Biomedical subjects

M C Zink

Publications and source records attributed to M C Zink.

64 records · Page 4Linked to original sources

PubMed1987

Electron microscopic investigation of intracellular events after ingestion of Rhodococcus equi by foal alveolar macrophages.

It has been suggested that R. equi causes pulmonary disease in foals by persisting within the lung as a facultative intracellular parasite of alveolar macrophages. This paper describes an ultrastructural study of the intracellular events after ingestion of R. equi by foal alveolar macrophages, in an attempt to determine the mechanism of intracellular survival of R. equi. Secondary lysosomes of alveolar macrophages recovered from foals by bronchoalveolar lavage were labelled with electron-dense ferritin, and the cells were challenged with either viable or formalin-killed R. equi. After 0-, 3-, 8- or 24-h incubation, the cells were fixed and processed for electron microscopy. There was no evidence of phagosome-lysosome fusion after ingestion of either viable or non-viable R. equi by foal alveolar macrophages. Rhodococcus equi persisted and multiplied within dilated phagosomes, which were often lined by elongate microvillous structures. After 24-h incubation, 75% of the ingested bacteria were still structurally intact. Macrophages with ingested viable R. equi were irreversibly damaged and released intracellular bacteria into the surrounding medium. These data confirm that R. equi is a facultative intracellular parasite of foal alveolar macrophages and is able to persist and multiply within the phagosome, apparently inhibiting phagosome-lysosome fusion by some as yet unknown mechanism.

Animals↗

PubMed1987

Lentivirus-induced arthritis. Chronic disease caused by a covert pathogen.

Lentiviruses are exogenous, nononcogenic retroviruses that cause persistent infections in monocytes and macrophages. Among the clinical manifestations of such infections in sheep and goats is a slowly progressive arthritis, primarily involving the carpal joints of adult animals. Initially, clinical disease begins as synovitis; this progresses to involve surrounding connective tissues and osseous structures as inflammation increases and progresses. Inflammatory cells include macrophages, lymphocytes, and plasma cells. Macrophages and monocytes are the only cells that are infected with virus and in the inflamed joint may represent 50 per cent of the cells in the synovial fluid. However, only a small number of these cells are infected. Cytotoxic T lymphocytes predominate over helper T lymphocytes in the synovial fluid. The role of these cells in the pathogenesis of disease is not currently known. The pathogenesis of disease caused by these lentiviruses is related to the infection of the monocyte-macrophage cells in the animal. This event, along with virus-specific factors, render the host incapable of eliminating the virus. Despite persistence of the virus, viral replication is maintained at a tightly restricted level at all times in the infected animal. This is achieved by factors that regulate the maturation of monocytes. Basically, the infection is latent in monocytes and its precursors and becomes more productive as the cells mature. The maturing infected macrophage presents a portion of the viral proteins that it synthesizes on its cell surface in close association with class II major histocompatibility complex antigens. Lymphocytes react with this cell and produce interferon. This lymphokine induces further expression of Ia antigens. This feedback loop of Ia expression, together with persistence of the virus, maintains macrophages in a constant state of antigen presentation. This forms the trigger for the inflammatory condition that eventually leads to the degenerative lesions seen in the joint.

Animals↗

PubMed1987

Experimental infection of piglets by aerosols of Rhodococcus equi.

The purpose of this study was to investigate experimental infection of the piglet as a model of Rhodococcus equi pneumonia in the foal. Three litters of eight piglets each were exposed to an aerosol of 3.4 X 10(7) R. equi per piglet per day for seven consecutive days. Over the next 23 days the piglets were observed for clinical signs of disease. Periodically after infection one piglet from each litter was killed, the lungs were cultured quantitatively for R. equi and the gross and microscopic pulmonary lesions were assessed. The only clinical evidence of disease was the occurrence of elevated temperatures in the infected piglets. Rhodococcus equi was slowly cleared from the piglets' lungs during the 23 days following aerosolization. Piglets sacrificed seven to ten days after aerosolization had the most extensive pulmonary lesions, consisting of severe consolidation of the cranioventral lobes. Microscopic examination revealed thickened interalveolar septa and alveoli containing many neutrophils and macrophages with intracytoplasmic Gram-positive coccobacilli. The pulmonary lesions in these piglets differed from those of naturally infected foals in that they were not characterized by macrophage-rich abscesses and the infection gradually resolved.

Actinomycetales Infections↗

PubMed1986

The morphology and behavior of feline cutaneous mastocytomas.

Correlation of histopathology with the behavior of cutaneous mastocytomas in 85 cats revealed two distinct histologic subtypes which were predictive of biologic behavior. The first subtype comprised 65 cats of various breeds which had solitary, discrete, dermal tumors composed of slightly atypical mast cells. Most tumors in this group were histologically and behaviorally benign. However, seven solitary tumors with marked anisocytosis and mitotic activity recurred or spread to other sites within 2 to 3 months. The second subtype occurred in 18 cats which had discrete subcutaneous nodules composed primarily of histiocyte-like cells with equivocal cytoplasmic granularity after staining with toluidine blue. They were identified as mast cells by electron microscopy. Seventeen of the 18 affected cats were Siamese. The histiocytic mastocytomas occurred predominantly in young cats (less than 4 years) and were usually multiple. In the four cats of this group for which we have prolonged follow-up data, the tumors underwent apparently spontaneous regression within 2 years of initial tumor detection. Two other cats had tumors which contained mixtures of mast cell and histiocytic morphologies.

Animals↗

PubMed1986

In vitro bactericidal efficacy of equine polymorphonuclear leukocytes against Corynebacterium equi.

Polymorphonuclear leukocytes from adult horses were separated from whole blood, using a 2-step Percoll gradient, and were tested for bactericidal function against Corynebacterium equi. Staphylococcus aureus, an organism against which equine neutrophils have proved efficacy, was a positive control. The percentage of uptake after a 15-minute preincubation of the neutrophils and bacteria in the presence of normal horse serum was also calculated. The results indicated that equine neutrophils effectively phagocytosed and killed C equi and S aureus. The percentage of uptake for S aureus (95% +/- 3%) was greater than that for C equi (85% +/- 6%) (P less than 0.001), but the bactericidal efficacy was equivalent. More than 90% of the ingested or attached bacteria were destroyed during the 3-hour incubation period (mean percentage of C equi killed = 96 +/- 2%; mean percentage of S aureus killed = 91 +/- 8%). These results indicated that a failure of bacterial killing by neutrophils is unlikely to be important in the pathogenesis of C equi pneumonia in the horse.

Animals↗

PubMed1985

In vitro phagocytosis and killing of Corynebacterium equi by alveolar macrophages of foals.

Bronchoalveolar lavage was performed 5 times, sequentially, on 3 healthy foals while each foal was 6 to 63 days of age. Phagocytosis and bactericidal assays were performed on recovered alveolar macrophages. Corynebacterium equi and alveolar macrophages at a ratio of 10:1 were incubated for 1 hour in medium containing 1% heat-inactivated rabbit anti-C equi serum. After incubation, greater than 90% of the alveolar macrophages contained at least 1 ingested bacterium and each alveolar macrophage contained 9.4 +/- 1.0 bacteria (mean +/- SE). After alveolar macrophages and C equi were incubated for 1 hour in medium containing heat-inactivated pooled normal horse serum, approximately 24% of the alveolar macrophages contained at least 1 bacterium and each alveolar macrophage contained 0.8 +/- 0.7 bacteria. From 6 to 61 days of age, each foal had significantly (P less than 0.05) decreased phagocytic activity by alveolar macrophages, but a significant change in killing of C equi by alveolar macrophages was not found in the foals from 21 to 61 days of age. After incubating alveolar macrophages and C equi for 4 hours in vitro, approximately 75% of ingested C equi remained viable.

Animals↗

PubMed1984

Cellular constituents of clinically normal foal bronchoalveolar lavage fluid during postnatal maturation.

Bronchoalveolar lavage was performed 5 times, sequentially, on 3 healthy foals when each was between 2 and 63 days of age. Total and differential counts were performed on recovered cells. The lungs of foals less than 19 days of age contained few alveolar macrophages recoverable by bronchoalveolar lavage. This number increased sharply during the first 2 to 3 weeks of life, but remained relatively constant subsequently. Approximately 86% of the alveolar cells in the lungs of foals up to 3 weeks of age were alveolar macrophages. During the first 2 months of life, this number decreased to approximately 71%, whereas the relative percentage of lymphocytes increased from 5% to 20%.

Animals↗

PubMed1982

The interaction of Corynebacterium equi and equine alveolar macrophages in vitro.

The in-vitro interaction of Corynebacterium equi and foal alveolar macrophages was examined qualitatively and quantitatively using cells collected by sequential bronchoalveolar lavage at 2-week intervals from birth until 14 weeks of age. Total and differential counts were performed on the recovered cells. Macrophages were identified using the non-specific esterase strain. Cultures of the alveolar macrophages were challenged with C. equi suspensions and the process and extent of ingestion was examined by light and electron microscopy. Few macrophages were recovered from the lungs of foals less than 20 days old. The numbers increased with age in a biphasic pattern. The majority of the recovered cells were alveolar macrophages. Foal alveolar macrophages were capable of significant ingestion of C. equi only in the presence of immune serum. The ingestion of C. equi by foal alveolar macrophages was confirmed by electron microscopy.

Aging↗

PubMedDate not supplied

Comparison of acute endotoxin-induced lesions in A/J and C57BL/6J mice.

Resistance to the action of endotoxin varies among inbred strains of mice, indicating that a component of this resistance has a genetic basis. Different responses to endotoxin that are characteristic of individual inbred strains represent phenotypes that can be used to genetically map the response modifier genes. This study compares the acute histologic lesions in 8-week-old male A/J and C57BL/6J (B6) mice injected intraperitoneally with endotoxin of E. coli O265:B6 (15 mg/kg). Animals of both strains exhibited splenitis, splenic lymphoid hyperplasia, splenic lymphoid necrosis, and sequestration of neutrophils in the pulmonary alveoli. The B6 mice showed increased margination of white blood cells to the pulmonary vascular endothelium relative to A/J mice. A large number of degenerating neutrophils was observed in the liver sinusoids of most B6 animals, while this lesion was much less severe in A/J mice. This difference was quantified, demonstrating a highly significant difference in neutrophil infiltration in B6 mice relative to A/J mice. Analysis of this phenotype in F1 mice demonstrates that major genes encoding the trait are not X-linked, imprinted, or maternally inherited and do not show the codominant inheritance expected if Lps(d) were primarily responsible. The distinctive, quantitative nature of these differences provides a useful assay for mapping genes that modify endotoxin responsiveness using the AXB and BXA recombinant inbred (RI) strains derived from A/J and B6 mice.

Animals↗

PubMedDate not supplied

Early activation of PBMC and appearance of antiviral CD8+ cells influence the prognosis of SIV-induced disease in rhesus macaques.

We studied 15 macaques inoculated with SIV and identified three phases of infection. Phase 1 was characterized by activated lymphocytes in blood and infected cells in the CSF. In phase 2, activated cells were not detected but virus was recovered from mitogen-stimulated PBMC, while in phase 3, virus was recovered from mitogen-stimulated PBMC only after depletion of CD8+ lymphocytes, indicating effective control of the virus in peripheral blood. Early development of phase 3 status correlated with a longer period of clinical normalcy.

Animals↗