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Biomedical subjects

C A Demko

Publications and source records attributed to C A Demko.

13 recordsLinked to original sources
PubMed1995

Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection.

The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed (n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients.

Adolescent↗
PubMed1995

Cross-sectional and longitudinal studies of naturally occurring antibodies to Pseudomonas aeruginosa in cystic fibrosis indicate absence of antibody-mediated protection and decline in opsonic quality after infection.

Most patients with cystic fibrosis (CF) develop chronic endobronchial infection with mucoid Pseudomonas aeruginosa. It has been suggested that opsonic antibodies to the mucoid exopolysaccharide of P. aeruginosa protect older CF patients (> 12 years of age) who have remained free of colonization by this organism. Serum antibodies from chronically infected CF patients had greater total complement-dependent opsonic activity than did those of older noncolonized patients (P < .02), but when bound antibody was equalized, opsonic quality was greater for the latter group (P < .03). In longitudinal studies, antibody titers to mucoid P. aeruginosa rose greatly after initial infection, but opsonic quality declined (P = .002). Twenty CF patients who passed age 12 free of P. aeruginosa colonization developed chronic P. aeruginosa lung infection at ages 14-35 years. Thus, naturally occurring antibodies do not protect CF patients from P. aeruginosa infection, and opsonic quality of serum antibodies deteriorates as infection becomes established.

Adolescent↗
PubMed1986

Pseudomonas cepacia: decrease in colonization in patients with cystic fibrosis.

The incidence and prevalence of Pseudomonas cepacia pulmonary colonization were noted to be increasing in patients with cystic fibrosis (CF). Previous work had indicated a greater prevalence of P. cepacia among siblings (with CF) of patients colonized by P. cepacia as well as an association of initial positive P. cepacia cultures with a hospitalization. Because of uncertainty regarding the source and mode of transmission, limited precautionary measures were instituted in 1983, including physical separation of hospitalized patients colonized with P. cepacia from non-colonized patients, reeducation of staff concerning basic infection control procedures, explanation to families regarding these precautionary efforts, and institution of separate summer camp sessions. Repeated environmental cultures throughout the hospital were negative for P. cepacia. Coincident with the institution of control measures, a sharp decline in incidence occurred (8.2% in 1983 versus 1.7% in 1984). These results are suggestive of patient-to-patient transmission. Because P. cepacia infections have been associated with shorter survival in some patients with CF, we will continue our current segregation measures.

Anti-Bacterial Agents↗
PubMed1985

Pseudomonas cepacia colonization among patients with cystic fibrosis. A new opportunist.

Pseudomonas cepacia colonization among patients with cystic fibrosis (CF) at our center has increased from 7% (of 419 patients) to 15% (of 450 patients) over the past 5 yr (July 1978 through June 1983). The proportion of patients dying with P. cepacia colonization has increased over this 5-yr period (Year 1, 9% (1/11) of the deaths were associated with P. cepacia; Year 5, 55% (16/29) were associated with P. cepacia). These observations have led to a heightened concern regarding the presence of P. cepacia in the CF population. Characteristics of the patient population that might relate to P. cepacia colonization were reviewed. Increasing numbers of patients in good clinical condition became colonized with P. cepacia. Females in good clinical condition who acquire P. cepacia appear to be at special risk of developing severe and unexpected pulmonary complications that often end in death. In contrast, males, regardless of clinical condition, appear less likely to experience an immediate decline in clinical status. Hospitalization is potentially implicated in contributing to the increase in P. cepacia colonization because many patients' initial positive cultures were concurrent with or followed a hospital stay. Sixteen patients with CF and P. cepacia had siblings with CF, 6 of whom subsequently acquired P. cepacia. This frequency is more than double that in our overall CF population.

Adult↗
PubMed1984

Function of human alveolar macrophages from normal volunteers and cigarette smokers: effect of cystic fibrosis serum.

Previous studies demonstrated that serum from cystic fibrosis (CF) patients specifically inhibited Pseudomonas phagocytosis by both normal and CF alveolar macrophages. In the present study, inhibition of Pseudomonas aeruginosa phagocytosis by CF serum was significantly less on macrophages from heavy smokers than on cells from normal volunteers (P less than 0.01). Normal volunteer cells cultured for 10 days were also less affected by CF serum as compared to cells cultured for 24 hours from the same individual (P less than 0.01). Altered morphology (increased size and spreading on glass surfaces) and increased intracellular glycosidases of these cells were suggestive of a difference in the state of activation compared to normal cells. Macrophages from heavy smokers and 10-day cultures from normal volunteers were inhibited by heated CF serum, suggesting that complement-mediated opsonization was responsible for attachment or ingestion of P. aeruginosa in CF serum by these macrophages.

Blood Proteins↗
PubMed1982

Phagocytosis of Pseudomonas aeruginosa by polymorphonuclear leukocytes and monocytes: effect of cystic fibrosis serum.

It has been shown previously that serum from chronically infected patients with cystic fibrosis inhibits the phagocytosis of Pseudomonas aeruginosa by both normal and cystic fibrosis alveolar macrophages. In the present study, the ability of peripheral monocytes and polymorphonuclear leukocytes from normal volunteers and cystic fibrosis patients to phagocytize P. aeruginosa was shown not to be inhibited in the presence of serum from cystic fibrosis patients.

Cystic Fibrosis↗
PubMed1981

Serum bactericidal effect on Pseudomonas aeruginosa isolates from cystic fibrosis patients.

The bactericidal activity against Pseudomonas aeruginosa strains isolated from cystic fibrosis patients was determined in a 10% concentration of normal serum or autologous cystic fibrosis serum. Of the 167 strains tested, 77 (46%) were sensitive (greater than 95% killed) in normal serum. Mucoid strains were more frequently sensitive than nonmucoid strains. Twenty-three sensitive strains tested in ethyleneglycoltetraacetic acid-chelated serum were resistant (less than 10% killed), suggesting only classical pathway activation. Absorption of cystic fibrosis serum with the autologous P. aeruginosa strain resulted in decreased killing by that serum. All sera, including the chelated and absorbed sera, had comparable total hemolytic complement levels. Patients in poor clinical condition (5 out of 12), in contrast to patients in good or moderate condition(1 out of 30), were more likely to have P. aeruginosa strains that were serum resistant in autologous serum but sensitive in normal serum. Sera from these five patients in poor clinical condition were capable of killing heterologous P. aeruginosa strains. These results suggest the presence of a protective or "blocking" activity in serum from some patients in poor clinical conditions. This association of a blocking activity with clinical condition may signal a transition point in the progression of cystic fibrosis lung disease and thus may be another contributory factor in the failure of the cystic fibrosis host to control infection.

Antibodies, Bacterial↗
PubMed1980

Ultrastructure and function of alveolar macrophages from cystic fibrosis patients.

Alveolar macrophages were isolated from three cystic fibrosis patients, and the structure and function of these cells were compared to that of normal alveolar macrophages. The cystic fibrosis (CF) and normal alveolar macrophages were able to phagocytize Pseudomonas in the presence of normal serum, but cells from both sources had decreased phagocytosis of Pseudomonas in the presence of CF serum. Phagocytosis of Staphylococcus was not inhibited. Ultrastructural studies showed CF macrophages to be morphologically normal, however, in contrast to CF polymorphonuclear cells, they had not been heavily engaged in phagocytosis. The similarities between CF and normal macrophages suggest that the chronic pulmonary infection of CF may be due to an extrinsic factor in an altered lung environment rather than to any intrinsic cellular defect of the alveolar macrophage.

Adolescent↗
PubMed1979

Multiple of isolates of Pseudomonas aeruginosa with differing antimicrobial susceptibility patterns from patients with cystic fibrosis.

Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis were studied in an effort to determine the unique characteristics of the infecting strains and to elucidate the pattern of colonization. Of 413 patients studied, 81% were chronically infected with P. aeruginosa. Patients from whom P. aeruginosa was never or only occasionally isolated were in better clinical condition than the chronically infected patients. Isolates were classified into six morphologic varieties: classic, rough, mucoid, gelatinous, dwarf, and enterobacter. Most patients had two or more of these varieties. Such multiple varieties from the same individual were of the same serotype but often differed in antibiotic susceptibility as determined by both the disk and the minimal inhibitory concentration methods. These differences were apparent when mucoid strains were compared with nonmucoid strains and when nonmucoid strains were compared with one another. Studies of antibiotic susceptibility should be performed on each morphologically different type of P. aeruginosa obtained from patients with cystic fibrosis.

Adolescent↗
PubMed1979

Inhibitory effect of cystic fibrosis serum on pseudomonas phagocytosis by rabbit and human alveolar macrophages.

This report presents experimental observations indicating the presence of an inhibitory activity in cystic fibrosis (CF) serum which impairs phagocytosis of Pseudomonas aeruginosa by rabbit as well as human alveolar macrophages. Of the 49 patient serum samples studied, 40 consistently showed greater than or equal to 60% inhibition, 3 showed no inhibition and 6 were in the range of 20-60% inhibition of Pseudomonas phagocytosis. In parallel studies, the phagocytosis of S. aureus and S. marcescens was found not to be inhibited by CF serum. Mixing of CF serum with normal serum could not overcome the inhibitory effect, indicating the presence of an inhibitory factor rather than the lack of a necessary component. The inhibitory activity is not lost upon exposure of serum to glass, upon freezing the serum once, or upon heating at 56 degrees C for 30 minutes.

Adolescent↗
PubMed1978

Uniparental inheritance of mitochondrial genes in yeast: dependence on input bias of mitochondrial DNA and preliminary investigations of the mechanism.

In Saccharomyces cerevisiae, previous studies on the inheritance of mitochondrial genes controlling antibiotic resistance have shown that some crosses produce a substantial number of uniparental zygotes, which transmit to their diploid progeny mitochondrial alleles from only one parent. In this paper, we show that uniparental zygotes are formed especially when one parent (majority parent) contributes substantially more mitochondrial DNA molecules to the zygote than does the other (minority) parent. Cellular contents of mitochondrial DNA (mtDNA) are increased in these experiments by treatment with cycloheximide, alpha-factor, or the uvsp5 nuclear mutation. In such a biased cross, some zygotes are uniparental for mitochondrial alleles from the majority parent, and the frequency of such zygotes increases with increasing bias. In two- and three-factor crosses the cap1, ery1, and oli1 loci behave coordinately, rather than independently; minority markers tend to be transmitted or lost as a unit, suggesting that the uniparental mechanism acts on entire mtDNA molecules rather than on individual loci. This rules out the possibility that uniparental inheritance can be explained by the conversion of minority markers to the majority alleles during recombination. Exceptions to the coordinate behavior of different loci can be explained by marker rescue via recombination. Uniparental inheritance is largely independent of the position of buds on the zygote. We conclude that it is due to the failure of minority markers to replicate in some zygotes, possibly involving the rapid enzymatic destruction of such markers. We have considered two general classes of mechanisms: (1) random selection of molecules for replication, as for example by competition for replicating sites on a membrane; and (2) differential marking of mtDNA molecules in the two parents, possibly by modification enzymes, followed by a mechanism that "counts" molecules and replicates only the majority type. These classes of models are distinguished genetically by the fact that the first predicts that the output frequency of a given allele among the progeny of a large number of zygotes will approximately equal the average input frequency of that allele, while the second class predicts that any input bias will be amplified in the output. The data suggest that bias amplification does occur. We hypothesize that maternal inheritance of mitochondrial or chloroplast genes in many organisms may depend upon a biased input of organelle DNA molecules, which usually favors the maternal parent, followed by failure of the minority (paternal) molecules to replicate in many or all zygotes.

Alleles↗
PubMedDate not supplied

Pseudomonas aeruginosa isolates: comparisons of isolates from campers and from sibling pairs with cystic fibrosis.

Sputum or deep throat specimen cultures were obtained from 47 cystic fibrosis (CF) patients residing together at an eight-day summer camp. Pre-camp, initial day, final day and post-camp cultures were obtained and Pseudomonas aeruginosa isolates were characterized by morphology, serotype, pigment production, serum sensitivity, antibiotic susceptibility patterns, hemolysis on blood agar, and CO2 growth requirement. Of the 47 patients, four were not chronically colonized with Pseudomonas and did not become colonized at camp. Analysis of the isolates from the other 43 revealed no significant alteration in the Pseudomonas colonization pattern. Cultures obtained from four sibling pairs among the campers and from 20 additional pairs of siblings revealed that siblings in 20/24 pairs had at least one identical serotype in common. Of the criteria used for characterization, serotyping was the most definitive method for strain identification. Serotyping by both the Homma system and the International system did not detect any serotype at a frequency of more than 31%. In this study, the predominant P. aeruginosa strain of the colonized patients did not change, and non-colonized individuals did not become colonized with P. aeruginosa.

Adolescent↗