"Ecologic confounders" in the context of a spatial analysis of the air pollution-mortality relationship.
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Monocular deprivation during a critical period in postnatal development leads to a shift in functional and anatomical ocular dominance at the expense of the deprived eye. We analyzed the complete two-dimensional pattern of [(3)H]proline-labeled afferents in primary visual cortex (area 17) of cats monocularly deprived of vision at eye opening. Substantial shrinkage of deprived eye territory in favor of the normal eye extended into optic disc and monocular segment representations. However, small domains of deprived eye afferents were distributed evenly over the entire visual field representation. Interestingly, normal and deprived eye afferents overlapped extensively in the ipsilateral and in the peripheral contralateral visual field representation of the deprived eye, so that ipsi- and contralateral ocular dominance patterns are not at all complementary. We suggest that this could be the result of both an earlier maturation of crossed versus uncrossed visual pathways and of a maturational gradient within area 17 leading to a lower vulnerability of the central visual field representation to monocular deprivation. Quantitative analysis, using a triangulation algorithm which confirmed previously described larger spacing of adjacent ocular dominance columns in strabismic cats, revealed no difference in spacing of ocular dominance domains in area 17 between monocularly deprived and normals cats. In addition, column spacing was very similar in the same animal and in littermates, indicating that the genetic influence on columnar layout is stronger than previously assumed.
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T-wave alternans (TWA) has been linked to increased vulnerability to ventricular fibrillation in different settings including myocardial ischemia. In this study, we propose a methodology for the characterization of TWA induced by transient, regional ischemia. We studied the prevalence, magnitude and spatio-temporal relationship between TWA and ischemia in 95 patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Two electrocardiogram records of each patient, a control recording before PTCA and the PTCA record, were analyzed using a robust, recently proposed method for TWA analysis. The detected episodes were characterized in terms of their time-course, lead distribution and alternans waveform. One third of the patients (33.7%) showed TWA episodes during PTCA. The highest prevalence (51.7%) and amplitude were found in patients with left anterior descendent artery occlusion. The onset of TWA was detected after the first 1-2 min of occlusion, suggesting that some level of ischemia must be attained before TWA arises, while disappearance of TWA following reperfusion was much more rapid. The TWA lead distributions and waveforms showed distinct distributions according to the occluded artery reflecting the regional nature of the TWA phenomenon.
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Sin Nombre virus (SNV) is thought to establish a persistent infection in its natural reservoir, the deer mouse (Peromyscus maniculatus), despite a strong host immune response. SNV-specific neutralizing antibodies were routinely detected in deer mice which maintained virus RNA in the blood and lungs. To determine whether viral diversity played a role in SNV persistence and immune escape in deer mice, we measured the prevalence of virus quasispecies in infected rodents over time in a natural setting. Mark-recapture studies provided serial blood samples from naturally infected deer mice, which were sequentially analyzed for SNV diversity. Viral RNA was detected over a period of months in these rodents in the presence of circulating antibodies specific for SNV. Nucleotide and amino acid substitutions were observed in viral clones from all time points analyzed, including changes in the immunodominant domain of glycoprotein 1 and the 3' small segment noncoding region of the genome. Viral RNA was also detected in seven different organs of sacrificed deer mice. Analysis of organ-specific viral clones revealed major disparities in the level of viral diversity between organs, specifically between the spleen (high diversity) and the lung and liver (low diversity). These results demonstrate the ability of SNV to mutate and generate quasispecies in vivo, which may have implications for viral persistence and possible escape from the host immune system.
The objective of this study was to define phenotypic changes of antigen-presenting cells (APCs) and T cells in a murine model of antigen-induced airways inflammation that involves intraperitoneal sensitization with ovalbumin (OVA)/adjuvant followed by antigen aerosolization. We investigated the APC and T-cell compartments both after sensitization (primary immune response) and after challenge (secondary immune response) at the thoracic lymph nodes (initiation site) and the lung (effector site). Our findings document a major cellular expansion in the lymph nodes after both sensitization and challenge. After sensitization, this expansion was comprised mainly of B cells, a considerable proportion of which expressed B7.2. At this time, T cells were markedly expanded and activated as assessed by CD69 expression; further, although GATA-3 and signal transducer and activator of transcription-6 were expressed at this time point, expression of interleukin (IL)-4, IL-5, and IL-13 messenger RNA (mRNA) levels were marginal. However, in vitro stimulation of lymph-node cells with OVA led to cytokine production. In contrast, 24 h after challenge, but not after sensitization, there was a major expansion of dendritic cells and macrophages in the lungs. This expansion was associated with enhanced expression of both B7.1 and B7.2. We also observed expansion of activated CD3(+)/CD4(+) T cells expressing the T helper-2-associated marker T1/ST2 in the lung, most notably 5 d after challenge. Further, IL-4, IL-5, and IL-13, but not interferon-gamma mRNA were expressed at high levels 3 h after challenge. This study helps to elucidate the "geography" of immune responses generated in a conventional murine model of allergic airways inflammation.
Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case-control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991-1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors--calcium and magnesium--on mortality from cerebrovascular (ICD-9 430-438) and ischemic heart (ICD-9 410-414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the effect of these covariates.
Activation of phosphoinositide (PI) 3-kinase is a required signaling pathway in fibroblast migration directed by platelet-derived growth factor. The pattern of 3' PI lipids in the plasma membrane, integrating local PI 3-kinase activity as well as 3' PI diffusion and turnover, influences the spatiotemporal regulation of the cytoskeleton. In fibroblasts stimulated uniformly with platelet-derived growth factor, visualized using total internal reflection fluorescence microscopy, we consistently observed localized regions with significantly higher or lower 3' PI levels than adjacent regions (hot and cold spots, respectively). A typical cell contained multiple hot spots, coinciding with apparent leading edge structures, and at most one cold spot at the rear. Using a framework for finite-element modeling with actual cell contact area geometries, we find that although the 3' PI pattern is affected by irregular contact area shape, cell morphology alone cannot explain the presence of hot or cold spots. Our results and analysis instead suggest that these regions reflect different local 3' PI dynamics, specifically through a combination of mechanisms: enhanced PI 3-kinase activity, reduced 3' PI turnover, and possibly slow/constrained 3' PI diffusion. The morphological polarity of the cell may thus bias 3' PI signaling to promote persistent migration in fibroblasts.
The geographic information system approach has permitted integration between demographic, socio-economic and environmental data, providing correlation between information from several data banks. In the current work, occurrence of human and canine visceral leishmaniases and insect vectors (Lutzomyia longipalpis) as well as biogeographic information related to 9 areas that comprise the city of Belo Horizonte, Brazil, between April 2001 and March 2002 were correlated and georeferenced. By using this technique it was possible to define concentration loci of canine leishmaniasis in the following regions: East; Northeast; Northwest; West; and Venda Nova. However, as for human leishmaniasis, it was not possible to perform the same analysis. Data analysis has also shown that 84.2% of the human leishmaniasis cases were related with canine leishmaniasis cases. Concerning biogeographic (altitude, area of vegetation influence, hydrographic, and areas of poverty) analysis, only altitude showed to influence emergence of leishmaniasis cases. A number of 4673 canine leishmaniasis cases and 64 human leishmaniasis cases were georeferenced, of which 67.5 and 71.9%, respectively, were living between 780 and 880 m above the sea level. At these same altitudes, a large number of phlebotomine sand flies were collected. Therefore, we suggest control measures for leishmaniasis in the city of Belo Horizonte, giving priority to canine leishmaniasis foci and regions at altitudes between 780 and 880 m.
The AIDS epidemic has spread and reached various population groups differently. The epidemic's dynamics have also differed according to the characteristics of different areas within cities, related to the principal modes of spread. This study analyzes the AIDS epidemic in women in the city of Rio de Janeiro using the space referential. The epidemic is on the rise among women, particularly in the Northern and Western Zones of the city. In this group it constitutes a "sub-epidemic", to the extent that it displays different characteristics in terms of clinical presentation, access to health services, and knowledge of risks. There was a high proportion of unknown transmission category among the women, thus revealing ignorance of their own risk situation. In addition, the high proportion of unknown level of schooling emphasizes the implications of the investigative system on quality of data recorded for women.
In the Middle Atlantic region of the U.S.A., the vector of Lyme disease, human granulocytic ehrlichiosis, babesiosis, and other human and veterinary pathogens is the black-legged tick, Ixodes scapularis Say. In 1997 and 1998, 663 adult I. scapularis ticks were collected from 320 transects spanning 66,400 km2 in five states of the Middle Atlantic region. Tick abundance patterns were clustered, with relatively high numbers along the coastal plain of the Chesapeake Bay, decreasing to the west and south. There were significant associations between tick abundance and land cover, distance to water, distance to forest edge, elevation, and soil type.
Questions persist regarding male germ stem cells and how they mature during the prespermatogenic period of testicular development. We successfully labeled the prespermatogonia with green fluorescence protein (GFP) by using Oct-4 enhancer/promoter. This study shows that GFP was specifically expressed in prespermatogonia, spermatogonia and spermatids that faithfully reproduce the endogenous expression of Oct-4. Histochemical analysis revealed that most of the TRA98-positive gonocytes are also positive for GFP. However, the frequency of GFP expressing cells out of TRA98 expressing cells decreased together with the maturation of gonocytes in the first week after birth. To compare the stem cell activity between GFP-positive and -negative populations, we performed a transplantation of sorted cells into testes from an individual population. Colonization efficiency of germ cells from a GFP-positive population resulted in a 30-fold increase in colonization compared with a GFP-negative population. Since the expression of Oct-4 in prespermtogonia correlates well with the stem activity, Oct-4 might be a crucial molecule in the stem cell property of spermatogonia but not in cell survival.
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