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Biomedical subjects

A A Wadee

Publications and source records attributed to A A Wadee.

At least 19 recordsLinked to original sources
PubMed2002

HLA class I and class II antigens associated with multiple myeloma in southern Africa.

While the exact aetiology of myeloma is unknown, genetic factors feature among the potential risk factors. The HLA phenotypes in African blacks with myeloma (the commonest haematopoietic malignancy in this group) have not been characterized. The purpose of this study was to determine the HLA class I and class II phenotypes of patients with multiple myeloma and to compare the findings to an ethnically matched control group of 100 individuals. Analysis of the HLA class I and class II phenotypes in 62 myeloma patients revealed: (i) a corresponding statistically significant association with HLA B18 [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.013-39.727; P < 0.005]; (ii) no statistically significant association with HLA B13, Cw2, Cw6 or the DR and DQ antigens; and (iii) a statistically significant negative (protective) association with HLA Cw7 (OR 0.4; 95% CI 0.21-0.87; P < 0.005). This study suggests that although genetic factors may play a role in the multifactorial aetiology of multiple myeloma, with the exception of HLA B18, there is no specific association between HLA types and multiple myeloma in South African blacks.

Adult↗
PubMed2000

In the rationing of healthcare in indigent African populations, which services should come first?

Governments, worldwide, have enormous difficulties in affording adequate funds for healthcare and its maintenance. In developing populations, almost all of whom are indigent, the diverse health problems being faced with limited funds are insufficiently appreciated. Information is given, for both developed and developing populations, principally those in sub-Saharan Africa, regarding various countries' gross national product (GNP) per capita, the percentage of GNP devoted to health services, and the allocation of health funds per capita. To illustrate the formidable health problems prevailing, some data are given on the magnitudes of morbidity/mortality situations, both for communicable and non-communicable diseases. Some examples are provided which exemplify opposing points of view regarding strongly contesting health claims for priorities in monetary support. Additionally, examples are given of some impoverished countries, which, despite highly adverse circumstances, have achieved enviable health statistics. In this respect it would be highly beneficial were the circumstances and means employed in these and similar contexts given wide publicity.

Adult↗
PubMed1997

Acute phase proteins in major depression.

Extensive evidence exists associating depression with changes in the immune system. The present study evaluates the levels of complement components C3 and C4, C-reactive proteins, and IL-6 in patients who met DSM-III-R diagnostic criteria for major depressive disorder, as well as controls. Whereas no significant differences between the mean levels of C3 could be detected between depressed patients and controls, the levels of C4, IL-6 (where detected), and C-reactive protein were significantly raised in the group with a depressive disorder. Our study suggests an interaction between psychological state and immune systems operative in host defenses.

Acute-Phase Proteins↗
PubMed1997

An evaluation of the capillus HIV-1/HIV-2 latex agglutination test using serum and whole blood.

The capillus HIV-1/HIV-2 latex agglutination (LA) test was evaluated for its potential as an initial screening test in primary health care. For the serum study, panels totalling 289 HIV-positive sera and 323 known HIV-negative sera plus 50 individual seroconversion samples were tested by capillus. Paired blood specimens were also collected in heparinized and plain tubes from 501 consecutive patients with newly diagnosed sexually transmitted diseases (STDs) attending an STD clinic at a Transvaal hospital. Overall, an initial sensitivity of 99.3% and an initial specificity of 99.7% were obtained by visual reading of the capillus HIV-1/ HIV-2 LA tests on serum samples. Capillus also detected 40 (80%) of the 50 seroconversion samples. Of the 501 paired plain and heparinized blood specimens, serum testing by enzyme immunoassay (EIA) and indirect immunofluorescence/ Western blot (IFA/WB) showed 147 (29%) to be HIV Ab positive. Capillus testing of the paired specimens correctly identified all 147 known positive patients and 345 of the 346 negative patients, thus showing an initial sensitivity of 100% and an initial specificity of 99.7% for the testing of heparinized whole blood by a relatively unskilled health worker. It was concluded that the capillus HIV-1/HIV-2 LA test would be suitable for use as a primary screening test in small outlying laboratories or primary health care clinics.

Blotting, Western↗
PubMed1995

The pro-oxidative riminophenazine B669 neutralizes the inhibitory effects of Mycobacterium tuberculosis on phagocyte antimicrobial activity.

The effects of clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 on phagocyte functions have been investigated. Clofazimine, at concentrations attainable in vivo, and B669, in particular, increased the intracellular killing ability of phagocytes following appropriate cell stimulation. Similarly, nitro blue tetrazolium reduction, hydrogen peroxide production, lysosyme release and hexose monophosphate shunt activity were all increased by treating phagocytes with the riminophenazines. It has previously been shown that a 25 kDa glycolipoprotein derived from Mycobacterium tuberculosis inhibits phagocyte functions associated with phagocyte antimicrobial activity. The present study confirms these observations. A further aspect of the study examined the ability of riminophenazines to reverse the inhibition of phagocyte functions by the 25 kDa mycobacterial fraction. Whilst both riminophenazines were capable of partially but significantly reversing the inhibition due to the mycobacterial fraction, the restorative capacity of B669 was greater than that of clofazimine.

Anti-Bacterial Agents↗
PubMed1995

The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants.

The expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated. Class II expression as determined by a cell ELISA was effectively induced by various phagocyte stimulants. A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression. Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens. A 25-kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described. This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon-gamma (IFN-gamma) or opsonised yeast when added at the initiation of experiments. The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25-kD mycobacterial fraction. However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25-kD mycobacterial fraction. The results suggest the potential use of these agents as modulators of phagocyte function.

Antigens, Bacterial↗
PubMed1994

HLA expression in hepatocellular carcinoma cell lines.

The present study undertook to investigate the biological significance of human leucocyte antigen expression in hepatocellular carcinoma and to elucidate the role of potential modulating agents on human leucocyte antigen expression. These studies used several hepatic tumour-derived cell lines as in vitro model systems. The cell lines included PLC/PRF/5 (Alexander cell line), Hep3B, HepG2, TONG PHC, HA22T/VGH, HA59T/VGH and Mahlavu. The cell lines K562 and Raji were used as negative and positive controls, respectively. K562, a B lymphoid-derived cell line, was shown to express negligible amounts of human leucocyte antigens, while Raji, an erythromyeloid-derived cell line, expressed both class I and class II human leucocyte antigens as well as their respective invariant chains, beta 2-microglobulin and Ii. Using an ELISA, experiments performed on these cell lines confirmed the natural expression of class I and class II antigens by the HA22T/VGH and HA59T/VGH cell lines, whereas PLC/PRF/5 displayed class II surface antigens only. The effects of modulating agents such as interferon-gamma sodium butyrate and clofazimine on human leucocyte antigen expression were investigated using the HA22T/VGH, HA59T/VGH and TONG PHC cell lines. These agents increased class II and class II human leucocyte antigen expression on HA22T/VGH and TONG PHC cells, but had no effect on the HA59T/VGH cell line. The results suggest a potential use for these agents as modulators of human leucocyte antigen expression by human heptocellular cell lines.

Butyrates↗
PubMed1993

Recurrent spontaneous abortion: histocompatibility between partners, response to immune therapy, and subsequent reproductive performance.

PROBLEM: Immunological factors may account for previously unexplained cases of recurrent abortion. METHOD: After screening 76 couples for causes of recurrent spontaneous abortion and measuring maternal antipaternal immunity, 23 primary spontaneous recurrent aborters were immunized once with their husbands' leukocytes. Testing for antipaternal cytotoxicity was repeated in 21 couples. Seroconversion was significantly less frequent in couples who shared more than one human leukocyte antigen [one of five (20%) versus 13 of 16 (81%), P < .02]. RESULTS: Twelve of 16 women (75%) who became pregnant had live children and five of those have had a second live child. All 12 women who achieved successful pregnancies had become antipaternal cytotoxic antibody-positive after immunization, whereas all four patients who had repeat abortions had failed to seroconvert (P < .001). However, this relationship is not necessarily causative, as the successful group also tended to have fewer previous abortions and less human lymphocyte antigen sharing. CONCLUSION: Except for transient illness after immunization, one moderately small for gestational age baby and one premature labor at 32 wk, no complications were observed after immunization.

Abortion, Habitual↗
PubMed1992

[Pneumococcus-induced septicemia in normal and splenectomized rabbits].

A new rabbit model to study the consequences of splenectomy in host resistance to induced pneumococcal septicaemia is presented. A simple, fast, non-invasive and complication-free technique of bacterial inoculation into the rabbit airways, using transcutaneous cannulation of the trachea, is also described. Sixteen normal and 24 splenectomised animals were used. The optimal dose of pneumonococcus (serotype B, type III) was found to be 1 x 10(7) organisms. The above dose of bacteria given transtracheally failed to cause signs of pneumonia or death in any of the normal rabbits. However the same dose introduced using the same technique resulted reproducibly in the death of the low-resistance splenectomised animals.

Animals↗
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↗