Plasminogen activities and concentrations in patients with sporadic Creutzfeldt-Jakob disease

Human plasminogen has been shown to interact with the abnormal disease-specific prion protein. Till now, no data are available for patients with Creutzfeldt-Jakob disease (CJD). Therefore, we compared plasminogen concentrations and plasminogen activities in patients with sporadic CJD and controls with other dementia, which were collected in the framework of the German CJD Surveillance study. Patients with CJD had significantly higher plasminogen concentrations than patients with other forms of dementia and plasminogen specific activities were lower in CJD patients. The reasons for these abnormalities are not clear at the moment. The results may reflect a disease-specific prion protein and plasminogen interaction in patients with CJD. Other possible explanations are plasminogen polymorphisms and genotypes with distinct plasminogen activity levels in CJD than in controls, which should be a subject for further studies.     

Segments of puumala hantavirus nucleocapsid protein inserted into chimeric polyomavirus-derived virus-like particles induce a strong immune response in mice

Insertion of a short-sized epitope at four different sites of yeast-expressed hamster polyomavirus major capsid protein VP1 has been found to result in the formation of chimeric virus-like particles. Here, we demonstrate that the insertion of 45 or 120 amino acid-long segments from the N-terminus of Puumala hantavirus nucleocapsid protein into sites 1 (amino acids 80-89) and 4 (amino acids 288-295) of VP1 allowed the highly efficient formation of virus-like particles. In contrast, expression level and assembly capacity of fusions to sites 2 (amino acids 222-225) and 3 (amino acids 243-247) were drastically reduced. Immunization of BALB/c mice with chimeric virus-like particles induced a high-titered antibody response against the hantavirus nucleocapsid protein, even in the absence of any adjuvant. The strongest response was observed in mice immunized with virus-like particles harboring 120 amino acids of hantavirus nucleocapsid protein. According to the immunoglobulin subclass distribution of nucleocapsid protein-specific antibodies a mixed Th1/Th2 response was detected. The VP1 carrier itself also induced a mixed Th1/Th2 response, which was found to be reduced in mice immunized with virus-like particles harboring 120 amino acid-long inserts. In conclusion, hamster polyomavirus VP1 represents a promising carrier moiety for future vaccine development.     

In vivo imaging of leukocyte trafficking in blood vessels and tissues

Selective recruitment of blood-borne leukocytes to tissues and their proper positioning within them is crucial for the many integrated functions of the immune system. Intravital microscopy (IVM) techniques have been employed for more than a century to study these events at the single-cell level in living animals. Conventional video-based IVM allows the visualization of extremely rapid adhesion events at the interface between blood and tissue. Multiphoton IVM is a relatively new tool for imaging the slower dynamics of cell migration and cell-cell interactions in the extravascular space in three dimensions. Fueled by the burgeoning development of sophisticated fluorescent markers and increasingly powerful imaging tools, we are currently witnessing the emergence of a new field in immuno-imaging, in which leukocyte function and cell-cell communication is explored in a truly physiological context.     

Age, alcohol consumption, and all-cause mortality

PURPOSE: Numerous epidemiological studies on middle aged men suggest that moderate alcohol consumption lowers all-cause mortality. Uncertainty exists whether this finding also applies to younger adults. METHODS: The authors studied the age specific association between alcohol consumption and all-cause mortality in a cohort of 19,943 male employees in the German construction industry (age range 25-64 years) who underwent an occupational health examination between 1986 and 1992 and were followed with respect to vital status over an average period of 10 years. Information on alcohol consumption at baseline examination relied on self report and strongly correlated with biological markers of alcohol consumption. Covariates considered in the proportional hazard regression analysis included age, nationality, smoking status, and comorbidity. RESULTS: Age specific analysis revealed that the J/U-shaped association between alcohol consumption and all-cause mortality is limited to men aged 35 years and above. In contrast, a linear positive dose-response relationship was observed for men aged 25 to 34 years (p-trend=0.02). CONCLUSIONS: Recommendations regarding alcohol consumption and potential health benefits should not be generalized to all ages.     

The effect of CYP19 and COMT polymorphisms on exercise-induced fat loss in postmenopausal women

OBJECTIVE: To examine whether genetic polymorphisms in CYP19 [intron 4 (TTTA)n; n = 7 to 13 and a 3-base pair deletion, which is in strong linkage disequilibrium with the seven repeat] and COMT (Val108/158Met) modified the change in BMI, total and percentage body fat, or subcutaneous and intra-abdominal fat during a year-long exercise intervention trial. These genes metabolize estrogens and androgens, which are important in body fat regulation. RESEARCH METHODS AND PROCEDURES: A randomized intervention trial was used, with an intervention goal of 225 min/wk of moderate-intensity exercise for one year. Participants (n = 173) were postmenopausal, 50 to 75 years old, sedentary, overweight or obese, and not taking hormone therapy at baseline. RESULTS: Exercisers with two vs. no CYP19 11-repeat alleles had a larger decrease in total fat (-3.1 kg vs. -0.5 kg, respectively, p = 0.01) and percentage body fat (-2.4% vs. -0.6%, respectively, p = 0.001). Exercisers with the COMT Met/Met vs. Val/Val genotype had a smaller decrease in percentage fat (-0.7% vs. -1.9%, respectively, p = 0.05). Among exercisers, women with the COMT Val/Val genotype and at least one copy of the CYP19 11-repeat allele vs. those with neither genotype/allele had a significantly larger decrease in BMI (-1.0 vs. +0.1 kg/m2, respectively, p = 0.009), total fat (-2.9 vs. -0.5 kg, respectively, p = 0.004), and percentage body fat (-2.6% vs. -0.4%, respectively, p < 0.001). DISCUSSION: Genetic polymorphisms in CYP19 and COMT may be important for body fat regulation and possibly modify the effect of exercise on fat loss in postmenopausal women.