muramidase and Crohn-Disease

The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory.

Topics: Barrett Esophagus; Celiac Disease; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Ulcerative; Crohn Disease; Gastritis; Gastrointestinal Diseases; Humans; Inflammation; Muramidase

Paneth cells are secretory intestinal epithelial cells located at the base of the crypts of Lieberkühn in the small intestine. They display prominent cytoplasmic granules, containing antibacterial proteins such as lysozyme, secretory phospholipase A2 type IIA, and alpha-defensins, which are released into the intestinal lumen in response to a range of stimuli. In this, they resemble circulating leukocytes, which also elaborate and secrete lysozyme and alpha-defensins as part of an antibacterial defense function, and the resemblance is sustained at other levels. The cells also strongly and specifically express the NOD2 gene product, one of an emerging family of critical, intracellular mediators of innate immune responses, which is also highly expressed in peripheral blood mononuclear cells, and they express RNA for tumor necrosis factor alpha, a major myelomonocytic cell-derived cytokine, which has a crucial role in the pathogenesis of diseases such as rheumatoid arthritis and Crohn's disease (CD). Thus, these cells, which are derived from the pluripotent intestinal epithelial stem-cell lineage, are sessile, resident host-defense cells, which may share with leukocytes the beneficial function of secreting antimicrobial peptides, as well as the potentially harmful capacity for promoting inflammation and tissue damage. Paneth cells are most abundant in the distal small intestine, which is the region most frequently affected by CD, and there is great interest in the potential role of these cells in this condition. This brief review summarizes current knowledge and speculates on how the study of these fascinating cells might be advanced.

Topics: alpha-Defensins; Animals; Cell Differentiation; Crohn Disease; Humans; Immunity, Innate; Intestines; Leukocytes; Muramidase; Nod2 Signaling Adaptor Protein; Paneth Cells

Topics: alpha 1-Antitrypsin; Arachidonic Acid; Arachidonic Acids; Crohn Disease; Feces; Humans; Leukocyte Count; Muramidase

Topics: Bacteria; Burns; Cell Wall; Colitis, Ulcerative; Crohn Disease; DNA, Bacterial; Humans; Inflammation; Leukemia; Muramidase; RNA, Bacterial

Serum lysozyme levels were determined in healthy volunteers, patients with Crohn's disease, and patients with ulcerative colitis. The mean concentration in Crohn's disease was significantly greater than in the other groups. In patients with Crohn's disease, as well as in patients with ulcerative colitis, the lysozyme levels correlated with the severity of the disease process and with the extent of the lesions: the more severe the disease and the more extensive the involvement, the higher the lysozyme levels. However, the lysozyme values of the different groups overlapped considerably. Our results indicate that lysozyme determinations have only limited discriminative value for the diagnosis of Crohn's disease and for determining the severity and the extent of the disease process in the individual patient.

Topics: Adolescent; Adult; Aged; Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Female; Humans; Male; Middle Aged; Muramidase

We have developed a new simple solid-phase luminescence immunoassay (LIA) for the determination of faecal lysozyme. The assay utilises a polyclonal capture antibody coated to polystyrene beads and acridinium ester-labelled human lysozyme as tracer. Samples are incubated with polystyrene beads and tracer overnight at 4 degrees C. After a thorough washing step, emitted light is measured by an automated luminometer for 2 seconds. The standard curve uses five standards ranging from 0.025 to 6.4 mg/l. The method has a sensitivity of 0.02 mg/l. Dilution recoveries for three samples were 88, 104 and 108%. Intraassay coefficients of variation (CV, n = 24) were 10.1% and 11.7% for a healthy control and a patient sample; interassay CV (n = 16) were 6.7% and 13.1% for the same healthy control but another patient sample. The normal range of faecal lysozyme in 80 healthy controls was found to be 0.02-1 mg/l (97.5 percentile) with a median of 0.28 mg/l. Fifty-three patients with Crohn's disease had faecal lysozyme values ranging from 0.16 to 100.7 mg/l with a median of 1.75 mg/l, and 30 patients with ulcerative colitis showed levels between 0.09 and 118 mg/l with a median of 1.11 mg/l. The assay has proved useful for differentiating healthy individuals from those with inflammatory bowel disease and might be a valuable tool for diagnosing or evaluating inflammatory bowel disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Feces; Female; Humans; Immunoglobulin G; Indicators and Reagents; Isotope Labeling; Luminescent Measurements; Male; Middle Aged; Muramidase; Radioimmunoassay; Reference Values

Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin; Clinical Trials as Topic; Crohn Disease; Defecation; Female; Humans; Ileum; Leukocytes; Male; Metabolic Clearance Rate; Middle Aged; Muramidase; Radiography; Radioisotopes; Radionuclide Imaging; Selenium; Sulfasalazine; Taurocholic Acid

IL-18 is emerging as an IL-22-induced and epithelium-derived cytokine which contributes to host defence against intestinal infection and inflammation. In contrast to its known role in Goblet cells, regulation of barrier function at the molecular level by IL-18 is much less explored. Here we show that IL-18 is a bona fide IL-22-regulated gate keeper for intestinal epithelial barrier. IL-22 promotes crypt immunity both via induction of phospho-Stat3 binding to the Il-18 gene promoter and via Il-18 independent mechanisms. In organoid culture, while IL-22 primarily increases organoid size and inhibits expression of stem cell genes, IL-18 preferentially promotes organoid budding and induces signature genes of Lgr5

Topics: Animals; Crohn Disease; Dysbiosis; Escherichia coli; Escherichia coli Infections; Immunity, Mucosal; Interferon-gamma; Interleukin-18; Interleukin-22; Interleukins; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Mice, Knockout; Muramidase; Organoids; Paneth Cells; Promoter Regions, Genetic; STAT3 Transcription Factor; Tight Junctions

Significant progress has been made since the first report of inflammatory bowel disease (IBD) in 1859, after decades of research that have contributed to the understanding of the genetic and environmental factors involved in IBD pathogenesis. Today, a range of treatments is available for directed therapy, mostly targeting the overactive immune response. However, the mechanisms by which the immune system contributes to disease pathogenesis and progression are not fully understood. One challenge hindering IBD research is the heterogeneous nature of the disease and the lack of understanding of how immune cells interact with one another in the gut mucosa. Introduction of a technology that enables expansive characterization of the inflammatory environment of human IBD tissues may address this gap in knowledge.. We used the imaging mass cytometry platform to perform highly multiplex image analysis of IBD and healthy deidentified intestine sections (6 Crohn's disease compared to 6 control ileum; 6 ulcerative colitis compared to 6 control colon). The acquired images were graded for inflammation severity by analysis of adjacent H&E tissue sections. We assigned more than 300,000 cells to unique cell types and performed analyses of tissue integrity, epithelial activity, and immune cell composition.. The intestinal epithelia of patients with IBD exhibited increased proliferation rates and expression of HLA-DR compared to control tissues, and both features were positively correlated with the severity of inflammation. The neighborhood analysis determined enrichment of regulatory T cell interactions with CD68. Altogether, our study shows the power of imaging mass cytometry and its ability to both quantify immune cell types and characterize their spatial interactions within the inflammatory environment by a single analysis platform.

Topics: Adolescent; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Case-Control Studies; CD8-Positive T-Lymphocytes; Cell Communication; Cell Proliferation; Cellular Microenvironment; Child; Colitis, Ulcerative; Colon; Crohn Disease; Epithelial Cells; Female; HLA-DR Antigens; Humans; Image Processing, Computer-Assisted; Intestinal Mucosa; Macrophages; Male; Microscopy, Confocal; Muramidase; Proteome; Proteomics; Severity of Illness Index; T-Lymphocytes, Regulatory

Vitamin D exerts a regulatory role over mucosal immunity via the vitamin D receptor (VDR). Although Paneth cells and their products are known to regulate the commensal and pathogenic microbiota, the role that VDRs in Paneth cells play in these responses is unknown.. We identified the decreased intestinal VDR significantly correlated with reduction of an inflammatory bowel disease risk gene ATG16L1 and Paneth cell lysozymes in patients with Crohn's disease. We generated Paneth cell-specific VDR knockout (VDR. Lysozymes in the Paneth cells were significantly decreased in the VDR. We provide new insights into the tissue-specific functions of VDRs in maintaining Paneth cell alertness to pathogens in intestinal disorders. Targeting the VDR affects multiple downstream events within Paneth cells that inhibit intestinal inflammation and establish host defense against enteropathogens.

Topics: Animals; Autophagy; Autophagy-Related Proteins; Biopsy; Colon; Crohn Disease; Dextran Sulfate; Disease Models, Animal; Female; Humans; Ileum; Immunity, Mucosal; Male; Mice; Mice, Knockout; Microbiota; Muramidase; Paneth Cells; Receptors, Calcitriol; Vitamin D

Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Paneth cells are normally present in human cecum and ascending colon, but are rarely found in descending colon and rectum; Paneth cell metaplasia in this region and aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. Here, we examined the impact of aberrant lysozyme production in colonic inflammation. Targeted disruption of Paneth cell lysozyme (Lyz1) protected mice from experimental colitis. Lyz1-deficiency diminished intestinal immune responses to bacterial molecular patterns and resulted in the expansion of lysozyme-sensitive mucolytic bacteria, including Ruminococcus gnavus, a Crohn's disease-associated pathobiont. Ectopic lysozyme production in colonic epithelium suppressed lysozyme-sensitive bacteria and exacerbated colitis. Transfer of R. gnavus into Lyz1

Topics: Animals; Clostridiales; Colitis, Ulcerative; Crohn Disease; Female; Gastrointestinal Microbiome; Goblet Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Muramidase; Paneth Cells; STAT6 Transcription Factor

Secretion of antimicrobial proteins is an important host defense mechanism against bacteria, yet how secretory cells maintain function during bacterial invasion has been unclear. We discovered that Paneth cells, specialized secretory cells in the small intestine, react to bacterial invasion by rerouting a critical secreted antibacterial protein through a macroautophagy/autophagy-based secretion system termed secretory autophagy. Mice harboring a mutation in an essential autophagy gene, a mutation which is common in Crohn disease patients, cannot reroute their antimicrobial cargo during bacterial invasion and thus have compromised innate immunity. We showed that this alternative secretion system is triggered by both a cell-intrinsic mechanism, involving the ER stress response, and a cell-extrinsic mechanism, involving subepithelial innate immune cells. Our findings uncover a new role for secretory autophagy in host defense and suggest how a mutation in an autophagy gene can predispose individuals to Crohn disease.

Topics: Autophagy; Autophagy-Related Proteins; Biological Transport; Carrier Proteins; Crohn Disease; Endoplasmic Reticulum Stress; Intestine, Small; Muramidase; Mutation; Paneth Cells

Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2. Thus, we delineated a genetic pathway, consisting of Nod2-LRRK2-Rip2-Rab2a, which is required for lysozyme sorting. Taken together, our results indicate that the lysozyme-sorting process in Paneth cells is orchestrated by a number of host factors and highlight the importance of Paneth cell function in intestinal homeostasis.

Topics: Animals; Cells, Cultured; Crohn Disease; Homeostasis; Humans; Intestines; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mice; Mice, Inbred C57BL; Mice, Knockout; Muramidase; NF-kappa B; Nod2 Signaling Adaptor Protein; Paneth Cells; Protein Transport; rab GTP-Binding Proteins; Receptor-Interacting Protein Serine-Threonine Kinase 2; Receptor-Interacting Protein Serine-Threonine Kinases; Secretory Vesicles

Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial proteins, including lysozyme. However, invasive pathogens can disrupt the Golgi apparatus, interfering with secretion and compromising intestinal antimicrobial defense. Here we show that during bacterial infection, lysozyme is rerouted via secretory autophagy, an autophagy-based alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum (ER) stress, required extrinsic signals from innate lymphoid cells, and limited bacterial dissemination. Secretory autophagy was disrupted in Paneth cells of mice harboring a mutation in autophagy gene

Topics: Animals; Autophagy; Autophagy-Related Proteins; Carrier Proteins; Crohn Disease; Endoplasmic Reticulum Stress; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; Muramidase; Mutation; Paneth Cells; Salmonella enterica; Salmonella Infections

Impaired Paneth cell expression of antimicrobial protein (AMP) lysozyme is found in patients with Crohn's disease with the autophagy gene ATG16L1 risk allele, in mice with mutations in autophagy genes Atg16L1, Atg5 and Atg7, and in Irgm1 knockout mice. Defective autophagy is also associated with expansion of resident Gram-negative bacteria in the intestinal lumen. These findings suggest that autophagy may control extracellular resident microbes by governing expression of lysozyme. To test the hypothesis that autophagy may have a defensive role in host response to resident extracellular microbes, we investigated the relationship between gut microbes, autophagy, and lysozyme. RAW 264.7 macrophages were treated with fecal slurry (FS), representing the resident microbial community; lipopolysaccharide (LPS); or butyrate, representing microbial products; or a representative resident Gram-negative bacterium Desulfovibrio vulgaris (DSV). FS, LPS, and DSV inhibited lysozyme expression, whereas butyrate had no effect. Induction of autophagy by rapamycin countered this inhibition, whereas silencing of the autophagy gene Irgm1 exacerbated the inhibitory effects of LPS on lysozyme expression. LPS also inhibited lysozyme activity against DSV and autophagy reversed this effect. Our results provide a novel insight into an interaction between gut bacteria, autophagy and AMP whereby autophagy may defend the host by countering the suppression of antimicrobial protein by Gram-negative bacteria.

Topics: Animals; Autophagy; Crohn Disease; Desulfovibrio vulgaris; Desulfovibrionaceae Infections; Feces; Gastrointestinal Microbiome; Gene Expression Regulation; GTP-Binding Proteins; Humans; Lipopolysaccharides; Macrophages; Mice; Mice, Knockout; Muramidase; Paneth Cells; RAW 264.7 Cells; RNA, Small Interfering; Sirolimus

Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.

Topics: alpha-Defensins; Biomarkers; Biopsy; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Gene Expression Profiling; Humans; Immunohistochemistry; Inflammatory Bowel Diseases; Intestinal Mucosa; Muramidase; Proctocolectomy, Restorative; Retrospective Studies

Epithelial cells that cover the intestinal mucosal surface maintain immune homeostasis and tolerance in the gastrointestinal tract. However, little is known about the molecular mechanisms that regulate epithelial immune functions. Epithelial cells are distinct in that they are highly polarized; this polarity is, at least in part, established by the epithelium-specific polarized sorting factor adaptor protein (AP)-1B. We investigated the role of AP-1B-mediated protein sorting in the maintenance of gastrointestinal immune homeostasis.. The role of AP-1B in intestinal immunity was examined in AP-1B-deficient mice (Ap1m2(-/-)) by monitoring their phenotypes, intestinal morphology, and epithelial barrier functions. AP-1B-mediated protein sorting was examined in polarized epithelial cells from AP-1B knockdown and Ap1m2(-/-) mice.. Ap1m2(-/-) mice developed spontaneous chronic colitis, characterized by accumulation of interleukin-17A-producing, T-helper 17 cells. Deficiency of AP-1B caused epithelial immune dysfunction, such as reduced expression of antimicrobial proteins and impaired secretion of immunoglobulin A. These defects promoted intestinal dysbiosis and increased bacterial translocation within the mucosa. Importantly, AP-1B deficiency led to mistargeting of a subset of basolateral cytokine receptors to the apical plasma membrane in a polarized epithelial cell line and in colonic epithelial cells from mice. AP1M2 expression was reduced significantly in colonic epithelium samples from patients with Crohn's disease.. AP-1B is required for proper localization of a subset of cytokine receptors in polarized epithelial cells, which allows them to respond to cytokine signals from underlying lamina propria cells. The AP-1B-mediated protein sorting machinery is required for maintenance of immune homeostasis and prevention of excessive inflammation.

Topics: Acute-Phase Proteins; Adaptor Protein Complex 1; Adaptor Protein Complex beta Subunits; Adaptor Protein Complex mu Subunits; alpha-Defensins; Animals; Antimicrobial Cationic Peptides; beta-Defensins; Cathelicidins; Cell Membrane; Cell Membrane Permeability; Colitis; Colon; Crohn Disease; Down-Regulation; Epithelial Cells; Homeostasis; Humans; Immunoglobulin A; Interleukin-17; Intestinal Mucosa; Lipocalin-2; Lipocalins; Mice; Mice, Knockout; Muramidase; Oncogene Proteins; Proteins; Receptors, Cytokine; Ribonuclease, Pancreatic; Ribonucleases; S100 Proteins; Signal Transduction; Th17 Cells; Tumor Necrosis Factor-alpha

Increased oxidative stress has been previously demonstrated in patients with Crohn's disease (CD). However, to date, this parameter has not been assessed in a comparative study of patients in prolonged remission and those with the active disease. We report here our study of lipid peroxidation, antioxidant and inflammation status in serum derived from 16 active CD patients, 27 clinically stable patients, and 15 healthy controls. Results The extent of lipid peroxidation was higher in CD patients than in the healthy controls, while the levels of lipid peroxides (PD) and of thiobarbituric acid-reactive substances (TBARS) were significantly (P < 0.01) higher in serum obtained from patients with active CD (22 and 30%, respectively) than in that obtained from patients in remission. An analysis of the antioxidant status revealed that the beta-carotene levels in sera derived from all CD patients - patients with active or stable CD (49.4 +/- 15 and 95.6 +/- 25 mg% beta-carotene, respectively) - were higher than that in the controls (145 +/- 40 mg%). Serum activity of glutathione peroxidase (GSH-Px) was significantly (P < 0.001) higher (by 31%) in the patients with active CD than in the control group. There was no significant difference in GSH-Px activity between patients in remission and the controls. In terms of the inflammatory status, we found significantly (P < 0.01) higher levels of C-reactive proteins (CRP) and of tumor necrosis factor alpha (TNFalpha) in patients with active CD than in CD patients in remission. There was a significant correlation between those parameters and the extent of lipid oxidation. Neutrophils, which are a potential source of oxygen-free radicals, were activated by incubation with phorbol myristate acetate (PMA). Superoxide and lysozyme release were significantly reduced in neutrophils derived from patients with active CD (by 25 and 28%, respectively) in comparison to the control group. However, stimulated neutrophils from stable patients demonstrated only a minimally non-significant lower release of superoxide and lysozyme compared to the controls. Conclusion The results obtained in this study demonstrate an enhanced inflammatory and oxidative stress and a decreased antioxidant status in patients with active CD. As the patients improved and became clinically stable, the oxidative parameters decreased, approaching normal values. As neutrophil activation was also lower in patients with active disease, neutrophil activation may represen

Topics: Adult; Antioxidants; beta Carotene; C-Reactive Protein; Case-Control Studies; Crohn Disease; Female; Glutathione Peroxidase; Humans; Inflammation Mediators; Lipid Peroxidation; Lipid Peroxides; Male; Middle Aged; Muramidase; Neutrophil Activation; Neutrophils; Oxidative Stress; Respiratory Burst; Superoxides; Thiobarbituric Acid Reactive Substances; Time Factors; Tumor Necrosis Factor-alpha

Reduced ileal Paneth cell alpha-defensin expression has been reported to be associated with Crohn's disease, especially in patients carrying NOD2 mutations. The aim of this study was to independently assess whether NOD2, alpha-defensins and Crohn's disease are linked.. Using quantitative real-time polymerase chain reaction (RT-PCR), we measured the mRNA expression levels of key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A), inflammatory cytokines [interkelukin 6 (IL6) and IL8], and a marker of epithelial cell content, villin (VIL1) in 106 samples from both affected ileum (inflamed Crohn's disease cases, n = 44) and unaffected ileum (non-inflamed; Crohn's disease cases, n = 51 and controls, n = 11). Anti-human defensin 5 (HD-5) and haematoxylin/eosin immunohistochemical staining was performed on parallel sections from NOD2 wild-type and NOD2 mutant ileal Crohn's disease tissue.. In Crohn's disease patients, DEFA5 and DEFA6 mRNA expression levels were 1.9- and 2.2-fold lower, respectively, in histologically confirmed inflamed ileal mucosa after adjustment for confounders (DEFA5, p<0.001; DEFA6, p = 0.001). In contrast to previous studies, we found no significant association between alpha-defensin expression and NOD2 genotype. HD-5 protein data supports these RNA findings. The reduction in HD-5 protein expression appears due to surface epithelial cell loss and reduced Paneth cell numbers as a consequence of tissue damage.. Reduction in alpha-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal Crohn's disease.

Topics: Adult; Aged; alpha-Defensins; Crohn Disease; Female; Gene Expression; Genotype; Group II Phospholipases A2; Humans; Ileum; Immunoenzyme Techniques; Interleukin-6; Interleukin-8; Male; Middle Aged; Muramidase; Nod2 Signaling Adaptor Protein; Paneth Cells; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: alpha-Defensins; Animals; Crohn Disease; Gene Expression; Humans; Immunity, Innate; Intestine, Small; Mice; Muramidase; Paneth Cells; Salmonella typhimurium

The impact of chronic inflammation on the expression of human alpha-defensins 5 and 6 (HD-5, HD-6), beta-defensins 1 and 2 (hBD-1, hBD-2) and lysozyme in epithelial cells of small and large intestine was investigated. Intestinal specimens from 16 patients with ulcerative colitis (UC), 14 patients with Crohn's disease (CD) and 40 controls with no history of inflammatory bowel disease were studied. mRNA expression levels of the five defence molecules were determined in freshly isolated epithelial cells by real-time quantitative RT-PCR. Specific copy standards were used allowing comparison between the expression levels of the different defensins. HD-5 and lysozyme protein expression was also studied by immunohistochemistry. Colonic epithelial cells from patients with UC displayed a significant increase of hBD-2, HD-5, HD-6 and lysozyme mRNA as compared to epithelial cells in controls. Lysozyme mRNA was expressed at very high average copy numbers followed by HD-5, HD-6, hBD-1 and hBD-2 mRNA. HD-5 and lysozyme protein was demonstrated in metaplastic Paneth-like cells in UC colon. There was no correlation between hBD-2 mRNA levels and HD-5 or HD-6 mRNA levels in colon epithelial cells of UC patients. Colonic epithelial cells of Crohn's colitis patients showed increased mRNA levels of HD-5 and lysozyme mRNA whereas ileal epithelial cells of Crohn's patients with ileo-caecal inflammation did not. Chronic inflammation in colon results in induction of hBD-2 and alpha-defensins and increased lysozyme expression. hBD-1 expression levels in colon remain unchanged in colitis. The high antimicrobial activity of epithelial cells in chronic colitis may be a consequence of changes in the epithelial lining, permitting adherence of both pathogenic bacteria and commensals directly to the epithelial cell surface.

Topics: Adult; Case-Control Studies; Colitis, Ulcerative; Colon; Crohn Disease; Defensins; Epithelial Cells; Female; Humans; Ileum; Immunohistochemistry; In Situ Hybridization; Intestinal Mucosa; Male; Middle Aged; Muramidase; RNA, Messenger

The normal intestinal epithelium is increasingly being recognised as an important component of the mucosal innate protection against microorganisms. Human neutrophil defensins 1-3 (HNP 1-3) and lysozyme are components of the systemic innate immunity. The aim of this study was to investigate the expression of HNP 1-3 and lysozyme in normal and active inflammatory bowel disease (IBD) mucosa.. Mucosal tissue sections were studied by immunohistochemistry using antibodies to neutrophil defensins 1-3 and lysozyme. Extracts of purified intestinal epithelial cells were used for immunoblotting studies and antimicrobial activity against the phoP negative strain of Salmonella typhimurium.. Surface epithelial cells strongly immunoreactive for neutrophil defensins and lysozyme were seen in active ulcerative colitis and Crohn's disease (but not normal or inactive IBD) mucosal samples. Many of these cells coexpressed both of the antimicrobial proteins. Immunoblotting studies confirmed the expression of neutrophil defensins in extracts of purified ulcerative colitis epithelial cells, which also demonstrated antimicrobial activity.. HNP 1-3 and lysozyme are expressed in surface enterocytes of mucosa with active IBD and they may play an important role in intestinal host defence against luminal microorganisms.

Topics: alpha-Defensins; Cell Extracts; Colitis, Ulcerative; Colony Count, Microbial; Crohn Disease; Enterocytes; Epithelial Cells; Humans; Immunoenzyme Techniques; Inflammatory Bowel Diseases; Intestinal Mucosa; Muramidase; Neutrophils; Salmonella typhimurium

Cell wall deficient forms of mycobacteria may be important in the pathogenesis of Crohn's disease and sarcoidosis. However, no method has been available to localize this type of organisms in tissue sections. We developed an in situ hybridization method for the demonstration of Mycobacterium paratuberculosis spheroplasts (cell wall deficient forms) in paraffin embedded tissue sections.M. paratuberculosis spheroplasts were prepared by treatment with glycine and lysozyme. Pieces of beef were injected with the prepared spheroplasts. The samples were fixed in buffered formalin and paraffin embedded. A M. paratuberculosis-specific probe derived from the IS900 gene was used. Specificity was controlled by using an irrelevant probe and by hybridizing sections with spheroplasts from other bacteria. Beef samples injected with M. paratuberculosis spheroplasts were the only samples that hybridized with the probe. Beef samples containing acid-fast or spheroplast forms of M. smegmatis and M. tuberculosis as well as the acid-fast forms of M. paratuberculosis did not hybridize with the probe. Unrelated bacterial controls, i.e. Helicobacter pylori and Escherichia coli were also negative in the assay. In situ hybridization with the IS900 probe provides a specific way to localize M. paratuberculosis spheroplasts in tissue sections and may be useful for studies of the connection between M. paratuberculosis and Crohn's disease and sarcoidosis. The assay may also be valuable for studies on Johne's diseased animals.

Topics: Animals; Cattle; Crohn Disease; Glycine; Humans; In Situ Hybridization; Meat; Muramidase; Mycobacterium avium subsp. paratuberculosis; Sarcoidosis; Spheroplasts

This study was undertaken to determine whether measurement of fecal lysozyme is helpful in determining disease activity in inflammatory bowel disease. In 112 patients with Crohn's disease, 46 patients with ulcerative colitis, and 40 controls, fecal lysozyme concentration was measured. Results were correlated with CDAI and AI in Crohn's disease and with Truelove and Witts' grading in ulcerative colitis. Fecal lysozyme concentration (mean +/- SEM) was significantly (P < 0.001) higher in Crohn's disease (75 +/- 14 microg/g) and ulcerative colitis (238 +/- 33 microg/g) than in controls (6 +/- 1 microg/g). There was only a weak correlation between fecal lysozyme concentration and CDAI (r = 0.32; P = 0.001) and AI (r = 0.38; P < 0.0005) in patients with Crohn's disease and with Truelove and Witts' grading (r = 0.47; P = 0.001) in ulcerative colitis. When CDAI > or = 150 or AI > or = 100 were used as the standard for active disease, fecal lysozyme concentration was elevated in 78% of patients with active colonic Crohn's disease. In ulcerative colitis fecal lysozyme concentration was increased in active disease (95% in grade II and 94% in grade III) as compared 33% in grade I. Measurement of fecal lysozyme is of little help in diagnosing and determining disease activity of inflammatory bowel disease as whole, but it may be of help for diagnosis and assessment of activity of colonic IBD.

Topics: Adult; Case-Control Studies; Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Feces; Female; Humans; Male; Muramidase; Prospective Studies; Sensitivity and Specificity

1) To investigate which neutrophil-derived proteins in feces most accurately reflect disease activity in inflammatory bowel disease. 2) To examine the extracellular release of these proteins by activated neutrophils and their stability in feces by in vitro study.. We studied 41 patients (91 samples) with ulcerative colitis (UC), 34 patients (105 samples) with Crohn's disease (CD), and 25 control subjects. Fecal levels of lactoferrin (Lf), polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase (MPO), and lysozyme (Lys) were measured by ELISA. We also measured fecal hemoglobin (Hb) and alpha 1-antitrypsin (alpha 1-AT), useful markers of disease activity in UC and CD, respectively. For the in vitro study, blood samples were stimulated with phorbol myristate acetate or latex beads. For the assessment of stability, homogenized stool samples were stored at 4 degrees C, 25 degrees C, and 37 degrees C for various periods.. 1) Fecal Lf, PMN-E, MPO, and Lys concentrations were significantly increased in the active phase of the disease compared to the inactive phase in both UC and CD. 2) Fecal Lf, PMN-E, MPO, and Lys concentrations correlated significantly with fecal Hb concentration in UC, whereas fecal Lf, PMN-E, and MPO concentrations correlated significantly with alpha 1-AT concentration in CD. In UC, fecal Lf, PMN-E, MPO, and Lys concentrations were high in 15, 9, 14, and 14 samples, respectively, of 25 samples with normal Hb concentration. In CD, fecal Lf, PMN-E, and MPO concentrations were high in 19, 10, and 16 samples, respectively, of 30 samples with normal alpha 1-AT concentration. 3) The extracellular release of Lf was the most efficient and this molecule was the most stable in feces.. Both our clinical and our in vitro studies suggested that Lf is the most suitable of these proteins to use as neutrophil-derived fecal marker of inflammation for clinical application.

Topics: Adult; alpha 1-Antitrypsin; Biomarkers; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Feces; Hemoglobins; Humans; Lactoferrin; Leukocyte Elastase; Middle Aged; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Proteins

To characterize the antigen specificity of circulating anti-neutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD).. Analysis of the prevalence of circulating ANCAs in patients with ulcerative colitis and Crohn's disease, by both non-specific methods (immunofluorescence against fixed neutrophil leukocytes) and specific antigen techniques (against purified neutrophil leukocyte constituents).. Indirect immunofluorescence against fixed polymorphonuclear leukocytes, and solid-phase enzyme-linked immunosorbent assay (ELISA) against neutrophil constituents (alpha-granules, elastase, myeloperoxidase, cathepsin g, lysozyme and lactoferrin).. Although results using immunofluorescence were typical of other studies (ulcerative colitis positive in 41%, Crohn's disease in 10%), ELISA studies showed antibody activity against neutrophil components in 69% of patients with ulcerative colitis and 39% of those with Crohn's disease. Antibodies in ulcerative colitis were commonly directed (in descending order) against lysozyme, cathepsin G, elastase, and lactoferrin, and in Crohn's disease against lysozyme.. Correlation of indirect immunofluorescence data and ELISA results indicated that even this large panel of specific antigens fails to identify all the ANCA targets in IBD. The lack of correlation between the findings of ANCAs, either in general or versus a specific target, and disease extent or activity in ulcerative colitis supports the suggestion that ANCAs are unlikely to be of primary importance in pathogenesis.

Topics: Adult; Aged; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Cathepsin G; Cathepsins; Cholangitis, Sclerosing; Colitis, Ulcerative; Crohn Disease; Cytoplasmic Granules; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Inflammatory Bowel Diseases; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Serine Endopeptidases; Vasculitis

The aim was to study the level of salivary proteins with antimicrobial properties in persons with Crohn's disease. Twenty-five patients were recruited, 13 with ongoing symptoms (acute group) and 12 free of clinical signs of the disease at the time of the investigation (nonacute group). A control group matched to the nonacute group was also included in the study. Unstimulated and stimulated whole saliva samples were collected, and the secretion rates estimated. Unstimulated saliva was analyzed for concentrations of total protein, peroxidase, thiocyanate, slgA, lactoferrin, lysozyme, and for specific bacteria aggregation ability. Numbers of mutans streptococci and lactobacilli in saliva were determined, and dental caries status was examined. No differences were found among the groups regarding salivary flow rate, total protein, or any of the antimicrobial proteins. However, three patients with Crohn's disease had no detectable slgA in saliva compared with none in the control group. The lactobacillus count and the number of decayed tooth surfaces were higher in the nonacute group than in the control group.

Topics: Adult; Aged; Case-Control Studies; Colony Count, Microbial; Crohn Disease; Dental Caries; Dental Caries Susceptibility; DMF Index; Female; Humans; Immunity, Innate; Immunoglobulin A, Secretory; Lactobacillus; Lactoferrin; Male; Middle Aged; Muramidase; Peroxidases; Prevalence; Risk Factors; Saliva; Salivary Proteins and Peptides; Salivation; Secretory Rate; Streptococcus mutans

After surgical excision of bowel, Crohn's disease is likely to recur around the anastomosis. It is suggested that this may indicate a biological effect of suture materials on gastrointestinal immunology. To investigate this, the influence of six suture materials on the function of macrophages obtained from the rat peritoneal cavity and human intestinal mucosa was assessed. All materials significantly impaired macrophage function.

Topics: Anastomosis, Surgical; Animals; Cell Adhesion; Cells, Cultured; Colon; Crohn Disease; Humans; Intestinal Mucosa; L-Lactate Dehydrogenase; Macrophages; Male; Muramidase; Phagocytosis; Rats; Recurrence; Sutures

In situ hybridisation has been used to detect mRNAs to the macrophage secretory products, lysozyme, interleukin 1 beta and tumour necrosis factor-alpha. Sections of paraformaldehyde fixed, frozen colonoscopic biopsies from patients with ulcerative colitis, Crohn's disease or normal controls were hybridised with specific radiolabelled probes and the signal detected by autoradiography. Lysozyme mRNA expression was more common in ulcerative colitis (22/27) and Crohn's disease (eight of eight) compared with controls (17/27). Positive cells were found mainly in the subepithelial region in normal colon, while in inflammatory bowel disease they also appeared in the deeper lamina propria. Immunocytochemistry in parallel sections showed that lysozyme mRNA was expressed only in macrophages or in metaplastic Paneth cells in longstanding inflammatory bowel disease. Tissue neutrophils did not express the lysozyme mRNA, though they have large stores of the protein. Tumour necrosis factor mRNA was detected in four of nine controls compared with 11/15 inflammatory bowel disease patients. For interleukin 1 beta, three of eight controls were positive compared with 10/13 with ulcerative colitis. The tumour necrosis factor signal was located mainly in the deeper lamina propria whereas the interleukin 1 beta was seen in subepithelial macrophages. These results confirm increased macrophage activation in inflammatory bowel disease and suggest functional heterogeneity within the intestinal macrophage population.

Topics: Adult; Aged; Colitis, Ulcerative; Crohn Disease; Female; Humans; In Situ Hybridization; Interleukin-1; Macrophage Activation; Macrophages; Male; Middle Aged; Muramidase; RNA Probes; RNA, Messenger; Tumor Necrosis Factor-alpha

Riboprobe in situ hybridization (rISH) demonstrates active lysozyme synthesis in ulcerative colitis and Crohn's disease. Maximal labeling was seen in Paneth cells, macrophages, and granulomas. Diffuse infiltration of the mucosa by lysozyme-rich polymorphs characterizes ulcerative colitis but obscures reactivity in other cell lineages in immunohistochemical studies; lysozyme mRNA is not detected in polymorphs, rISH giving a clearer picture than immunohistochemical studies of the active synthesis of lysozyme within the gut in inflammatory bowel disease. In ulcerative colitis, strong signals localized to Paneth cell metaplasia were found in 11 of 20 cases and to a lesser degree in non-Paneth cell lineages in regenerative mucosa in 13 of 20 cases. In Crohn's disease, abundant labeling was seen in tuberculoid granulomas (5 of 20) and over macrophage aggregates in the lamina propria in another 7, characteristic patterns not encountered in ulcerative colitis. Low levels of lysozyme messenger RNA were found in the ulceration-associated cell lineage ("pseudopyloric metaplasia"). These results support the view that neutrophils are largely responsible for elevated fecal lysozyme levels in ulcerative colitis and macrophages for elevated serum lysozyme levels in Crohn's disease.

Topics: Colitis, Ulcerative; Crohn Disease; Gene Expression; Humans; Immunohistochemistry; Inflammatory Bowel Diseases; Muramidase; Nucleic Acid Hybridization; RNA, Messenger

Three variants of the immunoenzymometric assay of human lysozyme with HRP-labeled antibodies were compared. The highest sensitivity (with a detection limit of 0.2 micrograms lysozyme/L) was achieved by a one-step assay lasting 2 h. Between-batch precision for the techniques was 6-11%. Lysozyme reference values were determined in serum, cerebrospinal fluid and urine. In serum they are age-dependent and in urine sex-dependent when related to creatinine excretion. Serum lysozyme is increased in only 57% of the patients with active rheumatoid arthritis and is also unreliable for indicating remission. In Crohn's disease the serum lysozyme reflects activity better, but it does not exceed the diagnostic value of alpha-1-acidic glycoprotein (orosomucoid). The lysozyme quantification in cerebrospinal fluid is useful in distinguishing between viral or bacterial meningitis.

Topics: Acute Disease; Adolescent; Adult; Aged; Aging; Arthritis, Rheumatoid; Body Fluids; Clinical Enzyme Tests; Crohn Disease; Diagnosis, Differential; Enzyme Stability; Evaluation Studies as Topic; Humans; Immunoenzyme Techniques; Infant, Newborn; Meningitis; Meningitis, Viral; Middle Aged; Muramidase; Nervous System Diseases; Reference Values

To elucidate the value of faecal lysozyme determination in the differential diagnosis of patients with atypical abdominal complaints, stool samples of healthy controls, patients with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) were analysed. Faecal lysozyme concentration in healthy controls ranged from 0 to 6 mg/l with a mean of 3 mg/l. Patients with IBS had similar faecal lysozyme levels. In contrast, faecal lysozyme concentrations in patients with IBD were increased (range 6 to 104 mg/l). The difference between patients with IBS and IBD was highly significant (P less than 0.001). The determination of faecal lysozyme concentration may provide a useful test in the work-up of patients with abdominal complaints. In addition, the faeces lysozyme concentration appeared to be an objective parameter of the inflammatory activity of IBD in 11 patients investigated.

Topics: Colitis, Ulcerative; Colonic Diseases, Functional; Crohn Disease; Diagnosis, Differential; Feces; Humans; Inflammatory Bowel Diseases; Muramidase

Fecal lysozyme excretion was determined in two hundred children and adolescent. In sixty three infants with enteritis due to Rotavirus the fecal lysozyme level was found to be significant higher than in the feces of a group of healthy infants (p less than 0.01). Elevated fecal lysozyme excretion could be detected in patients with untreated Crohn's disease. After treatment with Salazosulfapyridine, Prednisone and elemental diet during six week a significant drop in fecal lysozyme level was observed (p less than 0.01). In eighteen adolescent with Colitis ulcerosa and Crohn's disease the lysozyme level of colonic mucosa was found to be significant higher than a control group (p less than 0.01). The fecal lysozyme excretion can be used as an indicator for the clinical activity of the disease, as a control for therapeutic efficiency and a marker for a relapse.

Topics: Adolescent; Adult; Child; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Feces; Female; Gastroenteritis; Humans; Infant; Infant, Newborn; Intestinal Mucosa; Male; Muramidase; Rotavirus Infections

Rectal biopsies were collected from control subjects, patients with ulcerative colitis both active and quiescent, and from patients with Crohn's disease, both with and without rectal involvement, as judged by histological assessment. Tissue homogenates were assayed for neutrophil (vitamin B12 binding protein, myeloperoxidase, lysozyme) and lymphocyte (5' nucleotidase) selective markers. Patients with acute but not those with quiescent colitis had striking increases of the neutrophil markers. Neither patient group with ulcerative colitis showed a change in the lymphocyte marker enzyme activity. Patients with Crohn's disease involving the rectum showed significant, but less marked, increases in the activity of the neutrophil markers that were found in active ulcerative colitis. Patients with Crohn's disease, not involving the rectum, showed normal or reduced levels of neutrophil markers. Patients with Crohn's disease, both those with and without rectal involvement, had increased activities of the lymphocyte selective marker. This distinguishes this inflammatory response from that of ulcerative colitis and provides further biochemical evidence of abnormalities in apparently uninvolved mucosa from Crohn's patients.

Topics: 5'-Nucleotidase; Adult; Aged; Colitis, Ulcerative; Crohn Disease; Humans; Lymphocytes; Middle Aged; Muramidase; Neutrophils; Nucleotidases; Peroxidase; Rectum; Transcobalamins

Using an immunoperoxidase technique lysozyme (LZM) was identified in the ileum of patients with Crohn's disease in inflammatory cells of the lamina propria, in Paneth cells and in pseudopyloric gland metaplasia. These observations demonstrate a further analogy of pseudopyloric gland metaplasia with true pyloric glands, and may offer an additional explanation for the raised concentration of serum-LZM in patients with Crohn's disease.

Topics: Crohn Disease; Exocrine Glands; Humans; Ileum; Immunoenzyme Techniques; Intestinal Mucosa; Metaplasia; Muramidase; Pylorus

Serum lysozyme was reevaluated in inflammatory bowel disease and other gastrointestinal disorders. A total of 109 patients were divided into six groups: ulcerative colitis (28), Crohn's disease (9), simple atrophic gastritis (16), atrophic gastritis and pernicious anemia (23), functional dyspepsia (17), and controls (16). Elevated levels of lysozyme, compared with control levels, were found not only in ulcerative colitis and Crohn's disease but also in atrophic gastritis with or without pernicious anemia and in functional dyspepsia. The elevation of lysozyme, since it results from the product of granulocytes and macrophages present in increased amounts in the mucosa of inflammatory bowel diseases, is easily explained. The cellular infiltration in atrophic gastritis may also explain the elevated lysozyme levels. The higher lysozyme levels in some patients with functional dyspepsia could possibly reflect an underlying latent inflammatory process.

Topics: Adult; Aged; Anemia, Pernicious; Colitis, Ulcerative; Crohn Disease; Dyspepsia; Female; Gastritis; Humans; Male; Middle Aged; Muramidase

Beta-2-microglobulin (B2m) serum levels were measured by newly developed electroimmunoassay in a group of patients with inflammatory bowel disease. Increased serum B2m concentrations were found in 66.7% out of 93 subjects with Crohn's disease and in 56.0% out of 25 subjects with idiopathic proctocolitis. According to the author's view, serum B2m can be regarded as a useful adjunct to other immunological markers in diagnostic evaluation and monitoring of Crohn's disease. The high B2m level may reflect elevated biosynthesis and release from immunologically activated lymphocytes in areas of inflammation.

Topics: Adult; Antigen-Antibody Complex; beta 2-Microglobulin; Crohn Disease; Female; Humans; Immunoelectrophoresis; Leukocyte Count; Male; Muramidase; T-Lymphocytes

The determination of lysozyme has been shown to be more relevant than assumed until now. It can be used as a marker in the therapy of acute and chronic urinary tract infections. The determination of lysozyme in cerebro spinal fluid and blood serum are helpful to differentiate between bacterial and aseptic meningitides or infections. Elevated fecal lysozyme excretion in adolescents are an indicator for a chronic inflammatory bowel disease. Control of fecal lysozyme excretion can be used as a marker for a relapse and to monitor therapeutic efficiency in patients with inflammatory bowel disease. A consistent high level of fecal lysozyme excretion in adults over the age of 40 is an indicator for possible colorectal tumors and warrants further thorough investigation.

Topics: Adolescent; Adult; Bacterial Infections; BCG Vaccine; Colonic Neoplasms; Crohn Disease; Diagnosis, Differential; Feces; Humans; Macrophages; Meningitis; Monocytes; Muramidase

Topics: Bacterial Infections; Child; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Feces; Hepatitis A; Humans; Meningitis; Meningitis, Aseptic; Muramidase; Urinary Tract Infections; Virus Diseases

Topics: Adolescent; Colonic Neoplasms; Crohn Disease; Humans; Middle Aged; Muramidase; Rectal Neoplasms

In patients with Crohn's disease, the lysozyme concentration in plasma was compared with the Crohn's disease activity index, the granulocyte lysozyme content, the number of circulating neutrophilic granulocytes in peripheral blood and the unsaturated vitamin B12-binding capacity of the plasma cobalophilins as an index for the granulocyte decay. There was no difference in the lysozyme content of granulocytes from patients and controls. Patients with increased plasma lysozyme levels suffered from a more active disease and had larger numbers of circulating granulocytes in their blood than those with normal plasma lysozyme levels. The plasma lysozyme levels correlated well with the cobalophilin levels, in patients with increased levels even more markedly than in those with normal levels. The results suggest that in patients with Crohn's disease increased plasma lysozyme levels are due to an increase in granulocyte decay.

Topics: Adult; Cell Survival; Crohn Disease; Female; Granulocytes; Humans; Male; Muramidase; Protein Binding; Vitamin B 12

1. Biopsies of rectal mucosa were obtained for histology and enzyme analysis from 32 patients with inflammatory and functional bowel disorders, and the biopsies were classified morphologically as active colitis, quiescent colitis or normal. 2. Supernatant fractions of biopsy homogenates were assayed for their content of the proteolytic enzymes alpha-chymotrypsin, elastase and cathepsin D, and of protein, unsaturated vitamin B12-binding capacity, lysozyme, myeloperoxidase and N-acetyl-beta-glucosaminidase. 3. Mean unsaturated vitamin B12-binding capacity was significantly raised above normal in the active colitic mucosa, and mean lysozyme activity was raised above normal in both active and quiescent mucosae. 4. In active colitic mucosa there was no rise above normal in mean activities of any of the proteolytic enzymes, though a significant fall below normal occurred in mean N-acetyl-beta-glucosaminidase activity in the active colitic group.

Topics: Acetylglucosaminidase; Adolescent; Adult; Aged; Carrier Proteins; Cathepsins; Chymotrypsin; Colitis, Ulcerative; Crohn Disease; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Vitamin B 12

Lysozyme was measured using the synthetic substrate 3',4-dinitrophenyl tetra-N-acetyl-beta-chitotetraoside and the LKB Reaction Rate Analyser. This method has been evaluated by comparing levels obtained with serum samples from healthy individuals and patients with either cancer or inflammatory bowel disease with those obtained from the same specimens using a turbidimetric method. In terms of standard egg-white lysozyme, the colorimetric method gave much higher levels for all samples than the turbidimetric method; however, similar group differences were maintained. For individual serum specimens significant correlation between the two methods was found to occur only in the healthy group. Assay precision for the two methods was similar but the turbidimetric method could detect levels of lysozyme activity which were 10 times lower than those detected by the colorimetric method.

Topics: Biological Assay; Chitin; Colitis, Ulcerative; Colorimetry; Crohn Disease; Dinitrobenzenes; Female; Humans; In Vitro Techniques; Micrococcus; Muramidase; Nephelometry and Turbidimetry; Ovarian Neoplasms

Endotoxin (lipopolysaccharide, LPS) and LPS antibody in the blood were studied in 61 cases of ulcerative colitis (U.C.) by radioimmunoassay. Lysozyme (LZM) concentration was also studied by the turbidimetric method. As a result, it was found that the blood LPS value as well as serum LZM concentration reflects the clinical observations. The case of endotoxemia in the active phase group showed a positive correlation between the LPS value and LZM concentration. LPS antibody which could not be detected in many cases of the active phase, had a high titer in cases of remission with a long history of the disease. These results would suggest that in U.C. with damaged intestinal mucosal barrier, LPS originating from intestinal flora enters into the blood and aggravates the disease and further that this invading LPS releases LZM into the blood. The same studies were performed on 7 cases of Crohn's disease and the same result was obtained.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Colitis, Ulcerative; Crohn Disease; Endotoxins; Escherichia coli; Female; Humans; Lipopolysaccharides; Male; Middle Aged; Muramidase; Polysaccharides, Bacterial; Radioimmunoassay

Topics: Acute Disease; Adult; Colitis, Ulcerative; Crohn Disease; Female; Humans; Leukemia, Monocytic, Acute; Male; Middle Aged; Muramidase; Uremia

Lysozyme activity of macrophages and giant cells in various human granulomas were examined with immunoperoxidase bridge method in tissue sections. Various numbers of epithelioid cells and giant cells of epithelioid cell granulomas of tuberculosis, sarcoidosis and Crohn's disease exhibited intense granular cytoplasmic lysozyme activity. Foreign body granulomas induced with various substances showed negative or faintly positive lysozyme stain. Macrophages and giant cells of aspergillus granuloma associated with thymus hypoplasia and T-cell depression contained no lysozyme. The results suggest that cell-mediated immunology plays an important role for the lysozyme synthesis of macrophages in granuloma.

Topics: Aspergillosis; Child, Preschool; Crohn Disease; Foreign-Body Reaction; Granuloma; Humans; Macrophages; Muramidase; Sarcoidosis; T-Lymphocytes; Thymus Gland; Tuberculosis

The simultaneous demonstration of lysozyme using the unlabelled antibody enzyme method and mucosubstances by staining with the periodic acid-Schiff (PAS) and Alcian Blue pH 2.5 techniques has led to the identification of a new subpopulation of mucus-producing cells containing lysozyme in small intestinal specimens from normal rats and from patients with inflammatory bowel diseases. These cells, containing both mucosubstances and lysozyme, are located in the lateral walls of the crypts of Lieberkuhn, but can occasionally be found also in or near the tips of the villi. The specific staining for lysozyme was observed in the apical and/or basal cytoplasm of these mucus-producing cells and was readily detected in sections counterstained for mucosubstances with Alcian Blue. The localization of these mucus-producing cells was similar both in the normal rat and in the pathological human specimens. Absorption controls and controls where a non-immune serum was substituted for the specific antilysozyme serum confirmed the specificity of the lysozyme localization.

Topics: Animals; Crohn Disease; Humans; Intestinal Mucosa; Intestine, Small; Microvilli; Mucus; Muramidase; Periodic Acid-Schiff Reaction; Rats

In patients with Crohn's disease and ulcerative colitis, alterations in serum storage temperature produced significant changes in serum lysozyme activity (SLA) as measured by the lysoplate method. This was not the case in healthy controls or in a group with other gastrointestinal disorders. Electrophoretic separation of serum revealed two components of lysozyme-type lytic activity but only one in extracts of gut mucosa, leucocytes, and egg white. The major lytic component of serum migrated towards the cathode and reacted with specific antilysozyme serum, but the minor component which migrated towards the anode did not. Although the cause of this anionic lytic activity is uncertain, it contributes to total serum activity as estimated by any method utilising the lysis of Micrococcus lysodeikticus, and may possibly be related to the observed thermolability.

Topics: Adult; Colitis, Ulcerative; Crohn Disease; Electrophoresis, Agar Gel; Female; Hot Temperature; Humans; Male; Micrococcus; Muramidase

Lysozyme (EC 3.2.1.17) concentrations were measured in the serum and stools of patients with inflammatory bowel disease and compared with the concentrations in similar material from normal controls, patints with non-inflammatory gastrointestinal disease, and patients without gastrointestinal disease. By the turbidometric method, values of lysozyme (microgram/ml +/- SD) are considerably greater in the serum of patients with active Crohn's disease (9.2 +/- 2.7) than in the serum of healthy controls (4.4 +/- 2.0). They do not, however, distinguish individual patients with Crohn's disease from those with ulcerative colitis nor from those with a variety of other gastrointestinal conditions. The lysoplate method gives much higher values for serum lysozyme than the turbidometric method but there is a considerable overlap between the results for patients with Crohn's disease (60.1 +/- 30.7) and normal controls (27.4 +/- 17.5). There is only a moderate correlation between the results given by the two methods (r = 0.56) and it is suggested that factors other than enzyme activity and methodological variation are responsible for the observed differences. This is supported by the finding that, with Crohn's disease in remission, serum lysozyme values (lysoplate) return to normal values but with the turbidometric method remain raised. Mean faecal lysozyme levels, expressed either as a concentration or as total daily excretion, in patients with inflammatory bowel disease are very significantly greater than values in healthy controls and in diseased subjects without diarrhoea but are not significantly different from those subjects with other causes of diarrhoea.

Topics: Colitis, Ulcerative; Crohn Disease; Feces; Gastrointestinal Diseases; Humans; Muramidase; Nephelometry and Turbidimetry

The serum levels of lysozyme, serum electrophoresis, and serum immunoglobulins were determined prospectively in 101 patients with ulcerative colitis, ulcerative proctitis, Crohn's disease, or nonclassifiable nonspecific inflammatory bowel disease. Although the mean serum lysozyme concentration of patients with Crohn's disease (10.5 +/- 6.8 microgram/ml) and ulcerative colitis (9.6 +/- 4.1 microgram/ml) performed by a standardized lysoplate method was significantly greater than normal controls (6.0 +/- 1.5 microgram/ml), the results did not correlate with the diagnosis nor with the degree of disease activity. Individually separated protein fractions and serum immunoglobulins also did not correlate with the serum lysozyme levels. This study indicates that measurement of the level of serum lysozyme in individual patients is not helpful in determining the cause or degree of activity of nonspecific inflammatory bowel disease.

Topics: Adult; Blood Proteins; Colitis; Colitis, Ulcerative; Crohn Disease; Humans; Immunoglobulins; Middle Aged; Muramidase; Proctitis

In 51 untreated cases of ulcerative colitis and Crohn's disease some cellular (neutrophil alkaline phosphatase activity, neutrophil NBT reducing capacity, and neutrophil and plasma lysozyme activities) and humoral (serum orosomucoid and serum haptoglobin) indices of disease activity were quantitated. The most pronounced signs of disease activity, thus, were found in severe cases of ulcerative colitis. Combining lysozyme activities with other disease activity indices seems to facilitate the distinction between severe cases of Crohn's disease and ulcerative colitis. Beyond this the addition of the humoral indices seemed not to offer substantial help.

Topics: Adolescent; Adult; Alkaline Phosphatase; Child; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Haptoglobins; Humans; Male; Middle Aged; Muramidase; Neutrophils; Nitroblue Tetrazolium; Orosomucoid

Serum lysozyme activity was determined in the sera of 70 patients with inflammatory bowel disease by the lysoplate method. Serum lysozyme levels were significantly elevated only in patients with Crohn's disease of the small bowel. Patients with either granulomatous or ulcerative colitis had serum lysozyme values not different from normals, irrespective of activity of their disease.

Topics: Adult; Aged; Colectomy; Colitis; Colitis, Ulcerative; Crohn Disease; Female; Humans; Male; Middle Aged; Muramidase; Recurrence

Topics: Animals; Antibodies, Viral; Arteritis; Colitis, Ulcerative; Crohn Disease; Cytomegalovirus; Food Hypersensitivity; Humans; Immunity, Cellular; Lupus Erythematosus, Systemic; Mice; Milk; Muramidase; Rabbits; RNA Viruses

Lysozyme (LZM) was identified in ulcerative colitis in granulocytes, monocytes, and macrophages of the intestinal lamina propria. In contrast with findings in normal colon or rectum, in ulcerative colitis LZM was also detected in some mucosal crypt cells and metaplastic Paneth cells. In both ulcerative colitis and Crohn's disease LZM was present in inflammatory cells of crypt abscesses. In Crohn's disease intense LZM staining was seen in epitheloid cell granulomas. The present observations permit one explanation for the raised concentration of serum-LZM in patients with ulcerative colitis and Crohn's disease.

Topics: Colitis, Ulcerative; Crohn Disease; Epithelial Cells; Epithelium; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Muramidase

Topics: Adult; Colitis, Ulcerative; Crohn Disease; Female; Glycoproteins; Humans; Male; Muramidase

Serum lysozyme (muramidase) concentrations were determined in 55 patients with inflammatory bowel disease, 6 with miscellaneous bowel disease, 40 with pulmonary tuberculosis, and in 20 normal subjects. The mean (+/- SE) lysozyme concentration for each group was as follows: controls 6,95 +/- 0,36 microgram/ml; ulcerative colitis 9,61 +/- 1,02 microgram/ml; inactive Crohn's disease 7,61 +/- 0,53 microgram/ml; active Crohn's disease 20,77 +/- 2,17 microgram/ml; sputum-negative tuberculosis 13,05 +/- 1,06 microgram/ml; and sputum-positive tuberculosis 20,35 +/- 2,08 microgram/ml. The mean enzyme levels were significantly higher in patients with Crohn's disease than in those with ulcerative colitis (P less than 0,05) or in normal controls (P less than 0,01). Our findings suggest that serum lysozyme levels may be useful in differentiating active Crohn's disease from ulcerative colitis, but the results overlap somewhat. However, the enzyme level may be a useful index of disease activity in following up patients with Crohn's disease. As tuberculosis is endemic in this country it must first be excluded, because patients with pulmonary tuberculosis have similarly high levels of serum lysozyme.

Topics: Adolescent; Adult; Aged; Colitis, Ulcerative; Crohn Disease; Female; Humans; Intestinal Diseases; Male; Middle Aged; Muramidase; Tuberculosis, Pulmonary

Lysozyme concentrations in serum and urine were determined in 101 patients with Crohn's disease and 26 patients with ulcerative colitis. Lysozyme was assayed according to the lysoplate method of Osserman against a standard of humam lysozyme. The mean serum lysozyme concentrations (+/- S.E.M.) for each group were as follows: controls 8.4 +/- 1.8 (n equals 38), Crohn's disease 8.2+/-2.6 (n equals 101), ulcerative colitis 8.7+/-3.0 (n equals 26). No significant differences were found in serum lysozyme levels of the various groups of patients (2p is greater 0.05). There existed no correlation (r equals 0.12, n equals 129, p is greater than 0.05) with the activity of the disease. Serum lysozyme levels were significantly higher in patients affected by Crohn's disease of the small and the large bowel than in patients with involvement of the small intestine only and operated patients (2p is less than 0.05). The discriminative value of these findings with respect to the clinical course of such patients is limited because no significant differences are found between the levels of patients with Crohn's disease and controls. Neither in case of Crohn's disease nor ulcerative colitis were the mean urine lysozyme concentrations increased. These findings show that the determination of serum and urine lysozyme levels is unsuitable in respect of the differential diagnosis of inflammatory bowel disease as well as of the assessment of activity and extent of the disease.

Topics: Adolescent; Adult; Aged; Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Humans; Intestine, Large; Intestine, Small; Male; Middle Aged; Muramidase

The concentration of lysozyme in plasma (P) and in neutrophil leucocytes (N) was determined by a turbidimetric method in 32 patients with ulcerative colitis (U.C.), 11 patients with Crohn's disease (C.D.), 9 patients with haemorrhagic proctitis, and 39 healthy volunteers. In active U.C., P was significantly elevated (p less than 0.05), whereas C.D. showed normal values. Corresponding N was significantly reduced in active U.C. (p less than 0.05) but normal in C.D. In calculating the ratio N/P, highly significant lower values were found in active U.C. (p less than 0.001) compared to normal levels in C.D. The high P in active U.C. is presumed to reflect an accelerated destruction of neutrophil leucocytes as well as an intensified turnover rate. The reduced N is probably attributable to an inhibited synthesis. The findings suggest that lysozyme determinations are valuable in be differential diagnosis of active U.C. and C.D.

Topics: Adolescent; Adult; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Granulocytes; Humans; Leukocytes; Male; Middle Aged; Muramidase; Neutrophils

Topics: Adolescent; Adult; Alkaline Phosphatase; Child; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Granulocytes; Humans; Leukocytes; Male; Middle Aged; Muramidase; Neutrophils; Proctitis

Serum lysozyme levels were compared in patients with Crohn's disease (CD) and chronic ulcerative colitis (CUC) to determine if the two diseases could be differentiated by this parameter. The lysozyme concentrations were measured by three different methods: 1. the turbidimetric clearance of Micrococcus lysodeikticus utilizing egg white lysozyme as a standard; 2. the lysoplate assay of Osserman and Lawlor using a human lysozyme standard obtained from Dr. Osserman and 3. the lysoplate assay obtained as a commercial kit using human lysozyme as a standard. A series of 19 CD and 23 CUC patients were compared. Contrary to the report of Falchuk, et al, the serum lysozyme levels by any of the three methods were not statistically significantly different in the two diseases. The serum levels of those with severe, moderate, or inactive disease were also not significant for CD or CUC nor in serially followed patients did levels always correspont to changes in clinical course.

Topics: Adolescent; Adult; Aged; Biological Assay; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Female; Humans; Male; Methods; Micrococcus; Middle Aged; Muramidase; Nephelometry and Turbidimetry

Serum lysozyme (muramidase) concentrations were determined in five patients with Morbus Crohn before and after resection of inflammated bowel areas. The serum lysozyme activity which was elevated before surgical treatment in all patients fell to normal values after bowel resection within a few hours. Our findings suggest, that the elevated serum lysozyme reflects an increased lysozyme production in the inflammated bowel tissue.

Topics: Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Intestines; Muramidase

Topics: Biological Assay; Colitis, Ulcerative; Colorimetry; Crohn Disease; Humans; Micrococcus; Muramidase; Nephelometry and Turbidimetry; Spectrometry, Fluorescence

Serum lysozyme (muramidase) activity was determined by the Lyso-Plate diffusion technic in 419 subjects consisting of normal persons and patients with Crohn's disease, ulcerative colitis, nonspecific diarrhea and various other disorders. Lysozyme activity in the normal subjects did not exceed 37.8 microgram/ml. The values in the several groups of patients overlapped markedly with each other and with the normal range. Approximately two-thirds (62.1%) of the 37 patients with Crohn's disease had values that were within the normal range. In about half (51.8%) of the patients with this disease in whom the process was clinically active, serum lysozyme activity was increased. Of 10 patients with Crohn's disease who had undergone resection, heightened serum lysozyme activity was found only in the three patients in whom there was clinical evidence of recurrence of the disease. It is concluded that serum lysozyme activity is not a dependable means of distinguishing Crohn's disease from ulcerative colitis or nonspecific diarrheas. The determination would appear to be of value, however, in helping to identify activity, recurrence, or extension of the disease in patients with Crohn's disease.

Topics: Adolescent; Adult; Aged; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Diarrhea; Female; Humans; Male; Middle Aged; Muramidase; Recurrence

Estimation of lysozyme (LZM) activity in the serum was suggested as a valuable test to distinguish between Crohn's disease and ulcerative colitis. Subsequently several reports either supported or denied the original observation. Selection of patients and methodological differences were suggested as an explanation for the controversy. We estimated serum LZM in a large group of patients using the lysoplate method and human LZM as a standard. The conditions of the assay were strictly standardized. In 90 patients with Crohn's disease the LZM level was 8.3 +/- 2.1 (SD) microgram/ml, in 57 patients with ulcerative colitis was 7.4 +/- 2.0 (SD) microgram/ml, and in 40 healthy individuals it was 7.0 +/- 1.2 (SD) microgram/ml. Although the difference between the mean LZM levels in Crohn's disease and in ulcerative colitis was statistically significant, there was a definite overlapping of values between these two diseases. No significant correlation of LZM level to the duration or extent of the disease, activity, or treatment was found in Crohn's disease. In ulcerative colitis the LZM level was often a little higher in severe disease, especially when the whole colon was involved.

Topics: Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Muramidase

Serum lysozyme levels were determined by a turbidometric method using egg white lysozyme as standard in 100 patients with Crohn's disease, 86 with ulcerative colitis, 31 with coeliac disease, and in 38 normal control subjects. Though the levels in Crohn's disease were significantly higher than those in ulcerative colitis and in coeliac disease, there was marked overlap between the disorders and control subjects, and so they were of no value in differential diagnosis. There was some evidence that serum lysozyme levels reflected disease activity in Crohn's disease but not in ulcerative colitis.

Topics: Celiac Disease; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Muramidase

Topics: Adolescent; Adult; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Muramidase

Topics: Adult; Aged; Colitis, Ulcerative; Crohn Disease; Female; Humans; Male; Middle Aged; Muramidase

Topics: Adolescent; Adult; Aged; Crohn Disease; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Muramidase

Rectocolitis remains, at the present time, in spite of the large amount of work carried out, a condition of which the cause and the physiopathological mechanism are unknown: none of the theories proposed has been confirmed by the facts; none has made it possible to propose an effective therapeutic regimen. The diagnosis of haemorrhagic rectocolitis rests solely on an assembly of clinical, radiological, and anatomological findings, together with findings on progress of the disease; none of these findings taken separately being pathognomonic. Because of this it is essential in cases of inflammatory colic disorders to analyse critically these different elements before affirming the diagnosis that is often arrived at too easily. Different affections, even apart from Crohn's disease (parasitic, microbial, and iatrogenic affections, etc) may, in fact, give rise to radiological and clinical pictures close to those of haemorrhagic rectocolitis.

Topics: Autoimmune Diseases; Colitis; Colon; Crohn Disease; Diagnosis, Differential; Endoscopy; Gastrointestinal Hemorrhage; Genotype; Humans; Hypersensitivity; Infections; Intestinal Diseases, Parasitic; Intestinal Mucosa; Muramidase; Proctocolitis; Psychophysiologic Disorders; Radiography

Topics: Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Muramidase; Nephelometry and Turbidimetry

Topics: Crohn Disease; Humans; Methods; Muramidase

Serum lysozyme activity was measured in 18 patients with ulcerative colitis and 40 patients with Crohn's disease by both the turbidimetric and lysoplate method. Only one patient with ulcerative colitis and eight patients with Crohn's disease had increased serum lysozyme activity by either or both methods. Both methods appeared equally sensitive in detecting increased serum lysozyme activity. In Crohn's disease, the percent with elevated values increased with increase in disease activity.

Topics: Colitis, Ulcerative; Crohn Disease; Humans; Muramidase

Topics: Adult; Child; Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; False Positive Reactions; Humans; Muramidase

Topics: Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Muramidase

Serum lysozyme (muramidase) was determined in 72 patients with Crohn's disease or ulcerative colitis. Serum lysozyme was elevated in both disease groups. The mean enzyme level was significantly higher in Crohn's disease than in ulcerative colitis, but there was a considerable overlapping between the groups, which makes serum lysozyme determination of dubious value in the differential diagnosis between Crohn's disease and ulcerative colitis. No correlation was found between the serum lysozyme concentration and the activity of the diseases.

Topics: Adolescent; Adult; Aged; Child; Colitis, Ulcerative; Crohn Disease; Female; Humans; Male; Middle Aged; Muramidase

Serum lysozyme (muramidase) concentrations were measured in three groups of patients: control, ulcerative colitis and proctitis, and Crohn's disease. The mean +/-SD for each group was: control, 7 +/- 2; ulcerative colitis and proctitis, 7 +/- 2; and Crohn's disease, 10 +/- 4. Although a significant difference was seen between values in patients with Crohn's disease and values observed in those with ulcerative colitis or control patients, an important overlap was found between these groups. Further studies are necessary to explain the disparate results between this study and previous reports.

Topics: Adolescent; Adult; Aged; Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Muramidase; Proctitis

Topics: Colitis, Ulcerative; Crohn Disease; Humans; Muramidase

The distribution of muramidase (lysozyme) in normal and pathological human tissues has been studied, using an immunohistological technique. The enzyme was demonstrated in a variety of healthy tissues, including serous salivary acinar cells, lactating mammary tissue, Paneth cells, renal tubular cells, myeloid cells (including eosinophils), and histiocytic cells. In pathological tissues the most striking positivity was encountered in reactive histiocytic cells in granulomatous conditions such as tuberculosis and Crohn's disease. The finding of this study are related to previous reports of the distribution of human and animal muramidase and the implications of patterns of muramidase staining in pathological histiocytes are briefly discussed.

Topics: Bone Marrow; Bone Marrow Cells; Breast; Crohn Disease; Eosinophils; Histological Techniques; Humans; Immune Sera; Immunologic Techniques; Intestinal Mucosa; Kidney Tubules, Distal; Kidney Tubules, Proximal; Kupffer Cells; Lacrimal Apparatus; Lymph Nodes; Muramidase; Salivary Glands; Tuberculosis

Serum lysozyme (muramidase) concentrations were determined in patients with different types of inflammatory bowel disease and in normal subjects. The mean (plus or minus S.E.M.) lysozyme concentration for each group was as follows: controls, 8.8 plus or minus 0.3, ulcerative colitis, 9.3 plus or minus 0.6, Crohn's disease, 26.3 plus or minus 1.4. a and bacterial and nonbacterial enteritis, 8.9 plus or minus 0.7 mug per milliliter. Thus, mean enzyme levels were significantly greater in Crohn's disease than in ulcerative colitis (p smaller than 0.001), bacterial and nonbacterial enteritis (p smaller than 0.001) and healthy volunteers (p smaller than 0.001). The elevation of serum lysozyme in Crohn's disease may be related to tissue macrophages because no correlation was found between either the serum lysozyme concentration and the white-cell counts or the absolute numbers of circulating granulocytes or monocytes. Our findings suggest that serum lysozyme may be useful in the differential diagnosis of Crohn's disease from other types of bowel inflammation.

Topics: Adolescent; Adult; Aged; Child; Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Enteritis; Female; Humans; Leukocyte Count; Macrophages; Male; Middle Aged; Monocytes; Muramidase; Salmonella Infections

Topics: Colitis, Ulcerative; Crohn Disease; Granulocytes; Humans; Intestinal Mucosa; Leukocyte Count; Monocytes; Muramidase; Phagocytes

Topics: Clinical Enzyme Tests; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Muramidase

Topics: Animals; Colitis, Ulcerative; Crohn Disease; Diagnosis, Differential; Humans; Intestinal Mucosa; Mice; Muramidase

Topics: Crohn Disease; Humans; Muramidase

Serum lysozyme concentrations were determined in patients with clinically active and inactive Crohn's disease as well as in healthy volunteers. The mean serum lysozyme concentrations (+/- SE) for each group were as follows: controls, 8.8 +/- 0.4; active Crohn's disease, 20.8 +/- 0.8; and inactive Crohn's disease, 10.4 +/- 0.7 mug per ml. The mean lysozyme level was significantly greater in active Crohn's disease as compared to normal subjects (P less than 0.001) and patients with inactive disease (P less than 0.001). Moreover, in patients with clinically severe Crohn's disease there seems to be a trend toward greater lysozyme levels, as opposed to those with mild to moderately active disease. In patients followed serially during the course of their disease, serum lysozyme levels increased with exacerbations of the illness and decreased with clinical improvement. These findings suggest that the serum lysozyme concentrations may serve as a useful index of the activity of Crohn's disease and aid in monitoring the clinical course of such patients.

Topics: Crohn Disease; Diagnosis, Differential; Humans; Muramidase

Topics: Adolescent; Adult; Crohn Disease; Female; Humans; Male; Muramidase

In conditions with increased neutrophil production, the serum total vitamin B(12)-binding capacity (TBBC) is considered to correlate with the blood pool size of neutrophil granulocytes. The serum lysozyme, on the other hand, is a measure of neutrophil (and monocyte) turnover. The mean serum TBBC was significantly raised in patients with ulcerative colitis (range 1.23-5.51 ng/ml; mean 2.64 ng/ml) and patients with Crohn's disease (range 1.58-9.29 ng/ml; mean 2.93 ng/ml). The elevated values were shown to be due to rises in the granulocyte-secreted binding proteins, transcobalamins I and III. The TBBC was shown to rise with increasing activity of disease and to correlate roughly with the blood neutrophil granulocyte count. Patients with inflammatory bowel disease also had a significantly raised mean level of serum lysozyme (range 3.1 to 10.4 mug/ml; mean 6.8 mug/ml), but there was no correlation in individual patients between serum lysozyme and total B(12)-binding capacity. These results are taken to indicate an enlarged granulocyte pool and increased granulocyte turnover in inflammatory bowel disease.

Topics: Adolescent; Adult; Aged; Blood Proteins; Chromatography, Gel; Cobalt Radioisotopes; Colitis, Ulcerative; Crohn Disease; Granulocytes; Hemoglobins; Humans; Leukocytes; Middle Aged; Molecular Weight; Muramidase; Neutrophils; Protein Binding; Serum Albumin; Vitamin B 12

Topics: Animals; Appendicitis; Biological Evolution; Cell Division; Colitis, Ulcerative; Colonic Neoplasms; Crohn Disease; Ethionine; Gastritis; Germ-Free Life; Histocytochemistry; Humans; Intestinal Neoplasms; Intestines; Metaplasia; Microscopy, Electron; Muramidase; Peutz-Jeghers Syndrome; Puromycin; Rats; Stomach Neoplasms; Stomach Ulcer; Triparanol; Whipple Disease; Zinc

Topics: Adrenocorticotropic Hormone; Colitis; Colitis, Ulcerative; Crohn Disease; Dermatologic Agents; Feces; Ileitis; Muramidase

Topics: Anti-Infective Agents, Local; Crohn Disease; Muramidase