ABSTRACT
A large body of evidence suggests that oxidized LDL (oxLDL) has a role in atherogenesis. One effect is the impact on macrophage function. We have studied the effects of oxLDL and oxysterols on the binding of the transcription factors nuclear factor (NF)-kappaB and AP-1 to DNA. These transcription factors are involved in the regulation of several genes and expressed during activation of macrophages, for example by endotoxin (LPS). OxLDL did not induce binding of NF-kappaB. However, the LPS-induced response to NF-kappaB was substantially reduced after preincubation with oxLDL. Medium and highly oxidized LDL also decreased the constitutive DNA-binding of AP-1. Similar effects on AP-1-binding were seen with the oxysterols, 7beta-hydroxycholesterol, 24- hydroxy-, 25-hydroxy-, and 27-hydroxy-cholesterol. Our data therefore suggest an effect of oxLDL on the DNA-binding of AP-1, which might be mediated by the oxysterol content of oxLDL. A decreased LPS-induced TNF-alpha and IL-1beta mRNA and protein expression were found in macrophages incubated with oxLDL before LPS-exposure. These observations suggest that macrophages that internalize extensively oxidized LDL are suppressed in their response to inflammatory stimulation.
Subject(s)
DNA/metabolism , Interleukin-1/biosynthesis , Lipoproteins, LDL/pharmacology , Macrophages/drug effects , NF-kappa B/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis , Base Sequence , DNA-Binding Proteins/metabolism , Gene Expression , Humans , Interleukin-1/genetics , Lipopolysaccharides/pharmacology , Molecular Sequence Data , Nuclear Proteins/metabolism , Protein Binding/drug effects , Protein Synthesis Inhibitors/pharmacology , RNA, Messenger/biosynthesis , Serum Response Factor , Sterols/pharmacology , Transcription Factor AP-1/metabolism , Tumor Necrosis Factor-alpha/genetics , ets-Domain Protein Elk-4ABSTRACT
Studies of the prevalence of previously unrecognized physical illness among psychiatric patients have paid little attention to the treatment implications of such illness. The authors describe a study in California in which 78 inpatients received an augmented evaluation one to two weeks after their admission evaluation. The retest evaluation detected previously unrecognized physical conditions that were judged to be causal among patients and physical conditions that were judged to exacerbate the psychiatric condition among 56 patients. The authors discuss the treatment implications of the most common type of conditions detected, neurological and nutritional. They also delineate the barriers to recognizing and then treating previously unrecognized physical illnesses.
Subject(s)
Epidemiology , Mental Disorders/complications , Adult , California/epidemiology , Cross-Sectional Studies , Hospitals, State , Humans , Male , Mental Disorders/therapy , Nervous System Diseases/diagnosis , Nervous System Diseases/epidemiology , Nervous System Diseases/therapy , Nutrition Disorders/diagnosis , Nutrition Disorders/epidemiology , Nutrition Disorders/therapy , Psychiatric Status Rating Scales , PsychotherapyABSTRACT
The Jamison-Farabee consent decree in California mandates an outside psychiatrist's review of involuntary medication of state hospital patients. Patients' rights advocates presumably hoped the decree would facilitate more frequent medication refusal, while clinicians predicted the procedure would impair patient care. Outside review led to only a 1.1% rate of medication denial; half of the patients involved deteriorated afterward. Examination of a sample of patients subject to the decree and two comparable samples 1 year and 10 years earlier suggests that patients' successful medication refusal was no more frequent after implementation of the decree and that the procedure had negligible effects on patient care or outcome for patients not denied medication.
Subject(s)
Commitment of Mentally Ill/legislation & jurisprudence , Mental Disorders/drug therapy , Mentally Ill Persons , Patient Advocacy/legislation & jurisprudence , Patient Compliance , Psychotropic Drugs/therapeutic use , Attitude of Health Personnel , Attitude to Health , California , Hospital Records , Humans , Legal Guardians , Medical Staff, Hospital , Mental Disorders/psychology , Outcome and Process Assessment, Health Care , Risk AssessmentABSTRACT
An examination of tardive dyskinesia in 213 schizophrenic outpatients using the Abnormal Involuntary Movement Scale (AIMS) indicates that increasing age is significantly associated with the presence of this disorder while sex is not. Both sexes showed significant linear increases with increasing age. Although males did not evidence the statistically significant curvilinear trend previously reported in an inpatient study using the same methodology, they displayed an attenuated effect at the older age levels. A comparison of prevalence values between the outpatient sample and the inpatient sample previously studied indicated no greater prevalence in the outpatients. However, an examination of differences in AIMS total scores between these samples suggested the presence of many more marginal and mild movements in the outpatients. Reasons for the differences between the inpatient and outpatient studies are discussed.
