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N MacIntyre

Publications and source records attributed to N MacIntyre.

At least 19 recordsLinked to original sources
PubMed2003

Immunopathogenesis of experimentally induced proliferative enteropathy in pigs.

To characterize the immune response associated with Lawsonia intracellularis infection, twenty-eight, 7-week-old pigs were dosed orally with a pure culture of L. intracellularis. Animals were killed 3, 7, 14, 21, 28, 35, and 42 days postinfection. Light microscopic studies were undertaken to immunophenotype the immunologic response using specific antibodies to T-cell subsets (CD3, CD4, and CD8), B cells, major histocompatibility complex class II, cadherin, and macrophages over the course of time. The results indicate that there is a direct association between the presence of L. intracellularis and reduced T-cell and B-cell numbers. For the first time, this provides evidence of the presence of an immunosuppressive mechanism operating in this disease. Furthermore, macrophage marker studies indicated that macrophages may play a more complex and significant role in the disease process than has been previously reported, with activated macrophages accumulating in infected hyperplastic crypts.

Animals↗
PubMed2001

Detection of Pasteurella multocida in pigs with porcine dermatitis and nephropathy syndrome.

Comprehensive bacterial cultures were made on samples from 20 pigs that had died of porcine dermatitis and nephropathy syndrome after a short clinical illness. Eleven species of porcine bacterial pathogens and a range of commensal organisms were isolated. Pasteurella multocida was isolated from 16 of the 20 cases but the other pathogens occurred much less commonly. P. multocida was isolated from between one and five sites per case and from the tonsils, retropharyngeal lymph node or lungs in 14 of the 16 cases. Immunohistochemical investigations of kidneys from 30 cases of the syndrome (including the 20 cases in the bacteriological study) revealed P. multocida-specific staining in 26 of the cases, primarily in the renal tubular epithelial cells of the proximal convoluted tubules, but also in the glomeruli, in lesions of renal vasculitis and in the cytoplasm of interstitial mononuclear cells.

Animals↗
PubMed2001

Unmasking antigens for immunohistochemistry.

Preservation of tissue by fixation in a formalin solution, followed by dehydration and paraffin-wax embedding remains the predominant method of preparation for microscopic analysis of morphology. Whilst this may be optimal for morphological assessment, this technique has major disadvantages for subsequent immunohistochemical study as a result of the structural alteration of antigens that occurs during the processing procedure. However, the introduction of a range of antigen unmasking procedures has revolutionised immunohistochemistry, establishing the technique as a powerful tool in diagnostic pathology. Here, the development of enzymatic, non-enzymatic and heat-based antigen retrieval techniques is reviewed, and the methods in use currently are appraised.

Antigens↗
PubMed2000

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.

CONTEXT: Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. OBJECTIVE: To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. DESIGN: A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. SETTING: Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. PATIENTS: Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. INTERVENTION: Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). MAIN OUTCOME MEASURES: The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. RESULTS: The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. CONCLUSIONS: Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.

Antibodies, Monoclonal↗
PubMed1997

Immune response to murine cell lines of glial origin transplanted into the central nervous system of adult mice.

Temperature-sensitive simian virus 40 (SV40) T antigen-transformed central nervous system (CNS)-derived murine cell lines were used to analyse the host response to transplantation in the mouse adult brain. The cell lines were shown to be susceptible to immune recognition in vitro by cytotoxic effector cells indicating that tissue-specific privilege was not in operation. Histological examination at time points post-implantation showed characteristic responses similar to those seen during graft rejection. Astrocytosis and up-regulation of major histocompatibility complex (MHC) class I and MHC class II activation of resident microglia and recruitment of macrophages were observed in both allogeneic and syngeneic hosts 10 days post-implantation suggesting a trauma-induced response. However, the response in allogeneic hosts was more widespread and evident when the syngeneic responses had returned to normal levels. Evidence of T-cell infiltration was also more pronounced in the allogeneic hosts. Despite quite extensive host reactions to these cellular grafts at early time-points the implants appeared to survive in the host CNS long after the responses had abated and could be detected at the maximum time-point studied of 40 days.

Animals↗
PubMed1996

Pathogenesis and treatment of the adult respiratory distress syndrome.

The adult respiratory distress syndrome is an acute clinical illness characterized by noncardiogenic pulmonary edema and refractory hypoxemia. Injury to the alveolar-capillary barrier and lung inflammation lead to intrapulmonary shunting of blood, surfactant depletion, and pulmonary vascular obstruction. Numerous mediators contribute to the pathologic response. Conventional therapy includes treating underlying causes and positive pressure mechanical ventilation. Concern about pressure-induced lung injury had led to new strategies to accomplish adequate gas exchange. Novel therapeutic interventions have included extracorporeal support techniques, use of compounds designed to neutralize proinflammatory cytokines, and administration of surfactants, but these efforts have not definitely affected mortality in randomized trials. Potent antioxidant agents have shown promise in animal models of acute lung injury, but human studies are lacking. Inhaled nitric oxide appears to have temporary effects on pulmonary artery pressure and on ventilation or perfusion relationships, but longer-term efficacy and safety in patients suffering from adult respiratory distress syndrome is unknown and awaits results of ongoing clinical trials.

Adult↗
PubMed1996

Emergent management of acute asthma.

In almost no other field is the gap between diagnostic and therapeutic knowledge and its general application so great as it is in asthma. As previously mentioned, most asthma deaths are preventable. Identification of high-risk patients, intensive education about asthma (purpose of each medication; necessity of compliance, particularly with inhaled corticosteroids; proper use of inhalers and spacer devices; home use of PEFR meter), self-treatment of mild or moderate attacks with oral corticosteroids, and written crisis plan for severe attacks explicitly telling the patient what to do and whom to call are necessary. In addition, all potential exacerating factors should be eliminated (external triggers, medication, gastroesophageal reflux, allergic rhinitis, and sinusitis). High doses of inhaled corticosteroids should be provided to all those patients, and referral to a specialist is highly recommended for such high-risk patients.

Acute Disease↗
PubMed1995

Mechanical ventilation in asthma.

The goal of respiratory support in asthma is similar to the goals in other forms of respiratory failure: to support gas exchange while avoiding complications. The specific respiratory support goals for asthmatics are discussed in this article, as well as recommended ventilator adjustments to meet these goals.

Asthma↗
PubMed1995

Asthma rehabilitation program.

Comprehensive management of asthma includes proper use of medication adjustments in patient lifestyle, exercise conditioning, and patient education to maximize self-management capabilities. Pulmonary rehabilitation programs have used these strategies successfully to improve the functional status and reduce the health care costs of patients with chronic obstructive pulmonary disease. Adapting these programs to the asthmatic population is an important and cost-effective goal.

Adult↗
PubMed1994

Demand-flow airway pressure release ventilation as a partial ventilatory support mode: comparison with synchronized intermittent mandatory ventilation and pressure support ventilation.

OBJECTIVE: To evaluate airway pressure release ventilation as a partial ventilatory support mode by comparing a demand-flow airway pressure release ventilation system with synchronized intermittent mandatory ventilation and pressure support ventilation. DESIGN: Prospective, nonrandomized, cross-over trial. SETTING: Medical intensive care unit in a university medical center. PATIENTS: Sixteen consecutive patients without chronic obstructive pulmonary disease with mechanical ventilatory support of 25% to 75% of total minute ventilation on synchronized intermittent mandatory ventilation, or 25% to 75% of maximal pressure support level on pressure support ventilation. INTERVENTIONS: Each mode of mechanical ventilation was supplied to patients with comparable levels of partial support for 30 mins. MEASUREMENTS AND MAIN RESULTS: Among three different modes, demand-flow airway pressure release ventilation achieved the lowest peak airway pressure (airway pressure release ventilation 9.1 +/- 2.6 cm H2O; pressure support ventilation 18.4 +/- 4.6 cm H2O; synchronized intermittent mandatory ventilation 34.8 +/- 7.7 cm H2O; p < .001). Hemodynamic status and oxygenation status were similar among these three modes. Five (31%) of the 16 patients felt that demand-flow airway pressure release ventilation was a less comfortable mode than synchronized intermittent mandatory ventilation or pressure support ventilation. This finding had no clear correlation with their duration of airway pressure release, preset machine deflation rate, or inspiratory/expiratory ratio of machine breath. Gross asynchrony of effort and ventilator cycling was noticed in two (13%) patients while they were receiving demand-flow airway pressure release ventilation. CONCLUSIONS: We conclude that for patients who do not have chronic obstructive pulmonary disease, demand-flow airway pressure release ventilation can provide effective partial ventilatory support with lower peak airway pressure when compared with pressure support ventilation and synchronized intermittent mandatory ventilation. However, this airway pressure release ventilation system may be less comfortable than the other two modes, and asynchrony may occur in some patients.

Analysis of Variance↗
PubMed1994

Aerosol characteristics of 99mTc-pentetic acid (DTPA) and synthetic surfactant (Exosurf).

This study evaluated the feasibility of using 99mTc-pentetic acid (DTPA) as a radioactive tracer for aerosolized synthetic surfactant (DPPC, cetyl alcohol, tyloxapol). The 99mTc-DTPA was admixed with surfactant and aerosolized using a nebulizer system interfaced to a ventilator with a cascade impactor attached to the endotracheal tube. Particle size distribution for DPPC, cetyl alcohol, and 99mTc-DTPA were almost identical during the 0- to 15-, 15- to 30-, and 0- to 30-min collection periods. Tyloxapol exhibited a unique distribution pattern with increased deposition in large (> 10 microns) and small (0.65 to 1.1 microns) particles. The mass median aerodynamic diameter for all aerosolized components was in the respirable range of 2.1 to 2.5 microns. A mixture of 99mTc-DTPA with synthetic surfactant appears to be a reasonable method to evaluate surfactant deposition.

Aerosols↗
PubMed1993

Reproduction of porcine proliferative enteropathy with pure cultures of ileal symbiont intracellularis.

Porcine proliferative enteropathy is consistently associated with the presence of intracellular curved bacteria in epithelial cells in affected portions of intestine. Two strains of these intracellular bacteria were cultured in a cell culture system with rat enterocytes (IEC-18) and passaged several times and used as oral inocula for 14 gnotobiotic and 8 conventional pigs. DNA and immunological studies had identified these bacteria as belonging to a new taxon, Ileal symbiont (IS) intracellularis. Conventional pigs dosed with approximately 3.7 x 10(6) of these organisms passaged six times in cell culture developed severe lesions of proliferative enteropathy in the ileum. Other conventional pigs dosed with a lower titer or with organisms passaged 13 times developed moderate and minor lesions, respectively. All gnotobiotic pigs dosed with organisms failed to develop lesions. Control pigs, eight conventional and two gnotobiotic, dosed with diluent, uninfected cell material or left undosed failed to develop lesions also. Reisolation of IS intracellularis and demonstration of the organism in mucosal and fecal samples only occurred in conventional pigs dosed with organisms. Gnotobiotic pigs lacking a normal intestinal flora have not been shown to be colonized by the organism. Seroconversion to IS intracellularis or mucosal infiltration by inflammatory cells was not observed in experimentally affected pigs, confirming the weak immune response characteristic of the natural disease. These results support the identification of IS intracellularis as an etiological agent of proliferative enteropathy in pigs.

Animals↗
PubMed1993

Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects.

It has long been hypothesized that a defective beta 2-adrenergic receptor (beta 2AR) may be a pathogenic factor in bronchial asthma. We examined the gene encoding the beta 2AR to assess the frequency of polymorphisms in 51 patients with moderate to severe asthma and 56 normal subjects. Nine different point mutations were found in both heterozygous and homozygous forms at nucleic acid residues 46, 79, 100, 252, 491, 523, 1053, 1098, and 1239. No mutations resulting in large deletions or frame shifts were detected. Of these nine polymorphisms, four were found to cause changes in the encoded amino acids at residues 16, 27, 34, and 164. The most frequent polymorphisms were arginine 16 to glycine (Arg16-->Gly) and glutamine 27 to glutamic acid (Gln27-->Glu). The other two polymorphisms, valine 34 to methionine, and threonine 164 to isoleucine, occurred in only four subjects. The incidence of beta 2AR homozygous polymorphisms was no greater in asthmatic patients as compared with controls (Arg16-->Gly: 53% versus 59%, Gln27-->Glu: 24% versus 29%, respectively; P = NS). Some subjects were found to have both of these polymorphisms simultaneously, but there was no difference in incidence between the two groups, with 23% of asthmatics and 28% of normal subjects being homozygous for both polymorphisms. The apparently normal subjects with both polymorphisms did not have subclinical hyperreactive airways disease as determined by methacholine challenge testing. In the asthma group, one mutation (Arg16-->Gly) identified a subset of patients with a distinct clinical profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Phenotypic analysis of lymphocyte populations in the lungs and regional lymphoid tissue of sheep naturally infected with maedi visna virus.

We have analysed the phenotype of lymphocytes in lung and regional lymph node of symptomatic and asymptomatic sheep infected with the ovine lentivirus, maedi visna virus (MVV). Compared to equivalent tissues from age-matched, non-infected controls, MVV-infected sheep show increased numbers of lymphocytes in the lung, both in the bronchus-associated lymphoid tissue (BALT) and in the alveolar septae. Both CD8+ and CD4+ T lymphocyte numbers in alveolar septae were increased, particularly in animals with clinical respiratory disease. The ratio of CD8+ to CD4+ lymphocytes was similar to that in normal lung. In both MVV-infected and uninfected animals a high proportion of pulmonary lymphocytes, particularly in the alveolar septae, did not express the CD5 antigen, suggesting that they were activated. The number of activated cells was higher in infected sheep. Variable numbers of alveolar macrophages containing MVV-core protein were present in alveolar lumina, the majority of positive cells showing morphological evidence of activation. In regional lymphoid tissue there were increased numbers of CD8+ and gamma delta expressing T cells in lymphoid follicles and germinal centres of infected animals. The specificity of these cells is unknown and we could find no evidence for the presence of cells productively infected with the virus in these structures. This study shows that activated T lymphocytes, particularly of the CD8 subset, play a major part in the pathogenesis of MVV-induced pulmonary and regional lymph node lesions.

Animals↗
PubMed1992

Immunocytological responses in porcine proliferative enteropathies.

The ileum, colon, and mesenteric lymph nodes of pigs naturally affected by either of the two major forms of proliferative enteropathy, namely, intestinal adenomatosis or hemorrhagic enteropathy, were examined for immunocytological responses to infection by immunocytochemistry, using antibodies directed against elements of the porcine immune system. In both forms, there was mucosal proliferation of immature enterocytes which lacked substantial major histocompatibility complex class II expression and a marked accumulation of immunoglobulin A (IgA) at the apical cytoplasm of affected enterocytes in association with intracellular Campylobacter-like organisms. In intestinal adenomatosis, there was only a mild infiltration of CD8+ and CD25+ T cells in the intestinal lamina propria. In hemorrhagic enteropathy, there was a moderate infiltration of CD8+ and CD25+ T cells and IgM+ B cells in the lamina propria. In rats and humans, villous enterocytes are thought to act as antigen-presenting cells, with major histocompatibility complex class II molecules present on their surface, capable of initiating a T-cell response (particularly of CD8+ T cells) in response to bacterial antigens. Therefore, the selection of immature crypt cells by the intracellular Campylobacter-like organisms for entry and multiplication may represent a remarkable microbial adaptation associated with local immunomodulation and enhanced bacterial survival. The accumulation of IgA within affected enterocytes may represent a reduced capability of the cells to process nonspecific IgA or an accumulation of specific IgA.

Animals↗