A two-step, two-signal model for the primary activation of precursor helper T cells

I present here a new model for the primary activation of precursor helper T cells. Observations demonstrate that the immune system learns not to respond to extrathymic, organ-specific self-antigens because of their early appearance in development. The immune system thus discriminates between peripheral self-antigens and foreign antigens and, when mature, usually makes an immune response against only the latter. Contemporary models for the activation and inactivation of T helper (Th) function do not account for such discrimination. The model proposed here is consistent with contemporary findings and incorporates a mechanism of peripheral self-nonself discrimination.     

Modulation of mitochondrial respiration by nitric oxide: investigation by single cell fluorescence microscopy

With the electro-driven import of rhodamine 123, we used single cell fluorescence microscopy to single out the contribution of nitric oxide (NO) in controlling mitochondrial membrane potential expressed by (stationary growing) rhabdomyosarcoma and neuroblastoma cells in culture. The experimental design and the computer-aided image analysis detected and quantitated variations of fluorescence signals specific to mitochondria. We observed that 1) the two cell lines display changes of fluorescence dependent on mitochondrial energization states; 2) mitochondrial fluorescence decreases after exposure of the cells to a NO releaser; 4) the different fluorescence intensity measured under stationary growing conditions, or after activation and inhibition of constitutive NO synthase, is consistent with a steady-state production of NO. Direct comparison of single cell fluorescence with bulk cytofluorimetry proved that the results obtained by the latter method may be misleading because of the intrinsic-to-measure lack of information about distribution of fluorescence within different cell compartments. The kinetic parameters describing the reactions between cytochrome oxidase, NO, and O2 may account for the puzzling (20-fold) increase of the KM for O2 reported for cells and tissues as compared to purified cytochrome c oxidase, allowing an estimate of in vivo NO flux.     

Effect of thrombolytic therapy on platelet expression and plasma concentration of PECAM-1 (CD31) in patients with acute myocardial infarction

OBJECTIVE: Cholelithiasis is a common problem in hospitals of the Peruvian Andes; however, its prevalence in Andean communities is unknown. To estimate the prevalence of gallstone disease in this locale, we conducted a cross-sectional community study in three high-altitude Peruvian rural villages (i.e., > 3000 m above sea level). METHODS: We examined 911 volunteers > 15 yr of age from three villages for gallstone disease by history and ultrasonography. Risk factors for gallstone disease were examined in 382 volunteers from one village. RESULTS: The age-adjusted prevalence of gallstone disease ranged from 4-10% in men and from 18-20% in women. Women had significantly higher age-adjusted prevalence rates than did men. The prevalence of gallstone disease increased significantly with age and decreased significantly with alcohol consumption. Although not statistically significant, we found a positive association between gallstone disease and body mass index. CONCLUSION: The results of this study indicate that gallstone disease, commonly perceived as a disease of the developed world, is also a common problem in high-altitude Peruvian communities.     

Recruitment of ZipA to the septal ring of Escherichia coli is dependent on FtsZ and independent of FtsA

Cell division in prokaryotes is mediated by the septal ring. In Escherichia coli, this organelle consists of several essential division proteins, including FtsZ, FtsA, and ZipA. To gain more insight into how the structure is assembled, we studied the interdependence of FtsZ, FtsA, and ZipA localization using both immunofluorescence and Gfp tagging techniques. To this end, we constructed a set of strains allowing us to determine the cellular location of each of these three proteins in cells from which one of the other two had been specifically depleted. Our results show that ZipA fails to accumulate in a ring shape in the absence of FtsZ. Conversely, depletion of ZipA does not abolish formation of FtsZ rings but leads to a significant reduction in the number of rings per unit of cell mass. In addition, ZipA does not appear to require FtsA for assembly into the septal ring and vice versa. It is suggested that septal ring formation starts by assembly of the FtsZ ring, after which ZipA and FtsA join this structure in a mutually independent fashion through direct interactions with the FtsZ protein.