 could be used to construct phenotypes that distinguish among bone marrow culture-derived (BMCD) macrophages that were either unstimulated or primed by gamma interferon or fully activated for tumor cell killing by gamma interferon in combination with lipopolysaccharide (LPS). In the present study we examined in vivo-derived correlates for each of these stages of macrophage activation and found that the same protein phenotypes held true: both p47b and p71/73 were expressed by cytolytic peritoneal macrophages, including macrophages from a tumoral effusion, whereas macrophages primed in vivo by the intraperitoneal injection of either concanavalin A or methyl vinyl ether copolymer II expressed p47b but lacked p71/73. Neither resident nor inflammatory macrophage populations expressed p47b, and acute inflammatory macrophages, like unstimulated BMCD macrophages, expressed little or no p71/73. By contrast, resident and thioglycollate-elicited macrophages synthesized moderate levels of p71/73. When p71/73 also was expressed, there was a quantitative relationship between p47b expression and cytolytic activity in five different in vivo-activated macrophage populations. The results suggest that, regardless of the macrophage source or stimulus, it may be possible to assess macrophage activation status by reference to protein phenotypes utilizing p47b and p71/73.

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PubMed1986

Protein changes associated with stages of activation of mouse macrophages for tumor cell killing.

Bone marrow-derived mouse macrophages become activated for tumor cell killing by traversing a series of stages. The stages studied here were as follows: unstimulated (exposed to nothing but medium), primed (prepared to become cytolytic), fully activated (primed macrophages exposed to a triggering agent), and postcytolytic (previously activated macrophages that had gradually lost cytolytic activity after the removal of stimuli). Macrophages were labeled with [35S]methionine, lysed, and subjected to 2-D gel electrophoresis and fluorography. The priming agent used was recombinant mouse IFN-gamma, 10 to 20 U/ml. Bacterial lipopolysaccharide (LPS), 0.4 to 1 ng/ml, was used as the triggering agent. A total of 40 major changes was identified in macrophages treated with both agents. Twenty-six of these were seen in macrophages treated with IFN-gamma, and 35 were found in LPS-treated macrophages. Twenty-two of the 40 changes were found in both IFN-gamma- and LPS-treated macrophages. The major reason for this overlap was the autocrine action of IFN-alpha/beta secreted from LPS-treated macrophages. Changes in expression of specific proteins, designated p47b and p71/73, were found to correlate closely with the development and loss of the activated state. With the use of these proteins as markers, phenotypes could be constructed that distinguished unstimulated, LPS-treated, primed, and fully activated macrophages. Postcytolytic macrophages had a phenotype similar to unstimulated macrophages and could be reactivated by reexposure to inducing agents. They also reexpressed the protein markers that were characteristic of fully activated macrophages.

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PubMed1983

Effects of large doses of phenylbutazone administration to horses.

The effects of large doses of phenylbutazone were evaluated in clinically normal horses. The drug was given to 4 groups of 2 horses each at the rate of 30 mg/kg of body weight, orally, or 30, 15, or 8 mg/kg IV daily for up to 2 weeks. All horses became anorectic and depressed after 2 to 4 phenylbutazone treatments, and the horses given 15 or 30 mg/kg died on or between days 4 and 7 of treatment. A decrease in total blood neutrophil count occurred in all horses, and was associated with toxic left shift in horses given the 2 larger dosage schedules. The horses also had progressive increases in serum urea nitrogen, creatinine, and phosphorus concentrations, accompanied by decreasing serum calcium concentrations. There was a progressive decrease in total serum protein in all 8 horses. Gastrointestinal ulcerations, renal papillary necrosis, and vascular thromboses were the predominant postmortem findings.

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PubMed1982

Migration of a spiruroid nematode through the brain of a horse.

A pregnant 10-year-old Paint mare was examined because of an acute neurologic disturbance. Physical examination revealed signs consistent with extensive, asymmetric brain stem disease. The hemogram, serum chemical panel, and results of lumbosacral spinal fluid analysis were within normal limits. A primary diagnosis of equine protozoal myeloencephalitis was considered, and the mare was placed on treatment with trimethoprim-sulfadiazine. After 5 weeks of steady improvement, an acute exacerbation of neurologic signs necessitated euthanasia of the mare. At necropsy, large, malacic tracts were found extending through the brain stem and cerebral cortex. Cross sections of a nematode were observed microscopically and subsequently were identified as belonging to a single gravid female Draschia megastoma.

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PubMed1982

Caprine arthritis-encephalitis: clinicopathologic study.

Chronic arthritis caused by caprine arthritis-encephalitis virus was observed after the introduction of new animals into a goat herd. There were high frequency of carpal hygroma and clinical signs of stiffness. The disease was progressive and produced a debilitating lameness among 30% of the affected animals. Laboratory findings were limited to alterations in synovial fluid which showed increased numbers of lymphocytes. Pathologic changes were observed in the joints, bursae, and adjacent tissues. Vascular injury and capillary leakage resulted in exudation into synovial cavities. Fibrin coated the synovial lining and formed (amorphous) long thread-like or broad-based villi. The articular cartilage was eroded. Cartilage erosion and penetration of the articular cartilage by pannus were associated with the presence of subchondral pseudocysts. The morphologic changes in bone and synovial tissues were like those described in human rheumatoid arthritis, except that rheumatoid nodules were not observed.

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PubMed1979

An outbreak of eosinophilic bronchitis in horses possibly associated with Dictyocaulus arnfieldi infection.

Eight mature horses which had been affected with a moist cough for six weeks were found to have large numbers of eosinophils in tracheal mucus samples taken by transtracheal washing. These horses were kept on irrigated pasture and fed a hay-free diet. A companion yearling donkey was found to be passing Dictyocaulus arnfieldi larvae in its faeces. Two oral treatments with a dose of thiabendazole (440 mg/kg) resulted in the resolution of the clinical signs and the disappearance of eosinophils from transtracheal washings. The eosinophilic bronchitis seen in these horses was presumed to be a manifestation of prepatent D arnfieldi infestation.

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