ABSTRACT
BACKGROUND: Mutations in the human NOD2/CARD15 gene have been associated with Crohn's disease and Blau syndrome. The objective of the present study was to clone the murine form of NOD2 and characterize its tissue distribution, function and response to inflammatory stimuli. METHODS: Murine NOD2 was isolated using anchored polymerize chain reaction (PCR). Sequence analysis confirmed the identification of full-length cDNA representing the murine NOD2 gene. Using this sequence to search a Mus musculus supercontig database, NOD2 genomic DNA was identified. NOD2 was transfected into human embryonic kidney (HEK) cells and nuclear factor kappa B (NF-kappaB) activation was measured using a reporter assay. Tissue distribution and changes in transcription in mouse monocytes in response to inflammatory stimuli was determined by real time PCR. RESULTS: The NOD2 gene spans 39 KB and contains 12 coding exons on chromosome 8. Expression of mouse NOD2 into HEK cells resulted in NF-kappaB activation. NOD2 was found to be expressed in all mouse tissues analyzed except skin, with highest levels in lung, thymus and spleen. NOD2 mRNA levels increased greater than two-fold in a monocyte cell line in response to lipopolysaccharide, lipoteichoic acid, interferon-g and tumor necrosis factor-alpha. CONCLUSIONS: Common structural and functional features between human and mouse NOD2 were identified. This should allow for development of relevant animal models to evaluate the role of NOD2 in chronic inflammatory disorders.
Subject(s)
Carrier Proteins/genetics , Intracellular Signaling Peptides and Proteins , Amino Acid Sequence , Animals , Arthritis/genetics , Carrier Proteins/metabolism , Cell Line , Cloning, Molecular , DNA Primers , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , Databases, Genetic , Granuloma/genetics , Mice , Molecular Sequence Data , Monocytes/metabolism , NF-kappa B/physiology , Nod2 Signaling Adaptor Protein , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/physiology , Tissue Distribution , Uveitis/geneticsABSTRACT
BACKGROUND: In studies of patients with schizophrenia, the atypical antipsychotic risperidone has been shown to be comparable in efficacy to haloperidol and, at dosages of 4 to 8 mg/day, to have a lower rate of extrapyramidal side effects. However, little is known about the efficacy of risperidone in patients with schizophrenia refractory to treatment with typical antipsychotics, schizoaffective disorder, and psychotic mood disorders. The purpose of this study was to assess the efficacy of risperidone in the treatment of these disorders and to identify clinical factors associated with risperidone response. METHOD: By surveying treating clinicians and chart data, we assessed response to risperidone and factors associated with response to risperidone in 144 consecutive patients treated with the drug for at least 2 weeks at a regional state psychiatric hospital. RESULTS: Patients displaying a moderate-to-marked response to risperidone were more likely to be younger; receive diagnoses of bipolar disorder or schizoaffective disorder, depressive type; and have a shorter duration of illness and shorter length of stay prior to risperidone treatment. Response to risperidone was sufficient to allow discharge in 26% of patients with treatment-refractory schizophrenia hospitalized for at least 10 weeks prior to risperidone and in 11% of patients with treatment-refractory schizophrenia hospitalized for greater than 1 year. CONCLUSION: Risperidone may be a useful alternative or adjunctive treatment for patients with schizophrenia refractory to treatment with standard antipsychotic agents, schizoaffective disorder (especially the depressive type), and bipolar disorder when used in conjunction with mood stabilizers.
Subject(s)
Antipsychotic Agents/therapeutic use , Depressive Disorder/drug therapy , Psychotic Disorders/drug therapy , Risperidone/therapeutic use , Schizophrenia/drug therapy , Adult , Age Factors , Bipolar Disorder/drug therapy , Bipolar Disorder/psychology , Chronic Disease , Depressive Disorder/psychology , Drug Therapy, Combination , Female , Hospitalization , Hospitals, Psychiatric , Humans , Length of Stay , Male , Middle Aged , Probability , Psychotic Disorders/psychology , Schizophrenic Psychology , Severity of Illness Index , Treatment OutcomeABSTRACT
The aim of this study was to examine the outcome and comorbidity of patients with bipolar disorder presenting with first-episode as compared with multiple-episode mania. Based on studies from the prepharmacological era and the sensitization model of bipolar disorder, we hypothesized that compared with multiple-episode mania, first-episode mania would be associated with better outcome, milder severity, and less psychiatric comorbidity. Seventy-one hospitalized patients, age 12 years and older and meeting DSM-III-R criteria for bipolar disorder, were recruited over a 1-year period. Thirty-four (48%) first-episode and 37 (56%) multiple-episode patients were compared regarding demographics, phenomenology, comorbidity, family history, and short-term course. Compared with multiple-episode mania, first-episode mania was associated with significantly shorter hospitalization and a higher rate of comorbid impulse control disorders. These data provide indirect support for the sensitization model of bipolar disorder.
