Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study the HLA-DRB and DPB1 alleles as well as CD4 and CD3 polymorphisms were tested in 100 Belgian schizophrenic patients and 204 controls. Our results indicate a significant negative association of the DPB1 0101 allele with schizophrenia (relative risk [RR] = 0.27). Furthermore a significant positive and negative association could be noticed for the CD4*A4 allele and CD4*A7/A8 genotype, respectively (RR 1.79 and 0.47, respectively). These findings suggest that some contribution of HLA class II and CD4 genes to an autoimmune-like pathogenesis in schizophrenia might exist.
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PMID:Study of the possible association of HLA class II, CD4, and CD3 polymorphisms with schizophrenia. 772 11

We studied parameters of cellular immunity in 23 schizophrenic patients and compared them to 16 matched healthy controls and to 12 patients with rheumatoid arthritis (RA). None of the patients was receiving neuroleptic drug treatment before the study. We used highly sensitive methods to examine the interferon system by determination of the interferon-induced enzyme 2'-5' oligo-adenylate synthetase [2-5A] in peripheral blood mononuclear cells. Tumor necrosis factor alpha (TNF-alpha) production was measured in the plasma and in vitro by bioassay of supernatants of stimulated blood cells and of unstimulated cells (spontaneous TNF secretion). In addition, we determined cell-mediated (spontaneous) cytotoxicity, major T cell subsets (CD3, CD4 and CD8 positive cells) and serum neopterin levels. No statistically significant differences could be found between the patients with schizophrenia and the control group in any of the tests used, and no particular subgroup of patients could be identified. In contrast, RA patients had increased serum neopterin and TNF levels, increased LPS-induced TNF production in vitro, increased 2-5A levels and a decrease in CD8 cells associated with an increase in CD4 cells. Thus, in the group of patients studied, we could find no substantiation for the presence of either autoimmune or occult viral cofactors in the pathogenesis of schizophrenia.
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PMID:No evidence for autoimmunity in schizophrenia. 893 82

To date, triple drug therapies for HIV have resulted in spectacular reductions in the number of virus particles and often remarkable recovery from disease in infected people. There is still, however, a great need for improved therapies. A battery of drugs aimed at different stages in the life cycle of HIV will enable switching of treatments if resistant viruses emerge or if patients are unable to tolerate particular therapies. Intense efforts are now underway to produce drugs that target chemokine receptors used by HIV to gain entry into cells. HIV needs two receptors on the host cell surface for efficient attachment and infection. HIV first interacts with CD4 but requires a coreceptor to penetrate the cell membrane. The first coreceptor, identified in 1996, is a member of the family of chemokine receptors, members of the G-protein coupled 7TM superfamily, which are involved in the trafficking of leukocytes in immune surveillance and inflammation. Such a therapeutic approach would differ from those used successfully to date, which focus largely on proteins coded by the HIV virus itself, and which are required for the replicative cycle of the virus. Many small, orally bioavailable molecules that block various 7TM receptors are used to treat a panoply of diseases including ulcers, allergies, migraines, and schizophrenia. These molecules are the cornerstone of the pharmaceutical industry's contribution to the fight against so many diseases, and it is hoped that a small molecule inhibitor of coreceptors can be developed that will become an invaluable drug in the fight against AIDS.
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PMID:Chemokine receptors--future therapeutic targets for HIV? 995 9

T-cell subsets (CD3+, CD4+, CD8+, NK-cells) and the CD4+/CD8+ ratio were measured in 56 schizophrenic patients admitted to hospital with an acute psychosis. Thirty-five patients with chronic schizophrenia and 21 drug-naive first episode schizophrenic patients were compared with 16 healthy controls. T-cell subsets were quantified in the acute state of the illness (day 0), after 7 days of treatment and at the time of discharge. In the acute state, schizophrenic patients showed higher CD3+ and CD4+ cells (p = 0.05) and a higher CD4/CD8 ratio (p = 0.02) than healthy controls, while NK-cells were lower (p = 0.05). In first episode patients, all T-cell alterations normalized during treatment. In the chronic group the ratio remained high, whereas the initially low number of NK-cells normalized over time. These findings, supporting immune system dysregulation in schizophrenia, are discussed in relation to psychopathology, the stage of illness and effects of medication.
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PMID:T-cell subsets in schizophrenia: a comparison between drug-naive first episode patients and chronic schizophrenic patients. 1042 11

To date, the available therapies for the treatment of HIV infection are targeted against proteins encoded by the virus itself. Thus, combination drug therapies for HIV with reverse transciptase and protease inhibitors have resulted in spectacular reductions of viraemia, often leading to a remarkable improvement in symptoms and recovery from disease in infected people. There is still however, a great need for improved therapies since many patients are unable to take these drugs, either for reasons of intolerance, strain resistance, complexity of regimen or prohibitive cost. Multiple therapies aimed at different events in the HIV life cycle will ensure switching of treatments to combat resistant viruses, and also allow treatment flexibility if patients are unable to tolerate particular therapies. One event that could provide a key to reducing or even eliminating viral infection would be to prevent the virus from entering the host cell. Intense efforts are now underway to produce drugs that target chemokine receptors, one of the essential components for HIV cell entry. HIV needs two receptors on the host cell surface for efficient attachment and infection. The first is CD4 and the second, identified in 1996, is a member of the family of chemokine receptors, members of the G-protein coupled 7TM superfamily, which are involved in the trafficking of leukocytes in immune surveillance and inflammation. Many small, orally bioavailable molecules that block various 7TM receptors are used to treat a panoply of diseases including ulcers, allergies, migraines, and schizophrenia. These molecules are the cornerstone of the pharmaceutical industry's contribution to the fight against so many diseases. Small molecule inhibitors of the HIV-coreceptors are now entering the first stages of clinical trials as new therapeutics for the fight against AIDS.
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PMID:Chemokine receptors--the next therapeutic target for HIV? 1191 44

There are some reports describing concurrent changes in lymphocytic and monocytic activities in schizophrenia. In this study we investigated T cell activity in schizophrenic patients by measuring the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) by T cells and the percentages of CD4+ and CD8+ cells in blood. The release of IL-2 and sIL-2R by T cells was evaluated in dilute whole blood after in-vitro stimulation with phytohemagglutinin. IL-2 levels and the percentage of CD4-cells tended to decrease and sIL-2R levels decreased significantly in schizophrenic patients. Haloperidol and perazine significantly decreased IL-2 levels and increased sIL-2R levels and the percentage CD4-cells. IL-2 and sIL-2R levels were lower in patients with a predominance of positive symptoms. The neuroleptic-induced increase in sIL-2R levels was higher in patients with a predominance of positive symptoms compared with those in whom both positive and negative symptoms were severe. The study has shown that T-cell activity is reduced in schizophrenia and that neuroleptics may have immunomodulatory properties.
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PMID:In-vitro immunomodulatory effects of haloperidol and perazine in schizophrenia. 1260 15

In vitro and preclinical studies show that biochemical and behavioral effects of olanzapine are quite similar to those of clozapine. In recent years, some cases of reported agranulocytosis due to olanzapine have been published. However, none of these studies compared the hematological and immune parameters before and after treatment. The present study is aimed at investigating the influence of olanzapine on the immune cell parameters by comparing these before and in the third month of olanzapine treatment in patients of schizophrenia. Twenty patients who were diagnosed as schizophrenic depending on the DSM-IV diagnostic criteria were included in the study. The immune parameters of patients were compared by measuring them before the treatment and 3 months after treatment. Immune parameters were analyzed by using flow-cytometry equipment labeled Coulter Epics Elite ESP. The positivity of cell-surface antibody was evaluated as percentage. The rates of CD8 in the third month of the treatment were considerably increased relative to pretreatment. Furthermore, rates of CD4/CD8 were significantly decreased in the third month of the treatment relative to before treatment. These findings suggest that immune impairment may occur during olanzapine treatment in patients with schizophrenia.
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PMID:The influence of olanzapine on immune cells in patients with schizophrenia. 1269 84

Recent advances in immunological research regarding the differentiation between the type-1 and type-2 immune response are discussed. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of type-2 monocytes/macrophages, too. On the contrary, several parameters of the specific cellular immune system are blunted, e. g. the decreased type-1 related immune parameters in schizophrenic patients. This study was performed as a double-blind, placebo-controlled, randomized evaluation of risperidone and celecoxib versus risperidone and placebo. Fifty schizophrenic patients were included in the study: 25 patients received risperidone and placebo, and 25 patients received risperidone and celecoxib for 5 weeks after the wash-out period. The treatment effect was calculated by ANCOVA. In parallel, serum levels of sTNF-R1 and sIL- 2R, and the percentages of CD3(+)-, CD4(+)-, and CD19(+) lymphocytes were estimated. As expected, both groups of schizophrenic patients showed significant improvement. However, the celecoxib add-on therapy group showed a significant group effect in the PANSS total score. The cytokines and lymphocytes reflected the type-1/type-2 balancing effects of COX-2 inhibitors. Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to the total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug shows beneficial effects on the symptomatology of schizophrenia indicates that immune dysfunction in schizophrenia is not just an epiphenomenon, but related to the pathomechanism of the disorder.
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PMID:COX-2 inhibition as a treatment approach in schizophrenia: immunological considerations and clinical effects of celecoxib add-on therapy. 1499 74

The existence of atypical lymphocytes with specific morphological characteristics in the peripheral blood of schizophrenic patients has been suggested in several reports over the last 40 years. In our study this observation was examined not only by using the formerly applied method of light microscopy for general cell distribution and lymphocyte morphology but also by applying flow cytometry, a well established immunological method for lymphocyte patterns such as lymphocyte subgroups and lymphocyte activity. In contrast to the previously published data, our results demonstrated no differences in cell distribution (lymphocytes, polymorphonuclear cells, eosinophil and basophil granulocytes, monocytes), lymphocyte morphology ("atypical lymphocytes" vs. "normal lymphocytes"), distribution of lymphocyte-subtypes (T-cells (CD3(+)), T-helper-cells (CD3(+)/CD4(+)), cytotoxic T-cells (CD3(+)/CD8(+)), B-cells (CD19(+)), NK-cells (CD3(-)/CD56(+))) or state of T-lymphocyte activity (CD25(+) or HLA-DR(+)-cells) in schizophrenic patients compared to healthy controls. We suggest that possible immunological alterations in schizophrenia do not correlate with morphological characteristics of lymphocytes observable by light microscopy or an altered state activity of T-lymphocytes examined by flow cytometric parameters. Further studies should concentrate on intracellular and functional aspects of the different lymphocyte subgroups.
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PMID:Search for atypical lymphocytes in schizophrenia. 1504 33

The nerve systems affect immune functions by releasing neurotransmitters through lymphocyte cell-surface receptors. A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. There is wide evidence for a decreased risk of rheumatoid arthritis (RA) in patients with schizophrenia which is associated with the excessive stimulation of D2-like receptors by dopamine. However, the reason for the negative association between RA and schizophrenia is unknown. We previously demonstrated that dendritic cells (DCs) could synthesize and store dopamine, DC released dopamine to naive CD4 T cells upon DC-T cell interaction and affected helper T-cell differentiation. Because DCs have been proposed to play a pivotal role in the initiation and perpetuation of RA by presentation of arthritogenic antigens to T cells, we here assessed effects and functions of dopamine on immune cells during the pathogenesis of RA. In this paper, we overview the series of our research findings, and present the possibility of drug discovery which target at dopamine receptors.
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PMID:[Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopamine in the pathogenesis of rheumatoid arthritis]. 1925 71


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