No evidence for involvement of the interleukin-10 -592 promoter polymorphism in genetic susceptibility to primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune aetiology. Family studies, which have shown a significantly increased incidence of primary biliary cirrhosis in the close relatives of patients, suggest that genetic factors play a significant role in determining disease susceptibility. Several studies have previously identified loci which appear to play a role in determining this susceptibility, including the MHC class II allele HLA DR8, and the class III encoded C4A null allele (C4AQ0). Here, we have studied another candidate susceptibility locus in primary biliary cirrhosis, an apparently functional biallelic polymorphism at position -592 in the promoter region of the gene encoding the immuno-modulatory cytokine interleukin-10. Interleukin-10 plays an important role in the functional control, in vivo, of autoreactive Th-1 type CD4+ T-cells, with experimental manipulation of interleukin-10 leading to significant modulation of disease development in animal models of autoimmunity. METHODS: Interleukin-10 -592 genotypes were studied by polymerase chain reaction in 171 well-characterised, histologically-staged, primary biliary cirrhosis patients and 141 locally matched controls. RESULTS: Of 171 primary biliary cirrhosis patients, 99 were homozygous for the commoner allele (C/C), 68/171 (40%) were heterozygotes (A/C), whilst 4/171 (2%) were homozygous for the rarer allele (A/A). These genotype frequencies were not significantly different from those seen in controls (p=0.49, odds ratio 1.2 [0.8-1.91). CONCLUSIONS: These findings, in the first study of IL-10 as a candidate locus in a human autoimmune disease, suggest that IL-10 -592 is not a susceptibility locus in primary biliary cirrhosis.     

Photoluminescence investigation of the carrier confining propertiesof multiquantum barriers

A comparative luminescence study of two Ga_0.52In_0.48P-(Al_0.5Ga_0.5) _0.52In_0.48P single-quantum-well (SQW) samples with bulk and multiquantum barrier (MQB) barriers is presented. When excess carriers are only created in the quantum wells (QW's) of the samples by resonant excitation using a dye laser, the luminescence efficiency of both samples as a function of temperature is found to be essentially identical. We find, therefore, no evidence for any enhancement in the confining potential of the MQB sample over the bulk barrier sample. From Arrhenius plots of the integrated luminescence intensity, it is found that carrier loss from the QW is dominated by a nonradiative loss mechanism with an activation energy considerably smaller than that expected from direct thermal loss of electrons and holes into the barriers. We suggest that the improved device characteristics reported for lasers containing MQB's is due to effects other than the quantum interference of electrons     

Novel content addressable memory

The design and performance of a content addressable memory (CAM) LSI using a newly developed cell circuit is presented. The LSI has all the functions necessary to implement a high-speed data searching system and is fabricated using a 3 mu m CMOS double-metallisation process. A cycle time of 60 ns with the basic associative operation taking 20 ns has been measured.<>     

Frazil Ice Blockage of Water Intakes in the Great Lakes

Each winter, municipal water supply and thermal power plants drawing water from the Great Lakes face the problem of their water intakes becoming blocked by frazil ice formed in the lakes. Little is known about the manner in which frazil forms, how it is drawn down to the depths at which the intakes are located, and how to prevent frazil from fully blocking intakes. This paper presents an overview of frazil formation and intake blockage in the Great Lakes. The paper first reviews the current understanding of the processes of frazil formation and intake blockage, and it adds new insight regarding the processes. It then describes the problem by way of case-study examples of frazil blockage of two intakes in Lake Michigan. Based on the case studies, and experiences with other intakes in the Great Lakes, the paper outlines methods for monitoring and mitigating frazil blockage. Two options are recommended: monitoring rate of water level drop in the pump forebay onshore from the intake, and rate of headloss increase between the intake and the forebay. Laboratory modeling of intake blockage is then presented.     

Use of thermally stimulated discharge measurements for the investigation of cure and characterization of thermoset-epoxy resins systems

Thermally stimulated discharge (TSD) measurements have been used to monitor the cure in thermoset resins and this paper attempts a critical assessment of its application to epoxy resin systems. These studies show that, whilst the method can be used for monitoring cure, there are problems concerned with the detailed interpretation of the TSD data. The observed TSD peaks are complex and associated with charge migration coupled with dipolar reorientation. Data for a wide range of systems and conditions used in cure are discussed.     

A flexible graphical user interface for performance modeling

We identify three goals for the graphical user interface (GUI) of a network simulation environment: user friendliness, model re-usability, and application extensibility. We address the user-friendliness issue by proposing a simple yet efficient approach to setup parameters for the simulation models. We address the application extensibility issue with a two-layer GUI architecture. The two layers are loosely coupled, and the first layer can be easily replaced without affecting the other components of the simulation environment. The concept of subnetwork is used to address the model reusability issue. Unlike most existing simulation packages, where a subnetwork is simply a method to group the nodes, the subnetwork construct in our approach is a first-class citizen in the simulation environment (i.e., all operations for a basic node also apply to a subnetwork). The port concept is used to define the I/O relationship between a subnetwork and the outside world. Parameter dialog boxes are used to set up the parameters for a subnetwork conveniently. Finally, a simple stack mechanism is used to measure subnetwork-wide output statistics.     

Stress in medical students

The object of this study was to examine the main stressors experienced by students in an Irish medical school and their effects on the attitude of the students towards their training. It also determined the students' knowledge of how they could receive help and their attitudes towards seeking such help. Data was collected by an anonymous self-report questionnaire distributed to a fifth year medical school class in the Hilary Term of the academic year. These 63 students had chosen medicine as a career mainly because of vocational and academic factors and almost two thirds of them had always wanted to do medicine. However four were no longer happy with that choice. Fifty-four percent of them had felt like making a complaint on at least one occasion, but did not do so. The perceived problems were mainly verbal in nature. 41% said that this had affected their attendance. The main source of perceived mistreatment was consultant staff. Rates of perceived racial and sexual discrimination were low. Other stressors included examinations, financial issues and family issues. 52% of students did not know the process by which they could make a complaint and 30% felt that seeking help or advice from staff would be damaging to their future career. This study analyses these issues and suggests ways of addressing them.     

Genetic analysis of ozone-induced acute lung injury in sensitive and resistant strains of mice

Sprague-Dawley rats sedated with intraperitoneal injection of diazepam (7.5 mg/kg) were placed in a plethysmograph to measure the changes in spontaneous respiration. Inhalation of methacholine (MCh) or acetylcholine (ACh) aerosol did not alter the volume of breathing, but increased respiratory frequency (RF) to the same extent in a concentration-dependent manner. On the other hand, the tachypnea effect of MCh lasted 11 min, and that of ACh only 3 min. Urethane anesthesia inhibited spontaneous respiration and the response to MCh. Atropine, salbutamol and aminophylline inhibited MCh-induced tachypnea. In sensitized rats, the response to MCh was potentiated 6 h after inhalation of ovalbumin aerosol. The results indicate that sedation with diazepam and inhalation of MCh aerosol used in this report are suitable for measuring airway responsiveness in terms of degree of increase of respiratory frequency.     

CYP2D6 allelic frequencies in young-onset Parkinson's disease

Parkinson's disease (PD) is thought to develop as a result of interactions between genetic susceptibility factors and environmental exposures. One candidate gene is CYP2D6, which codes for the debrisoquine 4-hydroxylase cytochrome P450. Impairment of debrisoquine 4-hydroxylase activity has been associated with an increased risk of PD in patients with younger age at disease onset. Genotyping studies in patients with an older age at onset have reported modest increases in risk associated with the CYP2D6 B and A alleles; however, the risk for young-onset PD has not been adequately evaluated. We designed a case-control study to investigate the role of nonfunctional CYP2D6 allelic risk factors for young-onset PD in a sizable patient population and compared the distributions of CYP2D6 genotypes between young-onset ( < or = 51 years) PD patients (n = 108) and controls (n = 236). In contrast with the results from genotyping studies conducted among patients with an older age at onset, there were no significant differences in CYP2D6 allelic frequencies between young-onset PD cases and controls. The frequency of the B allele was slightly lower in the young-onset PD cases than in the controls (0.14 versus 0.20) (X2 = 2.66, p = 0.10). The presence of one or more B alleles was not associated with an increased risk of young-onset PD (odds ratio 0.58; 95% CI 0.33 to 1.00), nor was the presence of one or more nonfunctional alleles (i.e., A, B, D, and D2) (odds ratio 0.68; 95% CI 0.41 to 1.13). This study suggests that the young-onset PD population may differ from the older-onset population with respect to risk factors.