muramidase and Cystic-Fibrosis

Antimicrobial proteins (AMP) are endogenous, gene-encoded proteins, which are able to kill bacteria, fungi and viruses at micro- and nanomolar concentrations. The constitutive as well as inducible production of AMP provides a rapid first-line of defense against invading microorganisms. The significance of such ancient defense system is reflected by the wide distribution of AMP in the plant and animal kingdom. There is increasing evidence that AMP may play an important role in several infectious and inflammatory diseases such as atopic dermatitis, cystic fibrosis and Crohn's disease. In this review we aim to provide a short overview about the role of antimicrobial proteins in human diseases. In addition, the use and selective induction of AMP for the development of novel potential therapeutic strategies are addressed. The benefits and possible restrictions of AMP utilization as a new class of antibiotic compounds are discussed.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Defensins; Gastrointestinal Diseases; Humans; Infections; Inflammation; Muramidase; Phagocytes; Proteins; Skin Diseases

The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.

Topics: Animals; Antimicrobial Cationic Peptides; Cathelicidins; Cystic Fibrosis; Defensins; Disease Models, Animal; Humans; Lactoferrin; Muramidase; Proteinase Inhibitory Proteins, Secretory; Proteins; Respiratory System; Toll-Like Receptors; Tuberculosis, Pulmonary; Virus Diseases

The hitherto existing results of determinations of enzymatic activities in stool are presented in this review. The chymotrypsin activity is diminished in advanced exocrine pancreatic insufficiency. The faecal alpha-amylase activity has up to now no significance in the diagnosis of pancreatic diseases. Up to five amylolytic enzyme activities are detectable. The alkaline phosphatase is mostly of intestinal origin. Up to 4 enzyme bands can be exhibited with the disc electrophoresis in polyacrylamide gel. Lysozyme and N-Acetyl-beta-D-glycosaminidase can also be detected in stool.

Topics: Alkaline Phosphatase; Amylases; Animals; Chymotrypsin; Colitis, Ulcerative; Cystic Fibrosis; Enzyme Induction; Feces; Hepatitis, Viral, Human; Hexosaminidases; Humans; Intestinal Mucosa; Malabsorption Syndromes; Muramidase; Pancreatic Diseases; Protozoan Infections; Rats; Trypsin

The potential usefulness of analysis of the salivary secretions in diagnosis and prognosis is beginning to be explored in depth. The preliminary work already undertaken indicates that modern methods applied to this secretion may provide information that is different from that obtained in other body fluids. Saliva is collected at the point of its manufacture and, therefore, is unaffected by collection or storage in the body. It is the product both of protein synthesis within the glands and of most of the known water and electrolyte exchange mechanisms. Salivary composition is affected by both autonomic and hormonal stimuli. As the specific influence of each of these factors is better understood, studies of this fluid will provide important clues to the understanding of disease and the evaluation of therapy. There are few places in the body where it is possible directly, utilizing a non-invasive technique, to examine the product of a large number of important biological processes. It is obvious that careful handling of collection and analytic techniques are essential if these secretions are to be utilized. Future investigations in clinical situations should take full advantage of the strong base of knowledge of the physiology of these glands. Development of this field depends on careful clinical investigations designed to make full use of our current knowledge.

Topics: Amylases; Blood Proteins; Cystic Fibrosis; Dental Caries; Digitalis Glycosides; Electrolytes; Glycoproteins; Humans; Hypertension; Immunoglobulin A, Secretory; Mouth Diseases; Muramidase; Parotid Gland; Physical Stimulation; Saliva; Salivary Gland Diseases; Salivary Proteins and Peptides; Secretory Rate; Specimen Handling; Submandibular Gland

Topics: Alcoholism; Aminopeptidases; Amylases; Aspartate Aminotransferases; Cholinesterases; Creatine Kinase; Cystic Fibrosis; Enzyme Activation; Enzymes; Female; gamma-Glutamyltransferase; Half-Life; Humans; Isoenzymes; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Muramidase; Myocardial Infarction; Pepsinogens; Phenobarbital; Porphyrias; Pregnancy

In the current scenario of high antibiotic resistance, the search for therapeutic options against Pseudomonas aeruginosa must be approached from different perspectives: cell-wall biology as source of bacterial weak points and our immune system as source of weapons. Our recent study suggests that once the permeability barrier has been overcome, the activity of our cell-wall-targeting immune proteins is notably enhanced, more in mutants with impaired peptidoglycan recycling. The present work aims at analyzing the activity of these proteins [lysozyme and Peptidoglycan-Recognition-Proteins (PGLYRPs)], alone or with a permeabilizer (subinhibitory colistin) in clinical strains, along with other features related to the cell-wall. We compared the most relevant and complementary scenarios: acute (bacteremia) and chronic infections [early/late isolates from lungs of cystic fibrosis (CF) patients]. Although a low activity of lysozyme/PGLYRPs per se (except punctual highly susceptible strains) was found, the colistin addition significantly increased their activity regardless of the strains' colistin resistance levels. Our results show increased susceptibility in late CF isolates, suggesting that CF adaptation renders P. aeruginosa more vulnerable to proteins targeting the cell-wall. Thus, our work suggests that attacking some P. aeruginosa cell-wall biology-related elements to increase the activity of our innate weapons could be a promising therapeutic strategy.

Topics: Bacteremia; beta-Defensins; Cell Wall; Cystic Fibrosis; Cytokines; Humans; Immunity, Innate; Muramidase; Pseudomonas aeruginosa

Finding the conditions for destabilizing actin-lysozyme complexes is of biomedical importance in preventing infections in cystic fibrosis. In this manuscript, the effects of different charge-mutants of lysozyme and salt concentration on the stability of actin-lysozyme complexes are studied using Langevin dynamics simulation. A coarse-grained model of F-actin is used in which both its twist and bending rigidities are considered. We observe that the attraction between F-actins is stronger in the presence of wild-type lysozymes relative to the mutated lysozymes of lower charges. By calculating the potential of mean force between F-actins, we conclude that the stability of actin-lysozyme complexes is decreased by reducing the charge of lysozyme mutants. The distributions of different lysozyme charge-mutants show that wild-type (+9e) lysozymes are mostly accumulated in the center of triangles formed by three adjacent F-actins, while lysozyme mutants of charges +7e and +5e occupy the bridging regions between F-actins. Low-charge mutants of lysozyme (+3e) distribute uniformly around F-actins. A rough estimate of the electrostatic energy for these different distributions proves that the distribution in which lysozymes reside in the center of triangles leads to more stable complexes. Also our results in the presence of a salt suggest that at physiological salt concentration of airway, F-actin complexes are not formed by charge-reduced mutants of lysozyme. The findings are interesting because if we can design charge-reduced lysozyme mutants with considerable antibacterial activity, they are not sequestered inside F-actin aggregates and can play their role as antibacterial agents against airway infection.

Topics: Actins; Cystic Fibrosis; Humans; Models, Chemical; Muramidase; Static Electricity

Malfunction of airway submucosal glands contributes to the pathology of cystic fibrosis (CF), and cell cultures of CF human airway glands show defects in Cl(-) and water transport. Recently, a transgenic pig model of CF (the CF pig) has been developed. Accordingly, we have developed cell cultures of pig airway gland epithelium for use in investigating alterations in gland function in CF. Our cultures form tight junctions (as evidenced by high transepithelial electrical resistance) and show high levels of active anion secretion (measured as amiloride-insensitive short-circuit current). In agreement with recent results on human airway glands, neurohumoral agents that elevate intracellular Ca(2+) potently stimulated anion secretion, while elevation of cAMP was comparatively ineffective. Our cultures express lactoferrin and lysozyme (serous gland cell markers) and MUC5B (the main mucin of airway glands). They are, therefore, potentially useful in determining if CF-related alterations in anion transport result in altered secretion of serous cell antimicrobial agents or mucus.

Topics: Amiloride; Animals; Biomarkers; Calcium; Cells, Cultured; Chlorides; Cyclic AMP; Cystic Fibrosis; Diffusion Chambers, Culture; Disease Models, Animal; Electric Impedance; Epithelial Cells; Exocrine Glands; Humans; Ion Transport; Lactoferrin; Methacholine Chloride; Mucin-5B; Muramidase; Swine; Tight Junctions; Trachea

The activity of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) can be mediated by surface G protein-coupled receptors such as the beta(2)-adrenergic receptor. In this study, we explored the effect of a long-acting beta(2)-adrenergic agonist, salmeterol, on the CFTR-dependent secretory capacity of a human CF tracheal gland serous cell line (CF-KM4), homozygous for the delF508 mutation. We showed that, compared with the untreated CF serous cells, a 24-hour pre-incubation period with 200 nM salmeterol induced an 83% increase in delF508-CFTR-mediated chloride efflux. The restoration of the bioelectric properties is associated with increased apical surface pool of delF508-CFTR. Salmeterol induced a decrease in ion concentration and an increase in the level of hydration of the mucus packaged inside the CF secretory granules. The effects of salmeterol are not associated with a persistent production of cAMP. Western blotting on isolated secretory granules demonstrated immunoreactivity for CFTR and lysozyme. In parallel, we measured by atomic force microscopy an increased size of secretory granules isolated from CF serous cells compared with non-CF serous cells (MM39 cell line) and showed that salmeterol was able to restore a CF cell granule size similar to that of non-CF cells. To demonstrate that the salmeterol effect was a CFTR-dependent mechanism, we showed that the incubation of salmeterol-treated CF serous cells with CFTR-inh172 suppressed the restoration of normal secretory functions. The capacity of salmeterol to restore the secretory capacity of glandular serous cells suggests that it could also improve the airway mucociliary clearance in patients with CF.

Topics: Albuterol; Cell Line; Cell Polarity; Chlorides; Colforsin; Cyclic AMP; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Electrophysiological Phenomena; Epithelial Cells; Exocytosis; Humans; Intracellular Space; Ions; Muramidase; Salmeterol Xinafoate; Secretory Vesicles; Serous Membrane; Trachea

Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF-related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein-specific levels and airway inflammation and infection.

Topics: Adolescent; Adult; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Cystic Fibrosis; Female; Humans; Immunity, Innate; Infant; Lactoferrin; Leukocyte Count; Leukocyte Elastase; Male; Muramidase; Respiratory Tract Infections; Secretory Leukocyte Peptidase Inhibitor; Young Adult

Nasal polyps frequently appear in patients with cystic fibrosis (CF). The aims of this study were to focus on what problems (symptoms, endoscopic findings, and laboratory correlates) nasal polyps cause the CF patient, and how these correlate to the total health situation of this patient group.. The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype.. The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found.. There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.

Topics: Adolescent; Adult; Antibodies, Bacterial; Child; Child, Preschool; Cystic Fibrosis; Endoscopy; Female; Humans; Interleukin-5; Interleukin-8; Male; Muramidase; Nasal Lavage Fluid; Nasal Polyps; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Risk Factors; Staphylococcal Infections

Antibacterial defenses in the airway are dependent on multifactorial influences that determine the composition of both fluid and/or electrolytes at the surface of the airway and the secretory products that aid in bacterial killing and clearance. In cystic fibrosis (CF), these mechanisms of airway protection may be defective, leading to increased colonization with Pseudomonas aeruginosa. Submucosal glands, a predominant site of cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in the airway, have been hypothesized to play an important role in protection of the airway. Furthermore, recent studies have suggested that the salt concentration at the airway surface may be a key factor in regulating the activity of antibacterial substances in the airway. To explore these issues, we have used a new model of the ferret tracheal airway to evaluate the contribution of submucosal glands in regulating airway surface fluid and electrolyte composition. Using tracheal xenograft models with and without submucosal glands, we have characterized several aspects of airway physiology that may be important in defining antibacterial properties. These endpoints included the contribution of submucosal glands in defining bioelectric properties of the surface airway epithelium, airway surface fluid (ASF) chloride composition, ASF volumes, and secretion of the antibacterial factor lysozyme. Findings from these studies demonstrate a significantly elevated secreted fluid volume (Vs) and chloride concentration ([Cl](s)) in ASF from airways with submucosal glands (Vs = 47 +/- 4 microl; [Cl](s) = 128 +/- 5 mM), as compared with xenograft airways without glands (Vs = 36 +/- 2 microl; [Cl](s) = 103 +/- 6 mM). Furthermore, a temperature labile factor secreted by submucosal glands appears to alter the baseline activation of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and/or diphenylamine-2-carboxylic acid-sensitive chloride channels in the surface airway epithelium. Lastly, the lysozyme content of tracheal airways with submucosal glands was 8.5-fold higher than were airways without glands. These studies demonstrate that submucosal glands affect both the ionic composition and bioelectric properties of the airway and suggest that models evaluating antibacterial properties of the airway in CF should take into account the contribution of glands in airway physiology.

Topics: Animals; Biological Transport; Chlorides; Cystic Fibrosis; Electrolytes; Epithelial Sodium Channels; Epithelium; Ferrets; Muramidase; Sodium Channels; Submucous Plexus; Trachea; Transplantation, Heterologous

Lysozyme is secreted in large quantities in human airways (10-20 mg/day), where it helps to defend against bacterial and fungal infection. Lysozyme expression is restricted to the serous cells of the submucosal glands, which also express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. It is often assumed that mucus secretion in human airways is coupled to anion secretion through CFTR Cl(-) channels located in the apical membrane. Therefore, a defect in CFTR function could cause abnormal mucus secretion leading to persistent bacterial infection and inflammation of the airways. In this study we measured simultaneous secretion of lysozyme and Cl(-) from human airway epithelial serous cells. Secretion of lysozyme was measured by a turbidimetric assay that relies on the ability of lysozyme to disrupt the wall of the bacterium Micrococcus lysodeikticus, thus causing a fall in the optical density of the sample. Secretion of Cl(-) was measured as short-circuit current in a modified Ussing chamber. Activation of Cl(-) secretion by stimulation of cAMP- or Ca(2+)-dependent pathways caused comparable increases in lysozyme secretion. Similarly, blockers of Cl(-) secretion, such as diphenylamine-2-carboxylate (DPC), also reduced lysozyme secretion. However, while treatment of airway submucosal gland cells with antisense oligonucleotides directed against CFTR reduced Cl(-) secretion, it had no significant effect on the total amount of lysozyme secretion. These results suggest a role for functional CFTR in regulation of lysozyme secretion in human airways.

Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Biological Transport; Cell Line; Chlorides; Colforsin; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Enzyme Inhibitors; Humans; Muramidase; Nitric Oxide Donors; Oligonucleotides, Antisense; Respiratory Mucosa; S-Nitrosoglutathione; Thapsigargin

Previous studies have implicated the novel peptide antibiotic human beta-defensin 1 (hBD-1) in the pathogenesis of cystic fibrosis. We describe in this report the isolation and characterization of the second member of this defensin family, human beta-defensin 2 (hBD-2). A cDNA for hBD-2 was identified by homology to hBD-1. hBD-2 is expressed diffusely throughout epithelia of many organs, including the lung, where it is found in the surface epithelia and serous cells of the submucosal glands. A specific antibody made of recombinant peptide detected hBD-2 in airway surface fluid of human lung. The fully processed peptide has broad antibacterial activity against many organisms, which is salt sensitive and synergistic with lysozyme and lactoferrin. These data suggest the existence of a family of beta-defensin molecules on mucosal surfaces that in the aggregate contributes to normal host defense.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Anti-Infective Agents; beta-Defensins; Blood Proteins; Bronchoalveolar Lavage; Cloning, Molecular; Cystic Fibrosis; Defensins; Humans; In Situ Hybridization, Fluorescence; Lactoferrin; Lung; Molecular Sequence Data; Muramidase; Peptide Fragments; Proteins; Recombinant Proteins; RNA, Messenger; Salts; Sequence Analysis, DNA

There is little information about specific changes in submucosal gland exocytosis in diseases such as allergic rhinitis (AR), nonallergic rhinitis (NAR), and cystic fibrosis (CF). Nasal lavage fluids were collected from normal, AR, NAR, and CF subjects. Concentrations of lysozyme, Alcian blue-staining mucoglycoconjugate material (AB + m), and human high-molecular-weight mucoglycoconjugates recognized by the 7F10 murine monoclonal antibody [7F10-immunoreactive mucoglycoconjugates (7F10-irm)] were measured. AB + m and 7F10-irm were characterized by Sepharose-2B column chromatography and glycosidase digestion. 7F10-irm was increased in CF (2.4-fold; P = 0.001) and AR (12.7-fold; P = 0.00007) subjects. AB + m was increased in CF (1.8-fold; P = 0.049) and AR (1.2-fold; P = 0.07) subjects. There were no changes in NAR subjects. On Sepharose-2B columns, AB + m peaks were at 1.3-3.0 x 10(6) and 0.36-0.65 x 10(6) Da. 7F10-irm showed four distinct peaks at 1.5, 1.2, 0.85, and 0.53 x 10(6) Da that were nearly identical in both normal and CF samples. Sialic acid was present in both 7F10-irm and AB + m. 7F10-irm and AB + m are mutually exclusive sialylated mucoglycoproteins that are significantly induced in AR and CF but not in NAR.

Topics: Animals; Antibodies, Monoclonal; Cattle; Chromatography, Ion Exchange; Cystic Fibrosis; Enzyme-Linked Immunosorbent Assay; Fibromyalgia; Glycoconjugates; Glycoside Hydrolases; Humans; Mucins; Mucoproteins; Muramidase; Nasal Mucosa; Neuraminidase; Rhinitis; Sinusitis; Submandibular Gland; Therapeutic Irrigation

Cellular mechanisms regulating airway secretion, secretory products of individual airway cell types, and control of airway cell growth and differentiation are poorly understood. In order to aid studies of these questions, we have established a system for culturing human tracheobronchial submucosal gland cells. Gland acini were isolated by enzymatic disaggregation from submucosal tissue obtained postmortem from patients without pulmonary diseases and from patients with cystic fibrosis. In culture, acini attached to a collagen substratum, and gland cells proliferated and formed confluent monolayers which were homogeneous by phase microscopy. In contrast to cells of freshly disaggregated acini which expressed either serous or mucous gland cell secretory antigens, in culture virtually all cells (greater than or equal to 95%) concurrently expressed both antigens as assessed by immunocytochemical staining with serous and mucous cell-specific antibodies. Similarly, electron microscopy revealed cells with serous- or mucous-type secretory granules, and cells containing both types of granules. Cultures incorporated 35S into high (greater than 10(6) D) and lower (greater than 700 kD; 150 kD) molecular weight molecules. Cholinergic and adrenergic agonists increased release of radio-labeled secretions. These findings demonstrate that human tracheal gland cells in culture retain immunocytochemical, ultrastructural, and functional features of both differentiated serous and mucous gland cells. This culture system will be useful for studying the biology and pathology of human tracheobronchial submucosal gland cells.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bronchi; Cell Differentiation; Cells, Cultured; Child; Child, Preschool; Cystic Fibrosis; Exocrine Glands; Female; Glycoconjugates; Humans; Infant; Infant, Newborn; Lactoferrin; Male; Microscopy, Electron; Middle Aged; Muramidase; Trachea

Seventeen patients with cystic fibrosis and 17 age-, race-, and sex-matched controls were examined under standardized conditions. Testing included slit-lamp biomicroscopy, fluorescein staining, rose bengal staining, Schirmer's basic tear test, tear film break-up time, tear pH, tear lysozyme, tear protein, lid and conjunctival cultures, and conjunctival impression cytology. Cystic fibrosis patients showed a statistically significant increase in the incidence of fluorescein staining and clinical blepharitis, as well as significantly decreased Schirmer testing and tear lysozyme. Ocular surface abnormalities in these patients may be attributable to aqueous and lipid tear film deficiencies. Cystic fibrosis patients showed normal conjunctival epithelial cell morphology, grew no pathogenic organisms, and had a decreased incidence of conjunctival bacterial colonization.

Topics: Adolescent; Adult; Blepharitis; Child; Conjunctiva; Cystic Fibrosis; Data Interpretation, Statistical; Eye; Female; Fluorescent Dyes; Humans; Hydrogen-Ion Concentration; Male; Muramidase; Tears

Topics: Adolescent; Bronchi; Child; Child, Preschool; Cystic Fibrosis; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Muramidase; Respiratory Tract Infections; Saliva

In adults, the inability to secrete ABH blood group substances in water-soluble form has been recognized as an independent risk factor for the development of chronic obstructive lung disease. We studied 50 patients (mean age 12.1 years) with cystic fibrosis and identified 33 ABH secretors and 17 non-secretors. There was no correlation between secretor status and clinical status, spirometry measurements, salivary and serum lysozyme levels or rates of respiratory tract colonization with P. aeruginosa and S. aureus.

Topics: ABO Blood-Group System; Adolescent; Child; Cystic Fibrosis; Follow-Up Studies; Humans; Muramidase; Salivary Glands

Topics: Animals; Cystic Fibrosis; Fatty Acids, Essential; Lung; Macrophages; Microscopy, Electron; Muramidase; Pseudomonas Infections; Pulmonary Alveoli; Rabbits; Respiratory Tract Infections; Staphylococcal Infections

The activity of lysozyme in saliva and serum was determined in 51 patients with cystic fibrosis. Measurements were made on two occasions at least 1 month apart and compared to those of 25 normal healthy individuals of the same ages, sex, and race. The mean serum lysozyme activity of normal individuals was 5.8 micrograms/ml (S.E. = 0.4), whereas that of cystic fibrosis patients was 10.8 micrograms/ml (S.E. = 0.5). The difference is significant (P less than 0.05). Initial mean values compared to those of repeated samples from the cystic fibrosis group were similar, whereas individual fluctuations occurred between test periods. The mean lysozyme activity of the saliva sample of normal individuals was 63.5 micrograms/ml (S.E. = 9.3) and the mean value from cystic fibrosis patients was 82.7 (S.E. = 6.9). This difference was not significant (P greater than 0.1). Mean values from specimens obtained a month or longer after the initial saliva samples were similar for the two episodes. There was no correlation between the serum and salivary values and the age, sex or race of the subjects, the Shwachman-Kulczycki scores, colonization with Pseudomonas aeruginosa, Staphylococcus aureus or Haemophilus influenzae or absolute white blood cell counts. In vitro studies failed to demonstrate bactericidal activity for mucoid and nonmucoid strains of P. aeruginosa or for S. aureus. Elevated lysozyme activity in cystic fibrosis may be related to either an increased granulocyte turnover because of chronic bacterial infection of the respiratory tract or to a basic defect in the lysosomal membrane allowing an increased release of the enzyme, or a combination of both.

Topics: Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Male; Muramidase; Saliva

We prospectively evaluated concentrations of beta-D-galactosidase, alpha-L-fucosidase, beta-D-N-acetylglucosaminidase, and lysozyme in urine from normal subjects, ambulatory patients with cystic fibrosis (CF), and CF patients with previously normal renal function who were receiving intravenous aminoglycoside (AG) therapy. Enzyme activities were generally low or negligible in subjects not receiving AG. Enzymuria was documented during 12 of 13 AG treatment courses and most frequently involved beta-D-N-acetylglucosaminidase excretion. In nine courses, enzymuria occurred in the absence of proteinuria or elevations of blood urea nitrogen and serum creatinine. In three courses attended by enzymuria and evidence of nephrotoxicity, neither the time of appearance nor the magnitude of enzymuria was different from that of nonnephrotoxic patients. In two of these three treatment courses, enzymuria preceded clinical evidence of nephrotoxicity of 16 and 5 days, and in the third course enzymuria and elevation of blood urea nitrogen and serum creatinine occurred simultaneously. We conclude that enzymuria is not a reliable predictor of nephrotoxicity due to AG in CF patients and is not an indication of discontinue AG therapy.

Topics: Acetylglucosaminidase; Adolescent; Adult; alpha-L-Fucosidase; Aminoglycosides; beta-Galactosidase; Child; Child, Preschool; Cystic Fibrosis; Female; Gentamicins; Glycoside Hydrolases; Humans; Kidney; Lung Diseases; Male; Middle Aged; Muramidase; Pseudomonas Infections; Tobramycin

Bronchial secretions from 207 children suffering from various pulmonary diseases and from 15 healthy controls were tested concentration of IgA, IgG, lactoferrin and lysozyme. The results obtained suggest that in many cases of chronic lung diseases in children the levels of lactoferrin and immunoglobulins, especially secretory IgA, are very low. In severe infections (cystic fibrosis, bronchiectases) significant increase of IgG concentration was observed.

Topics: Adolescent; Bronchi; Bronchiectasis; Bronchitis; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Lactoglobulins; Muramidase; Recurrence; Respiratory Tract Diseases; Respiratory Tract Infections

The concentration of immunoglobulins, lactoferrin and lysozyme we compared in bronchial secretions obtained from children with various chronic lung diseases. The IgG, lactoferrin and lysozyme, but not secretory IgA, concentrations were shown to be increased during chronic inflammatory response.

Topics: Adolescent; Bronchi; Bronchiectasis; Bronchitis; Bronchography; Bronchoscopy; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Lactoglobulins; Muramidase; Respiratory Tract Diseases

The concentrations of nine plasma proteins were determined by quantitative immunoelectrophoresis in sputum specimens from 29 patients with cystic fibrosis (CF) and from 24 patients with severe asthma and chronic bronchitis. The results suggested that the population of CF patients could be divided into two groups in spite of an absence of difference in clinical status between the groups. Average concentrations of seven plasma proteins in sputum of group I CF patients were identical with those in sputum of patients with bronchitis, but the average concentrations of six of these proteins in sputum from group II CF patients were higher than those in specimens from the bronchitic patients and were similar to corresponding concentrations in sputum from patients with asthma, all of whom were examined while in status asthmaticus. The average concentrations of 14 secretory proteins were the same in all sputum specimens whether or not they were produced by patients with cystic fibrosis, asthma or bronchitis. It was concluded that the concentrations in the bronchopulmonary secretions of proteins associated with host defence were not diminished in patients with cystic fibrosis, and failure to produce adequate concentrations of proteins with antimicrobial activity was unlikely to be responsible for the above average susceptibility to chest infection in cystic fibrosis. It is suggested that there exists a group of CF patients in whom a pulmonary allergic reaction generates an inflammatory response as severe as that characterizing status asthmaticus and that this response could be detrimental.

Topics: Adult; Aged; Albumins; Asthma; Beta-Globulins; Blood Proteins; Bronchitis; Child; Child, Preschool; Cystic Fibrosis; Female; Glycoproteins; Haptoglobins; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Lactoferrin; Male; Middle Aged; Muramidase; Sputum; Transferrin

Topics: Bradykinin; Bronchi; Bronchial Spasm; Bronchitis; Chromatography; Cystic Fibrosis; Expectorants; Globulins; Glycoproteins; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Infections; Mucins; Muramidase; Saliva; Sputum

Topics: Albumins; Bronchi; Cystic Fibrosis; Humans; Immunoglobulins; Mucus; Muramidase; Sputum

Topics: Agammaglobulinemia; Asthma; Bronchitis; Chronic Disease; Cystic Fibrosis; Humans; Marfan Syndrome; Muramidase

Topics: Adolescent; Ammonia; Amylases; Calcium; Carbohydrates; Child; Chlorides; Cystic Fibrosis; Electrophoresis; Female; Humans; Male; Muramidase; Phosphorus; Potassium; Proteins; Saliva; Sodium; Submandibular Gland; Urea; Uric Acid

Topics: Amylases; Carboxypeptidases; Chymotrypsin; Cystic Fibrosis; Deoxyribonuclease I; Deoxyribonucleases; DNA; Endopeptidases; Humans; Hyaluronoglucosaminidase; In Vitro Techniques; Muramidase; Pancreas; Papain; Ribonucleases; Solubility; Sputum; Streptodornase and Streptokinase; Streptokinase; Trypsin

Topics: Cystic Fibrosis; Humans; Muramidase; Pancreas