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T R Martin

Publications and source records attributed to T R Martin.

At least 109 records · Page 6Linked to original sources
PubMed1992

Recombinant murine interferon-gamma reversibly activates rat alveolar macrophages to kill Legionella pneumophila.

The interaction of interferon (IFN)-gamma, rat alveolar macrophages, and Legionella pneumophila was studied in vitro to define the effector cell potential of alveolar macrophages against an intracellular pathogen in a model in which the efficacy of IFN-gamma could be tested in vivo. Alveolar macrophages preincubated with IFN-gamma up-regulated Ia antigen and killed 0.5-4 logs of L. pneumophila over 4 days compared with 1-2 logs of bacterial growth in untreated cells. The bactericidal effect was dose dependent, evident over a wide range of bacterial inocula, and not suppressed by hydrocortisone. Preincubation with IFN-gamma was unnecessary and insufficient, as intracellular replication was reversed by exposure to IFN-gamma up to 48 h after infection, and neutralization of IFN-gamma after infection permitted bacterial growth. IFN-gamma thus converts alveolar macrophages from target cells to effector cells in host defense against L. pneumophila and may be of therapeutic benefit in legionellosis.

Animals↗
PubMed1992

Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality.

The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils within the airspaces of the lungs. In order to determine if neutrophil activating protein (NAP)-1/interleukin-8 (NAP-1/IL-8) could be an important cause of neutrophil influx and activation in ARDS, we examined fluid, which was either directly aspirated or lavaged with saline from the lungs of patients with ARDS. NAP-1/IL-8 was present in significantly higher concentrations in the fluids of patients with ARDS compared with control subjects. There was a significant correlation between the percentage of neutrophils in the lavage fluids and the NAP-1/IL-8 concentration (r2 = 0.74). Furthermore, the NAP-1/IL-8 concentration of the pulmonary edema fluid was equivalent to the optimal concentration required to induce neutrophil chemotaxis in vitro. Although not all of the chemotactic activity of the edema fluid was removed by an anti-NAP-1/IL-8 affinity column, the data established that NAP-1/IL-8 is an important neutrophil chemotaxin in the airspaces of patients with ARDS. In addition, those patients with very high concentrations of NAP-1/IL-8 in their bronchoalveolar lavage fluids had a higher mortality rate than those patients with lower concentrations of NAP-1/IL-8. The correlation between NAP-1/IL-8 concentration and mortality is not paralleled by total protein concentration and mortality.

Adolescent↗
PubMed1992

Lipopolysaccharide binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide. Implications for cytokine production in normal and injured lungs.

A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli O111B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNF alpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNF alpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pHi or [Cai++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNF alpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNF alpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNF alpha expression by alveolar macrophages within the lungs.

Acute-Phase Proteins↗
PubMed1992

Pasteurella multocida chorioamnionitis from vaginal transmission.

A 21 year old primigravida with a twin pregnancy developed Pasteurella multocida chorioamnionitis. Infection occurred at 27 weeks gestational age after prolonged rupture of membranes. The twin in the separate sac presenting proximal to the cervix suffered infection and died shortly after birth whereas the other twin was not infected. The bacterium is believed to have caused ascending infection from asymptomatic colonization of the vaginal tract.

Adult↗
PubMed1991

Alveolar macrophage activation in experimental legionellosis.

Legionella pneumophila is a facultative intracellular parasite of alveolar macrophages. In vitro studies have shown that lymphokine-activated mononuclear phagocytes inhibit intracellular replication of L. pneumophila. To determine if recovery from legionellosis is associated with activation of alveolar macrophages in vivo to resist L. pneumophila, we studied an animal model of Legionnaires' disease. Rats were exposed to aerosolized L. pneumophila and alveolar macrophages were harvested during the recovery phase of infection. We compared these alveolar exudate macrophages with normal resident alveolar macrophages for the capacity to support or inhibit the intracellular growth of L. pneumophila. We also measured Ia expression as a marker of immunologic activation, and studied binding of bacteria, superoxide release, and the expression of transferrin receptors as potential mechanisms of resistance to L. pneumophila. For perspective on the specificity of these responses, we also studied alveolar exudate cells elicited by inhalation of heat-killed L. pneumophila, live Listeria monocytogenes, and live Escherichia coli. We found that alveolar exudate macrophages elicited by live L. pneumophila, but not heat-killed L. pneumophila, resisted the intracellular growth of L. pneumophila. Exudate macrophages in resolving legionellosis exhibited increased Ia expression, diminished superoxide production, and downregulation of transferrin receptors. Binding of L. pneumophila to exudate macrophages was indistinguishable from that to resident macrophages in the presence of normal serum, and augmented in the presence of immune serum. Alveolar exudate macrophages elicited by E. coli also inhibited growth of L. pneumophila, and exhibited a modest increase in Ia expression without change in transferrin receptors. Exudate cells induced by L. monocytogenes exhibited up-regulation of Ia without diminution of superoxide release. Alveolar cells harvested after inhalation of heat-killed L. pneumophila did not differ from resident alveolar macrophages in the expression of surface markers. These findings suggest that alveolar macrophages are immunologically activated in vivo to serve as effector cells in resolving legionellosis, and that live bacteria are required to induce this expression of immunity. The mechanism of resistance to parasitism by L. pneumophila may entail restriction of the intracellular availability of iron, but does not involve diminished bacterial binding or an augmented respiratory burst.

Animals↗
PubMed1991

Identification of two neutrophil chemotactic peptides produced by porcine alveolar macrophages.

We have purified to homogeneity two distinct 10-kDa proteins with potent chemotactic activity for neutrophils from porcine alveolar macrophages incubated for 24 h with Escherichia coli endotoxin (lipopolysaccharide (LPS), 10 micrograms/ml). Neutrophil chemotactic activity in alveolar macrophage supernatants was concentrated by adsorption to SP-Sephadex, and purified by cation exchange and reversed phase high performance liquid chromatography. The first peptide, alveolar macrophage chemotactic factor (AMCF)-I, had chemotactic activity for both porcine and human neutrophils. The chemotactic activity for porcine neutrophils was detectable at 3 x 10(-10) M, peaked at 3 x 10(-8) M, and was comparable to that of zymosan-activated porcine serum. Segmental instillation of AMCF-I into porcine lungs caused marked neutrophil accumulation at 4 h in both bronchoalveolar lavage fluid and in lung tissue. The second peptide, AMCF-II, was active at 1.4 x 10(-9) M for porcine neutrophils, but it was less active for human polymorphonuclear neutrophils than was AMCF-I. Oligonucleotide probes to regions of the N-terminal sequences of AMCF-I and AMCF-II hybridized to mRNA recovered from LPS-stimulated alveolar macrophages. The N-terminal sequences and amino acid compositions indicate that AMCF-I and AMCF-II are distinct proteins, but that both have homologies with a family of peptide chemoattractants produced by human blood monocytes and platelets. Thus, alveolar macrophages stimulated with LPS produce two distinct 10-kDa cytokines with potent chemotactic activity for neutrophils. This indicates that there are two different peptide pathways by which alveolar macrophages can recruit neutrophils into the lung.

Amino Acid Sequence↗
PubMed1991

Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome.

We studied the changes of coagulation and fibrinolysis in bronchoalveolar lavage (BAL) and plasma obtained serially at intervals after the onset of adult respiratory distress syndrome (ARDS). BAL procoagulant activity was increased at 3 days and tended to decrease thereafter. Tissue factor associated with factor VII was the major BAL procoagulant. Fibrinopeptide A was increased, indicating increased thrombin-mediated conversion of fibrinogen to fibrin. Fibrinolytic activity was usually undetectable in BAL at 3 days post-ARDS and remained depressed for up to 14 days despite unchanged concentrations of urokinase and variably detectable tissue plasminogen activator. Depressed fibrinolytic activity was associated with increased antiplasmin activity and plasminogen activator inhibitor 1 (PAI-1) while PAI-2 concentrations approximated those of control samples and did not change during evolving ARDS. Evidence of systemic coagulopathy and increased systemic fibrin degradation were commonly found in serial ARDS plasma samples, consistent with accelerated vascular and/or extravascular fibrin deposition in these patients. The data indicate that intra-alveolar as well as systemic derangements of fibrin turnover are common features of evolving ARDS. Concurrent local abnormalities of both coagulation and fibrinolytic pathways favor persistence of alveolar fibrin for up to 14 days after clinical recognition of ARDS.

Adult↗
PubMed1991

The function of lung and blood neutrophils in patients with the adult respiratory distress syndrome. Implications for the pathogenesis of lung infections.

Pulmonary infections are a frequent cause of morbidity and mortality in patients with the adult respiratory distress syndrome (ARDS), but the reason is uncertain. Because neutrophils are important for lung defense and are found in increased numbers in the bronchoalveolar lavage fluid of patients with ARDS, we compared the functional activities of neutrophils obtained from lavage fluid and pulmonary artery blood of 28 patients shortly after the onset of ARDS. The lavage fluids contained 81.3 +/- 9.9% neutrophils, of which more than 95% were viable by vital dye exclusion, and the total protein concentrations were increased (98.8 +/- 98.5 mg/dl). The production of superoxide anion and hydrogen peroxide by the neutrophils in lavage fluid was significantly impaired compared with simultaneously tested pulmonary artery and normal neutrophils, and the microbicidal activity of the lavage neutrophils for Staphylococcus aureus was significantly impaired. The migration of alveolar neutrophils in response to a variety of stimuli was markedly reduced as compared with both pulmonary artery and normal neutrophils. The alterations in superoxide anion production and chemotaxis could be reproduced by exposure of normal neutrophils to oxidants (glucose:glucose oxidase), but not to other mediators that have been found in ARDS lavage fluids. Although the pulmonary artery neutrophils from the same patients had impaired production of superoxide anion and hydrogen peroxide, their microbicidal activity and chemotactic responses were normal. These findings indicate that the function of alveolar neutrophils is impaired in the lungs of patients with ARDS. This could contribute to the high incidence of pulmonary infections in these patients.

Blood Bactericidal Activity↗
PubMed1991

Chlamydia pneumoniae, strain TWAR, infection in patients with chronic obstructive pulmonary disease.

TWAR, the only known serovar of Chlamydia pneumoniae, is a newly described bacterium that has been identified as a cause of both epidemics and endemic cases of pneumonia. The role of TWAR infection in patients with chronic obstructive pulmonary disease (COPD) is not known. We conducted a prospective study to establish whether TWAR infection is a common cause of acute exacerbations of COPD. We studied two groups of patients: 44 patients admitted to the hospital with acute exacerbations of COPD, and 65 stable clinic patients with COPD. We found that evidence of acute TWAR infection was infrequent in patients with exacerbations (5%). In contrast, the majority of patients from both groups had serologic evidence of previous TWAR infection (77%). This was not significantly greater than the prevalence found in a small group of patients of similar age and sex without lung disease from the same institution (73%). TWAR was not isolated from the oropharyngeal specimens obtained from 97 subjects, suggesting that it does not colonize the respiratory tract of patients with COPD. This study shows that at the time of low incidence in the community, acute TWAR infection is uncommon in patients with acute exacerbations of COPD. The majority of patients with COPD have, however, been infected with TWAR in the past. The clinical manifestations of these infections are not known and should be the focus of further studies.

Aged↗
PubMed1991

Signal transduction in human alveolar macrophages: diminished chemotactic response to FMLP correlates with a diminished density of Gi proteins and FMLP receptors.

Alveolar macrophages (AM) migrate less well in response to chemotactic ligands than do monocytes and neutrophils. The response of monocytes and neutrophils to chemotactic ligands is mediated at least in part by pertussis toxin-sensitive guanine nucleotide binding proteins (Gi proteins). Whether this is also true in AM is uncertain. We hypothesized that decreased chemotaxis by AM was due in part to diminished Gi protein and/or chemotactic receptor density in AM. G proteins are heterotrimers made up of alpha, beta, and gamma subunits; the predominant pertussis toxin-sensitive Gi proteins are those containing alpha i2 or alpha i3 subunits. Pertussis toxin pretreatment (0.5 microgram/ml) significantly reduced AM, monocyte, and neutrophil chemotaxis to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and human zymosan-activated serum (P less than 0.05). However, as previously noted, AM chemotaxis was much less than that observed in monocytes and neutrophils. Immunoblots using antibodies that are specific for alpha i2 and alpha i3 showed that AM contained approximately 3-fold less alpha i2 and approximately 10-fold less alpha i3 per microgram of plasma membrane protein than did monocytes or neutrophils. Similar results were obtained in immunoblots made using antibodies to common alpha subunit determinants and to the beta 36 subunit. A comparable approximately 4-fold reduction in density of receptors for [3H]FMLP was found in AM compared to neutrophils. The diminished density of Gi proteins and FMLP receptors was not due to a generally decreased density of plasma membrane proteins in AM, since the density of the membrane-associated tyrosine kinase hck was similar in AM, monocytes, and neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Differences in the expression of the cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice. Mast cells are not required for the cardiopulmonary changes associated with certain fatal anaphylactic responses.

We compared the changes in heart rate (HR), pulmonary dynamic compliance (Cdyn), and pulmonary conductance (GL) associated with three different models of anaphylaxis in genetically mast cell-deficient WBB6F1-W/Wv and congenic normal (+/+) mice. Intravenous infusion of a monoclonal rat anti-mouse IgE produced a marked tachycardia, diminutions in Cdyn and GL, and death in +/+ but not W/Wv mice, and +/+ mice sensitized to develop high circulating levels of IgE exhibited HR, Cdyn, and GL responses to rat anti-IgE challenge which were significantly less intense than those in nonimmunized +/+ mice. By contrast, virtually identical cardiopulmonary responses were observed in either +/+ or W/Wv mice challenged to elicit pure active anaphylactic responses or simultaneous active and anti-IgE-dependent anaphylaxis. These findings show that anaphylactic responses associated with significant tachycardia, reductions in Cdyn and GL, and death can occur in the virtual absence of tissue mast cells. This is true even though, in normal mice, such responses are associated with extensive degranulation of tissue mast cells. By contrast, certain models of anaphylaxis, such as that induced in nonsensitized mice by anti-mouse IgE, can not be elicited in the absence of mast cells.

Anaphylaxis↗
PubMed1990

Alveolar macrophage function in rats with severe protein calorie malnutrition. Arachidonic acid metabolism, cytokine release, and antimicrobial activity.

To investigate the effects of protein calorie malnutrition (PCM) on alveolar macrophage function, we measured antimicrobial activity, IL-1 and TNF production, and arachidonic acid metabolism in alveolar macrophages of infant rats with moderate and severe PCM. Groups of weanling male rats were fed a diet containing 0.8% protein (PCM) or 24% protein (control). A third group (pair fed) was fed limited amounts of the control diet that matched the mean daily dietary intake of the PCM group. After 4 wk on the diets, alveolar macrophages from all three groups functioned similarly with respect to surface adherence, phagocytosis and killing of Listeria monocytogenes, release of hydrogen peroxide and superoxide anion, and production of IL-1 and TNF. In contrast, Listeria-stimulated alveolar macrophages from the PCM group exhibited a marked shift in arachidonic acid metabolism, with impaired production of leukotriene B4 and enhanced release of thromboxane B2 and PGE2. The membrane arachidonic acid content and the uptake of [3H]arachidonate by alveolar macrophages did not differ among the three groups. The shift toward the cyclooxygenase pathway was not seen after 2 wk of dietary restriction and was reversed if PCM animals were fed the control diet for 1 wk. Thus, PCM does not affect the antimicrobial activity or cytokine production of alveolar macrophages, but causes alterations in arachidonic acid metabolism that may interfere with the modulatory functions of alveolar macrophages.

Animals↗
PubMed1990

Cancer incidence among Massachusetts firefighters, 1982-1986.

Previous investigations of cancer among firefighters have been limited to mortality data and have yielded inconsistent results. Case-control analyses were conducted in the present surveillance study in order to examine associations between firefighting and cancer incidence in Massachusetts. Subjects were identified through the Massachusetts Cancer Registry files for 1982-1986. Exposure status (firefighting) was determined from the usual occupation reported to the Registry. Nine different cancer types were examined among the 315 reported white male firefighters. Two "unexposed" reference populations were used: policemen and statewide males. Standardized morbidity odds ratios (SMORs) were statistically significantly elevated for melanoma (SMOR = 292; 95% C.I. = 170-503) and bladder cancer (SMOR = 159; 95% C.I. = 102-250) among firefighters compared with the state as a whole. When policemen were used as the reference group, the bladder cancer excess persisted (SMOR = 211; 95% C.I. = 107-414) and non-Hodgkin's lymphoma was elevated (SMOR = 327; 95% C.I. = 119-898); the melanoma excess was largely reduced (SMOR = 138; 95% C.I. = 60-319) but remained elevated among those aged 55-74 years (SMOR = 513; 95% C.I. = 150-1,750). Small number excesses (not significant) were also observed for pancreatic cancer and leukemia compared with police.

Adolescent↗
PubMed1990

The trachea and esophagus after repair of esophageal atresia and distal fistula: computed tomographic observations.

Five patients, whose esophageal atresia and distal tracheoesophageal fistula had been repaired in infancy, were examined by computed tomography at age 2 to 21 because of recurrent or persistent tracheal or esophageal problems. Their tracheas generally failed to have the roughly circular cross-sectional shape found in controls. The pars membranacea was often unusually broad, with much more section-to-section variation in area than in controls. Change in cross-sectional area with respiratory phase, in the one patient assessed, was much greater than in a control. These tracheal abnormalities help to explain the tracheal symptoms found in these and similar patients. Their esophagi contained much air and fluid.

Adult↗
PubMed1990

Principles of interfacing computers to medical equipment.

Table 3 shows a comparison of the interface standards considered. RS232 has the advantages of availability, flexibility and low cost. Variants on the standard overcome its limitations in data-rate and distance. The Centronics parallel standard is available on most personal computers and is particularly suitable for high data-rates over short distances. Other PC standards such as SCSI are special-purpose interfaces and therefore more difficult to use. GPIB is a robust and well-specified standard often used for the control of laboratory instruments.

Analog-Digital Conversion↗
PubMed1990

The pathogenicity, localization, and cyst structure of echinostomatid metacercariae (Trematoda) infecting the kidneys of the frogs Rana clamitans and Rana pipiens.

Light and scanning electron microscopy were used to examine the localization and pathogenicity of echinostomatid metacercariae infecting the kidneys of leopard frogs, Rana pipiens, and green frogs, Rana clamitans. Cysts occurred predominantly in the ventrolateral renal cortex, and at least some were confined to the lumen of the Bowman's capsules. Each vermiform metacercarial body was enclosed by a spherical cyst wall that had a uniform thickness. The wall was composed of a homogeneous material containing basic and keratinlike proteins, with sulfated acid mucopolysaccharides on the outer surface. Most cysts were enclosed by a fibrous capsule of host origin, or were surrounded by an inflammatory focus. Fibrosis was always focal, but its degree varied between individual hosts and between different cysts within the same host. Some heavily encapsulated cysts were darkened and contained disintegrating worms. In heavily infected kidneys, confluence of fibrotic or inflammatory foci resulted in the displacement of functional renal tissue. These data suggest that infection by echinostomatids may impair renal function and that the host's response affects parasite viability.

Animals↗
PubMed1989

Mast cells: immunologically specific effectors and potential sources of multiple cytokines during IgE-dependent responses.

Mast cells are critical effectors in many IgE-dependent responses, and the numbers and phenotype of certain mast cell populations can be influenced, through IL-3 and IL-4, by the same T cells that regulate IgE production. However, IgE can interact with cells other than mast cells, and different mast cell populations express significant variation in multiple important aspects of their phenotype, including mediator content and responses to cytokines and stimuli of activation. As a result it may be difficult to define the unique contributions of mast cells to IgE-dependent reactions. One approach for analysing the roles of various mast cell populations in individual biological responses is to attempt to elicit these reactions in mice in which the presence or absence of specific mast cell populations can be regulated experimentally. We have used genetically mast cell-deficient and mast cell-reconstituted mice to demonstrate that mast cells provide essential effector function in certain IgE-dependent responses involving the skin, stomach or lungs but are not necessary for the pulmonary alterations and death associated with active anaphylaxis. Similar approaches can be used to investigate the biological significance of the production, by mast cells stimulated with IgE and specific antigen, of cytokines similar or identical to IL-1, IL-3, IL-4, IL-5, IL-6, TNF-alpha/cachectin, IFN-gamma, GM-CSF, JE, MIP-1 alpha, MIP-1 beta and TCA3.

Animals↗