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Biomedical subjects

A Verbon

Publications and source records attributed to A Verbon.

35 records · Page 2Linked to original sources
PubMed1999

Elevated chemokine concentrations in sera of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients with tuberculosis: a possible role for mycobacterial lipoarabinomannan.

Levels of interleukin 8 (IL-8), gamma interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1beta (MIP-1beta) were elevated in patients with tuberculosis. IP-10 and MCP-1 levels were higher in human immunodeficiency virus (HIV)-seropositive patients than in HIV-seronegative patients with tuberculosis. Lipoarabinomannan induced IL-8, MCP-1, and MIP-1beta in vitro, which was partly inhibited by anti-tumor necrosis factor antibody.

Chemokine CCL2↗
PubMed1998

Mycobacterium xenopi in HIV-infected patients: an emerging pathogen.

BACKGROUND: Mycobacterium xenopi is associated with pulmonary disease in patients with loss of local or general host defence. OBJECTIVES: To determine the occurrence of M. xenopi in our hospital during 1987-1992 and 1993-1996, as well as the association of M. xenopi with HIV infection in 1993-1996; to evaluate the clinical significance of M. xenopi in HIV-seropositive patients. DESIGN: Retrospective review of charts and classification of patients based on earlier definitions derived from the American Thoracic Society. SETTING: Tertiary hospital. PATIENTS: Patients with a positive isolate of M. xenopi from January 1987 until December 1996. MAIN OUTCOME MEASURES: During 1993 1996, a significant increase in the number of patients with M. xenopi was found compared with 1987-1992. Of 25 patients, 22 were HIV-seropositive. RESULTS: The HIV-seropositive patients were classified as having definite (n = 5), probable (n = 9) and unlikely disease (n = 8) due to M. xenopi. Symptoms, median CD4 cell count, treatment and outcome did not differ between these groups. CONCLUSIONS: M. xenopi is an emerging pathogen, especially in HIV-infected patients. The criteria of the American Thoracic Society for disease due to non-tuberculous mycobacteria do not seem applicable to M. xenopi in HIV-infected patients. We suggest that two positive cultures of M. xenopi and no other likely cause of symptoms present should be considered the criteria for diagnosis of M. xenopi disease in HIV-infected patients.

Adult↗
PubMed1998

[Characterization of 100 patients with tuberculosis treated in the Academic Medical Center in Amsterdam].

OBJECTIVE: To inventory both clinical and demographical data of patients with tuberculosis in the AMC, as well as diagnostic procedures, response to therapy and rate of resistance. DESIGN: Retrospective, descriptive. SETTING: The Academic Medical Center. Amsterdam, the Netherlands. METHOD: The medical records of all patients with a bacteriologically confirmed infection with Mycobacterium tuberculosis complex between January 1993 and December 1995 were studied. RESULTS: 70 out of 100 patients with tuberculosis were not born in the Netherlands. Out of 50 patients tested 18 were HIV positive. The most common abnormality seen on X-rays of non-HIV positive patients were caverns. The X-ray of HIV positive patients showed no abnormalities in 39%; there was no correlation with CD4 cell count. In 74% of the patients with pulmonary tuberculosis the diagnosis was made by culture of the sputum. Treatment consisted of INH, rifampicin, pyrazinamide and ethambutol. Twelve patients were infected with resistant strains, of which two were multidrug resistant. Four patients died of tuberculosis. CONCLUSION: Tuberculosis was seen mostly among immigrants. Only half the patients with tuberculosis were tested for presence of HIV antibodies. Culture and staining of sputum played a key role in the diagnosis of tuberculosis. Multiresistant tuberculosis was present in 2% of the patients. Death due to tuberculosis in this population was 4%.

AIDS-Related Opportunistic Infections↗
PubMed1998

Serum concentrations of lipopolysaccharide activity-modulating proteins during tuberculosis.

Lipopolysaccharide (LPS) is the principal stimulator of host defense against gram-negative bacteria. LPS-binding protein (LBP), bactericidal/permeability-increasing protein (BPI), and soluble CD14 (sCD14) bind LPS and regulate its toxicity. Lipoarabinomannan, a cell wall component of Mycobacterium tuberculosis, resembles LPS with respect to induction of inflammatory responses through recognition by LBP and sCD14. LBP, BPI, and sCD14 were measured in serum of 124 patients with tuberculosis in various stages of disease, in persons who had been in close contact with patients with contagious pulmonary tuberculosis, and in healthy controls. Levels of these LPS toxicity-regulating proteins were elevated in patients with active tuberculosis compared with those in contacts and controls and declined during treatment. The levels of LBP and sCD14 were higher in patients with fever and anorexia. LPS-regulating proteins may play a role in host defense during tuberculosis, presumably through interaction with lipoarabinomannan.

Acute-Phase Proteins↗
PubMed1998

Tumor necrosis factor and interleukin-1 inhibitors as markers of disease activity of tuberculosis.

Serum concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)-1beta, and their circulating inhibitors soluble TNF receptor type I (sTNFRI), type II (sTNFRII), IL-1 receptor antagonist (IL-1ra), and soluble IL-1 receptor type II (sIL-1RII) were measured for 123 patients with tuberculosis (TB) in various stages of disease, in persons who had been in close contact with patients with contagious pulmonary TB, and in healthy controls. Levels of sTNFRI, sTNFRII, and IL-1ra, but not of sIL-1RII, were elevated in patients with active TB compared with contacts and controls and declined during treatment. The concentrations of these mediators did not differ between patients with pulmonary and extrapulmonary TB. The levels of sTNFRI and IL-1ra were higher in patients with fever and anorexia. Neither TNF nor IL-beta was detectable. We conclude that serum concentrations of sTNFRs I and II and IL-1ra may serve as markers of disease activity of TB. Sequential measurements of these cytokine inhibitors may be useful in the monitoring of antituberculous therapy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pott's puffy tumor due to Haemophilus influenzae: case report and review.

Osteomyelitis of the frontal bone may be associated with a purulent collection under the periosteum, causing swelling and edema over the forehead, a condition known as Pott's puffy tumor. We describe an 83-year-old man with a Pott's puffy tumor due to Haemophilus influenzae that was successfully treated with surgery and antibiotics. A review of 22 cases of Pott's puffy tumor shows that this condition usually occurs in children, is spread from frontal or ethmoid sinusitis, and is usually due to streptococci, staphylococci, or anaerobes. Suppurative complications such as epidural, subdural, and intracerebral abscesses are common. Only seven cases of Pott's puffy tumor in adults have been reported, and only one of these cases was caused by H. influenzae. Surgical drainage and antibiotic therapy remain standard therapy for this condition.

Aged↗
PubMed1994

Reinfection with Legionella pneumophila documented by pulsed-field gel electrophoresis.

A 50-year-old man with chronic lymphocytic leukemia experienced two episodes of community-acquired legionnaires' disease. For determining whether this was the result of relapse or reinfection, Legionella pneumophila strains, cultured from sputum specimens and his home water supply, were characterized by pulsed-field gel electrophoresis. Analysis of the restriction patterns and the clinical data indicated that the second disease period was most likely the result of reinfection. We conclude that after diagnosis of community-acquired legionnaires' disease in an immunocompromised patient, culturing of the domestic water supplies for L. pneumophila should be considered; if such cultures are positive, adequate measures to prevent reexposure have to be taken.

Anti-Bacterial Agents↗
PubMed1994

Development of a serological test for tuberculosis. Problems and potential.

The secreted antigens of 24K and 38K and the hsp of 12K and 16K are valuable as reagents in a serodiagnostic assay for tuberculosis. A combination of the TB72 assay with either the 16K or 24K antigen gives the best sensitivity and specificity. Antigens isolated from mycobacterial cultures are valuable in a serological test. Peptides cannot be used as antigens. The value of antigens obtained with recombinant DNA techniques remains to be determined. In HIV-seronegative patients with TB serodiagnosis is a valuable test both in pulmonary and extrapulmonary TB. Unfortunately, the results in HIV-seropositive patients are rather disappointing. The use of likelihood ratios seems to increase the potential of serodiagnostic assays. The value of serodiagnosis should be judged in context with other diagnostic methods such as direct microscopy, bacteriological culture or skin tests. A serological test is especially valuable in cases where direct microscopy, polymerase chain reaction or skin testing is negative and allows antituberculous therapy to be started before results of culture are known.

Antigens, Bacterial↗
PubMed1993

Evaluation of different tests for the serodiagnosis of tuberculosis and the use of likelihood ratios in serology.

A serologic test for the diagnosis of tuberculosis was evaluated in 91 newly diagnosed tuberculosis (TB) patients, of whom 15 were HIV positive, in 17 TB patients during treatment, and in 220 control subjects (including individuals from endemic areas and patients with sarcoidosis or Crohn's disease). Purified proteins of M. tuberculosis with molecular weights of 10,000, 16,000, 24,000, 30,000, 38,000, and 70,000 were tested by ELISA. In addition, monoclonal antibody TB72 was tested by competition ELISA. The cutoff values were set at the mean plus three standard deviations of the values obtained in 100 healthy Dutch army recruits. Only the ELISA with the 10,000, 16,000, and 24,000 antigens and the TB72 assay discriminated between patients with TB who were not HIV positive and control subjects. Specificity varied from 95 to 98% and sensitivity from 29 to 51% with the different antigens. Combination of the test results of the ELISA with the 16,000 antigen and the TB72 assay had a sensitivity of 65% (95% confidence interval, 53 to 75%) and a specificity of 96% (95% confidence interval, 92 to 98%). The assay was useful for the diagnosis of both pulmonary and extrapulmonary TB. Optimal use of the serologic assay could be obtained when likelihood ratios for each test value are calculated instead of using the test dichotomized (positive or negative). High posttest probabilities indicate the presence of TB; low posttest probabilities do not exclude the disease and should lead to additional investigations.

AIDS-Related Opportunistic Infections↗
PubMed1992

Characterization of B cell epitopes on the 16K antigen of Mycobacterium tuberculosis.

To characterize the antigenic parts of the 16K protein of Mycobacterium tuberculosis, overlapping peptides according to the amino acid sequence of the 16K protein were synthesized. In total, 14 peptides of 20 amino acids in length with an overlap of 10 amino acids and two additional decapeptides (amino acids 31-40 and 61-70) were tested with eight anti-16K MoAbs and human sera. The common recognition site of MoAbs F67-8 and F67-16 was LRPTFDTRLM (amino acids 31-40) and of MoAbs F159-1 and F159-11 DPDKDVDIMV (amino acids 61-70). However, for binding of the MoAbs to these peptides additional amino acids were required at either the N- or C-terminus, suggesting that some kind of conformation is required. The recognition sites of the MoAbs F23-41, F23-49, F24-2 and TB68 could not be identified using the peptides, indicating that the MoAbs only bound to conformational epitopes and not to peptides which may contain parts of these epitopes. The MoAbs bound to beta-galactosidase fusion proteins comprising parts of the 16K protein, indicating that some kind of native conformation is present on the recombinant proteins. Sera from 14 of 19 patients with tuberculosis and none from 19 controls reacted with the purified 16K protein. Sera from four of these 14 patients reacted with two overlapping peptides (amino acids 71-100). Apparently, antibodies in patients' sera against the 16K protein are predominantly directed against conformational epitopes.

Amino Acid Sequence↗
PubMed1992

Antibodies against secreted and non-secreted antigens in mice after infection with live Mycobacterium tuberculosis.

Mice from four different inbred strains were infected with live Mycobacterium tuberculosis and the immune response to M. tuberculosis was followed for 24 weeks, using Western blotting. Nearly all mice, irrespective of H-2 type, reacted with the 38-kDa protein band. Antibodies against this secreted 38-kDa protein were the first to appear, 4 weeks after infection. Thereafter the secreted 19-kDa protein and non-secreted antigens, such as the 65-kDa and 33-kDa proteins, were recognized. The immune response against the non-secreted antigens was influenced by the mouse strain. However, the 33-kDa protein band was recognized by all mouse strains after a second injection with live M. tuberculosis. The specificity of the antibodies was analysed in Western blot using sonicates of M. tuberculosis, M. kansasii, M. avium, M. terrae, M. gordonae and Escherichia coli. Antibodies against the 38-kDa and 33-kDa protein bands seemed to be specific for M. tuberculosis, while antibodies against the 19-kDa protein band showed limited cross-reactivity. Antibodies against the 65-kDa protein were strongly cross-reactive. These results suggest that the 38-kDa protein is secreted in vivo and, therefore, may be available to the humoral immune system at an early stage of infection. The non-secreted 33-kDa protein is only recognized by all mouse strains after prolonged contact with M. tuberculosis.

Animals↗
PubMed1992

The 14,000-molecular-weight antigen of Mycobacterium tuberculosis is related to the alpha-crystallin family of low-molecular-weight heat shock proteins.

Eight monoclonal antibodies (MAbs) directed against the 14,000-molecular-weight (14K) antigen of Mycobacterium tuberculosis reacted specifically with mycobacteria of the M. tuberculosis complex. The nucleotide sequence of the gene encoding the 14K antigen was determined by using recombinant DNA clones isolated from lambda gt11 and cosmid libraries of the M. tuberculosis genome. The DNA sequence of the 14K protein gene coded for a polypeptide of 144 amino acids with a calculated molecular mass of 16,277 Da. The 14K antigen has a marked homology with proteins belonging to the alpha-crystallin family of low-molecular-weight heat shock proteins, which includes the 18K antigen of M. leprae. The eight MAbs recognized at least four distinct epitopes localized within the following three regions of the 14K protein: amino acids 10 to 92 (MAbs F67-8 and F67-16), amino acids 41 to 92 (F159-1 and F159-11), and amino acids 41 to 144 (F23-41, F24-2, F23-49, and TB68).

Amino Acid Sequence↗
PubMed1991

[Development of a serological test for tuberculosis].

Antigens secreted by M. tuberculosis in the culture medium and antigens obtained from sonicated M. tuberculosis were characterized, at the laboratory of Tropical Hygiene of the Royal Tropical Institute and the division of Pulmonary Medicine at the Academic Medical Centre, in order to explore which antigens could be valuable in the development of a serological test for tuberculosis. Using murine monoclonal antibodies in immunoblot, a pattern of protein bands distinct from that of the corresponding M. tuberculosis sonicate was found in the culture medium. The major protein bands of the culture medium, of 24 and 12 kD, and the major protein band of 16 kD in sonicate were purified. These antigens were tested in ELISA with sera from 20 patients with tuberculosis, diagnosed by a positive culture of M. tuberculosis, and from 21 control subjects. The ELISA results obtained with these 3 antigens were combined and the mean value obtained in the control group plus 2 times the standard deviation was chosen as the cut-off level. Sixteen of the 20 patients with tuberculosis had antibodies against 1 of the purified antigens, while none of the control subjects had. By combining the results, obtained with these 3 antigens, 17 of the 20 patients with tuberculosis were positive in this serological test and none of the control subjects. The 24, 12 and 16 kD antigens may be valuable for the development of a serological test for tuberculosis.

Antigens, Bacterial↗
PubMed1991

Murine and human B cell epitope mapping of the Mycobacterium tuberculosis 10-kD heat shock protein using overlapping peptides.

The human immune response to the 10-kD M. tuberculosis protein was studied by a competition ELISA using monoclonal antibody (MoAb) SA-12. Twenty-five per cent of the sera from 20 patients with tuberculosis and none from 21 control subjects inhibited binding of SA-12 to the 10-kD antigen. To characterize the antigenic parts of the 10-kD antigen, overlapping decapeptides according to the amino acid sequence of the 10-kD protein were synthesized. In total, 91 sequential decapeptides, with an overlap of nine amino acids, were tested in ELISA with MoAb SA-12, human and murine sera (PEP scan). SA-12 recognized the amino acid sequence WDEDGEK (amino acid 50-56). All human sera, from patients with tuberculosis as well as from control subjects, gave almost identical undulating patterns of reactivity with the decapeptides. No relationship was found between the ability of the patients' sera to inhibit binding of MoAb SA-12 and the binding of these sera to the decapeptides comprising the epitope recognized by SA-12 in the PEP scan. Apparently, antibodies in patients' sera against the 10-kD protein are predominantly directed against discontinuous epitopes and, consequently, the continuous epitopes as presented in the PEP scan are not suitable to discriminate between patients with tuberculosis and control subjects. In the PEP scan, sera from BALB/c mice, both non-immunized and immunized with either live M. tuberculosis or the 10-kD protein gave similar patterns of reactivity, albeit different from the patterns obtained with the human sera. However, after immunization of the mice, clearly increased levels of antibodies to primary structures of the 10-kD protein were observed.

Amino Acid Sequence↗
PubMed1990

Antigens in culture supernatant of Mycobacterium tuberculosis: epitopes defined by monoclonal and human antibodies.

Antigens of Mycobacterium tuberculosis found in the supernatant of heat-treated cultures were characterized in order to explore whether antigens from this source could be used for the development of a serological test. Culture supernatants and sonicates of 12, 25 and 39 d cultures were analysed by SDS-PAGE. In culture supernatant, major protein bands of 65, 24, and 12 kDa were visible after Coomassie brilliant blue staining. Using murine monoclonal antibodies in Western blots, a pattern of protein bands distinct from that of the corresponding M. tuberculosis sonicates was found in all the culture supernatants. Gel permeation chromatography, in the presence of SDS, was used to separate the major protein bands in the culture supernatant. In ELISA, sera from 20 of 26 patients with tuberculosis reacted with fractions containing mainly 24 kDa or 12 kDa proteins, whereas none of the control sera reacted. In Western blots, each patient serum had its own characteristic banding pattern with culture supernatant, but all the sera from tuberculosis patients and control subjects reacted with protein bands of 65, 61, 58, 30 and 24 kDa. The 12 kDa protein was recognized only by sera from patients with tuberculosis in both Western blots and ELISA. This suggests that different kinds of epitopes on proteins of M. tuberculosis are detected by human antibodies in Western blots and ELISA. We assume that epitopes recognized in Western blots by patients with tuberculosis and control subjects are ubiquitous and are also present on normal commensal bacteria. Epitopes recognized by only some patients with tuberculosis in Western blots may be linear and M. tuberculosis specific. Epitopes recognized by tuberculosis patients but by none of the control subjects in ELISA may be conformation related and M. tuberculosis specific. The major protein bands found in supernatants of heat-treated cultures, 24 and 12 kDa, possess epitopes that may be M. tuberculosis specific and are potentially valuable for the development of a serological test.

Antibodies, Bacterial↗