Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon-(cid:1) — central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage parasites has generally been ascribed to humoral responses. A number of recent studies, however, have highlighted the existence of cellular immunity against blood-stage parasites, in particular, the prominence of IFN-(cid:1) production. Here, we have undertaken to chart the contribution of this prototypical cellular cytokine to immunity against pre-erythrocytic and blood-stage parasites. We summarize the various antiparasitic effector functions that IFN-(cid:1) serves to induce, review an array of data about its protective effects, and scrutinize evidence for any deleterious, immunopathological outcome in malaria patients. We discuss the activation and contribution of different cellular sources of IFN-(cid:1) production during malaria infection and its regulation in relation to exposure. We conclude that IFN-(cid:1) forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites and identify a number of implications for rational malaria vaccine development. J. Leukoc
Effect of Angiotensin II on Hematopoietic Progenitor Cell Proliferation

Angiotensin II (AII) induced the proliferation of hematopoietic progenitor cells (HPC) isolated from murine bone marrow or human cord blood. The formation of colonies with more than 50 cells increased approximately five‐sevenfold in cultures of murine lineage‐negative (Lin−) bone marrow cells both in the presence (day 10) and absence (day 13) of colony‐stimulating factors (CSF). This could be blocked with addition of Losartan, an antagonist of AIITR1. The increase in proliferation of early hematopoietic progenitors (Lin−Sca l+ cells) by AII was approximately threefold and occurred only in the presence of CSF, suggesting that AII may affect mesenchymal stromal cells to induce CSF production and might directly affect early HPC. These in vitro studies were replicated with human HPC isolated from cord blood. AII also accelerated the proliferation and formation of colony‐forming units (CFU)‐granulocyte/erythroid/macrophage/megakaryocyte and CFU‐granulocyte/macrophage colonies by CD34+CD38− enriched progenitors but only in the presence of CSF. Additional studies also indicated that AII can act to increase proliferation in suspension culture. Exposure of CD34+ cells to AII in suspension culture, prior to placement in a semisolid medium with erythropoietin, increased the formation of colonies with more than 50 cells and erythroid progenitors approximately five‐ and 20‐fold, respectively. Further, mRNA for the AT1a receptor was expressed by human bone marrow CD34+CD38− cells, CD34+CD38− cells, and lymphocytes, but not mature myeloid cells. Similarly, mRNA for the AT1a receptor was expressed on human stromal cell clones, offering further support to the hypothesis that AII acts partially through the mesenchymal compartment of the bone marrow. These data suggest that AII may be a factor which stimulates the proliferation of hematopoietic progenitors.
Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia.

BACKGROUND Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. METHODS Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control subjects, and more than 86,000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. RESULTS We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). CONCLUSIONS Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.
Clinical and pathologic comparison of simple left-to-right shunt congenital heart disease and transposition of the great arteries with ventricular septal defect.

BACKGROUND This study aimed to compare clinical and pathologic data for selected patients with congenital heart disease (CHD) and severe pulmonary hypertension (PH) treated with a diagnostic-treatment-and-repair strategy and to compare results for patients with pulmonary vascular disease (PVD) with simple left-to-right shunt CHD with patients with transposition of the great arteries (TGA) and ventricular septal defect (VSD). METHODS Group I comprised 38 patients with simple left-to-right shunt CHD and severe PH; group II included 11 older patients with TGA with VSD and severe PH; and group III comprised 6 autopsy cases of individuals with a normal circulation. The nature of the pulmonary arteries was determined by the Heath-Edwards classification system. All specimens were quantitatively analyzed. RESULTS Group I showed 31 patients with a change to grade I, 3 patients were grade II, 3 patients were grade III, and only 1 patient was grade IV. Group II showed 7 patients with a change to grade I, 2 patients were grade II, 1 patient was grade III, and only 1 patient was grade IV. The media wall thickness percentage (%MT), the media wall area percentage (%MS), and arteriole density were significantly higher in groups I and II than in group III. %MS was significantly higher in group II than in group I; no significant differences in %MT and arteriole density could be found between groups I and II. CONCLUSIONS The PVD in these selected patients with CHD and severe PH who were cared for with a diagnostic-treatment-and-repair strategy is generally reversible, and the changes in PVD in the patients with TGA and VSD were similar to those in the patients with simple left-to-right shunt CHD.
Congenital malformations in Israel.

The interest in congenital malformations increases when the infant mortality rate declines. When the preventable cases decline and form only a small part of the total infant mortality, attention is directed towards the remaining hard-core of infant mortality. At this stage, congenital malformations (CM), which are still to a certain degree a terra incognita, gain in importance and are rated at high priority. Infant mortality in Israel declined from 51 -7 per 1,000 live births in 1949 to 23-7 in 1964. During these 16 years, the mortality in the second half of infancy (infants aged 6-11 months) diminished to about one-fifth of the 1949 figure; the mortality at the ages 1-5 months declined to less than one-third; even the late neonatal mortality (1-3 weeks) decreased to less than half; but in the first week of life the decrease amounted to only 16-4 per cent. This is the period in which intra-uterine developments influence the mortality rather more than environmental circum stances. Most causes of death showed a more or less regular tendency to decline. But the share of CM in the total infant mortality increased from 9 8 per cent, in 1950 to 21 -3 per cent, in 1963 and 20 0 per cent, in 1964. Further improvement in the infant mortality will depend on understanding the bio logical processes underlying congenital malforma tions.
Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

ABSTRACT Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding α-, β-, and γ-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells.
Physical activity and breast cancer risk: impact of timing, type and dose of activity and population subgroup effects

Objective: To review (1) the epidemiological literature on physical activity and the risk of breast cancer, examining the effect of the different parameters of activity and effect modification within different population subgroups; and (2) the biological mechanisms whereby physical activity may influence the risk of breast cancer. Methods: A review of all published literature to September 2007 was conducted using online databases; 34 case-control and 28 cohort studies were included. The impact of the different parameters of physical activity on the association between activity and the risk of breast cancer was examined by considering the type of activity performed, the timing of activity over the life course and the intensity of activity. Effect modification of this association by menopausal status, body mass index (BMI), racial group, family history of breast cancer, hormone receptor status, energy intake and parity were also considered. Results: Evidence for a risk reduction associated with increased physical activity was found in 47 (76%) of 62 studies included in this review with an average risk decrease of 25–30%. A dose-response effect existed in 28 of 33 studies. Stronger decreases in risk were observed for recreational activity, lifetime or later life activity, vigorous activity, among postmenopausal women, women with normal BMI, non-white racial groups, those with hormone receptor negative tumours, women without a family history of breast cancer and parous women. Conclusions: The effect of physical activity on the risk of breast cancer is stronger in specific population subgroups and for certain parameters of activity that need to be further explored in future intervention trials.
A case‐control study of cancer of endometrium in athens

Eighty‐three women with invasive adenocarcinoma of the endometrium and 164 control women hospitalized for various orthopedic conditions were interviewed regarding demographic, reproductive, socio‐economic and biomedical characteristics, including their use of tobacco, drugs and exogenous estrogens. The data were analyzed by modelling rate ratio (r) through multiple logistic regression. The main results were as follows: women with invasive adenocarcinoma of the endometrium had earlier menarche (r = 0.82 for every additional year; one‐tailed p approx. 0.04), later menopause (r = 1.50 for a 5‐year difference; one‐tailed p approx. 0.004), and fewer live‐born children (r = 0.86 for every additional child; one‐tailed p approx. 0.08); they were also taller (r = 1.33 for a 5‐cm difference; one‐tailed p approx 0.03), whereas weight, adjusted for height, was not a statistically significant risk indicator (one‐tailed p approx. 0.38). Regular use of combination oral contraceptives was associated with a reduced risk of endometrial cancer (r = 0.56), whereas intake of menopausal estrogens for more than 6 months was associated with an increased risk (r = 2.04); however, because of the low frequency of use of exogenous estrogen preparations in Greece, neither of these 2 results was statistically significant. Tobacco smoking was associated with a significantly reduced risk of endometrial cancer; smoking 15–20 cigarettes per day for 20 years was associated with a rate ratio of 0.49 (one‐tailed p approx. 0.03). The protective effect of tobacco smoking was evident only among post‐menopausal women. These results indicate that the risk profile of endometrial cancer is similar in high‐risk and low‐risk countries, and underline the importance of unopposed estrogenic stimulation in the pathogenesis of this cancer.
Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis.

OBJECTIVE Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA-DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE. METHODS The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA-DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi-square tests and logistic regression analysis. RESULTS Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking. CONCLUSION Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA-DR-restricted immune response. The association of the SE with RF positivity is primarily due to HLA-DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.
Differential Activation of the Thoracic Multifidus and Longissimus Thoracis During Trunk Rotation

Study Design. Cross-sectional study. Objective. To develop a technique to measure electromyographic (EMG) activity of deep and superficial paraspinal muscles at different thoracic levels and to investigate activity of these muscles during seated trunk rotation. Summary of Background Data. Few studies have compared activity of deep and superficial paraspinal muscles of the thorax during trunk rotation, and conflicting results have been presented. Conflicting data may result from recording techniques or variation in activity between thoracic regions. Methods. EMG recordings were made from deep (multifidus/rotatores) and superficial (longissimus) paraspinal muscles at T5, T8, and T11 using selective intramuscular electrodes. Ten subjects rotated the trunk to end of range in each direction. EMG amplitude was measured in neutral, at end of range, and during four epochs, which represented four quarters of the movement. Results. During trunk rotation in sitting, longissimus EMG either increased with ipsilateral rotation (T5) or decreased with contralateral rotation (T5, T8, T11). In contrast, multifidus EMG was more variable and was either active with rotation in both directions (particularly T5) or with one movement direction. Conclusions. The deep and superficial muscles of the thorax are differentially active, and the patterns of activity differ between the regions of the thorax. Data from this study support the hypothesis that multifidus may have a role in control of segmental motion at T5. Variability in multifidus activity at T8 and T11 suggests that this muscle may also control coupling between rotation and lateral flexion.
The Heritability of Abstract Reasoning in Caribbean Latinos with Familial Alzheimer Disease

Background: Alzheimer disease (AD) is under substantial genetic influence. To better understand the genetic influence on component phenotypes of AD, we estimated the heritability (h2) of abstract reasoning and examined its relation with apolipoprotein Ε4 (APOE-Ε4). Methods: We studied abstract reasoning in 1,116 individuals from 210 Caribbean Hispanic families with late onset AD, using the similari- ties subtest scores from the Wechsler Adult Intelligence Scale. We computed h2, then performed analysis of variance to examine the effect of APOE-Ε4. Results: Abstract reasoning was highly heritable (h2unadjusted = 79.9%). After adjusting for covariates, the h2 was reduced to 32.6%, with education accounting for 40.8% of the variance. The APOE-Ε4 allele had no effect. Conclusion: Abstract reasoning was strongly influenced by genetic factors and education. Genes other than APOE contribute to the inheritance of abstract reasoning ability.
Experiences of alcohol dependence: a qualitative study.

INTRODUCTION AND AIMS OF THE STUDY Despite the increasing incidence of alcohol misuse and the costs it incurs, British society continues to hold equivocal and ambiguous attitudes towards drinking, and understanding of the nature of alcohol dependence and related issues is limited. This qualitative study aimed to investigate the experiences of individuals with alcohol dependence to enhance understanding of the illness, identify key issues and common themes and provide insight into the experiences of the participants during their alcohol dependent period and recovery. METHOD A qualitative approach, using narrative method, was used. Eight participants, all members of Alcoholics Anonymous (AA), were interviewed by the researchers. Using a grounded theory approach and content analysis, the in-depth narratives of the eight participants were systematically analysed. RESULTS While participants continued to deny the existence of a problem to those around them, their behaviours indicated that they were aware of the problem but were afraid to admit it openly through fear of other people's reactions. Participants generally regarded GPs as helpful but other health professionals less so, especially nurses and Accident and Emergency staff. Participants considered that the success of treatment depended on their own motivation and willingness to engage in radical behaviour change. They considered that reaching this stage represented a turning point in their illness. The point at which this stage was reached appeared to be different for each participant. CONCLUSIONS This systematic analysis of a small sample of alcohol dependent individuals gives insight into their experiences during alcohol dependency and the journey to recovery. The findings suggest that denial of the problem to the outside world occurs simultaneously with individuals being aware of their problem. Participants felt the illness carries a stigma and their negative experiences of health professionals other than GPs suggests that nurses and other health workers need to revise their understanding of alcohol dependence and their approach to it. AA was a significant factor in recovery for these participants.
Deficiency in Inducible Nitric Oxide Synthase Results in Reduced Atherosclerosis in Apolipoprotein E-Deficient Mice

Inducible NO synthase (iNOS) present in human atherosclerotic plaques could contribute to the inflammatory process of plaque development. The role of iNOS in atherosclerosis was tested directly by evaluating the development of lesions in atherosclerosis-susceptible apolipoprotein E (apoE)−/− mice that were also deficient in iNOS. ApoE−/− and iNOS−/− mice were cross-bred to produce apoE−/−/iNOS−/− mice and apoE−/−/iNOS+/+ controls. Males and females were placed on a high fat diet at the time of weaning, and atherosclerosis was evaluated at two time points by different methods. The deficiency in iNOS had no effect on plasma cholesterol, triglyceride, or nitrate levels. Morphometric measurement of lesion area in the aortic root at 16 wk showed a 30–50% reduction in apoE−/−/iNOS−/− mice compared with apoE−/−/iNOS+/+ mice. Although the size of the lesions in apoE−/−/iNOS−/− mice was reduced, the lesions maintained a ratio of fibrotic:foam cell-rich:necrotic areas that was similar to controls. Biochemical measurements of aortic cholesterol in additional groups of mice at 22 wk revealed significant 45–70% reductions in both male and female apoE−/−/iNOS−/− mice compared with control mice. The results indicate that iNOS contributes to the size of atherosclerotic lesions in apoE-deficient mice, perhaps through a direct effect at the site of the lesion.
Pharmacokinetics of Triamcinolone Acetonide After Intravenous, Oral, and Inhaled Administration

The pharmacokinetics of triamcinolone acetonide were studied after intravenous (2 mg), oral (5 mg), and inhaled (2 mg) administration. Triamcinolone acetonide concentrations were measured in plasma by high‐performance liquid chromatography/radioimmunoassay. After intravenous administration, triamcinolone acetonide was eliminated with a total body clearance of 37 L/h and a half‐life of 2.0 hours. The volume of distribution was 103 L, and oral bioavailability averaged 23%. Absorption was rapid, achieving maximum triamcinolone acetonide levels of 10.5 ng/mL after 1 hour. After inhalation, bioavailability averaged 22% with maximum levels of 2.0 ng/mL observed after 2.1 hours. The resulting systemic levels for all three treatments caused a significant decrease in the number of lymphocytes in blood.