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Biomedical subjects

F Papa

Publications and source records attributed to F Papa.

At least 37 records · Page 2Linked to original sources

Isolation and characterization of serologically reactive lipooligosaccharides from Mycobacterium tuberculosis.

Two major highly polar antigenic glycolipids were isolated from recent isolates of Mycobacterium tuberculosis from a wide range of geographical origins. The occurrence of these polar glycolipids was demonstrated by isolation, purification and chromatographic characterization and/or serological procedures in 12 strains. Based on their chromatographic properties, these polar glycolipids belong to the lipooligosaccharide family. Preliminary data on the use of these newly described antigens in the serodiagnosis of tuberculosis is presented.

Chromatography, Thin Layer↗

Circulating immune complexes in leprosy sera: demonstration of antibodies against mycobacterial glycolipidic antigens in isolated immune complexes.

Circulating immune complexes (CIC) were assayed in sera of leprosy patients. Using an immunoassay for two mycobacterial antigens--phenolic glycolipid-I (PGL-I) and glycolipid IV (SL-IV)--sera from 65 patients with leprosy (38 lepromatous, 18 borderline, and 9 tuberculoid) were studied. The CIC were isolated by polyethylene glycol (PEG) precipitation, washed, treated with an acid buffer, neutralized, and tested using an enzyme-linked immunosorbent assay (ELISA). We demonstrated that CIC could contain IgG and IgM antibodies reacting against PGL-I and SL-IV. The high levels of antibodies in the precipitable CIC showed concordance with high levels in the original sera, although some patients presented high levels of precipitable CIC in the absence of high titers of antibodies in their sera. It was concluded that some of the CIC observed in patients with leprosy were composed of IgG and IgM immunoglobulins against specific mycobacterial antigens.

Adolescent↗

Research secures the future of osteopathic medicine: Part 2: Readdressing the function and structure of colleges of osteopathic medicine.

Many problems exist within the contemporary medical education process in general and the osteopathic medical profession in particular. Part 2 of this series suggests that the single greatest impediment to solving these problems is an institutional infrastructure that is not congruent with the institution's functions, as defined in its mission statement. (This mission statement generally entails two primary goals: education and research). Two major divisions within the core's infrastructure are suggested: medical education and medical research. By restructuring their infrastructure, colleges of osteopathic medicine can more effectively address and support their primary functions of education and research.

Career Mobility↗

Time course of anti-SL-IV immunoglobulin G antibodies in patients with tuberculosis and tuberculosis-associated AIDS.

Immunoglobulin G (IgG) and IgM antibodies against the SL-IV antigen of Mycobacterium tuberculosis in the sera of patients with tuberculosis with negative serology for human immunodeficiency virus (HIV) infection (TB group; n = 97), patients with tuberculosis with positive serology for HIV infection (TB-HIV group; n = 59), and healthy controls (n = 289) were determined by enzyme-linked immunosorbent assay. All sera were obtained at the onset of tuberculosis, i.e., when clinical symptoms appeared. Clinical specimens were collected and cultured for the isolation of M. tuberculosis, and treatment with antituberculous drugs was started. Sera were also obtained from patients in the TB group at fixed intervals during treatment; sera were available from 13 patients in the TB-HIV group before the onset of tuberculosis. The best specificity and positive predictive values were obtained with the IgG assays. In the IgG assays at specificities above 96.0%, the sensitivities of the tests were 45.3 and 72.8% for the TB and TB-HIV groups, respectively, and the sensitivity was 51.9% when data from both groups were combined for analysis. For the TB group, results of this study indicated that the levels of IgG antibodies remain high during treatment. Thus, repetitive serological assays may not be useful for treatment follow-up. In the TB-HIV group, 12 of 13 patients had IgG-specific antibodies against the SL-IV antigen between 1 and 30 months before the onset of tuberculosis, so we suggest that the IgG antibody assay against SL-IV may be helpful for identifying tuberculosis in patients infected with HIV.

Acquired Immunodeficiency Syndrome↗

Comparison of bis-di-octadecylamide of trehalose dicarboxylic acid (BDA.TDA) with glycolipid SL-IV as ELISA antigens for the serodiagnosis of leprosy.

Two glycolipids--one synthetic and non-natural (BDA.TDA), the other natural and Mycobacterium tuberculosis species-specific (SL-IV)--were tested to determine their serological activity in sera obtained from leprosy patients, and to determine their discriminating ability in the detection of disease. The ELISA results obtained in the IgG antibody class show that both were useful substances capable of detecting multibacillary and paucibacillary disease in about 2 out of 3 leprosy patients. When these antigens were tested in parallel, the sensitivity of the ELISA test was increased by 10% without a decrease in specificity.

Antibodies, Bacterial↗

Relationships between titers of antibodies immunoreacting against glycolipid antigens from Mycobacterium leprae and M. tuberculosis, the Mitsuda and Mantoux reactions, and bacteriological loads: implications in the pathogenesis, epidemiology and serodiagnosis of leprosy and tuberculosis.

Analysis of cell-mediated immunity [(CMI) as judged from the Mantoux, Fernandez, and Mitsuda reactions and the presence of granulomas in biopsy material] against humoral immunity (measurements of anti-PGL-I, PGL-Tb1, and SL-IV IgG and IgM antibody titers by ELISA) were performed in selected human populations. The investigations yielded data indicating that humoral (B-cell) responses preceded protective CMI in both tuberculosis and leprosy. The B-cell responses were unrelated to (unfavorable) cell-mediated delayed-type hypersensitivity (DTH). Notwithstanding the difficulty in inferring sequential events from studies in humans, it was shown that in humoral responses there was an initial rise of specific IgM immunoglobulins that switched afterward to IgG production during subclinical tuberculosis and leprosy infections. In patent tuberculosis disease the IgM-to-IgG switch was observed in the majority of patients; in patent leprosy disease the switch was impaired in the majority of patients. The clinical, immunological, and laboratory data indicated that the B-cell responses were suppressed as protective CMI was re-established in the patients during the protracted subclinical infection. According to the data, the diagnosis of subclinical tuberculosis and leprosy may be accomplished using ELISA. The yearly risk of tuberculosis in apparently healthy persons but with significant antibody titers was estimated at 44%; the yearly risk for leprosy has not yet been established. The clinical, epidemiologic, and diagnostic implications of these findings are discussed.

Antibodies, Bacterial↗

IgG and IgM antibodies immunoreacting with a 2,3-diacyl trehalose-2'-sulphate in sera from leprosy patients.

The distribution of IgG and IgM antibodies immunoreacting with the sulpholipid I (SLI) and sulpholipid IV (SLIV) of Mycobacterium tuberculosis was examined in sera from leprosy patients. It was found that the immunological reactions correlated with the clinical spectrum of leprosy; and in multibacillary patients, antibody titres declined in response to successful treatment. The serological patterns were similar to the PGL I patterns, however, the IgG responses towards the sulpholipids were predominant over the IgM responses in the case of the sulpholipid antigens.

Antibodies, Bacterial↗

Antigenicity and specificity of selected glycolipid fractions from Mycobacterium tuberculosis.

Antigenicity of Mycobacterium tuberculosis glycolipids polyphthienoyl trehalose (PPTR), phenolic glycolipid (PGL-Tb1), tetraacyl trehalose-2'-sulphate (SL-I) and diacyl trehalose-2'-sulphate (SL-IV) was examined in rabbits. PPTR did not induce production of IgG antibodies in rabbits, while PGL-Tb1, SL-I and SL-IV glycolipids were efficient in this respect. Immune sera raised in rabbits immunoreacted exclusively with the corresponding antigens, which indicated that they were remarkably specific. Specificity of the immune sera was further examined using crude extracts of representative strains of 39 mycobacterial species, and the data showed that these immune sera reacted only with extracts of M. tuberculosis and M. africanum. An antiserum raised against whole cells of M. leprae immunoreacted with the purified SL-IV antigen from tubercle bacilli.

Animals↗

Human IgG antibodies immunoreacting with specific sulfolipids from Mycobacterium tuberculosis.

IgG and IgM antibodies immunoreacting with sulfolipids from Mycobacterium tuberculosis were detected in sera from tuberculosis patients. The method used was an enzyme linked immunoassay (ELISA) and the antigens were a 2, 3, 6, 6' tetraacyl trehalose-2'-sulfate (sulfolipid I, SL I) and a 2, 3 diacyl trehalose-2'-sulfate (sulfolipid IV, SL IV). The SL IV antigen was satisfactory for IgG assays. The sensitivity and the specificity of the test were, respectively, 59 and 100%; the predictive values of a positive and negative test were, respectively, 100 and 76%.

Antibodies, Bacterial↗

Glycolipids of recent clinical isolates of Mycobacterium tuberculosis: chemical characterization and immunoreactivity.

Five distinct glycolipids were readily detected in isolates of Mycobacterium tuberculosis. Spectroscopic methods and chemical degradation techniques allowed the structural identification of four of these glycolipids. The specific phenolic glycolipid antigen previously characterized from the Canetti strain was found in all the strains examined, with identical structural features (triglycosyl phenol phthiocerol dimycocerosate). The other three glycolipids identified were acylated trehaloses: penta-acyl trehalose (containing phthienoyl substituents), tetra-acyl trehalose 2'-sulphate (with C40-C50 hydroxyphthioceranoyl substituents) and diacyl trehalose 2'-sulphate (with C16 and C18 substituents). The two latter glycolipids as well as the phenolic glycolipid immunoreacted with whole-cell antiserum, indicating their surface location. The occurrence of these glycolipid antigens in recent clinical isolates suggests their possible utilization in the serodiagnosis of tuberculosis and the rapid identification of M. tuberculosis with specific antisera.

Chromatography, Thin Layer↗

Immunological response to homologous and heterologous phenolic glycolipid antigens in tuberculosis and leprosy.

The occurrence of IgM antibodies immunoreacting in an ELISA test with five phenolic-glycolipids (GPL) antigens (PGL-Tb 1, from M. tuberculosis; PGL-I, from M. leprae; PGK-K-I, from M. kansasii; Mycoside G, from M. marinum; and Mycoside B, from M. bovis), was examined in the sera of 46 tuberculous patients, 48 multibacillary leprosy patients, 40 paucibacillary leprosy patients and in 134 healthy controls. The sensitivity (97.9) and the specificity (91.8) observed in tuberculous patients with the homologous antigen PGL-Tb 1 underlined the interest of this antigen for case finding in tuberculosis epidemiology. The sensitivity and the specificity observed in multibacillary leprosy patients, respectively 91.7 and 91.8, and in paucibacillary leprosy patients, respectively, 35.0 and 91.7, confirmed the limited value of homologous antigen PGL-I for the serological case finding of leprosy patients in endemic areas with a strong incidence of paucibacillary leprosy forms. The data obtained with the heterologous PGL antigens in tuberculosis and multibacillary leprosy serology were higher than those observed in healthy controls and in paucibacillary leprosy patients. However the ELISA using the heterologous antigens was not useful in diagnosis of active tuberculosis or multibacillary leprosy forms. Healthy controls showed low immunoreactivity against PGL antigens, with the exception of mycoside B.

Adolescent↗

Specificity and antigenicity of mycoside G and other glycolipids from Mycobacterium marinum.

The purpose of this work was to examine the immunologic properties of the phenolicglycolipid produced by M. marinum (mycoside G). Cell mass processed with organic solvents yielded a lipid extract containing mycoside G and four other glycolipid fractions (G2 to G5). No mycoside G was found in the Mycobacterium marinum type strain. Neither mycoside G, nor fractions G2, G3 and G4 were immunogenic in the rabbit whereas fraction G5 was very immunogenic. The immune serum raised in the rabbit showed that fraction G5 is species specific since it was consistently detected in all Mycobacterium marinum strains examined so far.

Animals↗

Serological specificity of Mycobacterium tuberculosis glycolipids.

Six glycolipid fractions can be extracted from lipid crude extracts of Canetti type strains of M. tuberculosis. Among these fractions are two phenolglycolipids. The major component is a triglycosyl phenolphthiocerol dimycocerosate (PGL-Tb 1) and the second is a monoglycosyl diacyl phenolphthiocerol identical to mycoside B of M. bovis. Similar glycolipid compounds can also be found in wild strains of M. tuberculosis recently isolated from tuberculous patients. One of these compounds has been identified as PGL-Tb 1.

Antibodies, Bacterial↗

Structural elucidation of the major phenolic glycolipid from Mycobacterium kansasii. II. Presence of a novel dideoxyhexose.

A novel O-methyl-2,6-dideoxyhexose was isolated from the major phenolic glycolipid (previously called mycoside A) of Mycobacterium kansasii. Its molecular weight (162) was determined by gas chromatography-mass spectrometry analysis (chemical ionization with ammonia as reactant gas) of its underivatized reducing form. The methoxyl group was located by electron impact-mass spectrometry of its alditol acetate. The configuration was established by 1H NMR of its peracetylated derivative. The structure 2,6-dideoxy-4-O-methyl-arabino-hexopyranose is proposed for this new sugar. Evidence is also presented that the phenolic glycolipid previously called mycoside A is an antigen of M. kansasii since it reacts with rabbit antisera raised against whole M. kansasii.

Antigens, Bacterial↗

Specificity of a Mycobacterium kansasii phenolic glycolipid (mycoside A) immunoserum.

The specificity of Mycobacterium kansasii anti-mycoside A antiserum prepared in rabbits injected with purified samples of the phenolic glycolipid was evaluated by an enzyme-linked immunosorbent assay. Chloroform-methanol extracts from representative strains of 23 mycobacterial species and 50 strains of M. kansasii showed that all strains of M. kansasii and the representative strain of M. gastri formed the antigen, whereas none of the remaining species (including M. leprae) formed it. Consequently, it was found that the antiserum was highly specific and useful for diagnostic purposes.

Animals↗