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Biomedical subjects

R J Kearns

Publications and source records attributed to R J Kearns.

17 recordsLinked to original sources
PubMed1999

Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs.

The focus of this study was to examine the influence of age and diet on various parameters of immune function in young and old Fox Terriers and Labrador Retrievers. Eighteen young and old dogs were utilized for this study. Young and old dogs were fed a basal diet containing an (n-6):(n-3) ratio of 25:1 for sixty days (Phase I). Half of the dogs were then switched to a diet with an (n-6):(n-3) ratio of 5:1, and all were maintained on their respective diets for an additional sixty days (Phase II). Results from these studies revealed an age-associated decline in several immune parameters measured. Both these breeds demonstrated a reduction in sheep red blood cell titers, as well as in their ability to respond to different mitogens. Interestingly, this decline was greater in Fox Terriers, suggesting a decrease in cellular proliferative capacity in lymphocytes isolated from the larger breed. Neither cytokine production or DTH response was affected by age. Diet and breed interactions resulted in a significant increase in T- and B-cell mitogen responsiveness. In contrast, supplementation with n-3 fatty acids did not affect IL-1, IL-6 or TNF-alpha production. Supplementation with n-3 fatty acids resulted in increased PGE3 production from peritoneal macrophages but had no effect on PGE2 production from peripheral blood mononuclear cells or peritoneal macrophages. The n-3 fatty acid supplementation did not influence alpha-tocopherol status although older dogs had significantly lower serum alpha-tocopherol concentrations. Oxidative status of these dogs was assessed by serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Feeding an n-3-enriched diet did not affect 4-HNE levels but significantly decreased MDA levels in old dogs. In summary, this study indicates that feeding a diet containing an (n-6):(n-3) fatty acid ratio of 5:1 had a positive, rather than a negative, effect on the immune response of young or geriatric dogs.

Aging↗
PubMed1999

The effects of extracorporeal whole body hyperthermia on the functional and phenotypic features of canine peripheral blood mononuclear cells (PBMC).

In this study the effect of transient 42.3 degrees C whole body hyperthermia (WBH) on the distribution of PBMC phenotypes and in vitro blastogenic responsiveness was determined in dogs. Hyperthermia (n = 6) was induced by heating venous blood during extracorporeal circulation (venous perfusion WBH); perfused non-heated dogs (n = 4) were used as controls. Both euthermic and hyperthermic perfusion produced transient lymphopenia which normalized in controls after perfusion but persisted in hyperthermic animals throughout the 8-day post-perfusion observation interval. The transient lymphopenia in control dogs was non-selective. In contrast, WBH-associated lymphopenia was selective, in that CD5+ T lymphocytes were more sensitive to hyperthermia than sIg+ B cells and, within the T cell compartment, suppressor (CD8+) cells were more sensitive to hyperthermic stress than helper (CD4+) lymphocytes. Functional analyses showed that WBH caused persistent suppression of PBMC blastogenesis in response to T cell phytomitogens. Increased plasma cortisol levels were correlated to peak lymphopenia and hyporesponsiveness to phytomitogens. Despite these alterations, high grade WBH was well tolerated and there was no evidence of opportunistic infection.

Animals↗
PubMed1990

In vivo administration of anti-asialo-GM1 antibody enhances splenic clearance of Listeria monocytogenes.

Resistance of mice to infection by Listeria monocytogenes involves a biphasic response. The first phase consists of the first 48 h after infection, during which there is multiplication of Listeria in the liver and spleen of infected mice. In these nonimmune mice, macrophages and polymorphonuclear leukocytes are the effector cells involved in controlling multiplication. In the second phase, cell-mediated immunity develops, beginning on day 2, during which multiplication of Listeria is prevented by macrophages possessing increased microbicidal activity that is mediated through the action of lymphokines released by immunologically committed T lymphocytes. The purpose of the present study was to define a role for natural killer (NK) cells in natural resistance to Listeria during the first 48 h after infection, prior to the development of specific immunity. Splenic NK cell activity was enhanced following a sublethal intravenous injection of viable Listeria as early as 24 h after injection and remained elevated throughout the nonimmune phase of infection. Interestingly, treatment of mice with anti-asialo-GM1 significantly enhanced the ability of mice to clear Listeria from the spleen relative to infected controls possessing intact NK cell populations. This was evidenced by 23-fold fewer bacteria obtained from the spleens of anti-asialo-GM1-treated mice. In addition, Percoll-enriched NK cell populations obtained from 48-hour Listeria-infected mice do not exhibit in vitro listericidal activity. These observations suggest a regulatory role of NK cells in resistance against Listeria and preclude a role for NK cells in direct cytolysis. Perhaps these cells modulate the immune response to Listeria by down-regulating the activity of the immune cells crucial to listerial resistance.

Animals↗
PubMed1989

Efficacy of antibiotics in low-velocity gunshot fractures.

We have investigated the efficacy of intravenous antibiotic therapy as a prophylactic measure to prevent infection following low-velocity gunshot fractures. Ninety-six consecutive patients were randomized prospectively to either an antibiotic group (Group I) or a nonantibiotic group (Group II) and were followed in a special gunshot wound clinic. Only patients with fractures that could be treated by closed techniques and did not require internal fixation were included. Sixty-seven patients (73 fractures) were followed radiographically. At follow-up, 36 fractures in Group 1 and 37 fractures in Group II comprised the study group. A total of two infections, one in each group, was documented. No significant infection prophylaxis was demonstrated by the use of intravenous antibiotics in these injuries.

Adolescent↗
PubMed1989

Analysis of the kinetics of natural killer cell activity in mice during an active infection with Pseudomonas aeruginosa.

The present study was designed to determine the effect of Pseudomonas aeruginosa (PA) infection on the activity of natural killer (NK) cells in mice. Following a sublethal injection of the bacterium, increased NK cell activity is evident as early as 24 h and peaks within 72 h, returning to normal levels by 168 h. Interestingly, the route by which PA was administered was very important with respect to increased NK activity. For example, the greatest augmentation of activity was seen in the peritoneal cavity when mice were injected intraperitoneally and in the spleen when injected intravenously. Peripheral blood leukocytes expressed the greatest augmentation in animals which received an intravenous injection of viable PA. In addition, a nonviable preparation of PA was used and found to significantly augment NK cell activity in a dose-dependent manner. To determine whether the presence of the organism is required for augmentation of NK activity, the rate at which PA is cleared from the animals was evaluated. Regardless of the route of injection, PA is effectively cleared within 24 h, thus eliminating the possibility that viable PA is required for augmentation of NK activity. This augmentation is proximal to the route of injection with little systemic effect seen. The data presented in this report illustrate that both viable and nonviable preparations of PA produce a significant increase in NK cell activity. This augmentation may suggest a role for these cells as effectors in natural resistance to infectious disease.

Animals↗
PubMed1986

Florid reactive periostitis.

A case of florid reactive periostitis of the thumb is reported. This rare, benign, bone-producing lesion is easily confused with osteosarcoma. It is also known as parosteal or nodular fascitis. Careful histologic and radiographic evaluations are needed to establish the diagnosis and avoid unnecessary amputation. Marginal excision seems to be adequate treatment.

Adult↗
PubMed1985

Suppression of natural killer and lymphocyte functions associated with carcinogen-induced premalignant hyperplastic nodules in rat liver.

The effects of chemical carcinogenesis to produce premalignant hyperplastic nodules in rat liver on concomitant immune function were studied. Induction of hyperplastic nodules in Fischer rats was accomplished using a combined regimen of diethylnitrosamine, 2-acetylaminofluorene, and partial hepatectomy. Hyperplastic nodules were detected in carcinogen-treated rats from 5 to 23 weeks as confirmed by gross pathology, histopathology, and significantly elevated liver gamma-glutamyltransferase activity. Suppression of natural killer activity of either peritoneal or peripheral blood lymphoid, but not splenic, cells for YAC-1 target cells occurred during 5 to 20 weeks in carcinogen-treated rats. Spleen and blood lymphocyte mitogenic responses to concanavalin A and pokeweed mitogen were also suppressed at most intervals from 8 through 20 weeks. Control groups given individual carcinogen or partial hepatectomy alone or in dual combination were not suppressed in their immune function and failed to develop hyperplastic foci or changes in liver gamma-glutamyltransferase. Our findings indicate that immunosuppression of natural killer and lymphocyte mitogenic functions occurs for a protracted period concurrently with the development of the premalignant hyperplastic state in rat liver. The data suggest a potential role for immune competency during the onset of malignant neoplasia.

Animals↗
PubMed1984

Modulation of natural killer activity in mice following infection with Listeria monocytogenes.

Mice that received a sublethal, intraperitoneal dose of viable Listeria monocytogenes, virulent strain 10403, exhibited a systemic increase in natural killer (NK) activity. The kinetics of the response differed with respect to the various effector cell populations analyzed. Resident peritoneal cells and peripheral blood leukocytes demonstrated high NK activity on Days 3, 7, and 10. Peak spleen and bone marrow NK activity was observed on Day 3, returning to normal levels by Day 7. In contrast, peritoneal exudate cells, elicited with proteose peptone, expressed enhanced NK activity for 60 days following infection with viable Listeria. Augmented NK activity was detected with all cell types as early as 12 hr after infection. The intraperitoneal injection of nonviable antigenic preparations derived from L. monocytogenes, strain 10403, resulted in the enhancement of peritoneal and splenic NK activity. In contrast, mice that received an intraperitoneal injection of avirulent Listeria, strain 19113, failed to express enhanced levels of NK activity. The genetic trait of anti-listerial resistance which is associated with non-H-2 linked genes was of no importance with respect to enhanced NK activity. Listeria-resistant C57BL/6J and Listeria-susceptible DBA/2J mice both produced systemic augmentation of NK activity following infection. NK activity was not abrogated by macrophage depletion or by treatment with anti-Thy 1.2 serum plus complement. These results confirm the potent immunostimulatory capacity of virulent Listeria for NK activity and provide further insight into the kinetics of this response in various lymphoid compartments. The protracted augmentation of NK activity of elicited peritoneal exudate cells as compared to nonelicited peritoneal cells in Listeria-primed mice suggests that the influx of inflammatory cells may provide NK-enriched and/or accessory populations for immunopotentiation of NK activity in inflammatory sites.

Animals↗
PubMed1983

In vitro propagation of antigen-specific T lymphocytes that adoptively transfer resistance to Listeria monocytogenes.

Murine T cells generated against heat-killed Listeria monocytogenes or Listeria intracellular product (LIP) were propagated in a source of Interleukin 2. Both T-cell cultures were greater than 98% Lyt 1+, 2/3- and proliferated specifically against LIP and L. monocytogenes crude whole-cell antigen in vitro. Proliferation of both T-cell cultures required the presence of antigen and accessory cells syngeneic to the T cells at the left end of the major histocompatibility complex. The ability of these cultures to adoptively transfer protection against challenge with viable Listeria cells was dramatically different. As few as 10(6) LIP-specific T cells conferred significant protection against a lethal challenge of Listeria cells, whereas cultures induced against crude whole-cell antigen showed little or no protective function. The resistance conferred by LIP-specific T cells was specific in that the cells did not reduce the mortality seen after challenge with Salmonella typhimurium.

Animals↗
PubMed1983

Production of migration inhibitory factor by Listeria-immune mouse T lymphocytes, but not B lymphocytes.

Antigens and B cell mitogens have been reported to induce migration inhibition factor (MIF) production by mouse B cells. Immune resistance to the intracellular bacterium, Listeria monocytogenes is thought to involve T cells, but not B cells. Since Listeria-derived components are B cell, but not T cell mitogens, it was important to determine whether these materials could stimulate secretion of the lymphokine, MIF by T cells, B cells, or both. Thus populations of whole, unfractionated spleen cells, obtained from normal and Listeria-immune BDF1 mice, were cultured with or without 100 micrograms/ml of Listeria intracellular product (LIP). The culture supernatants obtained 24 h later were assayed for MIF activity using the in vitro macrophage migration inhibition assay. Data obtained show that immune T lymphocytes release MIF in response to specific Listeria antigens, but that spleen B cells from immune and normal mice, obtained as immune, nylon-wool-adherent cells treated with anti-T-cell serum plus complement, are not capable of releasing MIF. This suggests that release of lymphokines by Listeria-immune or normal B cells stimulated with Listeria-derived antigens and mitogens is unlikely to contribute to resistance against Listeria in vivo.

Animals↗
PubMed1978

Heat-labile B-cell mitogen obtained from Listeria monocytogenes.

A water-soluble extract of Listeria monocytogenes strain 10403 acts as a mitogen on cultured mouse spleen lymphocytes. This mitogen induced a response six to nine times that of controls, as measured by [3H]thymidine incorporation. The mitogen extract was derived from washed bacterial cells which were mechanically disrupted with a French press. The extract was centrifuged at 105,000 X g and filtered through a 0.22-micrometer filter. Similar levels of lymphocyte stimulation were observed in lymphocyte cultures prepared from spleens of nude mice, indicating the effect of this mitogen on B-cells. The mitogenic property of this extract was destroyed by heating to 56 degrees C. This heat treatment does not destroy the antigens in the extract, which stimulate spleen cell cultures obtained from specifically immune mice. Similarly prepared extracts from Staphylococcus epidermidis and Salmonella typhimurium did not show similar levels of mitogenic activity. The mitogenic property of the L. monocytogenes extract was present in two strains of Listeria tested and was not associated with mouse virulence.

Adjuvants, Immunologic↗
PubMed1977

Kinetics and maintenance of acquired resistance in mice to Listeria monocytogenes.

In the mouse system, acquired resistance to Listeria monocytogenes can only be demonstrated after immunization with viable microorganisms. A successful state of immunity cannot be elicited with formalin-killed organisms or bacterial cell-derived products. Viable, serologically cross-reactive organisms (not mouse pathogenic) do not induce a state of immunity as measured by acquired resistance. The duration of immunity, once established, is dose independent, and the absolute interval of its existence is not extended by secondary challenge with large numbers of viable organisms. The decline of immunity in actively immunized animals is not altered by antigenic challenge with formalin-killed cells or cell products. This indicates that the cellular requirements for the development of host resistance are similar for induction as well as maintenance. In vitro measurements of cellular immunity by migration inhibition indicate that formalin-killed organisms as well as cell products were recognized by actively sensitized lymphocytes obtained from immune animals.

Animals↗
PubMedDate not supplied

Adamantinoma. A case report with aspiration cytology and differential diagnostic and immunohistochemical considerations.

Fine needle aspiration biopsy of bone lesions is routinely used in the metastatic workup of patients with radiographically suspicious areas. However, caution must be used when interpreting smears from aspirates performed on primary bone neoplasms. These tumors are often heterogeneous, and problems with sampling may be encountered. We report a case of a 25-year-old male who presented with a 3-cm lytic lesion in the tibia. A diagnosis of benign fibroosseous lesion was based on the clinical presentation, radiographic appearance and presence of numerous sheets and single cytologically bland spindle cells. Subsequent curettage of the specimen revealed an adamantinoma with a prominent fibrous component. Most of these rare, locally aggressive neoplasms are located in the tibia. They are characterized histologically as having a fibrous background with islands of basaloid, spindle or squamoid cells. Furthermore, a differentiated, regressing variant with an osteofibrous dysplasia-like appearance also exists. Smears consisting primarily of spindle cells or fibrous tissue may lead to an erroneous diagnosis of a fibrohistiocytic neoplasm, fibrous dysplasia, fibrous cortical defect or ossifying fibroma. Pertinent cytomorphologic features should aid in establishing the correct diagnosis of adamantinoma.

Adult↗
PubMedDate not supplied

Enhanced splenic bacterial clearance and neutrophilia in anti-NK1.1-treated mice infected with Pseudomonas aeruginosa.

The purpose of the present study was to further delineate the role of natural killer (NK) cells in the early stages of resistance to infection by Pseudomonas aeruginosa, strain PAO1. Intravenous injection of the monoclonal antibody alpha-NK1.1 resulted in an 82% reduction in NK cell activity of normal mice, as measured by a standard 4-hour 51Cr release assay. Splenic bacterial clearance was examined in mice treated with this antibody 12 h prior to infection with a sublethal dose (10(6)) of PAO1. At 2, 4, and 6 h postinfection there was significant enhancement (up to 10-fold) of clearance in mice treated with alpha-NK1.1 when compared to untreated infected control animals. Interestingly, the enhanced clearance of PAO1 in the spleens of NK-depleted mice was found to be coupled to a significant increase in neutrophils. Normal murine spleens were found to contain 1-2% neutrophils, which increased to 6-7% following sublethal infection. However, in mice treated with alpha-NK1.1 and infected, splenic neutrophils increased up to 15% during the early stages of infection. The data presented here suggests that NK cells do not have direct bactericidal activity against Pseudomonas, but may regulate other effector cells, such as neutrophils-an indirect role for natural killer cells, probably mediated in vivo by their production and secretion of cytokines.

Animals↗