Expression of iron absorption genes in mouse large intestine

OBJECTIVE: The large intestine has been reported to have a capacity for iron absorption and expresses genes for iron absorption normally found in the duodenum. The importance and function of these genes in the large intestine are not understood. We therefore investigated the cellular localization and regulation of expression of these genes in mouse caecum and colon. MATERIAL AND METHODS: Gene expression was measured by real-time PCR using RNA extracted from iron-deficient and hypoxic mouse large intestine, compared to controls. Protein localization and regulation were measured by immunohistochemistry using frozen sections of the large intestine from the same mice. RESULTS: Dcytb (duodenal ferric reductase) was expressed at very low levels in the large intestine, compared to the duodenum, while Ireg1 and DMT1 were expressed at significant levels in the large intestine and were increased in iron-deficient caecum, proximal and distal colon, with the most significant increases seen in the distal colon. Hypoxia increased Ireg1 expression in the proximal colon. Immunohistochemistry detected significant levels of only IREG1, which was localized to the basolateral membrane of colonic epithelial cells. CONCLUSIONS: Iron absorption genes were expressed at lower levels in mouse caecum and colon than in the duodenum. They are regulated by body iron requirements. Colonic epithelial cells express basolateral IREG1in the same fashion as in the duodenum and this protein could regulate colonic epithelial cell iron levels.     

Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase

OBJECTIVE: To map the antibody response to human citrullinated alpha-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase. METHODS: Serum samples obtained from patients with RA, disease control subjects, and healthy control subjects were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated alpha-enolase peptides. Antibodies specific for the immunodominant epitope were raised in rabbits or were purified from RA sera. Cross-reactivity with other citrullinated epitopes was investigated by inhibition ELISAs, and cross-reactivity with bacterial enolase was investigated by immunoblotting. RESULTS: An immunodominant peptide, citrullinated alpha-enolase peptide 1, was identified. Antibodies to this epitope were observed in 37-62% of sera obtained from patients with RA, 3% of sera obtained from disease control subjects, and 2% of sera obtained from healthy control subjects. Binding was inhibited with homologous peptide but not with the arginine-containing control peptide or with 4 citrullinated peptides from elsewhere on the molecule, indicating that antibody binding was dependent on both citrulline and flanking amino acids. The immunodominant peptide showed 82% homology with enolase from Porphyromonas gingivalis, and the levels of antibodies to citrullinated alpha-enolase peptide 1 correlated with the levels of antibodies to the bacterial peptide (r2=0.803, P<0.0001). Affinity-purified antibodies to the human peptide cross-reacted with citrullinated recombinant P gingivalis enolase. CONCLUSION: We have identified an immunodominant epitope in citrullinated alpha-enolase, to which antibodies are specific for RA. Our data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA.     

The role of long‐term physical exercise on performance and brain activation during the Stroop colour word task in fibromyalgia patients

The Stroop colour word test (SCWT) has been widely used to assess changes in cognitive performance such as processing speed, selective attention and the degree of automaticity. Moreover, the SCWT has proven to be a valuable tool to assess neuronal plasticity that is coupled to improvement in performance in clinical populations. In a previous study, we showed impaired cognitive processing during SCWT along with reduced task‐related activations in patients with fibromyalgia. In this study, we used SCWT and functional magnetic resonance imagingFMRI to investigate the effects of a 15‐week physical exercise intervention on cognitive performance, task‐related cortical activation and distraction‐induced analgesia (DIA) in patients with fibromyalgia and healthy controls. The exercise intervention yielded reduced fibromyalgia symptoms, improved cognitive processing and increased task‐related activation of amygdala, but no effect on DIA. Our results suggest beneficial effects of physical exercise on cognitive functioning in FM.     

The Contribution of National Disparities to International Differences in Mortality Between the United States and 7 European Countries

Objectives. This study examined to what extent the higher mortality in the United States compared to many European countries is explained by larger social disparities within the United States. We estimated the expected US mortality if educational disparities in the United States were similar to those in 7 European countries.Methods. Poisson models were used to quantify the association between education and mortality for men and women aged 30 to 74 years in the United States, Belgium, Denmark, Finland, France, Norway, Sweden, and Switzerland for the period 1989 to 2003. US data came from the National Health Interview Survey linked to the National Death Index and the European data came from censuses linked to national mortality registries.Results. If people in the United States had the same distribution of education as their European counterparts, the US mortality disadvantage would be larger. However, if educational disparities in mortality within the United States equaled those within Europe, mortality differences between the United States and Europe would be reduced by 20% to 100%.Conclusions. Larger educational disparities in mortality in the United States than in Europe partly explain why US adults have higher mortality than their European counterparts. Policies to reduce mortality among the lower educated will be necessary to bridge the mortality gap between the United States and European countries.The United States has lower life expectancy at birth than most Western European countries. In 2009, life expectancy in the United States was 76 years for men and 81 years for women, between 2 and 4 years less than in several European countries.1 The disadvantage is greater for women than for men and originated in the 1980s.2 The US health disadvantage is found not only for life expectancy, but also for self-reported health measures,3,4 biomarkers,3 and many specific causes of death5,6 across the entire life course.3–5,7A recent report by the National Research Council suggests that smoking and obesity explain an important part of the US mortality disadvantage.2,8,9 However, an approach that solely emphasizes behavioral differences is impoverished by ignoring the role of socioeconomic and environmental determinants.10 A substantial body of research suggests that most behavioral risk factors are socially patterned; lower education or income are associated with a higher prevalence of smoking, excessive alcohol consumption, obesity, and poor dietary patterns.11–19 In addition, European countries and the United States differ in many aspects of the physical and social environment that can affect population health and that are in turn socially patterned within each country. For example, the socioeconomic distribution of access to healthy food differs between countries.20 Social environmental factors related to safety, violence, social connections, social participation, social cohesion, social capital, and collective efficacy have also been shown to influence health and in turn differ between countries and socioeconomic groups.21 Indeed, differences in mortality between the United States and Europe are larger among those with a lower educational level,6 suggesting that larger educational disparities in mortality, which partly coincide with differences in behavior, partly explain why Americans have higher mortality than Europeans.The United States is characterized by relatively higher levels of income inequalities,22 residential and racial segregation,23–25 and financial barriers to health care access2,26 than any European country. Social protection policies and benefits are also less comprehensive in the United States than in Europe, including policies on early education and childcare programs,27 access to high-quality education,28 employment protection and support programs,29,30 and housing29,31 and income transfer programs.31,32 A plausible hypothesis is that the more unequal distribution of resources and less comprehensive policies contribute to the more unfavorable risk factor profile and poorer health of lower-educated Americans as compared with corresponding Europeans.4,33,34 A follow-up report by the National Research Council and the Institute of Medicine published in 2013 concluded that there is a lack of evidence on how these factors explain the US health disadvantage.21 The aim of this article is to assess to what extent larger educational disparities in mortality explain why Americans have higher mortality than Europeans.     

Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure

OBJECTIVE: To determine the relative contribution of patient non-adherence, provider failure to prescribe prophylaxis, and drug failure to the continued occurrence of Pneumocystis carinii pneumonia (PCP), and to determine correlates of non-adherence. DESIGN: Retrospective case-control study. METHODS: Patients with confirmed or presumptive PCP from May 1995 to September 1997 who had at least 6 months of prior HIV care (cases) were compared to controls matched for initial CD4 cell count and date of initial HIV care. RESULTS: The incidence of PCP declined by 85% in the 28 months of the study. Of the 118 cases of PCP identified, 59 (50%) were in HIV care for > 6 months prior to PCP diagnosis. In a multivariate logistic regression model, risk factors for PCP among patients in HIV care were patient non-adherence [odds ratio (OR), 12.4; 95% confidence interval (CI), 6.4-23.5], use of prophylaxis other than trimethoprim-sulfamethoxazole (OR, 27.0; 95% CI, 13.8-52.9), and absence of antiretroviral use (OR, 7.5; 95% CI, 4.5-12.5). Provider non-adherence occurred in one out of 59 cases (2%), and five out of 106 controls (5%). Of the patients who developed PCP on prophylaxis, 18 cases (30%) appeared due to drug failure; there were no cases of apparent drug failure among patients on trimethoprim-sulfamethoxazole. In multivariate analysis, non-adherence was more common among patients of non-white race, those with a history of injecting drug use, and those with active substance abuse or psychiatric illness. CONCLUSIONS: Patient non-adherence was the most common reason for the occurrence of PCP among patients in HIV care; provider non-adherence was uncommon. Drug failure occurred only among patients on prophylaxis other than trimethoprim-sulfamethoxazole.     

Increased expression of interleukin 1alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis

OBJECTIVE: To investigate if there is a molecular correlate in muscle tissue to the persisting decreased muscle function in patients with chronic, inactive polymyositis (PM) and dermatomyositis (DM). METHODS: Muscle function was assessed using a muscle function index of myositis. To assess disease activity both histopathological investigation of muscle biopsies and magnetic resonance imaging (MRI) scans of the thigh muscles were performed. Inactive chronic disease was defined as persisting muscle weakness and absence of inflammatory infiltrates in muscle biopsy and absence of signs of inflammation on MRI. Expression of interleukin 1alpha (IL-1alpha), IL-1beta,, adhesion molecules, and MHC class I molecules in muscle tissue was investigated with immunohistochemistry. RESULTS: Muscle weakness was confirmed by a reduction of muscle function score. No signs of inflammation typical for myositis were observed. The most striking finding in our study was the strong expression of IL-1alpha and MHC class I molecules in muscle tissue from patients with inactive chronic PM and DM. Increased IL-1alpha expression was evident in capillaries and increased MHC class I expression was detected in muscle fiber membranes. CONCLUSION: IL-1alpha and MHC class I molecules may have an importance in the pathogenesis of the chronic muscle weakness and fatigue in patients with PM and DM.     

Exploring sex differences in case fatality in acute myocardial infarction or coronary death events in the northern Sweden MONICA Project

OBJECTIVES: To investigate sex differences in reaching diagnosis, medical management and case fatality (CF) in acute myocardial infarction (AMI) in the population aged 35-64 years in northern Sweden. METHODS: Within the framework of the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases (MONICA) Project, definite AMI was monitored in people aged 35-64 years from 1989 through 1995 (target population 510 000 in 1991). SETTING: In a population based coronary register, all coronary events were recorded in nine hospitals in 1989-95. RESULTS: The number of events included in the definite coronary myocardial infarction register was 2483 men and 669 women. On admission, a higher proportion of men with definite AMI had chest pain or ECG changes typical for AMI (P < 0.0001). Disagreement between clinical diagnosis and classification by MONICA criteria occurred more often in women (P=0.008). A significantly higher proportion of men was admitted in the coronary care unit and they were significantly more often treated with thrombolytics, nitroglycerine, beta-blockers, or antiplatelet agents. Women received significantly more diuretics, inotropics or calcium antagonists. Diabetes, conferring a worse prognosis, was more common in women (20 vs. 15%; P=0.003). Prehospital CF was significantly higher in men (24.1 vs. 18.3%; P=0.005), but in patients treated in hospital, the CF was significantly lower in men (12.7 vs. 21.2%; P < 0.001). Total CF was equal in men and women. CONCLUSIONS: Several factors contributing to the excess in-hospital CF in women were identified, including greater problems in diagnosis of AMI in women which may be one of the reasons for less intensive treatment in women. Differences in co-morbidity, most notably diabetes and medical treatment between men and women with acute AMI may also have played a part.     

Hyperphosphatemia and hypocalcemia accompanying rapid cell lysis in a patient with Burkitt's lymphoma and Burkitt cell leukemia

Hyperphosphatemia, hypocalcemia and acute oliguric renal failure resulting from uric acid nephropathy developed in a patient with Burkitt's lymphoma and Burkitt cell leukemia after effective chemotherapy. A review of other reported cases in which the patients had similar metabolic abnormalities is presented, and the pathophysiology is discussed. The clinical setting in which these metabolic developments are most likely to occur is defined, and an approach for their prevention and management is presented.