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Biomedical subjects

H Yeager

Publications and source records attributed to H Yeager.

At least 19 recordsLinked to original sources

Parapneumonic empyema. A pitfall in diagnosis.

Two patients eventually shown to have empyema were encountered in which the initial thoracentesis revealed fluid compatible with either a simple or a complicated parapneumonic effusion. In both cases, the diagnosis of empyema was made by a second thoracentesis done at a close interval of time from a different site. Therefore, the physician should approach parapneumonic effusions systematically, and remember that in some cases, multiple thoracenteses may be required to make the correct diagnosis of an empyema.

Adult

Nonopsonic uptake of Mycobacterium avium complex by human monocytes and alveolar macrophages.

The uptake of Mycobacterium avium complex (MAC) microorganisms by human peripheral blood monocytes (PBMs) and alveolar macrophages (AMs) is not well understood. We have previously shown, under opsonic conditions, that humoral factors are important in mediating the uptake of MAC by PBMs. However, the receptor-ligand interactions occurring under nonopsonic conditions remain unclear. We compared the uptake of untreated human PBMs and AMs in a serum-free medium with phagocytes treated to remove surface receptors. Removal of complement receptors CR1 and CR3, the Fc receptor (FcR), and the transferrin receptor (TfR) resulted in significantly lower levels of MAC uptake in serum-free medium by both PBMs and AMs. The addition of barley beta-glucan or mannan from Saccharomyces cerevisiae inhibited MAC uptake by untreated phagocytes in a dose-dependent manner. MAC uptake by PBMs or AMs was never completely abrogated by combining treatments (removal of CR1, CR3, FcR, and TfR and adding mannan or beta-glucan), indicating still-unknown mechanisms of uptake under nonopsonic conditions. We conclude that CR1, CR3, FcR, TfR, the mannose receptor, and possibly a separate beta-glucan-inhibitable receptor all may be involved in nonopsonic uptake of MAC by both PBMs and AMs.

Cells, Cultured

O(6)-methylguanine-DNA methyltransferase and uracil DNA glycosylase in human broncho-alveolar lavage cells and peripheral blood mononuclear cells from tobacco smokers and non-smokers.

Because interindividual variations in the activities of DNA repair enzymes may be a risk factor in the pathogenesis of lung diseases, O(6)-methylguanine-DNA methyltransferase (O(6)-MT) and uracil DNA glycosylase (UDG) were measured in broncho-alveolar lavage cell (BALC) and peripheral blood mononuclear cell (PBM) samples from 57 healthy volunteers (25 smokers and 32 non-smokers). According to cotinine determination in 39 cases where serum for this was available, 38% of the self-acclaimed non-smokers had greater than 10 ng/ml of cotinine in their serum. Whether grouped into smokers and non-smokers according to clinical history or by serum cotinine, there were no statistically significant differences between these groups in O(6)-MT or UDG in either of the cell types. However, a tendency towards lower values in smokers was seen. The highest intraindividual variation in O(6)-MT activity was 7-fold, while the highest interindividual variation reached 18-fold. For UDG, the respective values were 24- and 307-fold. Although the distribution of O(6)-MT in BALC was different from that in PBM, the data are consistent with unimodality in both of the cell types. These findings suggest that exposure to cigarette smoke is not entirely responsible for the wide interindividual variation in O(6)-MT and UDG DNA repair activities.

Adult

Eosinophilic pneumonia associated with reaction to radiographic contrast medium.

We have described what we believe to be the first published case of a reaction to radiographic contrast medium followed by a diffuse eosinophilic pneumonia. This association seems to confirm what is know about the immunologic mechanisms of such reactions, and though further verification of causation is needed, we found it to be the most plausible explanation.

Adult

Natural killer cell-mediated lysis of Mycobacterium-avium complex-infected monocytes.

Since the precise mechanism of host responses to infection with Mycobacterium-avium complex (MAC) is unclear and since cytotoxic lymphocytes may be involved in the destruction of cells infected with intracellular pathogens, we investigated the ability of normal peripheral blood lymphocytes to kill MAC-infected monocytes in a short-term isotope release assay. Nylon wool-passed lymphocytes lysed MAC-infected but not uninfected monocytes during a 4-hr assay. Infected monocytes were less sensitive to cell-mediated killing than the standard natural killer (NK) cell-sensitive cell line K562, although the kinetics of lysis were similar. The release of lymphocyte-derived mediators such as tumor necrosis factor, interleukin-2 (IL-2), and interferon-alpha and -gamma could not be implicated as a cause of monocyte death. Through the use of cell-specific monoclonal antibodies plus complement, the phenotype of the effector cell was that of an NK cell (CD3 negative, partially CD8 negative, and CD16 positive). The use of highly purified, negatively selected NK cells confirmed these results. NK cell-mediated lysis of infected monocytes decreased MAC viability, indicating that this cytotoxic activity would not favor dissemination of the organism. The killing of MAC-infected monocytes was reduced by K562 cells, suggesting that these targets shared common recognition/binding structures. These results suggest that NK-cell function may be important in the prevention of or response to MAC infection and may help explain the predilection of AIDS patients to develop widespread disease.

Acquired Immunodeficiency Syndrome

Inhaler and spacer use in obstructive airway diseases.

The role of inhaled aerosols in the treatment of obstructive airway diseases is increasing for both immediate bronchodilation and prophylactic anti-inflammatory effects. Inhaled aerosol agents are available in metered-dose inhaler and nebulizer forms. Maximum therapeutic benefit from metered-dose inhalers is assured when the correct inhaler technique is used. Spacer devices may be helpful in some patients.

Administration, Inhalation

Home oxygen therapy.

Home oxygen therapy is clearly beneficial for the chronically hypoxemic patient. Compressed gas, liquid oxygen and oxygen concentrators are the primary oxygen sources for home use. A number of oxygen-conserving devices are now available and may improve compliance. Reservoir cannulas, demand oxygen delivery systems and transtracheal oxygen are the latest examples of oxygen-conserving techniques.

Chronic Disease

Differences in uptake of mycobacteria by human monocytes: a role for complement.

We investigated the influence of serum factors on the uptake of various species of mycobacteria by human peripheral blood monocytes (PBM). On the basis of the percentage of PBM involved during in vitro uptake, the mycobacteria were of two distinct groups. The mycobacteria of one group, which consisted of Mycobacterium avium complex and M. chelonae, were taken up by many PBM; the other group, consisting of M. tuberculosis, M. kansasii, M. fortuitum, and M. gordonae, were taken up by fewer PBM. M. scrofulaceum was intermediate to these two groups on the basis of its uptake by PBM. Serum depleted of complement by heating or treatment with cobra venom factor significantly reduced the extent of PBM involvement with M. avium complex, indicating that complement is an important serum component mediating the uptake of M. avium complex organisms. Preincubation of mycobacteria with serum containing 10 mM EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and 10 mM MgCl2 resulted in uptake by a high percentage of PBM, while preincubation in heated serum or serum containing 10 mM EDTA resulted in a significantly reduced percentage of PBM involved in uptake of M. avium complex organisms, indicating that these organisms are activators of the alternative pathway of complement. Incubation of M. avium complex organisms in human serum consumed 51% of the hemolytic complement activity. Parallel experiments indicated that serum had a lesser effect on the uptake of M. tuberculosis. Thus, serum is important in in vitro M. avium complex uptake by PBM; complement has a major role in the effect of serum, but this role is less important with M. tuberculosis.

Adolescent

Tuberculosis update.

Tuberculosis cases are increasing in the United States, partly because of the emergence of AIDS and the rise in the homeless population. Faster culture methods usually allow identification within two weeks. Research is being done on serologic and recombinant nucleic acid methods of detecting tuberculosis in various body fluids and secretions. A six-month treatment regimen for tuberculosis has proved to be effective, as have shorter courses of prophylactic therapy for tuberculin skin test converters.

Antitubercular Agents

Chronic granulomatous disease in an adult.

We have described a 49-year-old man with chronic granulomatous disease. The diagnosis was established by a deficiency of NBT dye reduction by neutrophils, in addition to impairment in 14C-1-glucose utilization, 125I-iodination of zymosan, chemiluminescence, superoxide radical generation, and bactericidal activity toward S aureus. This adult patient exhibits many characteristics of chronic granulomatous disease of childhood but of less severity, which may explain his unusually long survival. It is thus important to consider the diagnosis of chronic granulomatous disease not only in children but also in adult patients having the characteristic pattern of recurrent infections.

Blood Bactericidal Activity

Determination of mycobacterial antigens in sputum by enzyme immunoassay.

An enzyme-linked immunosorbent assay (ELISA) was examined for its usefulness in detecting mycobacterial antigens in sputum. A double-antibody sandwich procedure was set up by using a commercially available hyperimmune serum directed against Mycobacterium bovis, BCG. The ELISA was able to detect 10 ng of protein per ml of BCG sonic extract. The system also clearly distinguished Mycobacterium tuberculosis organisms from Mycobacterium avium and Mycobacterium kansasii organisms. A total of 68 unknown sputum specimens submitted to the clinical laboratories for examination for tuberculosis were tested by ELISA. Of the 20 specimens that were smear positive and culture positive, 12 (60%) were positive by ELISA; 6 of the 11 (55%) smear-positive culture-negative samples were positive by ELISA; 1 of 2 (50%) of the smear-negative culture-positive samples was positive by ELISA; and only 3 of 35 (9%) of the smear-negative culture-negative samples were positive by ELISA. This approach offers promise as an aid in the presumptive differentiation of nontuberculous mycobacteria from the M. tuberculosis complex.

Antibody Specificity

Asbestos-associated chromosomal changes in human mesothelial cells.

Replicative cultures of human pleural mesothelial cells were established from noncancerous adult donors. The cells exhibited normal mesothelial cell characteristics including keratin, hyaluronic acid mucin, and long branched microvilli, and they retained the normal human karyotype until senescence. The mesothelial cells were 10 and 100 times more sensitive to the cytotoxic effects of asbestos fibers than normal human bronchial epithelial or fibroblastic cells, respectively. In addition, cultures of mesothelial cells that survived two cytotoxic exposures of amosite fibers were aneuploid with consistent specific chromosomal losses indicative of clonal origin. These aneuploid cells exhibit both altered growth control properties and a population doubling potential of greater than 50 divisions beyond the culture life span (30 doublings) of the control cells.

Asbestos

The ultrastructure of bronchial macrophages and lymphocytes in sarcoidosis.

A physical interaction between macrophages and lymphocytes was observed more frequently in bronchial lavage fluid obtained from patients with sarcoidosis than from normal volunteers, irrespective of their history of smoking. In this spontaneous interaction more than two lymphocytes were commonly seen adhering to a macrophage without evidence of cytoplasmic bridging or membrane fusion. To a greater extent than in normal volunteers, macrophages from patients with sarcoidosis were characterized by the appearance of a more highly irregular cell surface, more membrane bound inclusions, however, was positively correlated with the smoking history of the individual, and the number of surface projections (microvilli) of macrophages from smokers appeared to be reduced. Significant differences were not apparent in the nuclear or cellular diameters of macrophages from sarcoid and normal individuals.

Bronchi

Human alveolar macrophages: antigen-independent binding of lymphocytes.

To characterize the initial step in alveolar macrophage (AM)-lymphocyte (L) interaction in the human lung, we studied the ability of human AM to bind autologous blood L in vitro in the absence of antigen. AM were obtained by saline bronchial lavage through a fiberoptic bronchoscope. Monolayers of AM attached to glass bound autologous blood L prepared by Ficoll-Hypaque and nylon wool column separation. The AM-L binding increased from zero time to a maximum at 2 h and then declined to a zero time value at 18 h. The binding was dependent on the number of L added to the AM monolayers, with greatest binding at an AM:L ratio of 1:50. AM:L binding required viability of AM, but not of L, and was temperature dependent. Pretreatment of AM with iodoacetic acid, trypsin, neuraminidase, or colchicine diminished attachment of L at 2 h. Neuraminidase pretreatment of L resulted in increased binding to nontreated AM. Thus, a physical interaction between human AM and autologous peripheral blood L can occur in vitro in the absence of known antigen; similar interaction in vivo may play a role in the generation of cell-mediated immune responses in the lung.

Adult

Rickets in children receiving anticonvulsant drugs. Biochemical and hormonal markers.

Forty-one epileptic children, aged 2 to 16 years, receiving combinations of phenobarbital, phenytoin, and primidone, and 39 control children were studied. The epileptics demonstrated slight but significant reductions in serum calcium, phosphorus, and 25-hydroxyvitamin D concentrations, and a significant increase in serum alkaline phosphatase values. No significant difference in serum immunoreactive parathyroid hormone levels was noted. Further analysis of the data revealed that patients whose drug therapy included primidone had the lowest serum levels of calcium and 25-hydroxyvitamin D. They had also received the largest number of drugs for the longest duration, and had serum phenobarbital levels that were significantly higher than those of other patients. The minimal degree of vitamin D deficiency in our epileptic children contrasts with the results of other investigations and warrants emphasis. The reasons for this difference are not apparent.

Adolescent