PubMed Health⌕ Search

Biomedical subjects

D Lilic

Publications and source records attributed to D Lilic.

15 recordsLinked to original sources

Best practice in primary care pathology: review 2.

This second best practice review examines five series of common primary care questions in laboratory medicine: (1) laboratory testing for allergy, (2) diagnosis and monitoring of menopause, (3) the use of urine cytology, (4) the usefulness of the erythrocyte sedimentation rate, and (5) the investigation of possible urinary tract infection. The review is presented in a question-answer format. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.

Blood Sedimentation↗

Disseminated Bacillus Calmette-Guérin infection in a girl with hyperimmunoglobulin E syndrome.

Disseminated Bacillus Calmette-Guérin infection occurs in few well-defined immunodeficiencies, such as severe combined immunodeficiency, chronic granulomatous disease and paediatric acquired immunodeficiency syndrome. This severe complication of immunization against tuberculosis has been lethal in the majority of children who had primary immunodeficiency. Our patient, a 9-y-old girl with hyperimmunoglobulin E syndrome developed disseminated Bacillus Calmette-Guérin infection in infancy. Patients with hyperimmunoglobulin E syndrome (HIES) are susceptible to serious staphylococcal and fungal infections. Disseminated Bacillus Calmette-Guérin infection has not previously been reported in this rare immunodeficiency.

Adjuvants, Immunologic↗

Cytokine production differs in children and adults.

The susceptibility of normal, healthy children to infection has long been recognized, but the underlying mechanisms are poorly understood. As adequate cytokine production is crucial for optimal immune responses, we assessed antigen and mitogen-induced cytokine production in healthy children. Our results demonstrate that healthy children differ markedly compared with adults in their ability to produce cytokines (IL-2, interferon-gamma, IL-4, and IL-6). Maximal stimulation with mitogen demonstrated impaired cytokine production with markedly lower levels of all four cytokines produced compared with adult levels. When stimulated with antigens, median levels of IL-2 and IL-4 remained lower than adult values, IL-6 production was increased as was interferon-gamma, albeit not significantly. Although the study was carried out on peripheral blood mononuclear cells that represent a restricted compartment of the immune system, these data suggest that, in healthy children, cytokine production is decreased and/or altered and could result in a suboptimal immune response, which could be one of the factors underlying increased susceptibility to infection in children.

Adolescent↗

Chronic mucocutaneous candidiasis. I. Altered antigen-stimulated IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) production.

Patients with chronic mucocutaneous candidiasis (CMC) present with persistent infections with the opportunistic yeast Candida. Impaired cell-mediated responses to Candida have been documented in CMC patients, but the defect remains poorly understood. The importance of Th1 cytokines in resistance and Th2 in susceptibility to Candida infections has recently been demonstrated in murine models. In our studies we evaluated production of IL-2 and IFN-gamma (markers of Th1 type responses) as well as IL-4 and IL-6 (Th2 type markers) following stimulation with two kinds of Candida antigens (CAgs), polysaccharide antigens, tetanus toxoid and pokeweed mitogen. Our results demonstrate that CMC patients have impaired cytokine production upon in vitro stimulation with CAgs resulting in low or absent IL-2, increased IL-6 and either absent or increased IFN-gamma production. Cytokine production following stimulation by other antigens was unaltered. The overall cytokine-producing capacity assessed through mitogen stimulation was also intact. Addition of IFN-alpha or IFN-gamma to culture in an attempt to modify cytokine production did not have significant effects. Levels of soluble IL-6 receptors were not increased and could not account for increased IL-6 production. Our studies support the hypothesis that Candida antigens trigger a predominantly Th2 instead of a Th1 cytokine response in patients with CMC.

Adolescent↗

Chronic mucocutaneous candidiasis. II. Class and subclass of specific antibody responses in vivo and in vitro.

Patients with chronic mucocutaneous candidiasis (CMC) succumb to persistent infections with the opportunistic yeast Candida. Impaired cell-mediated responses to Candida have been repeatedly reported while antibody responses were mostly found to be normal. The underlying defect remains poorly understood. It has recently been shown that CMC patients are also susceptible to infections with encapsulated bacteria, and may have associated IgG2 and IgG4 deficiency. Our previous studies demonstrated altered cytokine production in CMC patients. As cytokines can influence production and isotype of specific antibody, in 10 patients with CMC we measured the levels and isotype distribution of serum antibodies to Candida antigens (CAg), pneumococcal polysaccharide (PPS) and tetanus toxoid (TT) antigens. Peripheral blood lymphocytes were also stimulated in culture and the antibodies made in vitro were measured. Our data demonstrated that in vivo, CMC patients had very high levels of IgG and IgA CAg-specific antibodies. CAg-specific and PPS-specific IgG1 was markedly higher than in controls. Children but not adults with CMC had significantly lower levels of IgG2-specific antibody to CAg and PPS compared with age-matched controls. Patients had significantly higher levels of IgG3-specific antibody to all three antigens tested. These findings were in accordance with increased total IgG and IgG3 levels seen in CMC patients. In vitro, CMC patients, particularly children, did not respond as frequently to antigen stimulation as did their healthy controls. The level of specific antibody produced was also lower to all antigens tested, as was the amount of total immunoglobulins following antigenic and particularly mitogenic stimulation. Addition of interferon-alpha (IFN-alpha) or IFN-gamma to cultures had variable, sometimes marked, effects. Our results demonstrate that CMC patients manifest subtle alterations in specific antibody responses to CAg, PPS and TT, which are most pronounced in children. This may relate to altered cytokine production also seen in these patients.

Adult↗

Influence of autologous monocytes on the pokeweed mitogen-induced generation of immunoglobulin-secreting cells in man.

The regulatory influence of autologous blood monocytes on the PWM-induced generation of Ig-secreting cells was assessed using a reverse haemolytic plaque forming cell (PFC) assay. The PWM-induced PFC responses of monocyte-depleted cells were low or absent in most cases. Addition of 12-42% freshly isolated monocytes fully reconstituted the IgM-, IgG- and IgA-PFC responses. With more monocytes added, the PFC responses declined. Monocytes precultured for 48 h supported the PFC responses of monocyte-depleted cells less well and addition of monocytes stimulated with phorbol myristate acetate (PMA) did not increase the response. The low responses of monocyte-depleted cells co-cultured with precultured monocytes were not increased by addition of supernatant from monocyte cultures. The PFC responses of mononuclear cells induced by PWM were significantly inhibited by unstimulated precultured monocytes, and to a larger degree by PMA-treated monocytes, indicating the presence of suppressor cells among the precultured monocytes. The PWM-induced thymidine incorporation by monocyte-depleted cells with precultured monocytes added was only slightly lower than that obtained with freshly isolated monocytes added, suggesting that the suppressive role of precultured monocytes was not due to cytotoxicity.

Antibody-Producing Cells↗

Induction and abrogation of suppressor cell function in humans: effect on B cell activation by different polyclonal activators.

In a reverse plaque forming cell (PFC) assay, the effect of concanavalin A (Con-A)-induced suppressor cells on polyclonally activated B lymphocytes was studied. Differentiation to PFC, as induced by pokeweed mitogen (PWM), Staphylococcus aureus or Epstein-Barr virus (EBV) was in all cases suppressed by the addition of ConA-pretreated cells. The EBV-stimulated cells showed the smallest PFC response and appeared least amenable to suppression. IgA-secreting cells were less suppressible than IgM- and IgG-secreting cells regardless of the polyclonal B lymphocyte activator used. The suppressor cells were radiosensitive.

Antibody-Producing Cells↗

Interleukin-1 in vivo modulates trauma-induced immunosuppression.

To elucidate the mechanisms underlying trauma-induced immunosuppression and decreased IL-2 production we evaluated: 1) the effect of trauma on IL-1 production at different time intervals and 2) the effect of IL-1 in vivo administration on immune functions (IL-1 production, IL2 production, NK cell cytotoxicity) in normal and traumatized mice. Experiments were performed on CBA/H mice a) subjected to scald injury (sacrificed 3 h and 6 h later) b) treated with IL-1 in vivo (human recombinant IL-1 beta 100 ng/mouse, sacrificed 21 h and 24 h later) and c) subjected to both IL-1 in vivo treatment and scald (IL-1 was given 18 h before scald, animals were sacrificed 3 h and 6 h after scald i.e. 21 h and 24 h after IL-1 administration). Our results demonstrate that trauma alone increases IL-1 production from 1 h to 24 h after trauma infliction. Recombinant IL-1 given in vivo also induces a significant rise in IL-1 production. When mice were subjected to both trauma and IL-1 in vivo treatment, the rise in IL-1 production was not additive. Trauma induced severe depression of IL-2 production which could not be overcome by in vitro addition of IL-1 to IL-2 producing splenocytes from traumatized mice. In contrast, IL-1 administered in vivo stimulated IL-2 production in normal mice, and when given prior to trauma infliction, it completely abrogated trauma-induced suppression of IL-2 production. The same effect was seen on NK cell cytotoxicity (an IL-2 dependent function).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗