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Biomedical subjects

A L Esposito

Publications and source records attributed to A L Esposito.

At least 19 recordsLinked to original sources
PubMed1992

In vitro, Candida albicans releases the immune modulator adenosine and a second, high-molecular weight agent that blocks neutrophil killing.

We previously described a lyophilized supernatant from germinated Candida albicans that blocks human neutrophil (PMN) O2- production and degranulation stimulated by several PMN agonists but does not block stimulation by PMA. In studies to further characterize this Candida hyphal inhibitory product (CHIP), we noted several physicochemical parallels with the purine nucleoside adenosine (Ado). A Sephadex G-10 semipurified fraction of CHIP had an absorption peak near 260 nm, an apparent m.w. of less than 400, and was resistant to boiling and proteases. Maximally effective doses of CHIP (100 micrograms/ml) and Ado (100 microM) blocked 0.1 microM FMLP-stimulated O2- production by 76.8 +/- 4.1 and 81.7 +/- 4.8%, respectively. Ado deaminase, known to inactivate Ado, reversed inhibition by both Ado and CHIP. Results were comparable for the effect of CHIP and Ado on FMLP-stimulated beta-glucuronidase and lactoferrin release. Activation of the respiratory burst by opsonized C. albicans yeast was also inhibited by CHIP and Ado, but the extent of inhibition was less than for FMLP. At yeast:PMN ratios of 4:1, 10:1, and 40:1, CHIP inhibited O2- by -3.8%, 14.3%, and 12.8%, respectively; Ado blocked production by 32.9%, 24.2%, and 11.5%, respectively. The effect of CHIP and Ado on Candida killing by PMN was compared using two viability assays in each of four experiments. Ado (100 microM) had no effect on killing, although CHIP (100 micrograms/ml) inhibited killing in the MTT assay at 15 and 45 min by 81.6 +/- 6.3 and 24.7 +/- 6.2%, respectively; as assayed by CFU, CHIP inhibited killing by 34.1 +/- 6.2 and 10.3 +/- 2.5%, respectively. The ability of CHIP to inhibit killing was not affected by adding Ado deaminase, providing additional evidence that an Ado-like effect by CHIP is not essential for killing inhibition. Killing of opsonized Streptococcus pneumoniae was also inhibited in a concentration-dependent manner. Reverse-phase HPLC of the semipurified fraction revealed a peak, eluting identically to authentic Ado, which was eliminated by adding Ado deaminase. Ado content of the G-10 fraction was sufficient to account fully for the FMLP-inhibitory activity. The antikilling activity was resistant to boiling and proteases but was eliminated by mild periodation. Fractions eluting from a Sephadex CL6B column between 0.8 and 2.0 x 10(6) m.w. had increased sp. act. for killing inhibition. Sp. act. increased as carbohydrate content increased, but killing inhibition by various Candida cell wall constituents was absent to modest compared to inhibition induced by CHIP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1992

Pulmonary infections acquired in the workplace. A review of occupation-associated pneumonia.

The risk of humans acquiring pneumonia as a result of their occupation appears to have declined during the twentieth century in developed countries, such as the United States. Thus, some conditions that are traditionally associated with the workplace, such as woolsorters' disease, represent illnesses that are of historical interest only. Nevertheless, the problem of occupation-associated pneumonia remains substantial. First, large outbreaks of zoonotic infections continue to occur, especially psittacosis among poultry farmers and abattoir workers. Second, clusters of illnesses caused by recently recognized pathogens are now being reported, including legionnaires' disease in industrial workers and Chlamydia pneumoniae infections in military personnel. Finally, epidemics of old conditions are appearing in new settings, such as tuberculosis among nursing home workers. Thus, the transmission, control, and treatment of pneumonias acquired in the workplace represent intriguing and challenging areas of concern to the epidemiologist and clinician.

Humans↗
PubMed1990

The effects of capsular polysaccharide on the capacity of serum to support the killing of type 3 Streptococcus pneumoniae by human neutrophils.

To assess the effects of purified capsular polysaccharide from type 3 S. pneumoniae (PPS-3) on the capacity of serum to support pneumococcal killing by human neutrophils, varying concentrations of PPS-3 (0.01-100 micrograms/ml) were incubated (4 degrees C) with pooled serum for 30 min, and the resulting preparation, termed absorbed serum, was evaluated in bactericidal and phagocytic assays. The ability of serum to promote the killing of type 3 S. pneumoniae was significantly reduced at greater than or equal to 1.0 micrograms/ml PPS-3; similarly, serum absorbed with greater than or equal to 1.0 micrograms/ml PPS-2 failed to support the killing of type 2 S. penumoniae. However, the impact of these penumococcal polysaccharides was serotype specific, since the killing of type 3 S. pneumoniae was not impaired in serum absorbed with PPS-2, and the killing of type 2 S. pneumoniae was not attenuated in serum treated with PPS-3. The failure of serum absorbed with PPS-3 to promote the killing of type 3 S. pneumoniae was primarily a consequence of impaired bacterial ingestion; the reduction in phagocytosis was associated with parallel changes in superoxide anion release. The defects in phagocytosis and killing induced by PPS-3 were not associated with alterations in classical or alternative complement pathway activity; however, they were highly correlated with changes in serum antibody levels to the polysaccharide. The addition of polyclonal human IgG to serum treated with PPS-3 did not restore its capacity to support killing; however, preopsonization of the bacterium with the IgG preparation did partially correct the deficiency. Finally, neutrophils preincubated with serum containing greater than or equal to 10.0 micrograms/ml PPS-3 exhibited an impaired bactericidal activity against type 3 S. pneumoniae. Thus, these studies demonstrate that the presence of PPS-3 decreases the capacity of serum to support the killing of type 3 S. pneumoniae by absorbing immunoglobulins and by generating factors that interfere with neutrophil function.

Adult↗
PubMed1990

In vitro assessment of chemotaxis by peripheral blood neutrophils from adult and senescent C57BL/6 mice: correlation with in vivo responses to pulmonary infection with type 3 Streptococcus pneumoniae.

To assess the effects of advanced age on the ability of circulating neutrophils to respond to biologically relevant chemoattractants, cells were isolated from the peripheral blood of pathogen and disease-free C57BL/6 mice and evaluated in a microchemotaxis chamber. The responses of granulocytes obtained from senescent mice (26-28 months) to the chemotactic peptide, FMLP, and to leukotriene B4 were similar to those found with cells from the younger animals (8-10 months). In contrast, the migration of neutrophils in response to sonicated type 3 Streptococcus pneumoniae was significantly greater with cells from the older animals. Similarly, the chemotactic response of neutrophils to zymosan-activated serum was greater with cells and serum from the senescent animals; however, the enhanced chemotaxis exhibited by granulocytes from the aged mice was a consequence of serum factors. Following the deposition of viable type 3 S. pneumoniae into the lower respiratory tract, the neutrophil influx at 24 h after challenge was significantly greater in the senescent mice; however, age-related differences in survival rates and LD50 were not detected. Thus, in the C57BL/6 mouse, senescence is not associated with deficiencies in the response of neutrophils in vitro to chemoattractants that contribute to lung host defense against the pneumococcus; further, in this murine strain, advanced age does not result in an attenuation of the pulmonary inflammatory reaction to infection with type 3 S. pneumoniae.

Aging↗
PubMed1990

An assessment of the factors contributing to the killing of type 3 Streptococcus pneumoniae by human polymorphonuclear leukocytes in vitro.

To characterize the factors that contribute to the killing of type 3 S. pneumoniae, human neutrophils were obtained from healthy donors and incubated with viable organisms. In contrast to prior observations with other pneumococcal serotypes, killing was not detected when 10(6) colony forming units (cfu) were incubated at 37 degrees C for 2-4 hours with 10(6) neutrophils in the presence of 20-80% fresh autologous serum; further, pneumococcidal activity was not found when preopsonized bacteria and primed neutrophils were employed in the standard assay. However, when the bacterium to cell ratio was reduced to 1:100 and 1:1000, microbicidal action was detected; a 10-fold reduction in the number of viable bacteria was observed when 2 x 10(3) cfu were incubated with 2 x 10(6) neutrophils and 80% autologous serum at 37 degrees C for 4 hours. To assess the effects of serum factors on killing, bactericidal assays were performed in the presence of normal human serum (NHS), heat-inactivated human serum (HIHS) and absorbed human serum (AHS); heating reduced and absorption eliminated the capacity of serum to support killing. Studies performed with mutanolysin, an enzyme that lyses type 3 pneumococci, demonstrated that the effects of HIHS and AHS on bactericidal activity were highly correlated with alterations in the ability of the sera to support phagocytosis. Studies of neutrophil activation revealed changes in the production of superoxide anion that correlated well with phagocytosis and killing; however, the results of assays of leukotriene B4 generation and degranulation (beta-glucuronidase and lactoferrin release) were more variable. In mixing experiments, the capacity of HIHS to support killing was normalized with NHS; however, the ability of AHS to promote killing was not restored with HIHS or NHS. Thus, these studies demonstrate the relatively limited capacity of human serum to support the killing of type 3 pneumococci, and they emphasize the importance of killing assays in assessing interactions between the bacterium and neutrophils.

Blood Bactericidal Activity↗
PubMed1989

The release of neutrophil chemoattractant activity by bronchoalveolar macrophages from adult and senescent mice.

To assess the effects of advanced age on the release of neutrophil chemoattractant activity by resident bronchoalveolar macrophages (BAM), cells from three strains of pathogen- and disease-free mice were secured by lung lavage and stimulated in vitro with unopsonized zymosan or the calcium ionophore, A23187. Chemoattractant release by BAM from adult (5-8 mos) and senescent (19-26 mos) C57BL/6 and DBA/2 mice in response to both stimulants was comparable; however, the generation of chemoattractant activity by BAM from senescent (18-20 mos) BALB/c mice was greater than that observed with cells from younger (4-6 mos) animals with both zymosan and A23187. In the presence of 50 microM piriprost potassium, a 5-lipoxygenase inhibitor, the release of chemoattractant activity and leukotriene B4 (LTB4) in response to zymosan and A23187 by BAM from both groups of C57BL/6 mice was significantly impaired. With BAM from BALB/c mice, 100 microM piriprost potassium was required to produce changes in A23187-stimulated chemoattractant and LTB4 release; of note, the generation of LTB4 in response to A23187 by BAM from aged BALB/c mice was significantly greater than that observed with cells from the younger animals under all conditions studied. Finally, with BAM from DBA/2 mice, 50 microM piriprost potassium significantly reduced chemoattractant activity in both groups of animals, but the lipoxygenase inhibitor had no effect on LTB4 production. Thus, although these studies revealed substantial age and strain-related differences in the release of neutrophil chemoattractant activity by murine BAM, they did not demonstrate deficiencies that might enhance the susceptibility of the senescent host to infection of the lower respiratory tract.

Aging↗
PubMed1989

The cardiac glycoside digoxin disrupts host defense in experimental pneumococcal pneumonia by impairing neutrophil mobilization.

Normal CD-1 mice were administered digoxin (4 micrograms/kg/24 h) and infected with type 3 Streptococcus pneumoniae in order to assess the effects of the cardiac glycoside on the chemotactic responsiveness of peripheral blood neutrophils and the mobilization of granulocytes from storage pools. The chemotactic responses to autologous zymosan-activated serum (C5a) by neutrophils obtained from uninfected digoxin-treated and control animals were similar; comparable observations were made with circulating granulocytes isolated from animals at 24 or 48 h after intratracheal challenge with 5 x 10(5) colony-forming units (cfu) of bacteria. However, at 4 and 6 h after intratracheal pneumococcal challenge, the number of immature neutrophils in the peripheral blood was significantly lower in the glycoside-treated animals versus controls; at 24 and 48 h, these differences were not apparent. Following the intravenous inoculation of pneumococci, the number of circulating immature neutrophils was also found to be significantly lower at 4 and 24 h in animals given the cardiac glycoside versus controls. We conclude that digoxin disrupts host defense in experimental pneumococcal pneumonia and bacteremia by impairing the mobilization of neutrophils.

Animals↗
PubMed1989

Pneumonia in the elderly.

Bacterial pneumonia has long been recognized as a common and highly lethal infection in the aged. However, the factors that enhance the senescent host's susceptibility to infection of the lower respiratory tract remain unclear. Elderly patients with pneumonia can present with a range of signs and symptoms, leading to difficulties in diagnosis. In addition, because of the number of potential pathogens producing the infection, the management of these patients is rarely straightforward. Clearly, pneumonia in the elderly continues to present physicians with research opportunities and clinical challenges.

Aged↗
PubMed1988

An assessment of the respiratory burst and bactericidal activity of alveolar macrophages from adult and senescent mice.

To assess the effects of advanced age on the nonspecific antimicrobial activity of resident alveolar macrophages (AM), superoxide anion (O2-) release and the phagocytic and bactericidal capacity of cells from three genetically distinct murine strains were evaluated. In initial experiments, resident AM, obtained by bronchoalveolar lavage of pathogen-free adult female CD-1 mice and studied in suspension, were found to produce O2- spontaneously and in response to phorbol myristate acetate (PMA) snd unopsonized zymosan. Maximum quantities of O2- were released following stimulation with 1 microgram/ml PMA and by a particle-to-cell ratio of 100:1 with zymosan; responses to the agonists peaked between 60 and 90 min. Resident AM obtained from pathogen and disease-free senescent (18-26-month-old) female C57BL/6, BALB/c, and DBA/2 mice released significantly more O2- in response to both PMA and zymosan than did cells secured from adult (4-8-month-old) animals. In vivo, the capacity of AM from adult and senescent animals to phagocytose Streptococcus pneumoniae (unencapsulated strain) and Staphylococcus aureus was comparable, and although the cells from the senescent mice tended to be more efficient in their ability to kill internalized bacteria, statistically significant differences between the two groups were not observed. The results of these studies indicate that the enhanced susceptibility of the senescent host to infection of the lower respiratory tract cannot be attributed to age-related changes in the nonspecific antimicrobial activity of resident AM.

Aging↗
PubMed1988

Comparison of the investigational drug, LY146032, with vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus.

The efficacy of LY146032 was compared with that of vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Emphysematous hamsters were challenged intratracheally with MRSA and given LY146032 (20 mg/kg 24h), vancomycin (40 mg/kg/24h) or normal saline by subcutaneous injection. Following infection with 2 X 10(9) cfu, survival among antibiotic-treated animals was significantly greater than that of the control group (P less than 0.01 at 96 h); however, no significant difference in survival between the hamsters given LY146032 and vancomycin was seen. To evaluate the influence of the antibiotics on the rate of bacterial killing within the lungs (pulmonary clearance), animals were challenged with a high inoculum (1 X 10(9) cfu) or low inoculum (1 X 10(6) cfu). Animals treated with LY146032 demonstrated a significant advantage in pulmonary clearance versus controls at both inocula; however, animals treated with vancomycin showed a statistically significant increase in pulmonary clearance versus controls only at the lower inoculum. We conclude that in this experimental model, LY146032 was as effective as vancomycin in treating infection with MRSA.

Animals↗
PubMed1988

Protease inhibitor eglin-c affects superoxide anion release but not bacterial killing by human polymorphonuclear leukocytes.

In order to assess the influence of the protease inhibitor eglin-c on superoxide anion (O-2) release by human polymorphonuclear leukocytes (PMN), cells were secured from normal donors and stimulated with phorbol myristate acetate (PMA), opsonized zymosan, or n-formyl-methionyl-leucyl-phenylalanine (FMLP). In the presence of 100 micrograms/ml eglin-c, the activation time was prolonged and the maximum linear rate of O-2 formation was depressed following stimulation with PMA; a concentration of 1000 micrograms/ml eglin-c was required to produce a similar effect with opsonized zymosan. Eglin-c did not influence the activation time following stimulation with FMLP, but at 2000 micrograms/ml, the protease inhibitor attenuated the rate of O-2 production in response to the chemotactic peptide. In the presence of cytochalasin B, the inhibitory effect of eglin-c on O-2 release following stimulation with FMLP became more pronounced. In spite of these alterations in O-2 formation, the protease inhibitor did not impair the bactericidal activity of PMN against Staphylococcus aureus. Therefore, we conclude that although eglin-c can disrupt the activation and the activity of the superoxide-generating system of human PMN, the effect is stimulus dependent and is not associated with an alteration in the microbicidal capacity of neutrophils against S. aureus.

Anions↗
PubMed1979

Bacterial pneumonia in the elderly: a reappraisal of conventional therapy, with a note on cefamandole.

Community-acquired bacterial pneumonia in the elderly has for years been attributed almost exclusively to Streptococcus pneumoniae. Recent technical advances have provided bacteriologic and epidemiologic data demonstrating that other pathogens are important causes of pulmonary infection in older patients. This report reviews these data and reappraises the conventional therapy of community-acquired bacterial pneumonia in geriatric patients. Some properties of a new antibiotic, cefamandole nafate, are described.

Adult↗
PubMed1979

A diagnostic approach to the adult with fever of unknown origin.

The evaluation of the condition of a patient with fever of unknown origin requires a knowledge of those disorders that produce this syndrome, an awareness of the potential significance of subtle findings in the history and physical examination, and an appreciation of the value in this clinical setting of specific diagnostic procedures. In this report, we review these aspects of fever of unknown origin and outline a diagnostic approach to the persistently febrile patient.

Adult↗
PubMed1978

Fever of unknown origin in the elderly.

An extensive literature survey was performed and hospital records were reviewed in order to identify cases of fever of undetermined origin in patients aged 65 or older. Analysis of the 111 cases discovered demonstrates a characteristic but not unique spectrum of underlying disorders. Potentially curable entities such as abdominal abscess, bacterial endocarditis, tuberculosis and giant-cell arteritis account for more than half of the serious illnesses presenting with prolonged pyrexia in elderly subjects. A diagnostic approach to the management of the persistently febrile geriatric patient is discussed.

Aged↗