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Biomedical subjects

A A Wadee

Publications and source records attributed to A A Wadee.

At least 37 records · Page 2Linked to original sources
PubMed1992

Supernatants derived from CD8+ lymphocytes activated by mycobacterial fractions inhibit cytokine production. The role of interleukin-6.

Our study examined the effects of supernatants derived from CD8+ lymphocytes treated with high molecular weight components of Mycobacterium tuberculosis on cytokine production. Such suppressor but not control supernatants increased the production of IL-4 and IL-6 whilst suppressing IL-1 beta, TNF-alpha, IL-2 and IFN-gamma production by monocytes and lymphocytes. The effects on cytokine production were time dependent being observed as early as 4 hours with peak activity observed at 24 hours. The inhibition of IL-1 beta and TNF-alpha by monocytes appeared to be related to increases in IL-6 levels present in supernatants of non-adherent lymphocytes incubated with mycobacterial components. This was confirmed by studies demonstrating that the addition of recombinant IL-6 to cultures depressed the production of these cytokines. Furthermore the addition of monoclonal anti-IL6 to such cultures restored the production of IL-1 beta and TNF-alpha. The results suggest that mycobacterial components inhibit host cellular functions by manipulating the host's cytokine network.

Antigens, Bacterial↗
PubMed1991

The synergistic effects of gamma interferon and clofazimine on phagocyte function: restoration of inhibition due to a 25 kilodalton fraction from Mycobacterium tuberculosis.

A 25 kDa glycolipoprotein from Mycobacterium tuberculosis has been shown to inhibit phagocyte functions associated with antimicrobial activity. These include the intracellular killing ability, reduction of nitro blue tetrazolium, hydrogen peroxide production and lysosyme release of polymorphonuclear leukocytes and peripheral blood monocytes. The present study undertook to investigate the synergistic effects of gamma interferon and clofazimine on restoring the inhibitory activities of the 25 kDa glycolipoprotein on these phagocyte functions. Gamma interferon and clofazimine at concentrations of 25 units/ml and 0.3 micrograms/ml acted synergistically by completely restoring all these systems. Independent use of these agents were unable to affect phagocyte functions or to restore the inhibition caused by the 25 kDa mycobacterial component. These studies indicate the possible use of these two phagocyte priming agents for the immunotherapy of tuberculosis.

Clofazimine↗
PubMed1991

Immune responses of two Mastomys sibling species to Yersinia pestis.

This study assessed the in vitro cell-mediated immune responses of Mastomys natalensis, with a diploid chromosome number of 2n = 32, and Mastomys coucha, with a diploid chromosome number of 2n = 36, to Yersinia pestis. Splenic mononuclear (MN) cells of uninfected M. natalensis proliferated in response to crude fraction 1 of Y. pestis and two subfractions derived from fraction 1 in vitro. Proliferation was dose dependent and followed the time kinetics of other well-known mitogens. Further characterization of the two fractions revealed similar protein profiles in sodium dodecyl sulfide-polyacrylamide gel electrophoresis and indicated a heat-stable protein of 25 kDa responsible for the mitogenic activity. No such response was observed with MN cells from M. coucha. The unresponsiveness of M. coucha-derived MN cells appears to be related to an inability to respond to Y. pestis organisms. The results may help explain the relative resistance and susceptibility of M. natalensis and M. coucha to Y. pestis infection.

Animals↗
PubMed1991

Production of a suppressor factor by CD8+ lymphocytes activated by mycobacterial components.

The lipid component present in high-molecular-mass fractions with molecular masses of greater than 200 kDa derived from Mycobacterium tuberculosis extracts passaged through Sephacryl S.200 columns activate CD8+ lymphocytes to suppress lymphocyte blastogenesis. Suppression is mediated by the release of suppressor molecules by these CD8+ lymphocytes. Release of suppressor molecules occurs as early as 2 h following pulsing with the high-molecular-mass mycobacterial components and is maximal at 24 h, after which their release declines rapidly. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting indicates that the active components are carbohydrate moieties with approximate molecular masses of 122 to 148 kDa. Our results suggest a mechanism of interaction between mycobacteria and host mononuclear cells such that mycobacterial lipids, once exposed, activate CD8+ suppressor lymphocytes. Activation of these lymphocytes results in the release of carbohydrate-containing molecules that ultimately inhibit the blastogenesis of other lymphocytes.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Fruit allergy: demonstration of IgE antibodies to a 30 kd protein present in several fruits.

A patient who had experienced allergic responses to various fruits developed an acute anaphylactic reaction after the ingestion of a local strain of cling peaches. The patient's serum, but not control sera, contained IgE antibodies reactive to extracts from peaches, guavas, bananas, mandarins, and strawberries in an ELISA. The patient's serum, however, did not demonstrate elevated levels of IgE antibodies to extracts from apples, pears, and nectarines. Adsorption of the patient's serum with extracts from peaches, strawberries, and mandarins resulted in a decline of detectable IgE antibodies to these fruits. Adsorption with extracts from apples and pears had no such effect. These results demonstrate the specificity of the patient's IgE antibodies to selected fruits only. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting revealed a 30 kda of protein that was recognized by the IgE antibodies in the patient's serum. This protein was not present in extracts from pears or apples. Our results highlight the importance of specific allergens in considering acute allergic reactions to individuals exhibiting sensitivity to various foods or fruits.

Adult↗
PubMed1990

Antigen capture assay for detection of a 43-kilodalton Mycobacterium tuberculosis antigen.

This study describes the development of an enzyme-linked immunosorbent assay (ELISA) to detect Mycobacterium tuberculosis antigens in body fluids. A double-antibody sandwich procedure that used human and rabbit anti-M. tuberculosis immunoglobulin G antibodies was followed. The ELISA was able to detect as little as 0.8 micrograms of protein of M. tuberculosis sonic extract. Of 253 cerebrospinal fluid specimens submitted for analysis, 11 (4.3%) false-positive results were recorded. Analysis of 317 pleural and ascitic fluid specimens resulted in 6 (1.9%) false-positive recordings. No false-negative results were recorded for any of the body fluids tested. This technique is rapid (5.5 h) and sensitive, may be developed and used in many laboratories with limited resources, and may prove useful in the diagnosis of extrapulmonary and pulmonary tuberculoses. Analysis of these body fluids by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting indicated that the antibody used in the ELISA detects a mycobacterial antigen of 43 kDa. Such antigens were not detected in body fluids of nontuberculous patients.

Antigens, Bacterial↗
PubMed1990

The relationship of antibody levels to the clinical spectrum of human neurocysticercosis.

One hundred proven cases of cerebral cysticercosis were studied with an enzyme linked immunoassay (ELISA) employing cyst fluid as antigen, with a view to detecting specific antibodies in serum and cerebrospinal fluid (CSF). Antibody levels were correlated with the clinical presentation of the patients, the type and number of cysts detected on their brain scans, the anatomical position of these cysts and the presence of lymphocytes in the CSF. Patients could be divided into two distinct categories, one with low levels of antibody in the serum and absent antibody in the CSF, and the other with high levels in both the serum and the CSF. This differentiation matched the clinical presentation of a benign and a malignant group. Antibody levels could not be related to the type of cysts as observed on the brain scan, but depended on the anatomical position of the cyst, being lower if the cysts were confined to the cerebral cortex. A correlation of antibody levels with the number of cysts was only found in the benign group.

Adolescent↗
PubMed1989

HLA frequencies in the Indian population of Johannesburg.

The HLA class I antigen and haplotype frequencies of the three major Indian groups resident in the Johannesburg area, i.e. Hindus, Muslims and Tamils, were determined. The HLA-A, B and C antigens were tested in 460 healthy individuals. There were striking differences in antigen and haplotype frequencies between the various groups. Of interest was the finding of a complete lack of Aw34 in any of these groups. Although different haplotype frequencies appeared prominent in the different groups, all three groups demonstrated the haplotypes Aw33, B44, B35, Cw4 and B7, Cw7 in linkage disequilibrium. The results indicate dissimilarities between the various groups, underscoring the fact that use of these analyses is essential for the various applications of HLA testing.

Gene Frequency↗
PubMed1989

A 25-kilodalton fraction from Mycobacterium tuberculosis that inhibits hexose monophosphate shunt activity, lysozyme release, and H2O2 production: reversal by gamma interferon.

This study examined the effects of a 25-kilodalton (kDa) glycolipoprotein derived from Mycobacterium tuberculosis on phagocyte functions associated with antimicrobial activity. The 25-kDa fraction inhibited the ability of both polymorphonuclear cells and cultured monocytes to release lysozyme and produce hydrogen peroxide. In addition, the glycolipoprotein was capable of reducing hexose monophosphate shunt activity and interfered with the ability of polymorphonuclear cells to reduce Nitro Blue Tetrazolium. Inhibition of these antimicrobial systems was optimal at a 50-micrograms/ml concentration of the 25-kDa fraction. Gamma interferon, but not alpha interferon, partially reversed the inhibitory effect of the mycobacterial component in all of the systems assessed. These studies indicate important mechanisms in the understanding of the pathogenesis of tuberculosis and suggest that gamma interferon may have a therapeutic role in mycobacterial diseases.

Blood Bactericidal Activity↗
PubMed1989

A 180-kilodalton protein from Mycobacterium tuberculosis defined by a human T cell clone.

A high molecular weight protein from Mycobacterium tuberculosis (M. tuberculosis) has been identified, that is recognized by peripheral blood mononuclear cells from several tuberculous patients and by a T cell clone derived from a patient with tuberculous pleurisy. Purification of this fraction demonstrated biological activity to reside in a 180-kDa protein component. This mycobacterial protein appears to exist in some, but not all mycobacteria as the clone reacts to M. tuberculosis, BCG M. kansasii, M. flavescens and M. fortuitum, but not to M. intracellulare, M. scrofulaceum or a variety of gram-positive or gram-negative bacteria, or to PPD. Specific anti-genic challenge of the T cell clone in the presence of irradiated antigen presenting cells results in proliferation and interleukin-2 (IL-2) production. Proliferation is restricted to HLA Class II antigens as antigenic recognition occurs only in the presence of either one of the two parental DR haplotypes. Peripheral blood mononuclear cells from several other patients with pulmonary tuberculosis also proliferate in response to this antigen, emphasizing the relevance of T cell cloning techniques in identifying important mycobacterial antigens.

Antigen-Presenting Cells↗
PubMed1988

Clofazimine reverses the inhibitory effect of Mycobacterium tuberculosis derived factors on phagocyte intracellular killing mechanisms.

The effects of clofazimine on phagocyte functions associated with antimicrobial activity have been investigated. Clofazimine at a variety of concentrations was capable of enhancing the spontaneous production of hydrogen peroxide and the intracellular killing ability of phagocytes; but had no effect on resting phagocyte lysozyme release, or hexose monophosphate shunt (HMPS) activity. However, when these latter functions were assessed in the presence of a phagocytic stimulus, clofazimine moderately increased both lysozyme release and HMPS activity. A 25 Kd glyco-lipoprotein derived from Mycobacterium tuberculosis has been shown to inhibit these antimicrobial functions. Clofazimine was capable of partially reversing the inhibitory effect of the mycobacterial component in all of the systems assessed. Partial restoration was observed at concentrations of 0.5 mg/l and was maximal at 2 mg/l. These studies indicate important mechanisms operative in the pathogenesis of tuberculosis and suggest that clofazimine may have clinical relevance in the treatment of mycobacterial diseases.

Bacterial Proteins↗
PubMed1988

Enzyme-linked immunosorbent assay for the detection of antibodies against Mycobacterium tuberculosis in bronchial washings and serum.

This prospective study evaluates an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies against Mycobacterium tuberculosis when applied to serum and bronchial washings (BW) of patients requiring bronchoscopy for definitive diagnosis. The ELISA employed an adsorbed fraction of mycobacterial sonicates as antigen. Of the 57 patients tested, 12 had tuberculosis (TB), 13 had malignant disease, 14 acute pneumonia or chronic destructive pneumonia, 13 had no demonstrable disease, and five had miscellaneous diseases. The mean optical density (OD) at 492 nm for a 1 in 40 dilution of serum of patients with TB was 0.338 +/- 0.218 and for control subjects was 0.162 +/- 0.098 (p = 0.0323). Values for neat BW were 0.317 +/- 0.122 for TB patients and 0.191 +/- 0.140 for control subjects (p = 0.0084). Using stepwise discriminant analysis, the ELISA on serum gave a sensitivity of 70.0 percent and specificity of 86.4 percent and 83.3 percent correct classification. When applied to BW, there was a 72.7 percent sensitivity, a 82.2 percent specificity, and patients were correctly classified in 80.4 percent of cases. It is concluded that the assay is a useful and reliable adjunct to conventional tests for tuberculosis.

Adult↗
PubMed1988

Differentiation of sarcoidosis from tuberculosis using an enzyme-linked immunosorbent assay for the detection of antibodies against Mycobacterium tuberculosis.

This study evaluates the ability of an enzyme-linked immunosorbent assay (ELISA) using adsorbed mycobacterial sonicates as antigen to differentiate between patients with tuberculosis (TB) and patients with sarcoidosis. The study group consisted of 11 patients with active sarcoidosis, seven patients with sputum-positive tuberculosis, and seven normal control subjects. Serum specimens were subjected to ELISA. Serum anti-TB IgG optical density measured at 492 nm (mean +/- SD); pulmonary TB, 0.291 +/- 0.040; normal control subjects, 0.092 +/- 0.011; and sarcoidosis, 0.064 +/- 0.033 (TB vs sarcoid, p less than 10(-6)). This ELISA is a valuable test for the differentiation between sarcoidosis and TB.

Adult↗
PubMed1987

An enzyme-linked immunosorbent assay using adsorbed mycobacterial sonicates for the serodiagnosis of tuberculosis.

Sera from 123 patients with confirmed tuberculosis and 576 patients with other non-mycobacterial diseases were tested for antibodies to an adsorbed mycobacterial sonicate antigen employing an enzyme-linked immunosorbent assay. The results show significant differences in IgG levels between sera from tuberculosis patients and controls. The results of delayed hypersensitivity skin-test reactions to purified protein derivative in both the patient and control groups were unrelated to antibody levels. The assay was able to detect antibodies for at least 4 months after diagnosis and treatment. Patients diagnosed as having tuberculosis 7 months or more before being tested did not demonstrate increased antibody levels. The assay could be useful not only as a screening technique for diagnosing tuberculosis in an immunised population but also as a means of monitoring antituberculosis treatment.

Antigens, Bacterial↗
PubMed1987

Anaphylactic shock due to cytarabine in a leukemic child.

In a young child with acute promyelocytic leukemia, treatment with a variety of chemotherapeutic agents produced an acute anaphylactic reaction. When cytarabine was removed from the chemotherapeutic regimen, no further anaphylaxis occurred. Employing an enzyme-linked immunosorbent assay with cytarabine coated onto the wells in bovine serum albumin, specific IgE antibodies to this drug could be demonstrated. Similar antibodies could not be demonstrated in the serum of normal controls or of two other patients receiving cytarabine. We therefore document anaphylactic shock mediated by specific IgE antibodies to cytarabine.

Anaphylaxis↗
PubMed1987

Regulation of immune responses in lymphatic filariasis.

The nature and intensity of immune reactions to filarial antigens appear to be controlled by two broad mechanisms: immunoregulation and immune tolerance. Parasite molecules of high molecular weight activate suppressor T lymphocytes; suppressive parasite products are present in sera from microfilaraemic patients. Prenatal or perinatal exposure to soluble parasite antigens may influence a person's future ability to react to filarial antigens.

Animals↗
PubMed1987

Development of specific IgE antibodies after repeated exposure to snake venom.

A patient who had been working with snakes for many years developed urticarial lesions on contact with the venom of the poisonous rinkals (Haemachates haemachatus). More recently, the patient complained of generalized allergic reactions occurring within minutes of exposure to the venom. The patient's serum, but not control sera, contained IgE antibodies that reacted with the specific snake venom in an ELISA and was demonstrated to associate with a 66 kd component of the venom with Western blotting. With an ELISA, the patient's serum was also demonstrated to contain IgG antibodies to the specific snake venom and to venom from three other snakes with which the patient had previously been in contact. The possibility of an acute allergic reaction should be considered in individuals continuously working with snakes or in individuals who have previously been bitten by snakes.

Adult↗