muramidase and Sarcoidosis

A 65-year-old man was diagnosed with systemic sclerosis on the basis of skin thickening and positivity of anti-Scl-70 antibodies. Because myogenic enzymes, such as creatinine phosphokinase and aldorase, were also elevated, myopathy or myositis associated with systemic sclerosis was considered. Muscle magnetic resonance imaging and gallium scintigraphy did not show abnormalities. Findings of muscle biopsy demonstrated presence of noncaseating granulomas with multinucleated giant cells. In addition, serum angiotensin-converting enzyme and lysozyme were elevated, and therefore a diagnosis of sarcoid myopathy was made. Further, renal sarcoidosis was revealed with renal biopsy. Prednisolone (40 mg/day) improved both the myopathy and nephritis. Sarcoid myopathy is a rare condition, but it should be considered when myogenic enzymes are elevated in the patient with systemic sclerosis. Further, muscle biopsy may be essential to make an accurate diagnosis in such condition.

Topics: Aged; Biopsy; Giant Cells; Granuloma; Humans; Kidney Diseases; Male; Muramidase; Muscle, Skeletal; Muscular Diseases; Prednisolone; Renin; Sarcoidosis; Scleroderma, Systemic; Treatment Outcome

Topics: Antibodies, Monoclonal; Autoimmunity; Beryllium; Biomarkers; Calcium; CD4-CD8 Ratio; Cytokines; Environmental Exposure; Etanercept; HLA-DR Antigens; Humans; Immunoglobulin G; Immunosuppressive Agents; Infliximab; Macrophages; Methotrexate; Muramidase; Peptidyl-Dipeptidase A; Prednisolone; Receptors, Tumor Necrosis Factor; Sarcoidosis; T-Lymphocytes

Sarcoidosis is a multisystem granulomatous disease of unknown origin. No single biological marker allows definitive diagnosis of sarcoidosis or may accurately predict the disease prognosis. However, some biological markers are helpful tools as diagnostic aids and disease activity markers. At the blood level, lymphopenia with CD4 depletion, elevated levels of serum-angiotensin converting enzyme, lyzozyme, beta 2 microglobulin and disturbed calcium metabolism resulting in hypercalcemia and hypercalciuria can help guide diagnosis. Lymphocytic alveolitis with a high CD4/CD8 ratio in bronchoalveolar lavage fluid is highly suggestive of the disease. A wide range of new biological markers are proposed but their pronostic significance is still controversial. In clinical practice, biological markers may help in monitoring treated patients with sarcoidisis.

Topics: beta 2-Microglobulin; Biomarkers; CD4 Lymphocyte Count; Humans; Hypercalcemia; Lymphopenia; Muramidase; Peptidyl-Dipeptidase A; Prognosis; Reproducibility of Results; Sarcoidosis; Sensitivity and Specificity

The clinical laboratory has a significant role in sarcoidosis. We summarized the biochemical data of laboratory tests in serum of patients with sarcoidosis. To clarify their importance, we put emphasis on the following aspects, including: 1. The data reflecting pathophysiology of sarcoidosis, such as angiotensin converting enzyme, lysozyme, adenosine deaminase, beta 2-microglobulin and intercellular adhesion molecule-1, 2. The data resulting from organ involvement, such as amylase, LDH, and Ca, 3. The data serving as an indicator of disease activity, 4. The data related to prognostic outcome, Keeping these differences in mind helps us make the best use of the clinical data of sarcoidosis.

Topics: Adenosine Deaminase; beta 2-Microglobulin; Biomarkers; Cell Adhesion Molecules; Humans; Intercellular Adhesion Molecule-1; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Measurement of serum angiotensin-converting-enzyme (SACE) is the most useful test for diagnosing and monitoring disease activity in sarcoidosis. Because elevated levels of SACE are not specific for sarcoidosis, other conditions in which SACE levels are also elevated are examined.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biopterins; Body Fluids; Humans; Muramidase; Neopterin; Peptidyl-Dipeptidase A; Sarcoidosis

The diagnosis of sarcoidosis depends on the clinical and radiologic features along with histologic evidence of epithelioid-cell granulomas on biopsy. The amount of histologic support required varies inversely with the certainty with which the pattern of clinical features is recognized. It is essential to exclude other recognized causes of granulomatous disease. On the basis of our experience and that of other workers, we believe that sarcoidosis must be considered in the differential diagnosis when optic nerve thickening is encountered on CT, MRI or echography. Chest roentgenography is the easiest way to confirm the diagnosis. However, as many as 15% of patients will have a normal x-ray film, and other tests may be needed to help confirm the diagnosis. Biopsy of the involved tissues may be the only way to make the diagnosis. Once a provisional diagnosis is made, investigation for systemic sarcoidosis should include chest roentgenography, determination of the serum ACE level, 67Ga scanning, pulmonary function studies, testing for delayed skin reactions (with tuberculin, C. albicans, Trichophyton and mumps virus) and blood studies (determination of the erythrocyte sedimentation rate and levels of immunoglobulins, albumin, calcium and alkaline phosphatase). Finally, conjunctival biopsy is simple to do and is quite useful in supporting the diagnosis if no other tissue is readily available.

Topics: Biopsy; Bronchoalveolar Lavage Fluid; Cerebrospinal Fluid; Gallium Radioisotopes; Humans; Magnetic Resonance Imaging; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Skin Tests; Tears; Tomography, X-Ray Computed; Transcobalamins; Tuberculin Test

Diagnosis of a dry eye is facilitated by prompt recognition of pertinent signs and symptoms and by utilisation of those office and laboratory procedures which help to confirm the diagnosis. Prior knowledge of those systemic diseases associated with keratoconjunctivitis sicca (KCS) alert the practitioner to a possible dry eye state. Conversely, a diagnosis of KCS may prompt recognition of a hitherto unsuspected systemic disease. In this review, I will discuss the signs and symptoms of KCS, its association with various systemic conditions, as well as the tests and procedures that contribute to its diagnosis.

Topics: Adolescent; Adult; Blepharitis; Child; Cornea; Dysautonomia, Familial; Epithelium; Erythema Multiforme; Humans; Keratoconjunctivitis; Lactoferrin; Muramidase; Osmolar Concentration; Pemphigoid, Benign Mucous Membrane; Rose Bengal; Sarcoidosis; Sjogren's Syndrome; Tears

Topics: Anaphylaxis; Anti-Glomerular Basement Membrane Disease; Antigen-Antibody Complex; Asthma; Complement System Proteins; Cytotoxicity, Immunologic; Humans; Immunoglobulins; Interferons; Lactoferrin; Leukocytes; Lung; Macrophages; Muramidase; Phagocytosis; Reagins; Respiratory Hypersensitivity; Rhinitis, Allergic, Seasonal; Sarcoidosis; Tuberculosis, Pulmonary

The cardinal immunologic changes in sarcoidosis consist of depression of delayed-type hypersensitivity, hyperreactive circulating antibody responses and the Kveim-Siltzbach skin test phenomenon. Depression of delayed-type hypersensitivity is demonstrated by skin tests using tuberculin, mumps, pertussis, trichophytin, oidiomycin, dinitrochlorobenzene and Californian keyhole limpet hemocyanin. The cultured lymphocytes from patients with depression of delayed-type hypersensitivity react poorly to phytohemagglutinin, and there is a close correlation between anergy of lymphocytes in culture and by cutaneous anergy. In vivo cutaneous anergy mirrors in vitro cellular hyporeactivity. Other technics used to expose immunologic defects in peripheral lymphocytes of patients with sarcoidosis include tests of T and B cell function, rosetie formation and migration inhibition. Whereas there is cutaneous anergy and impaired cellular immunity in patients with sarcoidosis, the reverse holds for circulating factors. There are increased circulating immunoglobulin levels, increased circulating antibody levels to Epstein-Barr, herpes simplex, rubella, measles and parainfluenza viruses, increase antibody response to mismatched blood and occasional false-positive Wassermann reactions, but there is no increase in circulating autoan tibodies. There is no evidence that patients with sarcoidosis belong predominantly to any particular histocompatibility locus. Worldwide figures for the Kveim-Siltzbach skin test are presented. They provide evidence of its specificity in various international series. The causes of nonspecific reactions are discussed.

Topics: Antibodies, Viral; Autoantibodies; B-Lymphocytes; Cell Migration Inhibition; Complement System Proteins; Dinitrochlorobenzene; Hemocyanins; Herpesvirus 4, Human; Histocompatibility Antigens; Humans; Hypersensitivity, Delayed; Immunoglobulins; Kveim Test; Lymphocyte Activation; Macrophage Migration-Inhibitory Factors; Mollusca; Muramidase; Sarcoidosis; T-Lymphocytes; Tuberculin Test

Sarcoidosis is a systemic granulomatous disease of unknown etiology with significant heterogeneity in organ manifestations and clinical course. Subjects with sarcoidosis share several features such as, non-necrotizing granuloma, hypergammaglobulinemia, increased local and circulating inflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a pluripotent chemokine modulating cellular function. Study included healthy controls (n = 28) and sarcoidosis patients (n = 65). Sera and BAL of sarcoidosis patients were collected and patients were followed longitudinally for 3 years, and demographics, stages, pulmonary function tests, and organ involvements were recorded. We evaluated MIF in the serum and bronchoalveolar lavage (BAL) fluid of sarcoidosis patients in association with clinical features and cytokines, IL-18, IL-10, IL-6, IFN-γ. We found serum MIF had a positive correlation with IL-10 and IFN-γ and % predicted total lung capacity (%TLC). Serum IL-18 had a significant positive correlation with serum lysozyme, but a negative correlation with %TLC and %DLCO. We identified two groups of sarcoidosis subjects with distinct clinical and cytokine features. A group with prominent extrapulmonary involvement, and low serum MIF, IL-10 and IFN-γ and a group with elevated serum MIF, IL-10 and IFN-γ levels. Our work provides understanding of phenotypic diversity in association with heterogeneity in cytokine landscape in sarcoidosis.

Topics: Bronchoalveolar Lavage Fluid; Cytokines; Humans; Interleukin-10; Interleukin-18; Interleukin-6; Macrophage Migration-Inhibitory Factors; Muramidase; Sarcoidosis

A 41-year-old man presented with itching of the skin surrounding his tattoos, blurred vision, fever, general fatigue, and arthralgia. Physical examination revealed skin bulges confined to the tattoo ink lines. Histological analyses of the skin revealed non-caseating granulomas surrounding the tattoo inks. Together with other clinical manifestations including uveitis, lymph nodes swelling, and elevated serum angiotensin-converting enzyme and lysozyme, he was diagnosed with systemic sarcoidosis. The administration of prednisolone alleviated the sarcoidosis-related symptoms, including skin changes. This case illustrates that skin changes on tattoos can be a presenting manifestation of systemic sarcoidosis and that skin biopsy is useful in early diagnosis.

Topics: Adult; Biopsy; Granuloma; Humans; Male; Muramidase; Peptidyl-Dipeptidase A; Pruritus; Sarcoidosis; Skin; Tattooing; Uveitis

We examined a 22-year-old woman who was admitted to our hospital with abdominal distention. At 19 years of age, the patient presented with hepatosplenomegaly. She was examined several times in another hospital; however, the cause was unidentified. Our evaluation showed severe pancytopenia and a spleen 13×24 cm in size. The serum levels of angiotensin-converting enzyme and lysozyme were elevated. She was diagnosed with liver sarcoidosis based on non-caseating epithelioid granuloma in liver biopsy tissue. To improve the symptoms, splenectomy was performed, and her pancytopenia and symptoms improved. Sarcoidosis should be considered in cases of massive splenomegaly.

Topics: Biopsy; Female; Granuloma; Humans; Muramidase; Pancytopenia; Sarcoidosis; Spleen; Splenomegaly; Young Adult

The presence of histologically evident epithelioid granuloma is required for the diagnosis of sarcoidosis worldwide. The Japan Society of Sarcoidosis and Other Granulomatous Disorders 2015 diagnostic criteria (JSSOG 2015 criteria) includes "clinically proven diagnosis" (involvement of at least 2 of 3 systems confirmed solely by clinical assessment) because of the frequency of sarcoidosis with ocular, cardiac, and respiratory involvement in Japan and the difficulty of obtaining specimens. Here, we describe in detail the clinical presentation of clinically diagnosed sarcoidosis.. We enrolled 68 consecutive patients with clinically diagnosed sarcoidosis (12 men, 56 women) based on the JSSOG 2015 criteria who were treated at Jichi Medical University between December 2018 and January 2000. We analyzed age at diagnosis, organ involvement, and laboratory findings.. Age at diagnosis was unimodal in women. Ocular, splenic, cardiac, and skin involvement, and hypercalcemia were observed in 95.6%, 8.8%, 7.4%, 5.9%, and 35.0% of patients, respectively. High serum lysozyme and soluble interleukin-2 receptor (sIL-2R) levels, bilateral hilar lymphadenopathy on chest radiography, high-grade atrioventricular block or fatal ventricular arrhythmia, and bundle branch block were found in 18.8%, 48.3%, 95.6%, 5.0%, and 10.0% of patients, respectively.. The age-specific distribution of clinically diagnosed sarcoidosis was similar to histologically diagnosed sarcoidosis in women, as previously reported. Rates of elevated serum lysozyme and sIL-2R levels were lower in this study than previously reported in histologically diagnosed patients in Japan.

Topics: Age Factors; Biomarkers; Female; Humans; Japan; Male; Muramidase; Receptors, Interleukin-2; Sarcoidosis; Societies, Medical; Time Factors

Sarcoidosis is a systemic granulomatous disease with unknown etiology. Many clinical presentations have been reported, and acute disease needs to be distinguished from subacute and chronic disease. The unpredictable clinical course of the disease prompted us to evaluate the clinical utility of biomarker serum detection in sarcoidosis follow-up.. Serum concentrations of chitotriosidase, ACE, KL-6, and lysozyme were analyzed by different methods in a population of 74 sarcoidosis patients (46 on steroid therapy at sampling) regularly monitored at Siena Sarcoidosis Regional Referral Centre and in a group of controls with the aim of comparing their contribution to clinical management of sarcoidosis patients.. KL-6 concentrations were significantly elevated in sarcoidosis patients with lung fibrosis and were significantly correlated with DLco and CPI score, while chitotriosidase was significantly higher in patients with extrapulmonary localizations. With a cut-off value of 303.5 IU/ml, KL-6 showed the best sensitivity (78%), while chitotriosidase reported the best specificity (85%) among the biomarkers.. KL-6 is a reliable biomarker of fibrotic lung involvement in sarcoidosis patients. Among biomarkers, KL-6 showed the best sensitivity and serum chitotriosidase the best specificity, even in patients on chronic steroid therapy, and seemed to correlate with extrapulmonary localizations.

Topics: Adult; Biomarkers; Female; Hexosaminidases; Humans; Lung Diseases; Male; Middle Aged; Mucin-1; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Sensitivity and Specificity

Topics: Adult; Antirheumatic Agents; Appetite; Cell Count; Central Nervous System Diseases; Fatigue; Humans; Infliximab; Magnetic Resonance Imaging; Male; Muramidase; Proteins; Sarcoidosis; Weight Loss

Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin-2 receptor (sIL-2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL-2R compared with two other common markers, angiotensin-converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL-2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL-2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL-2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression-specific signs by imaging analysis. Receiver-operator curve analysis showed that sIL-2R was a better marker at the threshold cut-off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL-2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow-up period. In conclusion, sIL-2R may be considered a good marker for diagnosis and a potential indicator of disease activity.

Topics: Aged; Biomarkers; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Receptors, Interleukin-2; Retrospective Studies; Sarcoidosis; Sensitivity and Specificity; Severity of Illness Index; Skin Diseases

Increased serum levels of angiotensin converting enzyme and lysozyme are considered as inflammatory markers for diagnosis of sarcoidosis which is an autoimmune inflammatory disease. The purpose of this study is to evaluate the significance of differences in serum angiotensin converting enzyme and lysozyme levels of patients with ocular involvement of other autoimmune inflammatory and infectious diseases.. This is a prospective study involving patients with ankylosing spondylitis, behcet's disease, presumed sarcoidosis, presumed latent tuberculosis, presumed latent syphilis, and control group. The serum levels of angiotensin converting enzyme and lysozyme were analyzed by enzyme-linked immunosorbent assay. Bonnferoni analysis was used to assess pairwise comparisons between the groups.. There was a significant increase in serum angiotensin converting enzyme level in patients with presumed sarcoidosis compared to ankylosing spondylitis (p = 0.0001), behcet's disease (p = 0.0001), presumed latent tuberculosis (p = 0.0001), presumed latent syphilis (p = 0.0001), and control group (p = 0.0001). The increase in serum lysozyme level was significant for patients with presumed sarcoidosis with respect to ankylosing spondylitis (p = 0.0001), behcet's disease, (p = 0.0001) presumed latent tuberculosis (p = 0.001), presumed latent syphilis (p = 0.033), and control group (p = 0.0001).. Elevated serum angiotensin converting enzyme levels are significant for patients with presumed sarcoidosis compared to ocular involvement of other autoimmune diseases such as behcet's disease and ankylosing spondylitis, and ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis. However, elevated serum lysozyme level might be also detected in ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis.. NCT02627209. Date of registration: 12/09/2015.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Behcet Syndrome; Child; Communicable Diseases; Enzyme-Linked Immunosorbent Assay; Female; Humans; Latent Tuberculosis; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Prospective Studies; Sarcoidosis; Spondylitis, Ankylosing; Syphilis

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.

Topics: Animals; Antibodies, Monoclonal; Bilirubin; Case-Control Studies; Cell Membrane; CHO Cells; Cricetinae; Cricetulus; Flow Cytometry; Humans; Intercellular Signaling Peptides and Proteins; Mice; Muramidase; Mutation; Peptides; Peptidyl-Dipeptidase A; Phenotype; Protein Binding; Protein Domains; Pulmonary Surfactant-Associated Protein C; Sarcoidosis; Surface Plasmon Resonance

The purpose of this study was to determine serum levels of B-cell-activating factor (BAFF) and its clinical association in patients with sarcoidosis. METHODS; Serum levels of BAFF from 37 patients and 21 healthy subjects were examined by ELISA. Serum angiotensin-converting enzyme (ACE), lysozyme and IFN-γ levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-γ, IL-4 or IL-10 and their expression of membrane and soluble BAFF were analysed by flow cytometry or ELISA. Peripheral B cell subsets were analysed by flow cytometry. BAFF expression in the granuloma of the skin was examined by immunohistochemistry. ANAs were determined by indirect IF using HEp-2 cells as a substrate.. Serum BAFF levels were significantly elevated in sarcoidosis patients when compared with healthy controls. The frequency of skin and eye involvement was significantly higher in patients with elevated serum BAFF than in patients with normal levels. Serum BAFF levels were correlated with serum levels of ACE, lysozyme and IFN-γ. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-γ induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naïve B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity.. Serum BAFF levels can be used as a surrogate marker of disease activity in sarcoidosis patients. Increased BAFF may be related to the pathogenesis of sarcoidosis.

Topics: Aged; B-Cell Activating Factor; B-Lymphocytes; Biomarkers; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-4; Male; Middle Aged; Monocytes; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Severity of Illness Index

Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

Topics: Amyloidosis; Amyloidosis, Familial; Humans; Muramidase; Sarcoidosis; Sarcoidosis, Pulmonary

Topics: Acute Kidney Injury; Aged; Comorbidity; Diagnosis, Differential; Fanconi Syndrome; Glycosuria; Humans; Kidney Diseases; Kidney Tubules, Proximal; Male; Muramidase; Renal Insufficiency; Sarcoidosis

Since early intervention using corticosteroids improves prognosis in some patients with cardiac sarcoidosis, early and accurate diagnosis of this clinical condition is important. However, it is still not easy to evaluate the activity of cardiac sarcoidosis in clinical practice. The aim of this study was to determine whether high-sensitive cardiac troponin T (hscTnT) is useful as an additional parameter to standard assessment in patients with cardiac sarcoidosis. Twelve patients who were diagnosed as having cardiac sarcoidosis at our institution were retrospectively studied. Evaluation of patients included clinical examinations, electrocardiography, echocardiography, 67-gallium-citrate (Ga) scintigraphy, 18F-fluoro2-deoxyglucose positron emission tomography (18F-FDG PET) and laboratory data including hs-cTnT, angiotensin-converting enzyme (ACE), lysozyme and B-type natriuretic peptide (BNP). The activity of cardiac sarcoidosis was judged mainly by using 18F-FDG PET. Localized uptake of 18F-FDG, which was considered to be active cardiac sarcoidosis, was seen in 8 patients. Based on the findings of 18F-FDG PET, hs-cTnT was considered to be a reliable parameter: sensitivity and specificity were 87.5% and 75.0%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%, respectively. On the other hand, these values in lysozyme and BNP markers were not as high as those in hs-cTnT. Although an ACE marker and Ga-67 scintigraphy showed specificity and PPV of 100%, both sensitivity and NPV were less than 50%. Furthermore, hs-cTnT levels decreased after steroid therapy in some patients. Hs-cTnT seems to be a useful marker for evaluating the activity of cardiac sarcoidosis.

Topics: Aged; Biomarkers; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Fluorodeoxyglucose F18; Glucocorticoids; Humans; Male; Middle Aged; Muramidase; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Positron-Emission Tomography; Predictive Value of Tests; Retrospective Studies; Sarcoidosis; Sensitivity and Specificity; Stroke Volume; Troponin T; Ventricular Function, Left

To compare the clinical characteristics of uveitic sarcoidosis in African American and non-African American patients with biopsy-proven sarcoidosis and to determine which diagnostic test results were most often suggestive of sarcoidosis in patients who were ultimately diagnosed as having the disease.. Retrospective review of consecutive patients with biopsy-proven sarcoidosis evaluated by the uveitis service between 1989 and 2009.. A total of 63 patients with uveitic sarcoidosis were identified: 39 (62%) were African American (P <.001) and 43 (68%) were female. African American patients presented at an earlier age (P <.001) and were more likely to have granulomatous anterior segment inflammation (P <.001). The levels of serum markers angiotensin-converting enzyme and lysozyme were elevated in 40% and 42% of patients tested, respectively. The levels of at least 1 marker were elevated in 18 patients (58%). Imaging study results were reported as consistent with sarcoidosis in 25 patients (69%) who underwent chest radiography and in 19 patients (100%) who underwent computed tomography.. In this series, African American patients were more likely to be diagnosed as having uveitic sarcoidosis and to present with uveitis if they were younger than 50 years. White patients were more likely to present when they were older than 50 years. A clinical picture that included granulomatous anterior segment inflammation was more common in African American patients. The use of serum markers (angiotensin-converting enzyme and lysozyme) positively identified more patients with biopsy-proven sarcoidosis when used in combination with appropriate chest imaging.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Black or African American; Female; Humans; Male; Mass Chest X-Ray; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Retrospective Studies; Sarcoidosis; Sarcoidosis, Pulmonary; Uveitis; Visual Acuity; White People; Young Adult

Accumulation of macrophages in multiple organs is a common feature of sarcoidosis and Gaucher disease. The vast number of storage macrophages in Gaucher patients has facilitated the discovery of suitable plasma markers like chitotriosidase and CCL18.. Plasma specimens of patients with sarcoidosis were examined on chitotriosidase activity and CCL18 protein levels.. Chitotriosidase was markedly increased, being on average 13.7-fold elevated (range: 1.1-43.3). The sensitivity of demonstrating sarcoidosis using plasma chitotriosidase values exceeded that using serum angiotensin-converting enzyme values. A 3.5-fold (range: 1-15) increase in CCL18 was also observed. The relative changes in chitotriosidase and CCL18 during the course of disease closely mimicked each other, suggesting an identical cellular source. In situ hybridization analysis confirmed massive production of chitotriosidase by sarcoid macrophages. The increase in plasma chitotriosidase correlated with the stage of disease, being highest in active sarcoidosis with extrapulmonary involvement. Therapy with steroids resulted in clear reduction of plasma chitotriosidase and CCL18 and relapse of disease activity was preceded by increases in these parameters.. Sarcoid macrophages secrete high quantities of chitotriosidase and CCL18. Determination of plasma chitotriosidase and CCL18 may be useful to monitor changes in granulomatous macrophages during the course of sarcoidosis.

Topics: Adult; Aged; Biomarkers; Bronchoalveolar Lavage Fluid; Chemokines, CC; Enzyme-Linked Immunosorbent Assay; Female; Hexosaminidases; Humans; In Situ Hybridization; Macrophages; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

The purpose of this study was to describe patients initially carrying a diagnosis of primary intraocular lymphoma who were ultimately diagnosed with ocular sarcoidosis.. The medical records of patients evaluated between 1995 and 2007 fitting the criteria described earlier were identified, and pertinent clinical findings allowing for the diagnosis of sarcoidosis are described.. Nine patients between the ages of 52 and 83 were referred with a diagnosis of primary intraocular lymphoma but were ultimately diagnosed with sarcoidosis. The most common clinical signs found in these patients that are atypical for primary intraocular lymphoma but common in sarcoidosis were multifocal choroiditis (n = 7) and cystoid macular edema (n = 6). Additional findings included keratic precipitates, posterior synechiae, and Koeppe nodules. Chest computerized tomography was consistent with sarcoidosis in seven of eight tested patients, and five of these patients had normal chest x-rays. Other findings included elevated angiotensin-converting enzyme and/or lysozyme, and biopsy revealing noncaseating granulomas.. Although primary intraocular lymphoma should always be in the differential diagnosis of older patients who present with signs of ocular inflammation, ophthalmologists must also consider other etiologies, including sarcoidosis. A chest computerized tomography may be helpful in the diagnosis, particularly when laboratory findings are supportive of sarcoidosis.

Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Diagnostic Errors; Eye Diseases; Eye Neoplasms; Female; Humans; Lymphoma, B-Cell; Magnetic Resonance Imaging; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Tomography, X-Ray Computed; Uveitis; Vitreous Body

Rheumatoid arthritis was diagnosed in a 30-year-old woman with erythema nodosum and arthritic symptoms since 1994, and she was treated with anti-rheumatic agents. Mediastinal and bilateral hilar lymphadenopathy and abnormal pulmonary shadows were detected in 1996, and she was admitted to our hospital in 1997. We also recognized the elevation of ACE and lysozyme, and found granulomas in a transbronchial lung biopsy and an arthrosis synovia biopsy. From these findings, sarcoidosis was diagnosed. Sarcoidosis demonstrating erythema nodosum, arthritis, and bilateral hilar lymphadenopathy is called Löfgren's syndrome. In Caucasians, Löfgren's syndrome is frequently encountered, but it is rare in Japanese. Our case had coexisting arthrosis symptoms, and satisfied the diagnosis criteria of rheumatic arthritis. Therefore, the differential diagnosis was important. We emphasize that it is necessary to consider Löfgren's syndrome when diagnosing patients with rheumatic features, even in Japan.

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Biomarkers; Diagnosis, Differential; Erythema Nodosum; Female; Humans; Lung; Lymphatic Diseases; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Syndrome; Synovial Membrane; Tomography, X-Ray Computed

A 53-year-old man was admitted to Osaka City University Hospital on July 21, 1998, for investigation of symptomatic hypercalcemia. Laboratory data on admission revealed that serum Ca had increased to around 12.6 mg/dl and there was a significant increase in urinary Ca excretion. The serum phosphate level remained normal. Although the serum PTH level was below the detection limit, serum 1,25-dihydroxyvitamin D (1,25(OH)2D) was increased. Diagnosis of sarcoidosis was supported by a negative tuberculin test and by the elevated levels of serum angiotensin-converting enzyme (ACE), lysozyme activity, and CD4/CD8 ratio in bronchoalveolar lavage specimen; there was however no imaging evidence of sarcoidosis such as bilateral hilar lymphnode enlargement on chest X-ray, high resolution CT or 67Ga citrate scintigraphy. Biopsy specimens from the cervical lymphnode revealed no epitheloid cell granulomas or giant cells. Administration of prednisolone achieved a decrease in serum ACE and 1,25(OH)2D levels, followed by restoration of serum Ca and urinary Ca excretion to the normal range, and finally by an increase of serum PTH to the normal level. These observations suggested that the hypercalcemia could be explained by extrarenal production of 1,25(OH)2D. We report here on this rare case of sarcoidosis with initial symptoms of symptomatic hypercalcemia resulting from extrarenal production of 1,25(OH)2D.

Topics: Bronchoalveolar Lavage Fluid; Calcitriol; Calcium; CD4-CD8 Ratio; Glucocorticoids; Humans; Hypercalcemia; Male; Middle Aged; Muramidase; Parathyroid Hormone; Peptidyl-Dipeptidase A; Prednisolone; Sarcoidosis; Treatment Outcome

Cardiac involvement is the major determinant of morbidity and mortality in patients with sarcoidosis, but clinical evaluation of the disease activity is occasionally difficult in cardiac sarcoidosis. The present study examined whether serum levels of interleukin-10 (IL-10) could reflect the disease activity of patients with cardiac sarcoidosis. Serum IL-10 levels were measured using an enzyme-linked immunosorbent assay, and compared with clinical manifestation, levels of angiotensin-converting enzyme (ACE), levels of lysozyme and accumulation of gallium-67 citrate. Sera were collected from 8 patients with cardiac sarcoidosis (CS group), 22 patients with miscellaneous heart diseases except for sarcoidosis (MHD group), and 8 healthy control subjects (HC group). Serum IL-10 levels of the CS group were significantly higher than those of the 2 control groups. Before steroid therapy, the levels of IL-10 in the CS group showed a significantly positive correlation with levels of ACE (r=0.868, p<0.05) and lysozyme (r=0.890, p<0.05). In 5 patients who were analyzed before and after steroid therapy, the levels of IL-10 tended to correlate with a decrease of an abnormal accumulation in gallium-67 citrate. Serum IL-10 levels may play a role in evaluation of the disease activity in patients with cardiac sarcoidosis.

Topics: Adult; Aged; Cardiomyopathies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Male; Middle Aged; Muramidase; Renin; Sarcoidosis

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

Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0. 05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases.

Topics: Clinical Enzyme Tests; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Sarcoidosis, Pulmonary; Sensitivity and Specificity

Topics: Adult; Diagnosis, Differential; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Meningitis; Muramidase; Peptidyl-Dipeptidase A; Radiography; Sarcoidosis

Measurement of the pulmonary clearance of aerosolized 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) as a marker of pulmonary parenchymal damage was performed in 10 non-smokers with sarcoidosis, none of whom was on medication, and the results compared with 12 normal controls. Posterior images were obtained using a single-headed gamma camera, with the subjects in a supine position, for 30 min after inhalation of aerosolized 99Tcm-DTPA had ceased. The pulmonary clearance of 99Tcm-DTPA was significantly increased in the sarcoidosis patients (57.6 +/- 22.1 min in the right lung, 62.2 +/- 22.7 min in the left lung) compared with the controls (79.3 +/- 10.2 and 78.4 +/- 7.7 min in the right and left lungs, respectively) (P < 0.05). Six of the 10 patients with sarcoidosis showed levels of pulmonary clearance, in both the right and left lungs, below the 95.5% confidence limit (mean +/- 2 S.D.) for the controls. Increased pulmonary clearance of 99Tcm-DTPA was also found in 2 of 4 patients with stage I sarcoidosis. No relationship was found between the pulmonary clearance of 99Tcm-DPTA and inflammatory markers (ACE, lysozyme) in the serum.

Topics: Adult; Aerosols; Aged; Female; Humans; Kinetics; Lung; Male; Middle Aged; Muramidase; Radionuclide Imaging; Reference Values; Sarcoidosis; Technetium Tc 99m Pentetate; Time Factors

A 30-year-old Japanese woman relapsed into sarcoidosis after two successive parturitions. The cutaneous lesions consisted of scar sarcoidosis, papular type, nodular type, and subcutaneous nodules with histologically typical "naked tubercles". Hypergammaglobulinemia, elevation of both serum angiotensin converting enzyme and lysozyme levels, and bilateral hilar lymphadenopathy were found in the acute and subacute stages, and spontaneously returned to normal levels 16 months after the onset. Our case suggests that parturition may trigger the onset of sarcoidosis.

Topics: Acute Disease; Adult; Female; Humans; Hypergammaglobulinemia; Labor, Obstetric; Muramidase; Peptidyl-Dipeptidase A; Pregnancy; Pregnancy Complications; Recurrence; Remission, Spontaneous; Sarcoidosis; Skin Diseases

Polyclonal elevation of immunoglobulins is classically described in sarcoidosis and could possibly be useful in the work-up of suspected sarcoidosis uveitis. Because exposure to viruses of the herpes group is high in all populations, determination of herpes serologies is probably suited for this purpose.. Therefore serum anti-herpes antibody patterns in sarcoidosis (SARC), HLA-B27 positive acute anterior uveitis (AAU), pars planitis (PP) and healthy age-matched controls were analysed. Frozen sera were analysed for exposure to CMV, HSV, VZV by ELISA IgG testing and to EBV-VCA by immunofluorescence. Complement fixing titers > or = 1/40 and an EBV-VCA titer > or = 1/1280 were considered elevated. For each patient exposed to 2 or more herpes viruses, a score made out of the number of elevated titers divided by the number of herpes viruses the patient was exposed to, was calculated and mean scores were compared using Student's t-test.. Mean score of patients with sarcoidosis was 0.47 +/- 0.27 (N = 18, mean age 60.2 +/- 21.4 years), significantly higher than AAU (N = 21; score 0.12 +/- 0.2; p < or = 0.000), than PP (N = 20; score 0.18 +/- 0.2; p < 0.003), and than age-matched healthy controls (N = 341, mean age 59 +/- 5.5 years; score = 0.15 +/- 0.14; p < 0.000).. Anti-herpes antibodies were found to be significantly elevated in sarcoidosis uveitis, suggesting that herpes serologies may be useful in the work-up of suspected ocular sarcoidosis, a disease for which sufficiently sensitive and specific tests are lacking.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Viral; Female; Herpesvirus 4, Human; Humans; Immunoglobulins; Keratitis, Herpetic; Male; Middle Aged; Muramidase; Sarcoidosis; Sarcoidosis, Pulmonary; Simplexvirus; Uveitis

Total neopterin (T-N), a by-product in the biopterin biosynthesis and an indicator of activation of the cellular immune system, and total biopterin (T-B) levels in cerebrospinal fluid (CSF), were measured in patients with various inflammatory neurological diseases and Parkinson's disease, and the following results were obtained. (1) In patients with neuro-sarcoidosis, neuro-Behçet's disease and meningitis, CSF T-N levels were markedly elevated in the exacerbation or acute stages of their neurological symptoms and remarkably decreased in the remission or chronic stages. In the neuro-sarcoidosis and neuro-Behçet's disease patients, however, CSF T-B levels showed no substantial change. (2) There was a significant positive correlation between CSF T-N levels and CSF/serum albumin ratios only in the meningitis patients. However, increases of CSF T-N levels were not associated with those of plasma T-N levels. (3) In the Parkinson's disease patients, CSF T-N levels remained normal, although CSF T-B levels significantly decreased. (4) A gradient for the CSF T-N value (lumbar greater than ventricular CSF), being reverse to the CSF T-B value, was observed. These results indicate that the significance of CSF T-N is quite different from CSF T-B, and that CSF T-N appears to be a valuable biochemical marker for evaluating the activity of inflammation within the central nervous system. Its measurement seems useful for therapeutic monitoring, especially of patients showing the chronic exacerbating-remitting course.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Behcet Syndrome; Biopterins; Female; Humans; Immunity, Cellular; Male; Meningitis; Muramidase; Neopterin; Nervous System Diseases; Sarcoidosis

Neurosarcoidosis is a well-recognised complication of systemic sarcoidosis but diagnosis may be difficult if there is no clear evidence of an extracerebral manifestation of the disease. We present the case of a 42-year-old woman with clinical features characteristic of cerebral sarcoidosis including tetraparesis, diabetes insipidus, diencephalic hyperphagia, personality changes, and memory loss. Diagnosis was supported by cerebrospinal fluid (CSF) findings and magnetic resonance imaging (MRI): CSF showed mild lymphocytic pleocytosis, intrathecal production of IgG without oligoclonal bands, and a raised level of lysozyme. MRI revealed multiple contrast-enhanced granulomas at the base of the brain with partial involvement of diencephalic and mesencephalic structures and parts of the spinal cord. There was no evidence of systemic manifestation of sarcoidosis. Administration of corticosteroids led to improvement of the symptoms.

Topics: Adult; Brain; Brain Diseases; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Spinal Cord; Spinal Cord Diseases

Serum angiotensin-converting enzyme activity (SACE) and lysozyme activity were measured in a group of 40 underground coal miners and two control groups, 20 subjects with sarcoidosis and 15 normal non-dust-exposed volunteers. The miners were grouped first according to whether they had recent exposure (still actively mining or retired three years or less prior to measurement) or temporally more distant exposure (retired more than three years prior to measurement). Secondly, they were grouped as to whether or not they had coal workers' pneumoconiosis (CWP). The subjects with sarcoidosis were grouped according to disease activity. As expected, the subjects with active sarcoidosis had elevated SACE activity compared with normal subjects. The coal miners as a group did not have elevation of their SACE activity. However, the coal miners with recent exposure had elevated SACE activity (57.1 +/- 3.9 U/ml) compared with normal controls (43.8 +/- 1.5 U/ml, p = 0.007). The SACE activity in miners without recent exposure was not elevated (39.8 +/- 1.3 U/ml) compared with the normal controls. No increase in SACE activity was found when the miners were grouped according to the presence or absence of CWP. In contrast, the miners' serum lysozyme activity was not elevated. Since alveolar macrophages are a potential source of SACE, elevation of SACE activity in underground coal miners may reflect alveolar macrophage activation caused by increased pulmonary mixed coal mine dust burden. Furthermore, since both SACE and serum lysozyme are elevated in association with silicosis, these findings may confirm that the macrophage responses to inhaled silica and coal dust differ.

Topics: Coal Mining; Humans; Lung Diseases; Macrophage Activation; Macrophages, Alveolar; Male; Middle Aged; Muramidase; Occupational Exposure; Peptidyl-Dipeptidase A; Pneumoconiosis; Sarcoidosis; Time Factors

In 30 patients with sarcoidosis we estimated immunohistochemically the activity of lysozyme in correlation to the activity of ACE in serum and found a positive correlation between these two parameters. We conclude, that the lysozyme content of sarcoidotic granulomas, estimated immunohistochemically, may be a useful morphological parameter of the activity of the disease, applicable on formol fixed and paraffin embedded bioptical material.

Topics: Adult; Biopsy; Female; Humans; Immunoenzyme Techniques; Lung Diseases; Lymph Nodes; Male; Mediastinoscopy; Muramidase; Peptidyl-Dipeptidase A; Prognosis; Sarcoidosis

The content of lysozyme in the phagocytosing peripheral blood cells was carried out in 50 patients with active pulmonary sarcoidosis depending on the clinical form, extension and duration of the pathological processes. The function of these cells showed essential changes in patients with widely spread old processes and those of long duration. The changes of lysozyme secretion by neutrophil granulocytes and monocytes were diverse that may be explained by different mechanisms of this process in the cells.

Topics: Chronic Disease; Lung Diseases; Lymphatic Diseases; Monocytes; Muramidase; Neutrophils; Phagocytosis; Sarcoidosis

The aim of this study was to explore whether amounts of angiotensin converting enzyme (ACE) and lysozyme produced within the lungs correlate more closely than serum levels of these enzymes, or other inflammatory markers, with chest radiographic profusion scores, lung function and therapy response in patients with pulmonary sarcoidosis. We have studied 25 patients, and levels in bronchoalveolar lavage (BAL) were used to determine "local" enzyme production by reference to serum and lavage albumin. Before treatment, serum lysozyme levels were elevated in more patients (80%) than serum ACE levels (40%). They also gave the best overall correlation with clinical measurements prior to treatment and falls in serum lysozyme closely parallelled improvement in lung function (transfer factor for carbon monoxide (DLCO)) on therapy. The only other markers showing significant correlations with disease severity were lavage neutrophil counts per ml and "local" ACE measurements prior to treatment. The value of pre-treatment levels of the different inflammatory markers in predicting response to corticosteroid therapy was explored and the only significant finding was that BAL lymphocyte percentages and numbers.ml-1 were initially higher in patients with lower post-treatment chest X-ray scores (p less than 0.01 and p less than 0.05, respectively). We conclude that serum lysozyme levels appear to be a more useful marker of overall disease activity in sarcoidosis than measurements of other inflammatory markers. However, BAL lymphocyte counts were the best predictive marker of radiographic response to corticosteroids.

Topics: Adult; Albumins; Biomarkers; Bronchoalveolar Lavage Fluid; Cell Count; Female; Humans; Lung Diseases; Lymphocytes; Macrophages; Male; Middle Aged; Muramidase; Neutrophils; Peptidyl-Dipeptidase A; Radiography; Sarcoidosis; Serum Albumin

Focally aggregated epithelioid cells and granulomatous epithelioid cell reactions of different genesis were investigated immunohistochemically by means of PAP method according to Sternberger. We studied the presence of histiocytic markers lysozyme and alpha 1-antichymotrypsin, the content of albumin and of immunoglobulins and the question of immunophagocytosis and the presence of fibronectin. Various forms of activation of epithelioid cells as well as histiocytes and Langhans giant cells were found thereby. In the former, a phagocytosis could never be demonstrated, whereas this was true in histiocytes and giant cells. Fibronectin was not found in epithelioid cells. The findings suggest that epithelioid cells are a specific form of reaction of histiocytic elements. Thus they are a special reaction of MPS in a multiple causal genesis and a morphogenesis according to its own characteristics within a hypersensitivity reaction of a delayed type. Epithelioid cells modulate the immune response and in this way the tissue reaction.

Topics: Albumins; alpha 1-Antichymotrypsin; Fibronectins; Granuloma; Humans; Immunoenzyme Techniques; Immunoglobulins; Immunohistochemistry; Lymph Nodes; Lymphoma; Muramidase; Phagocytes; Phagocytosis; Sarcoidosis; Tuberculoma; Tuberculosis, Lymph Node

Own experiences in practical application of immunohistochemistry are demonstrated in cases of lung fibrosis, sarcoidosis, tuberculosis and allergic vasculitis. Methods for demonstration of immunoglobulins (IgG, IgE) are useful in diagnosis of allergic vasculitis (IgG) and allergic alveolitis (IgE). Lysozyme is an important morphological parameter for the estimation of the activity of sarcoidosis. First results of application of antisera against mycobacteria and Kveim antigen are discussed in respect to more precise differential diagnosis of granulomatous lung diseases (sarcoidosis, tuberculosis).

Topics: Alveolitis, Extrinsic Allergic; Antigens, Bacterial; Humans; Immunoglobulins; Immunohistochemistry; Lung; Lung Diseases; Muramidase; Mycobacterium; Pulmonary Fibrosis; Sarcoidosis; Tuberculosis, Pulmonary; Vasculitis

The number and distribution of lysozyme and S100 immunoreactive cells were analyzed in ten cases of lymph node sarcoidosis. Three phases of granuloma development could be differentiated, each showing a typical immunohistological pattern. The early small granulomas consisted of lys- or very weakly lys+ mononuclear phagocytes and developed within an area of focalized accumulation of S100+ antigen-presenting cells. The mature large granulomas were composed of polygonal epithelioid cells with abundant cytoplasm showing very strong granular lysozyme positivity. S100+ cells could still be observed, mainly around the granulomas, but in diminished number. In the final fibrozing phase the epithelioid cells lost their lysozyme immunoreactivity and no S100+ antigen-presenting cells were present within or around the granulomas. In one patient granulomas with central necrosis and palisading, lys- epithelioid cells were also observed, possibly representing a different microenvironment (antigen/antibody equilibrium?). The change in the pattern and number of lysozyme and S100 immunoreactive cells probably reflects the development of the granulomas and is related to the activity of the disease.

Topics: Epithelium; Granuloma; Histocytochemistry; Humans; Lymph Nodes; Lymphatic Diseases; Muramidase; Necrosis; S100 Proteins; Sarcoidosis; Staining and Labeling

We determined the serum angiotensin converting enzyme and lysozyme levels in 221 patients with uveitis and in 67 control subjects. Angiotensin converting enzyme and lysozyme levels were found to be age dependent. Of the 221 patients, 12 had sarcoidosis. In patients with uveitis who had an angiotensin converting enzyme level above 50 units/l (mean + 2 S.D.), the sensitivity of the test was 84%, the specificity was 95%, and the predictive value was 47%. In these same patients the sensitivity was 60% for a lysozyme level above 8 mg/l (mean + 2 S.D.), the specificity was 76%, and the predictive value was 12%.

Topics: Adult; Aging; Eye Diseases; Female; Forecasting; Humans; Longitudinal Studies; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Uveitis

For a complete evaluation of a patient with suspected neurosarcoidosis, combination of the newer CSF, neurophysiological, and neuroradiological studies is needed. CSF enzyme studies are useful in cerebral lesions and especially in cranial nerve lesions where CT and MRI usually fail to show abnormalities. Evoked potential examinations are a helpful noninvasive method for detection of both cerebral and cranial nerve lesions. Although CT and MRI are mainly abnormal in patients with cerebral symptoms they can disclose unexpected CNS involvement even in patients with mainly cranial nerve affection. However, even the newest diagnostic methods are nonspecific, and histologically verified systemic sarcoidosis still remains the mainstay of diagnosis.

Topics: Adult; Aged; beta 2-Microglobulin; Brain; Central Nervous System Diseases; Evoked Potentials, Auditory; Evoked Potentials, Visual; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Tomography, X-Ray Computed

The proliferation of lymphocytes induced by Propionibacterium acnes (P. acnes) was measured by the in vitro incorporation of 3H-thymidine. The mean response rate of alveolar lymphocytes obtained by bronchoalveolar lavage was 2.23 +/- 0.89 in nine untreated sarcoidosis patients, 0.85 +/- 0.17 in five sarcoidosis patients given corticosteroids and 0.78 +/- 0.29 in 11 controls. The proliferation was significantly enhanced in the untreated patients compared to both the treated patients (p less than 0.01) and controls (p less than 0.001), but there was no significant difference in response rates between the treated patients and controls. The response rate of alveolar lymphocytes was significantly higher in four active patients (3.05 +/- 0.61) than in four inactive patients (1.77 +/- 0.44) (p less than 0.05) and in the controls (p less than 0.001). In sarcoidosis patients, the response rates showed a good correlation with activities of serum lysozyme (r = 0.695, p less than 0.01), and with percentages of lymphocytes in bronchoalveolar lavage fluid (r = 0.591, p less than 0.05). There was a low correlation between angiotensin-converting enzyme activities and the response rates (r = 0.508, p less than 0.1). Neither peripheral blood lymphocytes in sarcoidosis patients nor in controls showed any response to P. acnes, but alveolar lymphocytes of the untreated active sarcoidosis patients were sensitive to P. acnes. The lymphocytes activated by P. acnes may play a central role in the induction of alveolitis in sarcoidosis patients.

Topics: Adult; Aged; Bacterial Infections; Cell Division; Female; Humans; Lymphocytes; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Prednisolone; Propionibacterium acnes; Pulmonary Alveoli; Sarcoidosis

1 alpha,25-Dihydroxyvitamin D3, the active form of vitamin D3, induced maturation of circulating monocytes to form macrophage-epithelioid cells and multinucleated giant cells in vitro. Calcitriol not only promoted the differentiation of monocytes, as shown by the marked morphological changes and enhanced secretion of lysozyme, but also induced their prominent proliferation, as exhibited by enhanced DNA synthesis and the increased number of monocyte cell nuclei. The proliferation of monocytes was observed after the addition of physiological concentrations of calcitriol. Multinucleated giant cells were frequently observed among the monocytes. These marked morphological changes and the proliferation of monocytes were not observed in control cultures, which did not include calcitriol. These results indicate that calcitriol plays a critical role in the formation of the sarcoid granuloma and give an explanation of some of the clinical findings on sarcoidosis. In view of the evidence that sarcoid macrophages convert 25(OH)D3 to calcitriol, our results raise the possibility that the active metabolite of vitamin D3, which may be produced by macrophage-epithelioid cells, induces the differentiation and proliferation of circulating monocytes into macrophage-epithelioid cells, which in turn form sarcoidosis granulomas. This autostimulation mechanism of sarcoid granuloma formation may provide a model for future studies.

Topics: Adult; Calcitriol; Cell Differentiation; Cell Division; Cell Separation; Cells, Cultured; Epithelial Cells; Epithelium; Humans; Macrophages; Mitosis; Monocytes; Muramidase; Sarcoidosis; Time Factors

The levels of lysozyme (LZM) and beta 2-microglobulin (beta 2m) were measured in the cerebrospinal fluid (CSF) and serum of 32 patients with sarcoidosis, 20 of whom had neurosarcoidosis. LZM was analyzed by a new radioimmunoassay (RIA) modification. CSF LZM was elevated in 15 of 20 patients with neurosarcoidosis but in only 4 of 12 patients with extraneural sarcoidosis. CSF beta 2m values were elevated in 13 of 19 and in one of 11 patients, respectively. In neurosarcoidosis, both CSF LZM and beta 2m correlated to CSF leucocytes but not significantly to CSF albumin thus suggesting that LZM and beta 2m were secreted from cells within the central nervous system (CNS). In patients with sarcoidosis, elevations of CSF LZM and beta 2m revealed disease activity in the CNS. Both analyses were also useful in the follow-up of neurosarcoidosis.

Topics: Adult; Aged; beta 2-Microglobulin; Humans; Middle Aged; Muramidase; Nervous System Diseases; Sarcoidosis

The lysozyme activity in tissue samples from patients with lupus miliaris disseminatus faciei (LMDF), sarcoidosis and foreign body granuloma was investigated using the immunoperoxidase technique. The majority of epithelioid cells and giant cells in LMDF and sarcoidosis showed strong lysozyme staining in their cytoplasm. However, most macrophages and giant cells in foreign body granulomas, including granulomatous reactions to epidermal cysts and other foreign materials, stained weakly for lysozyme or were negative. These results suggest that LMDF is different from the foreign body reaction to inert substances, and may be induced by an immunological mechanism associated with cell-mediated immunity.

Topics: Adult; Aged; Female; Foreign-Body Reaction; Granuloma; Humans; Immunoenzyme Techniques; Lupus Vulgaris; Male; Middle Aged; Muramidase; Sarcoidosis; Skin

In the deteriorating group of sarcoidosis patients, progress towards pulmonary fibrosis is a major problem. In order to benefit from corticosteroids, it is important for the treatment to start early. We studied a group of 45 patients with sarcoidosis. Most of them were newly detected patients and none were under or had currently received corticosteroid therapy. The patients were followed for at least six months. We found that increased amounts of polymorphonuclear neutrophils (PMN) or lysozyme-positive macrophages (Lys+MF) and mast cells (MC) in bronchoalveolar lavage (BAL) could implicate a bad prognosis.

Topics: Bronchi; Erythema Nodosum; Female; Follow-Up Studies; Humans; Lung Neoplasms; Macrophages; Male; Mast Cells; Middle Aged; Muramidase; Neutrophils; Prognosis; Pulmonary Alveoli; Sarcoidosis; Syndrome; Therapeutic Irrigation

Two groups of sarcoidosis patients were studied. One group of 24 patients had previously had erythema nodosum (EN+), and the other group of 54 patients had never had any such extrathoracic manifestation of the disease (EN-). The two groups were similar with respect to age, disease duration, chest radiographic appearance, and granuloma mass as estimated from the serum concentration of lysozyme. Neutrophil phagocytic function was studied by a kinetic method which allows distinction between Fc- and C3b-receptor-mediated uptake. Fc-receptor function was normal in both groups. The function of C3b receptors was normal in the EN+ groups but significantly reduced in the EN- group. This observation indicates that sarcoidosis associated with erythema nodosum may represent a separate disease entity with respect to the pathogenetic mechanism involved in granuloma formation.

Topics: Adult; Erythema Nodosum; Female; Humans; Immunoglobulin G; Male; Middle Aged; Muramidase; Neutrophils; Phagocytosis; Receptors, Complement; Receptors, Complement 3b; Sarcoidosis; Time Factors

The object of this study was to evaluate the effectiveness of the immuno-suppressor Azathioprine (AZ) on chronic and severe pulmonary sarcoidosis, with a persistent activity resistant to prolonged corticotherapy. The study was done on 10 patients (4 women, 6 men) afflicted by an histologically proven and chronic sarcoidosis, resistant to steroid treatment. The treatment consisted of a daily oral intake of 150 mg of AZ for six months. Its effectiveness was evaluated before and after treatment, in comparison with a control group and a steroid-treated group of sarcoid patients. Serologic and alveolar functional and immuno-biologic tests were performed in 8 cases according to the activity criteria defined at the IXth International Congress on sarcoidosis. No clinical or hematological side effects were observed; a clear and prolonged radiological and clinical amelioration was observed in 7 out of 10 cases and in 3 cases a restoration of sensibility to the tuberculin skin test; in the 8 cases a significant improvement (p less than 0.01) was noted after the sixth month of treatment only in the alveolar fluid in the following parameters: ACE, all the proteins studied and the percentage of lymphocytes.

Topics: Adult; alpha 1-Antitrypsin; Azathioprine; Drug Evaluation; Female; Humans; Lung Diseases; Lymphocytes; Male; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

The phagocytic and complement receptor function of polymorphonuclear neutrophils (PMN) from patients with sarcoidosis was studied using a kinetic assay which allows the distinction to be made between Fc receptor-mediated and C3b receptor-mediated particle uptake. The study included one group (A) of patients with active disease (n = 20), and one group (B) with silent or inactive disease who since 10 years had no symptoms or radiological signs of sarcoidosis (n = 11). Abnormal C3b receptor function was observed in both groups but the impairment was most pronounced in the A group. The presence of C3b receptor dysfunction in both groups with a quantitative difference between the groups, is compatible with C3b receptor dysfunction being a primary causal factor of sarcoidosis.

Topics: Adult; Aged; Female; Humans; Immunoglobulin G; Lung Compliance; Lung Diseases; Male; Middle Aged; Muramidase; Neutrophils; Phagocytosis; Receptors, Complement; Receptors, Complement 3b; Respiratory Function Tests; Sarcoidosis

Seven patients with Hodgkin's disease were studied for the presence of lysozyme and alpha-1-antitrypsin activity by immunoelectron microscopy. As a result, Reed-Sternberg cells, Hodgkin's cells, and atypical cells were distinctly positive for lysozyme in four cases and weakly positive in the remaining three cases. These cells were also positive for alpha-1-antitrypsin in all cases. Because the cells of the monocyte-macrophage lineage also bore lysozyme and alpha-1-antitrypsin, it is suggested that Reed-Sternberg cells, Hodgkin's cells, and the atypical cells are derived from the monocyte-macrophage lineage.

Topics: alpha 1-Antitrypsin; Histocytochemistry; Hodgkin Disease; Humans; Immunoenzyme Techniques; Leukemia, Myeloid; Lymph Nodes; Lymphatic Diseases; Macrophages; Microscopy, Electron; Monocytes; Muramidase; Sarcoidosis; Tuberculosis

Topics: Adrenal Cortex Hormones; beta 2-Microglobulin; Calcium; Humans; Hydroxyproline; Immunoglobulin Light Chains; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Transcobalamins

Topics: Acute Disease; Adult; Aged; Blood Donors; Clinical Enzyme Tests; Humans; Immune System Diseases; Intestinal Diseases; Leukemia; Lung Diseases; Muramidase; Sarcoidosis

Chemotactic and chemokinetic activity was studied in sera from 57 patients with various stages of sarcoidosis. Reduced chemotactic activity was observed in 39% of the sera, mainly in sera from patients with parenchymal densities on chest radiographs. Increased chemokinetic activity was noted in more than one third of the fresh sarcoid sera. Asymptomatic patients showed higher chemokinetic activity in their sera than patients with symptoms. The presence of heat-stable chemokinetic inhibitors was suggested in one third of the cases. No relationship was found between these inhibitors and the inhibitors of neutrophil phagocytosis previously demonstrated in sarcoid sera. Although many of the findings show minor differences to those of normal sera, the liability in sarcoidosis to produce a variety of inhibitors directed against various functions of neutrophils would theoretically hamper the elimination of putative antigens. The presence of serum mediated stimulation and inhibition of neutrophil locomotion could be significant for the pathogenesis of the disease.

Topics: Aminopeptidases; Cell Migration Inhibition; Cell Movement; Chemotactic Factors; Chemotaxis, Leukocyte; Complement C3; Humans; Lactoferrin; Lung Diseases; Muramidase; Neutrophils; Orosomucoid; Phagocytosis; Sarcoidosis

67Ga scintigraphy, using a 67Ga accumulation score, was compared with serum lysozyme (LZM) and angiotensin-converting enzyme (ACE) levels in 34 patients with biopsy-proven, pulmonary sarcoidosis. Serum LZM and ACE values varied between 1.0 to 21.3 mg/l (mean 4.3 +/- 3.4 mg/l) and 33 to 146 U/l (mean 69 +/- 26 U/l), respectively. Normal values were found in 26 and 35% of the patients. All patients, however, had abnormal 67Ga uptake in the pulmonary hilar lymph nodes and/or parenchyma. The follow-up of untreated and treated patients supports the suggestion that 67Ga scintigraphy is more useful for assessing the extent and activity of the intrathoracic sarcoid lesions. Serum LZM and ACE measurements are helpful, but normal LZM and ACE values do not exclude activity and progression of disease in pulmonary sarcoidosis.

Topics: Adult; Aged; Female; Gallium Radioisotopes; Humans; Lung Diseases; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Radionuclide Imaging; Sarcoidosis

A 55-year-old woman was described who developed an acute myelomonocytic leukemia 4 years after remission of sarcoidosis. This association is of particular interest since pronounced T cell dysfunction appears in sarcoidosis. We traced serum angiotensin-converting enzyme and serum or urinary lysozyme levels of this patient.

Topics: Clinical Enzyme Tests; Female; Humans; Leukemia, Myeloid, Acute; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

During the last decade, many biochemical and immunologic advances have been made in the treatment and understanding of sarcoidosis. These studies have helped us to understand the basic mechanisms involved in granuloma formation, and many clinicians have used the information to diagnose and assess the activity of sarcoidosis. Further studies are needed to clearly establish the role of these advances in the everyday management of patients with sarcoidosis.

Topics: Bronchoscopy; Gallium Radioisotopes; Humans; Kveim Test; Lung Diseases; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Therapeutic Irrigation; Transcobalamins

Topics: Antibody Formation; Humans; Immunity, Cellular; Lung Diseases; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Topics: Antigen-Antibody Complex; Humans; Lung Diseases; Muramidase; Peptidyl-Dipeptidase A; Pulmonary Fibrosis; Sarcoidosis

Topics: Humans; Lung Diseases; Lung Volume Measurements; Muramidase; Peptidyl-Dipeptidase A; Radiography, Thoracic; Radionuclide Imaging; Sarcoidosis; Therapeutic Irrigation

A simple, rapid, reproducible method of quantifying tear lysozyme levels with a dual-channel spectrophotometer was used to compare normal subjects and those with dry-eye syndrome. The method was sensitive (80%) and specific (85%) and had a predictive value of a positive result of 83%. One patient with clinical manifestations of dry-eye syndrome and paradoxically elevated levels of tear lysozyme was found to have underlying sarcoidosis.

Topics: Humans; Lacrimal Apparatus Diseases; Muramidase; Sarcoidosis; Sjogren's Syndrome; Syndrome; Tears

The relationship between serum angiotensin-converting enzyme (SACE) and serum lysozyme (SLZ) was examined in 48 patients with sarcoidosis. The level of at least one enzyme was elevated in all 41 cases with active sarcoidosis; both enzymes were elevated in 24. SACE and SLZ were positively correlated. The elevation of SLZ or SLZ+SACE was most frequent in patients with pulmonary parenchymal involvement or extrathoracic manifestations. Both enzymes are suitable for disease monitoring, but in most cases the more specific SACE must be preferred as a measure of disease activity, although SLZ seems to be a little more sensitive. Blood for SACE analysis must arrive at the laboratory not later than 3 days after blood collection in order to avoid enzyme inactivation.

Topics: Adult; Aged; Humans; Lung Diseases; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Specimen Handling; Time Factors

Topics: Adult; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Prednisolone; Prognosis; Sarcoidosis

Topics: Antigen-Antibody Complex; Bronchi; Gallium Radioisotopes; Humans; Lung Diseases; Mediastinal Diseases; Muramidase; Peptidyl-Dipeptidase A; Pulmonary Alveoli; Sarcoidosis

The present study was carried out to compare radiological and physiological changes in sarcoidosis with biochemical markers for inflammatory cell populations. Of 53 patients with sarcoidosis, 28 had respiratory symptoms and 30 past or present bilateral hilar adenopathy without symptoms. A clinical score based on lung function tests and radiological findings correlated well with elevations of lysozyme and beta2-microglobulin in serum, indicating increased inflammatory cell activity in patients with more severe lung affection. A covariation between beta2-microglobulin and lysozyme was found, suggesting concomitant activation of macrophages and lymphocytes in sarcoidosis. Serum levels of lactoferrin were elevated in patients with a disease of short duration but did not correlate with the severity of the lung affection. The closing volume also seems to be abnormal in the early course of the disease, while elevated lysozyme and beta2-microglobulin levels rather seem to reflect the extent of the pulmonary affection.

Topics: Adult; Aged; beta 2-Microglobulin; Female; Humans; Inflammation; Lactoferrin; Lung; Lung Diseases; Male; Middle Aged; Muramidase; Radiography; Respiratory Function Tests; Sarcoidosis

Topics: Adult; Aged; Humans; Middle Aged; Muramidase; Sarcoidosis; Tuberculosis, Pulmonary

Topics: Female; Humans; Lung Diseases; Male; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Topics: Granuloma; Granulomatosis with Polyangiitis; Granulomatous Disease, Chronic; Humans; Lymphomatoid Granulomatosis; Lymphoproliferative Disorders; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Serum lysozyme (LZM) concentrations were correlated to the number of neutrophils and monocytes in patients with sarcoidosis and nongranulomatous diseases. In sarcoidosis patients with an increased activity of serum angiotensin converting enzyme (ACE), a positive correlation was noted between LZM and blood monocytes. In sarcoidosis patients with normal ACE activity, as well as in patients with non-granulomatous diseases, a correlation was found between blood neutrophils and LZM, but not between blood monocytes and LZM. LZM was found in bone marrow plasma and in serum in a ratio of 1.5 to 1. Sarcoidosis patients had 30% higher LZM levels than healthy controls. The concentration of LZM in bone marrow plasma did not correlate to detectable granulomas in bone marrow specimens. The positive correlation between blood monocytes and LZM in patients with clinically active sarcoidosis is possibly due to recruitment of bone marrow monocytes for the granuloma formation.

Topics: Bone Marrow; Humans; Leukocyte Count; Lung Diseases; Monocytes; Muramidase; Neutrophils; Peptidyl-Dipeptidase A; Sarcoidosis

In an attempt to obtain in vitro experimental models for sarcoidosis, the primary cultures of granuloma cells were initiated with lymph nodes from 10 sarcoidosis patients. The cells migrating from tissue explants became confluent at 2 wk of culture. These cells exhibited overall morphologic features and enzymatic activities resembling those of in vivo granuloma epithelioid cells. By light and electron microscopy, the epithelioid cell in vitro contained a clear, large nucleus with 1 or 2 prominent nucleoli. The cytoplasm was characterized by the occurrence of lysosomal dense bodies and electron-lucent vacuoles, besides many mitochondria and well-developed Golgi complexes. The cell surface exhibited many processes, mainly lamellipodia. Large amounts of angiotensin converting enzyme activity (3.9 to 50.1 nmol/min/ml) lysozyme activity (3.9 to 23.0 micrograms/ml) were demonstrated in the medium used for culture. The results indicated that the major cell population grown in these cultures is derived from the epithelioid cells in sarcoid granulomas.

Topics: Adult; Culture Techniques; Epithelium; Granuloma; Humans; Lymph Nodes; Male; Microscopy, Electron; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Topics: Humans; Hypokalemia; Leukemia, Myeloid, Acute; Muramidase; Sarcoidosis; Tuberculosis

Sera from 84 white patients with inactive sarcoidosis were analyzed for immunoglobulins, complement, autoantibodies, alpha 1-antitrypsin and lysozyme. The levels of serum factors were compared with levels in serum from a reference population which was matched for age, sex, ethnic background and geographic location. IgG, IgA, IgD, and C3 levels were similar for both groups, as were frequencies of rheumatoid factor, antinuclear antibody and anti-DNA antibody. Lysozyme levels were significantly lower in the inactive sarcoidosis group but the acute phase reactants alpha 1-antitrypsin, IgM as well as complement consumption were increased. The data suggest that the underlying etiological events of sarcoidosis continue, albeit at a subclinical level.

Topics: Adult; alpha 1-Antitrypsin; Antibodies, Antinuclear; Complement C3; Complement C4; Female; Humans; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Muramidase; Rheumatoid Factor; Sarcoidosis; Surveys and Questionnaires

The muramidase content of reactive cells in the lesions of human foreign body reactions, lepromatous and tuberculoid leprosy, sarcoidosis, tuberculosis, and granulomatous hepatitis, was assessed using specific anti-human muramidase antiserum and a peroxidase-anti-peroxidase marker system. Epithelioid and giant cells in sarcoidosis, tuberculosis, granulomatous hepatitis, and tuberculoid leprosy all showed the presence of muramidase in their cytoplasm. The muramidase content of macrophages in foreign body reactions and lepromatous leprosy varied and most multinucleate cells in these lesions gave a negative reaction. Possibly varying rates of muramidase secretion may account for these differences.

Topics: Cytoplasm; Foreign-Body Reaction; Hepatitis; Humans; Leprosy; Lung; Lymph Nodes; Muramidase; Sarcoidosis; Tuberculosis

Examination of the sarcoid granuloma by electron microscopic and electron microscopic immunocytochemical techniques shows that the sarcoid macrophage giant cell is rich in lysozyme, present within the centre of the syncytium in dense granules approximately 200 nm in diameter. The ultrastructure of the syncytium is that of an actively secretory cell, suggesting that the sarcoid macrophage giant cell actively produces as well as stores lysozyme, rather than being a fusion product of mononuclear cells which produce lysozyme, or being a site of storage of ingested lysozyme.

Topics: Humans; Macrophages; Microscopy, Electron; Muramidase; Sarcoidosis

Topics: Adolescent; Adult; Aged; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

The majority of patients with sarcoidosis in this large series have had a number of biochemical investigations performed. Abnormal calcium metabolism was demonstrated in 40% of the patients but permanent renal damage due to nephrocalcinosis as a result of persistent derangement of calcium metabolism was rare. Raised immunoglobulin levels were seen. Half the white and two-thirds of the West Indian patients had elevated IgG levels. Abnormal immunoglobulin levels carried no obvious diagnostic or prognostic significance. Raised alkaline phosphatase levels reflected space-occupying hepatic granulomas and occurred in 23% of patients. Serum angiotensin converting enzyme (SACE) was elevated in half the patients. The highest SACE activity was found in patients with severe parenchymal lung infiltration due to sarcoidosis, and the lowest levels in those with inactive disease or after successful management with steroid drugs. SACE levels were not significantly elevated in four other granulomatous conditions: Crohn's disease, primary biliary cirrhosis, Hodgkin's disease, and active tuberculosis.

Topics: Adult; Alkaline Phosphatase; Blood Proteins; Calcium; Female; Humans; Hydroxyproline; Immunoglobulins; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Phosphates; Prolactin; Sarcoidosis; Uric Acid

Serum angiotensin-converting enzyme (ACE) activity was related to clinical markers of disease activity, mainly chest X-rays, pulmonary function tests and serum lysozyme (LZM) in 41 sarcoidosis patients, who received corticosteroid treatment. Increased ACE activity before treatment predicted improvement of diffusion capacity during treatment, whereas chest X-rays improved regardless of the initial ACE value. ACE decreased after initiation of treatment both in sarcoidosis patients and in healthy volunteers. In sarcoidosis most decreases were parallelled by similar LZM changes, which did not occur in volunteers. When an apparently stable state had been achieved, ACE was no longer a reliable monitor of disease activity. It often fluctuated within normal limits without accompanying clinical or LZM changes. It was not dose-dependent during daily medication but increased during alternate day administration. This may reflect decreased suppression of ACE by steroids but may also indicate reactivation of the disease process. Elevated ACE values after cessation of treatment preceded or parallelled a relapse. LZM values did not add to the information provided by ACE measurements before, during or after treatment.

Topics: Adrenal Cortex Hormones; Adult; Aged; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Respiratory Function Tests; Sarcoidosis

Serum angiotensin-converting enzyme (SACE) was measured in 56 patients with sarcoidosis within three months after diagnosis. Serial analyses were performed in 42 patients, who were followed for two months to one year. SACE was elevated in 49 (70%) of the patients at some time during the period of observation. Erythema nodosum (EN) was present in 14 patients. Only one out of seven had elevated SACE during EN, but four months later SACE was elevated in all 14. In this group there was a negative correlation between SACE and S-lysozyme. Among 42 patients without EN the frequency of SACE elevation was rather constant, about 60%. In half of the patients SACE was normal at first examination, and subsequent elevation was observed in 19%. SACE and S-lysozyme were positively correlated. Enzyme activity was independent of mode of presentation, but a non-significant trend toward higher SACE in patients with pulmonary involvement was observed, and changes in SACE were roughly correlated to roentgenological changes. Among healthy controls, significantly higher SACE levels were found in children up to 17 years of age (reference interval 21.2-42.2 U/ml) than in adults aged 18-65 years (12.0-36.8 U/ml). The observations on patients with sarcoidosis demonstrate that a unique pattern of SACE occurs in those with EN, different from that of patients without EN. The findings support the view that EN is a hallmark of acute-onset sarcoidosis. The value of serial SACE analyses is emphasized.

Topics: Adolescent; Adult; Aged; Erythema Nodosum; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Circulating immune complexes (CIC) were detected in 100 out of 112 sera from 33 sarcoidosis patients. Five tests were used representing three different basic principles. All patients had detectable CIC at some stage of their disease. The three platelet tests detecting IgG complexes exhibited the highest positive titres in the acute cases. The ClqB-ELISA test, which detects complement fixing IgG complexes, was the test most frequently positive in the chronic cases. The presence of extra-pulmonary lesions or corticosteroid therapy did not influence the appearance or disappearance of CIC. No positive correlation was found between CIC and elevated levels of serum angiotensin-converting enzyme (ACE) and/or serum lysozyme (LZM). The evaluation of CIC in sarcoidosis requires a battery of different tests carried out at regular intervals during the follow up.

Topics: Antigen-Antibody Complex; Blood Platelets; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Humans; Immunoglobulin G; Muramidase; Peptidyl-Dipeptidase A; Rheumatoid Factor; Sarcoidosis

Topics: Adult; Aged; Antibody-Dependent Cell Cytotoxicity; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Giant cell myocarditis (GCM) as a distinct disease entity has been questioned. The superficial morphologic resemblance to cardiac sarcoidosis and incomplete histopathologic assessment of extracardiac organ systems in reported cases has suggested that GCM represents a predominant cardiac manifestation of generalized sarcoidosis. The morphologic and immunocytochemical features at autopsy of this rare disorder were seen in a 15-year-old boy. All other organs were free of granulomatous inflammation. Transition from normal myocardial fibers to giant cells was observed, without a limiting plasma membrane between the two different aspects of the fiber. Immunocytochemistry for cytoplasmic muramidase (CM) showed CM in neutrophils and tissue macrophages. Cytoplasmic muramidase was distinctly absent from the characteristic giant cells. The classification of GCM as a disease separate from generalized sarcoidosis may be justified.

Topics: Adolescent; Diagnosis, Differential; Granuloma, Giant Cell; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Muramidase; Myocarditis; Myocardium; Sarcoidosis

Topics: Adult; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Muramidase; Sarcoidosis

We studied the value of serum lysozyme as a helpful test in distinguising tuberculous involvement of intrathoracic glands from lymphoma. Nineteen of the 28 patients (all Asian immigrants) with intrathoracic glandular tuberculosis had raised serum lysozyme level as compared with 2 of the 29 patients with lymphoma. While a normal serum lysozyme level is unhelpful, a raised level in an Asian immigrant with hilar or mediastinal lymphadenopathy makes tuberculosis a highly probable diagnosis.

Topics: Africa, Eastern; Bronchial Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; India; Lymphatic Diseases; Lymphoma; Male; Muramidase; Sarcoidosis; Thoracic Neoplasms; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary; Wales

Serum angiotensin-converting enzyme (ACE) activity was studied in healthy controls, in 57 untreated sarcoidosis patients, and in 164 patients with other chest or lymph node diseases. The serum ACE activity of healthy persons was independent of sex, intake of meals, and smoking habits. There were no diurnal variations. Healthy children had a significantly higher ACE mean value than adults, whose ACE activity was not affected by age. The sarcoidosis patients had the highest ACE mean values, but those of patients with silicosis and asbestosis were also significantly elevated. Pulmonary cancer patients had decreased serum ACE activity, which was probably due to antimitotic treatment. Serum lysozyme (LZM) concentrations did not correlate with normal ACE activity, but the correlation between elevated ACE and LZM was significant in sarcoidosis and silicosis, and the trend was clearly the same for asbestosis. This indicates separate sources for these enzymes when ACE activity is normal, and a common source, i.e. macrophages, when ACE activity is increased. ACE production in certain diseases involving macrophages may be due to the bradykinin inhibiting effect of this enzyme.

Topics: Adolescent; Adult; Alveolitis, Extrinsic Allergic; Asbestosis; Bronchitis; Female; Hodgkin Disease; Humans; Lung Diseases; Lung Neoplasms; Lymphatic Diseases; Lymphoma; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Pneumonia; Pulmonary Fibrosis; Sarcoidosis; Silicosis; Thoracic Neoplasms; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary

Serum angiotensin I converting enzyme (ACE) and lysozyme have been measured in 23 controls, 115 patients with sarcoidosis, and 64 with other chest diseases. Both enzymes were significantly raised in sarcoidosis. ACE was raised above the normal range in 21 of 72 (29%) patients with definite sarcoidosis and in 17 of 38 (45%) of those who were untreated and seen within one year of presentation. The rise discriminated usefully between those with stable and progressive disease (5% and 62% respectively). Lysozyme was raised in 50 of 72 (69%) patients with sarcoidosis but also in 11 of 54 (20%) patients with other chest diseases. Discrimination between stable and progressive disease was useful only if very high levels were considered. Five patients had serial measurements after treatment with oral steroids and showed a progressive fall in levals of both enzymes, but patients with other diseases also showed a significant fall within the normal range when so treated. Measurement of these enzymes may help in the management of some cases of sarcoidosis, but results require critical interpretation.

Topics: Adult; Aged; Clinical Enzyme Tests; Female; Humans; Lung Diseases; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Prednisone; Sarcoidosis

The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with serum lysozyme (LZM) in patients with untreated sarcoidosis. Changes in the clinical picture were registered using chest X-ray, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and appearance of extrapulmonary lesions. During a clinically unchanged period the highest ACE activity and the corresponding LZM value (not the highest value) were used for the calculation. A statistically significant change in ACE was noted when a normal chest X-ray changed to a stage II lesion or vice versa, and when a signficant change in FVC occurred. All other changes were insignificant. On the other hand, statistically significant changes in ACE were found during stable periods according to chest X-ray, FVC or DLCO. ACE is frequently elevated in serum of patients with active sarcoidosis. The fluctuations in activity mostly parallel the clinical course of the disease. The behaviour and metabolism of the enzyme need further investigation. An increased concentration of serum LZM is frequent in patients with active sarcoidosis. The highest LZM values are not always seen simultaneously with the highest ACE values, indicating that they probably express different dimensions of the disturbances in the sarcoid granuloma.

Topics: Adult; Aged; Carbon Monoxide; Female; Humans; Lung; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Radiography; Sarcoidosis; Vital Capacity

The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concentrations measured during different phases of sarcoidosis coincided well with the clinical evaluation of the state of the disease. However, both enzymes, especially LZM, decreased before improvement was detected. Changes in these enzymes were in accord with the simultaneous clinical development in three fourths of cases. Incompatibility between clinical observations apnd LZM fluctuations was most frequently seen during active stable or inactive disease. LZM often decreased during the active stable phase and fluctuated irregularly during inactive disease. During the former phase LZM decrements possibly reflect decreasing activity of granulomatous macrophages and, in fact, precede detectable improvement. During inactive disease, on the other hand, cells were not connected with the disease process dominate LZM production. ACE changes paralleled the clinical development more often than corresponding LZM changes during stable sarcoidosis. This may have been misleading and due to a delayed reaction of serum ACE, compared with LZM, inreflecting the activity of granylomatous cells. This delayed reaction was also observed in connection with erythema nodosum. Stable ACE activity during inactive sarcoidosis indicated the usefulness of measurements when trying to predict a relapse. We conclude that ACE may be a secondary feature of sarcoidosis rather than a primary funtion of macrophage activity.

Topics: Humans; Muramidase; Phosphotransferases; Prognosis; Sarcoidosis

Topics: Adult; Evaluation Studies as Topic; Female; Humans; Immunodiffusion; Male; Middle Aged; Muramidase; Nephelometry and Turbidimetry; Sarcoidosis

Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicosis and 18 asbestosis patients were studied. These patients were compared with 57 untreated and 36 treated sarcoidosis patients. In all groups significantly raised ACE and LZM mean values were noted. Untreated sarcoidosis patients had the highest values. Raised ACE activity in silicosis and asbestosis has not been reported before, and weakens the differential diagnostic value of this enzyme determination for sarcoidosis. The similar patterns of increased ACE and LZM mean values in all three diseases suggest that these enzymes have a common source.

Topics: Adult; Aged; Asbestosis; Diagnosis, Differential; Female; Humans; Lung Diseases; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Silicosis

The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules.

Topics: Humans; Immunoenzyme Techniques; Inclusion Bodies; Macrophages; Microscopy, Electron; Muramidase; Sarcoidosis

Topics: Angiotensins; Humans; Lung Diseases; Macrophages; Monocytes; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

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

Topics: Adult; Humans; Leukocyte Count; Macrophages; Monocytes; Muramidase; Sarcoidosis

Topics: Granuloma; Humans; Lymph Nodes; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Topics: Child; Colitis, Ulcerative; Humans; Infections; Kidney Diseases; Leukemia; Muramidase; Sarcoidosis

Lysozyme (LZM) was demonstrated by an immunoperoxidase method in some but not all epitheloid-cell granulomas, free macrophages and giant cells in the lymph nodes and Kveim reaction papules of patients with sarcoidosis. In inactive disease, LZM staining was weak or absent in fibrotic lymph nodes. The pattern of LZM staining in Kveim reaction papules was similar to that seen in the "active" sarcoid lymph nodes. The presence of LZM in sarcoid tissue explains the high concentration of serum LZM in patients with active sarcoidosis and the extent of LZM distribution in tissues is probably an index of disease activity.

Topics: Epithelial Cells; Epithelium; Humans; Kveim Test; Lymph Nodes; Macrophages; Muramidase; Sarcoidosis

Serum lysozyme (LZM) determinations were done in 84 patients with clinically proven sarcoidosis. All patients were normocalaemic and had a normal renal function. An increased LZM activity was demonstrated in patients with pulmonary stage I and stage II disease, as well as in patients with extrapulmonary lesions. Treatment with corticosteroids rapidly normalized the LZM activity. A normal LZM activity was found in patients with cured sarcoidosis. The serum LZM activity seems to reflect the total mass of biologically active granulomas and is of great value in determining the activity of the disease. The dosage of corticosteroids can probably be administered according to the actual LZM level. Increasing LZM activity after stopping treatment may indicate progressive and uncured disease. Normal LZM activity in patients with even large pulmonary lesions seems to indicate inactive disease and unresponsiveness to treatment.

Topics: Adrenal Cortex Hormones; Adult; Aged; Calcium; Humans; Male; Middle Aged; Muramidase; Sarcoidosis

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Muramidase; Sarcoidosis; Steroids

In a study of 100 patients, the mean serum lysozyme value for patients with sarcoidosis and active uveitis was elevated, while the mean value for patients with inactive sarcoidosis and inactive uveitis was within the normal range. The mean value for patients with a clinical picture of sarcoid uveitis, but without an established diagnosis of sarcoidosis, was high. In patients with ophthalmologic findings compatible with sarcoidosis, but without radiologic, immunologic, or other clinical evidence of the disease, an elevated serum lysozyme level may be indicative of sytemic disease.

Topics: Clinical Enzyme Tests; Humans; Muramidase; Sarcoidosis; Uveitis

Parotid saliva from a patient suffering from sarcoidosis with salivary gland involvement has been shown to have a decreased level of alpha-amylase but increased levels of albumin and lysozyme. These observations suggest that in addition to impaired gland function, gland damage as a result of inflammation had occurred which permitted increased passage of constituents from serum into the gland secretion.

Topics: Acid Phosphatase; Albumins; Amylases; Muramidase; Parotid Gland; Peptide Hydrolases; Proteins; Ribonucleases; Saliva; Salivary Gland Diseases; Sarcoidosis

Topics: Aged; Female; Hepatomegaly; Humans; Leukemia; Leukemia, Myeloid; Leukocyte Count; Male; Middle Aged; Monocytes; Muramidase; Sarcoidosis; Splenomegaly; Tuberculosis, Miliary; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Clinical Enzyme Tests; Female; Humans; Male; Muramidase; Remission, Spontaneous; Sarcoidosis; Spleen; Splenic Diseases

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Marrow Examination; Female; Humans; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Male; Muramidase; Nitrophenols; Remission, Spontaneous; Sarcoidosis

Topics: Egg White; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Mass Screening; Muramidase; Pyelonephritis; Sarcoidosis; Tears; Tuberculosis

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphoma; Male; Middle Aged; Multiple Myeloma; Muramidase; Sarcoidosis; Seasons