Chronic ethanol has region-selective effects on Egr-1 and Egr-3 DNA-binding activity and protein expression in the rat brain

This study focused on the DNA-binding activity and protein expression of the transcription factors Egr-1 and Egr-3 in the rat brain cortex and hippocampus after chronic or acute ethanol exposure. DNA-binding activity was reduced in both regions after chronic ethanol exposure and was restored to the level of the pair-fed group at 16 h of withdrawal. Cortical Egr-1 protein levels were not altered by chronic ethanol exposure but increased 16 h after withdrawal, thus mirroring DNA-binding activity. In contrast, Egr-3 protein levels did not undergo any change. There was no change in the level of either protein in the hippocampus. Immunohistochemistry revealed a region-selective change in immunopositive cells in the cortex and hippocampus. Finally, an acute bolus dose of ethanol did not affect Egr DNA-binding activity and ethanol treatment did not alter the DNA-binding activity or protein levels of the transcription factor Spl. These observations suggest that chronic exposure to ethanol has region-selective effects on the DNA-binding activity and protein expression of Egr-1 and Egr-3 transcription factors in the rat brain. These changes occur after prolonged ethanol exposure and may thus reflect neuroadaptive changes associated with physical dependency and withdrawal. These effects are also transcription factor-selective. Clearly, protein expression is not the sole mediator of the changes in DNA-binding activity and chronic ethanol exposure must have effects on modulatory agents of Egr DNA-binding activity. (C) 2000 Elsevier Science Ltd, All rights reserved.

Bimanual coordination in chronic schizophrenia

Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia. a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0 degrees) and out-of-phase movements (hands separated by 180 degrees) at both speeds with an external cue on or off. All participants performed the in-phase movements well. irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved. (C) 2001 Academic Press.

Mutation screening of the c-MYB negative regulatory domain in acute and chronic myeloid leukaemia

Over-expression of the c-myb gene and expression of activated forms of myb are known to transform haemopoietic cells, particularly cells of the myeloid lineage. Truncations or mutations that disrupt the negative regulatory domain (NRD) of the Myb protein confer an increased ability to transform cells. Although it has proved difficult to link mutations in c-MYB to human leukaemia, no studies investigating the presence of mutations within the c-MYB NRD have been reported. Therefore, we have performed mutational analysis of this region, using polymerase chain reaction-single-stranded conformation polymorphism and sequence analysis, in 26 patients with acute or chronic myeloid leukaemia, No mutations were detected, indicating that mutation of this region of the Myb protein is not common in the pathogenesis or progression of these diseases.

Weight reduction improves biochemistry and histology in patients with chronic hepatitis C

Hepatitis C virus (HCV) is a major cause of chronic liver disease that may progress to cirrhosis. Antiviral treatment is successful in less than 50% of patients, is costly and causes debilitating side effects. For these reasons, additional therapies to limit the progression of liver disease are urgently required. Steatosis is found in 60% of patients with HCV and is strongly associated with more severe fibrosis. Improvements in biochemical parameters may be seen with weight reduction, however the effects on liver histology have not been investigated. We propose that in patients with chronic HCV and steatosis, obesity contributes to fat in the liver, which results in increased fibrosis and progression to cirrhosis. This study investigated the effect of weight reduction on liver biochemistry and histology in patients with HCV and the success of weight maintenance after an intensive intervention. We examined the effect of a 12 week diet and exercise program where all subjects were seen weekly by the Dietician, with the goal of achieving a 0.5 kg weight loss per week. Biochemistry was monitored monthly and a liver biopsy was performed prior to and 3-6 months after the intervention period. Patients then entered a 12 month weight maintenance program with monthly dietetic review. After 12 weeks there was a mean weight loss of 5.9 ± 3.2 kg and a mean reduction in waist circumference of 9.0 ± 5.0 cm. In 16 of the 19 patients, serum ALT levels fell progressively with weight loss. Mean fasting insulin fell from 16 to 11 mmol/L (p

Weight reduction in patients with chronic HCV reduces circulating insulin levels

Steatosis occurs in >50% of patients with chronic HCV. In patients with viral genotype 3, steatosis may be a cytopathic effect of the virus. However in many patients with HCV, the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease (NAFLD) ie related to increased body mass index (BMI). We studied the effect of a 12 week weight reduction program on metabolic parameters in subjects with chronic HCV genotype 1 (Group 1, n = 16), genotype 3 (Group 2, n = 13) and patients with NAFLD (Group 3, n = 13). A liver biopsy was performed prior to and 3-6 months after the intervention period in 15 patients. The mean (SD) BMI of subjects in groups 1, 2 and 3 was 30.7 (4.0), 29.0 (5.2) and 33.3 (7.7), respectively. There was no significant difference in the amount of weight loss, change in waist circumference, change in ALT or reduction in steatosis between the 3 groups. Mean (SD) weight loss was 5.1 (3.7) kg. In those patients who lost weight, serum insulin (mean (SD) mU/L) changed from 17.8 (7.8) to 11.5 (4.8) (p = 0.003), 12.4 (5.0) to 8.4 (4.3) (p = 0.02), and 16.9 (7.3) to 17.8 (8.1) (p = 0.76) in Groups 1, 2 and 3, respectively. A small amount of weight loss is associated with a reduction in circulating insulin levels in patients with chronic HCV, particularly in genotype 1. In patients with NAFLD, the lack of a significant decrease in circulating insulin with weight reduction may reflect the higher initial BMI or may be due to the pathogenesis of this disorder.

Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: A randomized, double-blind, placebo-controlled, crossover study

The pathophysiology of chronic fatigue syndrome (CFS) remains unclear; however, both biological and psychological factors have been implicated in establishing or maintaining this condition. People with CFS report significant and disabling cognitive difficulties such as impaired concentration that in some cases are exacerbated by exposure to chemical triggers. The aim of this study was to determine if neuropsychological deficits in CFS are triggered by exposure to chemicals, or perceptions about the properties of these substances. Participants were 36 people with a primary diagnosis of CFS, defined according to Centers for Disease Control (CDC) criteria. A randomized, double-blind, placebo-controlled, crossover design was used, with objective assessment of neuropsychological function and participant rating of substance type, before and after exposure to placebo or chemical trigger. Results showed decrements in neuropsychological tests scores on three out of four outcome measures when participants rated the substance they had been exposed to as chemical. No change in performance was found based on actual substance type. These results suggest that cognitive attributions about exposure substances in people with CFS may be associated with worse performance on neuropsychological tasks. In addition, these findings suggest that psychological interventions aimed at modifying substance-related cognitions may reduce some symptoms of CFS.