Designer T cells by T cell receptor replacement

T cell receptor (TCR) gene transfer is a convenient method to produce antigen-specific T cells for adoptive therapy. However, the expression of two TCR in T cells could impair their function or cause unwanted effects by mixed TCR heterodimers. With five different TCR and four different T cells, either mouse or human, we show that some TCR are strong--in terms of cell surface expression--and replace weak TCR on the cell surface, resulting in exchange of antigen specificity. Two strong TCR are co-expressed. A mouse TCR replaces human TCR on human T cells. Even though it is still poorly understood why some TCRalpha/beta combinations are preferentially expressed on T cells, our data suggest that, in the future, designer T cells with exclusive tumor reactivity can be generated by T cell engineering.     

Sex differences in emotional and psychophysiological responses to musical stimuli.

Although it is known that men and women differ in their music preferences and emotional reactions to music, little is known about sex differences in physiological reactions to music. In our study, we therefore set out to examine the differential reactivity to two musical stimuli that elicit distinct psychological and physiological reaction patterns. Fifty-three healthy subjects (mean age: 26.13, SD: 3.97; 26 males, 27 females) were examined. Heart rate, electrodermal activity, skin temperature, salivary cortisol, salivary alpha-amylase, and psychological variables were assessed during the course of the whole study. Following baseline assessment, two musical stimuli, which were carefully selected and rated in a pre-study as relaxing and pleasant (renaissance music) and arousing and unpleasant (heavy metal), respectively, were introduced. They were presented on two different days in a randomized order. Whereas psychological variables did not differ between men and women, results of electrophysiological measures indicate significantly different reactivity patterns between men and women. Women displayed elevated response curves to the arousing and unpleasant stimulus, whereas men did not. However, no differences were found with regards to endocrine measures in saliva. Our results demonstrate sex differences in reactivity patterns to musical stimuli in psychophysiological measures. In our study, we were able to show that women tend to show hypersensitivity to aversive musical stimuli. This finding is in accordance with previous literature on sex differences in emotion research. Furthermore, our study indicates that the confounding effects of sex differences have to be considered when using musical stimuli for emotion induction.     

Production of agglutinators and rheumatoid factors in plasma cells of rheumatoid and nonrheumatoid synovial tissues

Immunohistochemical studies were performed in synovial tissues from 40 patients with rheumatoid arthritis (RA), 9 with juvenile rheumatoid arthritis (JRA), 7 with psoriatic arthritis, and 4 with various rheumatic diseases. Overall synthesis of IgG– and/or IgM–rheumatoid factor (RF) was found in all patients with seropositive RA and JRA, in 75% of patients with seronegative RA, and in 1 patient with psoriatic arthritis. Agglutinator producing cells were found in 77% of the samples from seropositive RA and in 44% and 56% from seronegative RA and JRA patients, respectively. The percentage of IgG plasma cells synthesizing one or more of the 5 types of agglutinators studied was approximately 10% of plasma cells synthesizing IgG–RF. Intercellular and intracellular immune complex deposits were also found in patients with seropositive and seronegative RA and JRA. These findings suggest that synthesis of agglutinators by synovial tissue plasma cells of RA and JRA patients is a distinct—but definitely less prominent—function than that of RF synthesis.     

Histochemical localization of NADPH-diaphorase in neurons of the pheasant ileum

Localization patterns of NADPH-diaphorase-positive neurons in the pheasant ileum were investigated using an enzyme histochemical method. NADPH-diaphorase activity in the pheasant ileum was demonstrated in neuronal cells bodies and nerve fibres. The NADPH-diaphorase-positive nerve cells showed a polygonal shape and were present solitary or arranged in groups in the submucosal and muscular layers. Nerve fibres penetrated the wall of the ileum at its serosal surface, frequently in the vicinity of ileal arterial branches. They were abundantly present in muscular and submucosal layers of the ileum forming thicker nerves. Some nerve fibres traversed the submucosa into the lamina propria mucosae to form dense nerve plexuses. Fine nerve fibres were found to penetrate into intestinal villi encompassing the crypts underneath the epithelium. We conclude that the pheasant ileum is characterized by abundance of NADPH-diaphorase-positive nerve structures which may play a significant functional role in the small intestine of the pheasant.     

Comparison of leukocyte populations from bronchoalveolar lavage and induced sputum in the evaluation of cellular composition and nitric oxide production in patients with bronchial asthma

Bronchoalveolar lavage (BAL) or induced sputum (IS) techniques may provide leukocytes for the evaluation of airway inflammatory response in bronchial asthma. The aim of the present study was to compare features of leukocyte populations obtained by the two different methods regarding the cell types and their activity in patients with bronchial asthma. The nitric oxide (NO) level released from the cells was measured as a marker of their activity. Pulmonary leukocytes were obtained from the BAL and IS of 11 asthmatic patients in stable condition at the time of the study. The BAL and IS leukocyte populations varied in cell count and NO production. Macrophages were the predominant leukocyte population in BAL (median (Me) = 83.0%, range 67.9-88.4%), whereas sputum sediments were found to consist mainly of neutrophils (Me = 55.7%, range 29.0-64.9%). The IS leukocytes released much more NO (p = 0.0022) than the BAL leukocytes. In spite of these quantitative differences, a similar pattern of NO production was observed in BAL and in IS cells. Both BAL and IS leukocyte populations produced almost the same amounts of NO before and after lipopolysaccharide stimulation (p = 0.9063, p = 0.4801, respectively). Furthermore, a slight positive correlation Spearman's rank (RS) = 0.5578, p = 0.0594) was noticed between the neutrophil percentages and NO levels produced by BAL cells, whereas in IS a statistically significant correlation between the percentage of neutrophils and the levels of NO (RS = 0.6643, p = 0.0184) was observed. In conclusion, the BAL and IS leukocyte populations are different in cell type, their size and activity. Depending on the asthma severity and the type of cells needed in a study, either BAL or IS specimens may be chosen as a source of pulmonary leukocytes. The use of IS as a noninvasive technique is supposed to be potential value particularly in the study of the airway inflammatory response mediated mainly by neutrophils, i.e. during and/or after exacerbation of the disease. Based on our results, a possible contribution of neutrophils in the production of NO in the airways of asthmatic patients can be proposed apart from other cells such as macrophages.     

Role of prothrombin 19911 A>G polymorphism,blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

Journal of Thrombosis and Thrombolysis - The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism...     

The First Physical Therapy Summit on Global Health: implications and recommendations for the 21st century

The First Physical Therapy Summit on Global Health was convened at the 2007 World Confederation for Physical Therapy (WCPT) Congress to vision practice in the 21st century and, in turn, entry-level education and research, as informed by epidemiological indicators, and consistent with evidence-based noninvasive interventions, the hallmark of physical therapy. The Summit and its findings were informed by WHO data and validated through national databases of the countries of the five WCPT regions. The health priorities based on mortality were examined in relation to proportions of physical therapists practicing in the areas of regional priorities and of the curricula in entry-level programs. As a validation check and to contextualize the findings, input from members of the 800 Summit participants was integrated and international consultants refined the recommendations. Lifestyle-related conditions (ischemic heart disease, smoking-related conditions, hypertension, stroke, cancer, and diabetes) were leading causes of premature death across regions. Contemporary definitions of physical therapy support that the profession has a leading role in preventing, reversing, as well as managing lifestyle-related conditions. The proportions of practitioners practicing primarily in these priority areas and of the entry-level curricula based on these priorities were low. The proportions of practitioners in priority areas and entry-level curricula devoted to lifestyle-related conditions warrant being better aligned with the prevalence of these conditions across regions in the 21st century. A focus on clinical competencies associated with effective health education and health behavior change formulates the basis for The Second Physical Therapy Summit on Global Health.     

Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal

Background:  Adiponectin is a circulating protein with hepatoprotective effects.
Aims:  To study the relationship of excessive alcohol consumption and serum adiponectin levels (SAL).
Patients and Methods:  The SAL were determined in (i) heavy drinkers without advanced liver damage during the course of alcohol withdrawal, (ii) patients with chronic hepatitis C virus (HCV) infection, (iii) patients with alcohol-associated cirrhosis, and (iv) healthy volunteers that consumed excessive amounts of alcohol for only a short period of time. Further, primary human hepatocytes (PHH) and adipocytes were incubated in vitro with alcohol or serum of patients.
Results:  Patients with chronic alcohol consumption had significantly higher SAL than HCV-patients with comparable degrees of liver damage. In alcoholics, but not in HCV patients, SAL positively correlated with serum levels of aminotransferases. Further, SAL correlated with the amount of alcohol consumption but declined during the course of alcohol abstinence. After short-term excessive alcohol consumption SAL were not elevated in healthy individuals. Adiponectin mRNA was detectable in adipocytes but not in hepatocytes, and alcohol failed to induce adiponectin in both cell types. In contrast, serum of active drinkers induced adiponectin expression in adipocytes while serum from the same individuals collected after alcohol withdrawal had no effect.
Conclusions:  Alcohol exhibits a specific effect on SAL that is dose and time dependent, and correlates with the degree of hepatic damage. Alcohol does not seem to affect adiponectin expression directly in adipocytes but potentially via mediators systemically released as a result of the chronic alcohol intake.     

Preventing deaths from cryptococcal meningitis: from bench to bedside

Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is the most common form of meningitis and a leading cause of death among persons with HIV/AIDS in sub-Saharan Africa. Detection of cryptococcal antigen, which is present several weeks before overt signs of meningitis develop, provides an opportunity to detect infection early. Screening persons with HIV for cryptococcal infection when they access healthcare can identify asymptomatic infected patients allowing for prompt treatment and prevention of death. A newly developed point-of-care assay for cryptococcal antigen, as well as growing evidence supporting the utility and cost-effectiveness of screening, are further reasons to consider broad implementation of cryptococcal screening in countries with a high burden of cryptococcal disease.