Vortex Shedding in Steady Flow Through a Model of an Arterial Stenosis and Its Relevance to Mural Platelet Deposition

In this study, the development of unsteady vortical formations in the separated flow region distal to a stenosis throat is presented and compared with the platelet deposition measurements, to enhance our understanding of the mechanisms involved in platelet kinetics in flowing blood. Qualitative and quantitative flow visualization and numerical simulations were performed in a model of a streamlined axisymmetric stenosis with an area reduction of 84% at the throat of the stenosis. Measurements were performed at Reynolds numbers (Re), based on upstream diameter and average velocity, ranging from 300 to 1800. Both the digital particle image visualization method employed and the numerical simulations were able to capture the motion of the vortices through the separated flow region. Periodic shedding of vortices began at approximately Re=375 and continued for the full range of Re studied. The locales at which these vortices are initiated, their size, and their life span, were a function of Re. The numerical simulations of turbulent flow through the stenosis model entailed a detailed depiction of the process of vortex shedding in the separated flow region downstream of the stenosis. These flow patterns were used to elucidate the mechanisms involved in blood platelet kinetics and deposition in the area in and around an arterial stenosis. The unsteady flow development in the recirculation region is hypothesized as the mechanism for observed changes in the distribution of mural platelet deposition between Re=300, 900, and 1800, despite only a marginal variation in the size and shape of the recirculation zone under these flow conditions. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8710+e     

Canine X-linked severe combined immunodeficiency

Our laboratory has identified and characterized an X-linked severe combined immunodeficiency (XSCID) in dogs that is due to mutations in the common gamma (γc) subunit of the interleukin-2 (IL2), IL4, IL7, IL9, and IL 15 receptors. Canine XSCID, unlike genetically engineered γc-deficient mice, has a clinical and immunologic phenotype virtually identical to human XSCID. It appears that speciesspecific differences exist in the role of the γc and its associated cytokines in mice compared to their role in humans and dogs, suggesting γc-deficient dogs may be a more relevant model for studing the role of the γc in humans. We are utilizing this model for a variety of studies to address:

1. Fundamental questions concerning the role of the γc in cytokine regulation and lymphocyte development.
2. The pathogenesis of XSCID.
3. Strategies for improving bone marrow transplantation outcome.
4. Development and evaluation of strateies for gene therapy.
5. Human hematopoietic stem cell development.

     

CD45 expression by murine B cells and T cells: Alteration of CD45 isoforms in subpopulations of activated B cells

The CD45 family of high molecular weight cell surface glycoproteins is abundantly expressed by virtually all hematopoietic cells. CD45 molecules exist as multiple isoforms whose extracellular portions vary in protein structure and carbohydrate content but whose intracellular portions are highly conserved and possess tyrosine phosphatase activity. In this review we summarize current studies describing CD45 isoform expression on peripheral and thymic lymphocytes. Further, we analyze changes in CD45 isoform expression by selective populations of activated B cells.     

Mathematical Modeling of the Human Body During Water Replacement and Dehydration: Body Water Changes

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model. © 2000 Biomedical Engineering Society. PAC00: 8719Pp, 8719Uv, 8719Ff, 8710+e     

Inhibition of Phagocytosis-Associated Chemiluminescence by Superoxide Dismutase

During the process of phagocytosis, human leukocytes emit a burst of luminescence which can be measured in a liquid scintillation spectrometer. The enzyme superoxide dismutase, which removes superoxide anions (O(2.)), inhibited this chemiluminescence by 70% at a concentration of 100 mug/ml. The enzyme did not inhibit phagocytosis. These results support other studies indicating that O(2.) is elaborated by phagocytizing leukocytes. They also indicate that O(2.) plays a major role in phagocytosis-associated chemiluminescence, though not necessarily as the luminescing agent. Catalase and benzoate inhibited the chemiluminescence of phagocytosis to a slight extent, suggesting that hydrogen peroxide and hydroxyl radical, respectively, might also be involved in this phenomenon. The relationship between the mediators of chemiluminescence and those responsible for phagocytic bactericidal activity remains to be defined.     

Long distance transport of ragweed pollen as a potential cause of allergy in central Italy.

BACKGROUND: Ambrosia pollen is an important allergen in North America and, as recently discovered, in some European countries. In Italy, the most affected area is the northeast, whereas ragweed has not been reported in the central and southern parts of the country. OBJECTIVE: To identify the source of ragweed pollen detected in Florence and Pistoia in central Italy. METHODS: Ragweed pollen data were collected in Florence and Pistoia for a 6-year period (1999-2004). The relationship between pollen counts and local ground prevalent wind directions was evaluated with analysis of variance and the least significant difference test. Weather conditions were also evaluated on a large-scale circulation pattern by analyzing weather maps and air mass back trajectories. RESULTS: A highly statistically significant relationship between daily prevailing wind direction and pollen count was found in the period under investigation; the ragweed pollen peaks were recorded when winds from northeast in Florence and north-northeast in Pistoia were observed. The synoptic weather situation and the path of back trajectories suggest an area around southern Hungary as a possible source of Ambrosia pollen. Furthermore, the pollen count was above the clinical threshold several times in both Florence and Pistoia. CONCLUSIONS: Several factors indicate that the detection of ragweed pollen in central Italy is due to long distance transport. Taking into consideration the high allergenicity of Ambrosia pollen, the present findings, if confirmed, suggest that the number of sensitized individuals might significantly increase in the near future.     

Enhanced mitochondrial degradation of yeast cytochrome c with amphipathic structures

The dispensable N-terminus of iso-1-cytochrome c (iso-1) in the yeast Saccharomyces cerevisiae was replaced by 11 different amphipathic structures. Rapid degradation of the corresponding iso-1 occurred, with the degree of degradation increasing with the amphipathic moments; and this amphipathic-dependent degradation was designated ADD. ADD occurred with the holo-forms in the mitochondria but not as the apo-forms in the cytosol. The extreme mutant type degraded with a half-life of approximately 12 min, whereas the normal iso-1 was stable over hours. ADD was influenced by the ⁺/^– state and by numerous chromosomal genes. Most importantly, ADD appeared to be specifically suppressed to various extents by deletions of any of the YME1, AFG3, or RCA1 genes encoding membrane-associated mitochondrial proteases, probably because the amphipathic structures caused a stronger association with the mitochondrial inner membrane and its associated proteases. The use of ADD assisted in the differentiation of substrates of different mitochondrial degradation pathways.     

GJB2 mutations: passage through Iran

Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe.     

Infection of the reproductive tract and eggs with Salmonella enterica serovar pullorum in the chicken is associated with suppression of cellular immunity at sexual maturity

Salmonella enterica serovar Pullorum causes persistent infections in laying hens. Splenic macrophages are the main site of persistence. At sexual maturity, numbers of bacteria increase and spread to the reproductive tract, which may result in vertical transmission to eggs or chicks. In this study we demonstrate that both male and female chickens may develop a carrier state following infection but that the increases in bacterial numbers and spread to the reproductive tract are phenomena restricted to hens, indicating that such changes are likely to be related to the onset of egg laying. The immunological responses during the carrier state and through the onset of laying in hens were determined. These indicate that chickens produce both humoral and T-cell responses to infection, but at the onset of laying both the T-cell response to Salmonella and nonspecific responses to mitogenic stimulation fall sharply in both infected and noninfected birds. The fall in T-cell responsiveness coincided with the increase in numbers of Salmonella serovar Pullorum and its spread to the reproductive tract. Three weeks after the onset of egg laying, T-cell responsiveness began to increase and bacterial numbers declined. Specific antibody levels changed little at the onset of laying but increased following the rise in bacterial numbers in a manner reminiscent of a secondary antibody response to rechallenge. These findings indicate that a nonspecific suppression of cellular responses occurs at the onset of laying and plays a major role the ability of Salmonella serovar Pullorum to infect the reproductive tract, leading to transmission to eggs. The loss of T-cell activity at the point of laying also has implications for Salmonella enterica serovar Enteritidis infection and transmission to eggs, along with its control by vaccination offering a "window of opportunity" in which infection may occur.