PU.1 and multiple IFN regulatory factor proteins synergize to mediate transcriptional activation of the human IL-1 beta gene.

Both lymphoid and myeloid cells express two related members of the IFN regulatory factor (IRF) family of transcription factors, specifically IRF-4 and IFN consensus binding protein (ICSBP or IRF-8). We previously reported that macrophages express IRF-4 and in combination with the ETS-like protein PU.1 can synergistically activate a human IL-1beta reporter gene.

PU.1/Interferon Regulatory Factor interactions: mechanisms of transcriptional regulation.

The complexity of eukaryotic gene regulation is slowly being resolved. What has become clear is that transcriptional regulation is a multi-step process that involves the assembly of macromolecular complexes. This review will discuss the biology of the ETS family transcription factor PU.

Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-induced macrophage responses.

We previously showed that viable Mycobacterium tuberculosis (Mtb) bacilli contain distinct ligands that activate cells via the mammalian Toll-like receptor (TLR) proteins TLR2 and TLR4. We now demonstrate that expression of a dominant negative TLR2 or TLR4 proteins in RAW 264.7 macrophages partially blocked Mtb-induced NF-kappa B activation.

Structure and function of Toll-like receptor proteins.

Beginning in 1997 with the identification of the first human homologue of the Drosophila protein Toll, a family of related molecules have been identified in both humans and other mammals. These Toll-like receptor (TLR) proteins appear to represent a conserved family of innate immune recognition receptors. TLR proteins share extended homology with receptors for the cytokines interleukin 1 (IL-1) and interleukin 18 (IL-18).

Lipopolysaccharide binding protein potentiates airway reactivity in a murine model of allergic asthma.

The development of allergic asthma is influenced by both genetic and environmental factors. Epidemiologic data often show no clear relationship between the levels of allergen and clinical symptoms. Recent data suggest that bacterial LPS may be a risk factor related to asthma severity.

Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries.

The hypothesis that increased cellular proliferation in the vasculature may lead to replicative senescence has been tested in a model of neointima formation. We have used a biomarker of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), to detect senescence in rabbit carotid arteries subjected to single and double balloon denudations. We found an accumulation of senescent cells in the neointima and media of all injured vessels, in contrast to the near absence of such cells in control vessels.

Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.

Background: A recent review suggested an association between using unpublished scales in clinical trials and finding significant results.

Aims: To determine whether such an association existed in schizophrenia trials.

Method: Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register.

Zuclopenthixol acetate in psychiatric emergencies: looking for evidence from clinical trials.

Background: Case series and reviews have suggested the effectiveness of zuclopenthixol acetate in the acute management of disturbed behaviour caused by serious mental illnesses. This review investigates the trial-based evidence for these suggestions.

Methods: All randomized clinical trials comparing zuclopenthixol acetate to other 'standard' treatments for the acute management of those with serious mental illnesses were identified and, if possible, their results summated.

Interleukin-1/Toll receptor family members: receptor structure and signal transduction pathways.

Interleukin-1 (IL-1) is a central mediator of the inflammatory response. It plays a role in both systemic and local immune responses to invading microbes. There are two receptors (IL-1RI and IL-1RII) that mediate the cellular responses.

Transcriptional regulation of the human interleukin 1beta gene by fibronectin: role of protein kinase C and activator protein 1 (AP-1).

Interleukin 1beta (IL-1beta) is a multifunctional polypeptide considered a key cytokine during inflammation. Fibronectin (FN), a matrix glycoprotein highly expressed in injured tissues, can induce expression of IL-1beta in human blood monocytic cells. Herein, we explore the intracellular signals and transcriptional mechanisms responsible for IL-1beta induction by FN using human promonocytic U937 cells transfected with the human IL-1beta promoter connected to a reporter gene.

A lipopolysaccharide-specific enhancer complex involving Ets, Elk-1, Sp1, and CREB binding protein and p300 is recruited to the tumor necrosis factor alpha promoter in vivo.

The tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated by lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated kinase (ERK) kinase activity but not calcineurin phosphatase activity is required for LPS-stimulated TNF-alpha gene expression. In LPS-stimulated macrophages, the ERK substrates Ets and Elk-1 bind to the TNF-alpha promoter in vivo.

Thioridazine for schizophrenia.

Background: Thioridazine is a piperidine phenothiazine used for the treatment of people with schizophrenia. It has often been considered the drug of choice in the elderly because of reputed lower levels of extrapyramidal adverse events. It may, however, be more likely to cause cognitive adverse events, such as delirium or worsening of memory, and, on rare occasions, thioridazine has caused pigmentary retinopathy.

Activation of TNF-alpha transcription utilizes distinct MAP kinase pathways in different macrophage populations.

Stimulation of macrophages by lipopolysaccharide (LPS) leads to the rapid activation of MAP kinases (MAPK) and the subsequent induction of cytokine gene expression. We sought to determine whether LPS-inducible cytokine genes were differentially regulated in macrophages derived from different tissues. Our studies revealed that PD98059, an inhibitor of the extracellular-regulated kinase (ERK) pathway, blocked LPS-induced activation of tumor necrosis factor alpha (TNF-alpha) gene expression in a murine cell line derived from alveolar macrophages but not in a nonpulmonary macrophage cell line.

The biology of Toll-like receptors.

In 1997, a human homologue of the Drosophila Toll protein was described, a protein later to be designated Toll-like receptor 4 (TLR4). Since that time, additional human and murine TLR proteins have been identified. Mammalian TLR proteins appear to represent a conserved family of innate immune recognition receptors.

Zotepine for schizophrenia.

Background: Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making important inroads into this approach and zotepine is one such compound. It is a dopamine antagonist and claimed to be to be particularly effective for negative symptoms

Objectives: To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.

Olanzapine for schizophrenia.

Background: Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs.

Objectives: To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses.

Search Strategy: The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), The Cochrane Schizophrenia Group's Register (September 1999), EMBASE (1980-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999).

Zuclopenthixol decanoate for schizophrenia and other serious mental illnesses.

Background: There is a clear link between stopping antipsychotic medications and a relapse of psychotic symptoms. A series of long-acting intra-muscular preparations has been developed since the 1960s in the hope of reducing the frequency of relapse and, hence, overall disability. These depot preparations, active for weeks at a time, are frequently used for those who find taking oral medication on a regular basis difficult or unacceptable.

Seclusion and restraint for people with serious mental illnesses.

Background: Seclusion and restraint are interventions used in the treatment and management of disruptive and violent behaviours in psychiatry. The use of seclusion varies widely across institutions. The literature does offer numerous suggestions for interventions to reduce or prevent aggression.

Sulpiride for schizophrenia.

Background: The antipsychotic drug sulpiride was formulated over 20 years ago and was marked as having a low incidence of adverse effects and an effect on the negative symptoms of schizophrenia. This relatively inexpensive antipsychotic drug has a similar neuropharmacological profile to several novel atypical drugs.

Objectives: To estimate the clinical efficacy and tolerability of sulpiride.

Zuclopenthixol acetate in the treatment of acute schizophrenia and similar serious mental illnesses.

Background: People with schizophrenia or other psychotic illnesses may have delusions or hallucinations that may lead them to be aggressive or violent to themselves or others. Medication that is used in this context require the properties of rapid onset of effect (tranquillisation or at least initial sedation in order to quell aggressive or disorganised behaviour, but also antipsychotic effect), low frequency of administration and low levels of side effects, such as cardiological or neurological side effects, or pain at the injection site. Zuclopenthixol is the cis(Z)-isomer of clopenthixol, a neuroleptic of the thioxanthene group, used for treating people with psychotic symptoms.

Molindone for schizophrenia and severe mental illness.

Background: Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs is making important inroads into this approach. 'Atypical' is a term widely used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin.

Loxapine for schizophrenia.

Background: Loxapine is a drug with D2/D3 receptor antagonist activity and a higher affinity for D3 than D2. Some authors have suggested that loxapine is more effective than typical antipsychotics in reducing the negative symptoms of schizophrenia, that extrapyramidal side-effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as atypical.

Objectives: To determine the effects of loxapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.