text:
|Paracrine roles of NAD+ and cyclic ADP-ribose in increasing intracellular calcium and enhancing cell proliferation of 3T3 fibroblasts.
MedLine Citation:
|PMID: 11274199 Owner: NLM Status: MEDLINE
|CD38 is a bifunctional ectoenzyme synthesizing from NAD(+) (ADP-ribosyl cyclase) and degrading (hydrolase) cyclic ADP-ribose (cADPR), a powerful universal calcium mobilizer from intracellular stores. Recently, hexameric connexin 43 (Cx43) hemichannels have been shown to release cytosolic NAD(+) from isolated murine fibroblasts (Bruzzone, S., Guida, L., Zocchi, E., Franco, L. and De Flora, A. (2001) FASEB J. 15, 10-12), making this dinucleotide available to the ectocellular active site of CD38. Here we investigated transwell co-cultures of CD38(+) (transfected) and CD38(-) 3T3 cells in order to establish the role of extracellular NAD(+) and cADPR on [Ca(2+)](i) levels and on proliferation of the CD38(-) target cells. CD38(+), but not CD38(-), feeder cells induced a [Ca(2+)](i) increase in the CD38(-) target cells which was comparable to that observed with extracellular cADPR alone and inhibitable by NAD(+)-glycohydrolase or by the cADPR antagonist 8-NH(2)-cADPR. Addition of recombinant ADP-ribosyl cyclase to the medium of CD38(-) feeders induced sustained [Ca(2+)](i) increases in CD38(-) target cells. Co-culture on CD38(+) feeders enhanced the proliferation of CD38(-) target cells over control values and significantly shortened the S phase of cell cycle. These results demonstrate a paracrine process based on Cx43-mediated release of NAD(+), its CD38-catalyzed conversion to extracellular cADPR, and influx of this nucleotide into responsive cells to increase [Ca(2+)](i) and stimulate cell proliferation.
|L Franco; E Zocchi; C Usai; L Guida; S Bruzzone; A Costa; A De Flora
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Publication Detail:
|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2001-03-27
Journal Detail:
|Title: The Journal of biological chemistry Volume: 276 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2001 Jun
Date Detail:
|Created Date: 2001-06-11 Completed Date: 2001-07-19 Revised Date: 2006-11-15
Medline Journal Info:
|Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States
Other Details:
|Languages: eng Pagination: 21642-8 Citation Subset: IM
|G. Gaslini Institute, Largo G. Gaslini 5, 16147 Genova, Italy.
Export Citation:
|APA/MLA Format Download EndNote Download BibTex
|MeSH Terms
3T3 Cells
ADP-ribosyl Cyclase
Adenosine Diphosphate Ribose / analogs & derivatives, metabolism*, pharmacology
Antigens, CD*
Antigens, CD38
Antigens, Differentiation / chemistry, genetics, metabolism*
Binding Sites
Calcium / metabolism*
Cell Division / physiology*
Cell Membrane / metabolism
Coculture Techniques
Connexin 43 / genetics, physiology
Cyclic ADP-Ribose
Cytosol / metabolism
Membrane Glycoproteins
Models, Biological
Multienzyme Complexes / chemistry, metabolism
NAD / metabolism*
NAD+ Nucleosidase / chemistry, genetics, metabolism*
Oligodeoxyribonucleotides, Antisense / pharmacology
Recombinant Proteins / chemistry, metabolism
Reg. No./Substance:
|0/Antigens, CD; 0/Antigens, Differentiation; 0/Connexin 43; 0/Membrane Glycoproteins; 0/Multienzyme Complexes; 0/Oligodeoxyribonucleotides, Antisense; 0/Recombinant Proteins; 119340-53-3/Cyclic ADP-Ribose; 20762-30-5/Adenosine Diphosphate Ribose; 53-84-9/NAD; 7440-70-2/Calcium; EC 184.108.40.206/ADP-ribosyl Cyclase; EC 22.214.171.124/Antigens, CD38; EC 220.127.116.11/Cd38 protein, mouse; EC 188.8.131.52/NAD+ Nucleosidase
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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Jaime here...
What's up y'all
Top 10 observations de Jaime
[Note: The views and opinions expressed herein are not necessarily those of Srta Marglin. Accordingly, she assumes no responsibility for the views of the author. This page is subject to changes without notice.]:
1.) Those compression bags that you suck all the air out of in order to reduce the size of your luggage really work. Found at Target, $11 bucks or so, check it out..you won't be sorry
2.) When referring to estadounidenses my language instructor before all else wrote down the word 'greed' on my notebook..yikes..books check em' out
3.) I know that I wear the same shirt all the time (see posted photos)
...we're working on it
4.) Milk shakes taste (are) better north of the border..mojitos too
5.) Travel Guitars although functional just aren't the same
6.) You can wash your shoes in the dishwasher; after two weeks in Guatemala, you should...
7.) After two weeks south of the border, it's hard to start throwing your "used" toilet paper (my brother Rob refers to them as "shit wipes," I believe) in the toilet water again
8.) I really enjoy that Jennifer does all the computer posting/communiques...perhaps I am lazy...perhaps she is just much better at it :)
9.) Another use for children could be to eliminate the inevitable "reaching with the right arm self-portraits". Its a fun game...peruse our photos...give yourself 5 points for each one you find where the subject was also the photographer (everybody does it...that's right you too)
10.) Jennifer's friends and family have broken fingers...unless you want Jennifer to become muy triste...y'all better get acquainted with the comment button. Leave any ole' comment you like..ask us to take a photo. For instance, let's say we are on the cruise...don't you want to see some Jamaicans trying to sell us weed? I know I do. [Note to any of Srta. Marglin's students who might be viewing this page: Pictures good, Jamaican jails and being someone's "date" for the night, bad. Just say no.] Just ask: your wish is our command :)
Photos for the people:

subset: commoncrawl


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Lombardi Original Leather Belt - London Tan
designer's notes
Our signature Lombardi buckle-less leather belt! You are going to love it! The leather quality and stitching style are similar to that used by famous saddle makers where functional utility was not only the goal, but the requirement! A bohemian beauty for sure. No buckle, just a looped twist to keep it tight. Simple, beautiful, functional. Looks great on your favorite pair of jeans!
color: London Tan Leather Colors available: Black, Brits Brown, Rose, Apple Green, St. Barths Blue or Natural. All belts are 1.25" width x your needed length. Made in the USA quality material; U.S.A; style# 331524301


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The canine vector-borne infectious diseases (CVBDs) are an emerging problem in veterinary medicine and the zoonotic potential of many of these agents is a significant consideration for human health. The successful diagnosis, treatment and prevention of these infections is dependent upon firm understanding of the underlying immunopathology of the diseases in which there are unique tripartite interactions between the microorganism, the vector and the host immune system. Although significant advances have been made in the areas of molecular speciation and the epidemiology of these infections and their vectors, basic knowledge of the pathology and immunology of the diseases has lagged behind. This review summarizes recent studies of the pathology and host immune response in the major CVBDs (leishmaniosis, babesiosis, ehrlichiosis, hepatozoonosis, anaplasmosis, bartonellosis and borreliosis). The ultimate application of such immunological investigation is the development of effective vaccines. The current commercially available vaccines for canine leishmaniosis, babesiosis and borreliosis are reviewed.
Vector-borne diseases affecting the domestic dog are of major global significance for their impact on the health and well being of these companion and working animals, and also because for some of these diseases the dog acts as a reservoir species for infection of the human population. The most significant of these diseases are bacterial and microparasitic and these are summarized in Table 1. These diseases have received the attention of the veterinary and public health research communities in recent years and progress in such research forms the focus of the annual series of Canine Vector-Borne Disease (CVBD) workshops hosted by Bayer and now summarized in the pages of this journal.
Table 1. Major canine vector-borne diseases
The greatest research activity has focussed on the molecular speciation of the infectious agents, definition of their parasite vectors, the geographical distribution and movement of agents and vectors, the clinical syndromes expressed by infected dogs and people and elements of the pathogenicity of the causative organisms. The more challenging aspect for research remains an exploration of the pathology and secondary immunopathology established in dogs by these infections and the nature of the immune response made by the canine host to the pathogens. There are practical reasons why this important area of research has been poorly addressed to date, including: (1) the ethics and expense of working with the dog as an experimental animal, (2) the problem, for some diseases, of establishing reliable and repeatable in-vivo model systems, (3) the challenges in assembling significantly large populations of spontaneously-infected and well-characterized clinical populations, (4) the availability of appropriate immunological reagents and molecular methodology for dissection of the canine immune response relative to such investigations in man or laboratory rodents, and (5) the difficulty in attracting appropriate research funding for the investigation of canine disease. With the publication of versions of the canine genome [1] there have been rapid advances with respect to investigative technology for canine immunopathological research, so this is now less of an insurmountable problem. Numerous studies have shown the utility of the reverse transcriptase polymerase chain reaction (RT-PCR) for exploring the tissue expression of targeted genes [2], although the application of methods such as mRNA expression microarrays [3] and genome wide association studies (GWAS) [4,5] remain costly options.
The aim of the present review is to summarize the current state of knowledge regarding the pathology and immunology of CVBD in the host species. The review will focus on key diseases and cannot be exhaustive, but should give a feel for the current state-of-the-art in this important area of veterinary medicine. It should be noted that the scope of the review does not include the equivalent feline infections and that for at least one of these (feline bartonellosis; [6]) knowledge of immunopathology has progressed beyond that currently described for the dog.
Unique aspects of the canine vector-borne diseases
In addition to the practical issues defined above, simple aspects of the nature of the CVBDs make them particularly challenging for investigation. All of these infections are characterized by being formed of a unique triad that involves the infectious agent, the vector of that agent and the host animal (Figure 1) [7,8]. In many instances this integral and complex three-way relationship has likely evolved over millennia with fascinating selective advantages conferred by some aspects of the relationships. For example, the infectious agents are known to be able to manipulate the physiology (gene expression) and behaviour of the arthropod vectors to ensure their transmission [9] and during the process of taking a blood meal the arthropod vectors appear to be able to manipulate the host immune system through the release of potent salivary immunomodulators, thereby conferring an advantage to the co-transmitted microorganism in terms of establishment of disease and further transmission to naïve co-feeding vectors via the process of 'saliva-activated transmission' [8,10]. This group of infectious agents is also characterized by the ability to induce chronic or recrudescent disease in the canine host, likely by occupying particular tissue niches where they may be protected from the host immune response, or by manipulating host immunity to prevent a sterilizing response and permit persistent infection. The clinicopathological changes in any one dog may be complicated by the co-infections that may occur in endemic areas (e.g. combinations of leishmaniosis, monocytic ehrlichiosis and babesiosis; or borreliosis and anaplasmosis). Finally, the nature of the clinical signs expressed by the infected dog often relate to secondary immunopathology (e.g. the induction of autoantibodies or formation and deposition of immune complexes of antigen, antibody and complement) rather than direct cellular or tissue damage and the accompanying inflammatory response. With all of these complex interrelationships, our greatest knowledge gap relates to what is happening within the infected canine host.
Figure 1. The triad of canine vector-borne disease. The canine vector-borne diseases are characterized by the unique three-way interaction between the infectious agent, the vector and the host immune system. Vector salivary proteins injected into the dermal microenvironment during taking a blood meal modulate the host immune system creating a favourable environment for survival and replication of the infectious agent. This permits infection of co-feeding naïve vectors. The effects on host immunity are often to promote Th2-regulated humoral responses above the protective Th1-regulated cellular immune response. This allows persistence of the infection and encourages the development of inappropriate secondary immunopathology characterized by hypergammaglobulinaemia, autoantibody and immune complex formation.
The pathology of canine vector-borne diseases
The simple pathology of the CVBDs is relatively poorly described. Few investigations have ever been made of the primary site of interaction of the agent-vector-host triad, i.e. the cutaneous site of vector attachment and feeding, which also represents the site of transmission of the agent and the point of initial engagement with the host immune system. The histopathology of canine cutaneous tick-attachment sites has been described at the light microscopical level, including the central dermal cone-shaped zone of necrosis related to insertion of tick mouthparts and formation of 'cement' and the surrounding mixed chronic inflammatory infiltration of macrophages, lymphocytes, plasma cells, neutrophils and eosinophils [8,11]. However, given the increasing range of species-specific and cross-reactive reagents now available for immunohistochemical evaluation of canine tissue immune responses [12] it is surprising that the temporal kinetics and nature of these inflammatory responses has not been further defined. Such studies have been performed recently in sheep exposed twice to Hyalomma ticks, in which cutaneous attachment sites and regional draining lymph nodes had infiltration of CD1+ dendritic cells, CD8+ cytotoxic T lymphocytes and T cells bearing the γδ form of the T-cell receptor [13].
There have been numerous reports of the cutaneous pathology in the chronic stages of canine leishmaniosis (Figure 2) and in some of these the presence of intracellular amastigotes within the macrophages forming the granulomatous dermatitis has been highlighted immunohistochemically [14,15]. Immunohistochemical studies have also shown that in the relatively milder clinical lesions of exfoliative dermatitis there is a low parasite burden, associated with enhanced expression of class II molecules of the major histocompatibility complex (MHC) by keratinocytes and a dermal T-cell infiltrate dominated by CD8+ cells over the CD4+ T helper (Th) subpopulation. In contrast, with increasing severity of cutaneous disease (the nodular form) there is reduced expression of class II molecules of the MHC by epidermal Langerhans cells and keratinocytes and fewer infiltrating T lymphocytes [16,17]. The lymph nodes of asymptomatic Leishmania-infected dogs are hyperplastic, but when disease becomes symptomatic there is more often atrophy of the lymph node cortex [18].
Figure 2. Canine leishmaniosis. Skin biopsy from a dog with symptomatic visceral leishmaniosis. There is a mixed chronic inflammatory infiltration of the dermis associated with numerous macrophages laden with amastigotes (arrows). Haematoxylin and eosin, bar = 50 μm.
Limited investigations have been performed on the systemic pathological changes that accompany these diseases in spontaneously- or experimentally-infected dogs. Again, the most reported are the lesions that develop in canine leishmaniosis [19], for example the granulomatous inflammatory infiltrates that form with foci of infection in organs such as the liver [20] (Figure 3), and the range of secondary immunopathological (e.g. immune complex-mediated) lesions that arise in the renal glomeruli [21-23] (Figure 4), the nasal mucosa [24] or the uveal tract of the eye [25,26]. Immunohistochemistry has been used in several studies to determine the parasite load of infected tissues [27].
Figure 3. Canine leishmaniosis. Section of liver from a dog with visceral leishmaniosis. There is a discrete focus of granulomatous inflammation within the mid-zonal hepatic parenchyma. Macrophages within the focus will contain amastigotes. Haematoxylin and eosin, bar = 50 μm.
Figure 4. Canine leishmaniosis. Section of kidney from a dog with visceral leishmaniosis. There is marked lymphoplasmacytic interstitial nephritis with obliteration of the glomerulus and afferent and efferent arterioles by granulomatous inflammatory infiltration. Haematoxylin and eosin, bar = 100 μm.
Pathological descriptions have also been made of the synovial, renal ('Lyme nephropathy') and nervous system lesions in canine borreliosis [28,29]. The renal lesions are characterized by glomerulonephritis (with immunoglobulin [Ig] G, IgM and complement C3 subendothelial immune complex deposition), interstitial nephritis and tubular necrosis [29]. A detailed histopathological description of the lesions in dogs infected experimentally by exposure to infected ticks has been reported. These animals developed mixed inflammatory dermatitis at the site of tick attachment, hyperplasia within the draining lymph node and synovitis of nearby forelimb joints. The synovial reaction was either predominantly an acute neutrophilic inflammation with intraarticular fibrin deposition or a chronic lymphoplasmacytic reaction with plasma cells dominating over CD3+ T cells. Perineuritis and periarteritis were also described in the periarticular tissue [30]. In another experimental infection study, lymphoplasmacytic meningitis was also recorded in 3/20 infected dogs [31].
The bone marrow changes in chronic monocytic ehrlichiosis have been reported [32]. Dogs infected experimentally with Ehrlichia canis develop lymphoplasmacytic uveitis and meningitis [33] and experimental infection with Anaplasma phagocytophilum leads to splenic hyperplasia and mild non-specific reactive hepatitis [34]. The spectrum of Bartonella-associated inflammatory changes in individual canine patients, particularly dogs with endocarditis [35-40], has been described. The pathology of lesions of skeletal muscle [41] and the periosteum [42] has been described in dogs infected by Hepatozoon americanum. These are all primarily light microscopical descriptions and the lesions await further exploration by immunohistochemistry or characterization of lesional gene expression via RT-PCR or microarray investigation of fresh-frozen tissue extracts.
The immunology of canine vector-borne diseases
Understanding of the immune response to infection has expanded greatly in recent years and, as for many aspects of immunology, this new knowledge is based on application of the discovery of multiple functional subsets of T lymphocytes expressing the CD4 co-receptor molecule. The diversity in regulatory T-cell subsets (Figure 5) is best characterized in experimental rodents and man. Following the initial description of Th1 and Th2 cells by Mossman et al. [43] much of the early work defining the interrelationships between these populations was performed using the murine model of dermatotropic leishmaniosis. In this model there was clear dichotomy between the protective Th1 immune response in disease-resistant C57Bl6 mice and the Th2 response made by susceptible BALB/c mice [44]. More recently, the murine model system has enabled definition of the role of regulatory T lymphocytes (Treg) in chronic infections such as leishmaniosis. These cells inhibit the function of Th1 cells allowing persistence of infection, but more importantly limit the development of secondary immunopathology. In murine models it has also been suggested that effector Th1 cells may become a source of the key regulatory cytokine, interleukin (IL)-10, for the same reason [45] (Figure 6).
Figure 5. CD4+ T-cell subsets. There is increasing complexity in the network of functional CD4+ T-cell subsets. Under the influence of specific promoting cytokines (purple lettering) and transcription factors (not shown here), the naïve T cell may differentiate towards a functional subset promoting either cell-mediated and proinflammatory immunity (Th1, Th17 and Th9; black lettering), humoral immunity (Th2 and T follicular helper [TFh]; green lettering) or a suppressive response (induced Treg and Treg1; blue lettering). These subsets are not strongly polarized and there is considerable 'plasticity' in their actions, whereby one cell type can be reprogrammed to another at a different stage of the immune response. This is readily seen by the ability of multiple of the subsets to produce the immunosuppressive cytokine IL-10. The natural Treg appear separately, as this committed lineage leaves the thymus directly and is responsible for the control of allergen- and autoantigen-specific lymphocytes.
Figure 6. Plasticity of CD4+ T-cell subsets. The plasticity of CD4+ T-cell subsets is demonstrated in the murine model of leishmaniosis. In many chronic infectious diseases it is now recognized that sterilizing immunity is prevented by the action of T cells with regulatory function. Although regulatory T cells prevent complete elimination of the infection, they are crucial in inhibiting the development of secondary immunopathology. A balance is therefore achieved between infection-limiting Th1 immunity and immunopathology-limiting regulation. The regulatory activity might come from classical induced or natural Treg, but equally some Leishmania-specific Th1 cells may be re-programmed to become IL-10 producing regulatory cells.
The CD4 Th subset paradigm has also been used as a framework for understanding the immunomodulatory properties of arthropod salivary proteins released into the host dermal microenvironment upon taking a blood meal. Arthropod saliva is not only anticoagulant and anti-inflammatory in nature, but also contains potent immunomodulators that are now being characterized and purified. In general terms, the effect of these salivary molecules is to alter the host immune response within the skin and possibly also within draining lymphoid tissue. These molecules tend to promote Th2 immunity while suppressing the Th1 response. This provides a more favourable environment for the establishment of intracellular infection (for which Th1 immunity is the appropriate means of clearance of infection) and at the same time pushes immune balance towards conditions favouring secondary humoral immunopathology (e.g. autoantibody and immune complex formation) [8]. Few studies have examined the effect of arthropod salivary proteins on the canine immune system. Salivary gland extract from Rhipicephalus sanguineus co-cultured with canine peripheral blood mononuclear cells suppressed the production of total immunoglobulin and IgA (but not IgM) by lymphocytes stimulated with pokeweed mitogen or lipopolysaccharide [46].
For leishmaniosis, clear parallels were recognized between the susceptibility and resistance phenotypes in murine strains and in natural infection of the dog. Relatively early studies confirmed that the resistance of certain dogs to severe clinical leishmaniosis was also determined by a Th1 immune response with production of the key Th1 cytokine interferon (IFN)-γ [47]. Leishmaniosis has since become the single best understood vector-borne disease of the dog as it has rightly attracted appropriate funding commensurate with the significance of the canine disease for human health. Numerous investigations have confirmed the importance of Th1 immunity and further characterized cytokine gene expression in this disease. Asymptomatic spontaneously-infected dogs have greater expression of genes encoding IFN-γ and tumour necrosis factor (TNF)-α and a lower parasite burden within lymph nodes, compared with symptomatic dogs with high parasite burdens in which there is greater expression of genes encoding the immunosuppressive cytokines IL-10 and transforming growth factor (TGF)-β [48]. In contrast, within the spleen there was no clear difference in IFN-γ, IL-4 and IL-12 gene expression between asymptomatic and symptomatic dogs [49], but splenic IL-10 mRNA expression was greater in symptomatic dogs [50]. There was no clear evidence for higher expression of IL-10 mRNA in the bone marrow or blood lymphocytes of infected versus uninfected or symptomatic versus asymptomatic dogs [51,52]. A study of cytokine gene expression using RNA extracted from formalin-fixed tissue biopsies and real-time RT-PCR has shown elevation of mRNA encoding IL-4, IFN-γ and TNF-α compared with normal skin, but an association between cutaneous parasite burden and severity of skin lesions with only IL-4 gene expression. This was interpreted to suggest a Th2 bias within the cutaneous lesions [53].
Overall, these cytokine gene expression studies suggest that symptomatic infected dogs have insufficient Th1 (IFN-γ) with enhanced Treg (IL-10) activity, however interpretation of these investigations should be tempered by the facts that: (1) there is little standardization of the disease (e.g. spontaneous versus experimental infection, breed of dog, geographical setting, infectious load etc.), (2) there is variation in the body compartment tested (e.g. blood, lymph node, spleen, bone marrow or skin), (3) most of the studies employ conventional gel-based RT-PCR rather than real time RT-PCR employing multiple housekeeper genes for relative determination of copy number [54], and (4) gene expression rather than protein production is measured.
In the peripheral blood of symptomatic dogs there is a reported reduction in the proportions of circulating CD21+ B cells and CD14+ monocytes compared with asymptomatic dogs in which the major alteration is an elevation in the frequency of CD8+ T cells [55]. However, these data are controversial, as other studies have shown no difference in the proportions of different blood lymphocyte subpopulations between normal and infected dogs and in infected symptomatic dogs throughout the course of medical therapy [56]. The lymph nodes of Leishmania-infected dogs have proportionally more CD8+ T cells, reduced B cells and upregulation of MHC class II expression by lymphoid cells [18].
It has proven much more challenging to clearly relate the subisotype of the IgG antibody response to clinical status. Although there are clear associations between murine Th1 and IgG2a responses and Th2 and IgG1 responses, there is no consensus as to whether canine humoral immune responses are polarized in leishmaniosis. The confusion partly arises from inconsistency in nomenclature and the validity and specificity of reagents produced for the detection of canine IgG subclasses [57,58].
The genetic basis for protective immunity as recognized in particular breeds (e.g. the Ibizian hound and dogs raised in endemic areas) [59] has been explored by characterizing associations with genes of the canine MHC (the DLA system; specifically the DLA class II allele DLA-DRB1*01502) [60] and genes identified as associated with resistance in other species (Slc11a1 encoding the natural resistance associated protein 1 [NRAMP1]) [61]. A recent study has failed to confirm sequence differences in Slc11a1 between symptomatic and asymptomatic naturally-infected dogs [49]. The most exciting current investigation of canine leishmaniosis is that which forms one of the work packages of the European Union-funded LUPA project http://www.eurolupa.org/ webcite, in which susceptibility and resistance is being examined via GWAS studies of significant numbers of dogs with clinically well-characterized infection status and disease.
In contrast to leishmaniosis, the host immune response to the remaining major canine vector-borne pathogens is relatively poorly characterized. Logically, most of the focus for these infections has been on understanding the humoral immune response in order to develop serological diagnostic methods for detection of individual cases or population epidemiological studies. The combination of serology and PCR detection now forms the cornerstone for diagnosis in most of the CVBDs, but it is beyond the scope of this review to detail studies of the kinetics of the humoral immune response in the CVBDs.
There has been very limited exploration of other aspects of the immune response in these diseases; in particular how these infections might map to the CD4 T cell immunoregulatory model described above for leishmaniosis. Mixed breed dogs infected experimentally with E. canis and monitored for 4 months post infection had no significant changes in the concentration of serum IgG, IgM and IgA, the percentage of circulating CD4+ T cells or the in-vitro function of blood lymphocytes (as determined by mitogen stimulation and the ability of lymphokine-activated killer cells to cause lysis of a 51Cr-labelled target monocyte cell line). A transient elevation in blood CD8+ T cells was found at 6 weeks post infection [62]. Whilst the study of T cell and cytokine responses may not be crucial for diagnosis of the CVBDs, such knowledge should underpin the development of vaccines and immunotherapeutic approaches to the management of these infections.
In addition to the host immune response to the vector-borne agents, an important part of the pathogenesis of these infections often involves the secondary immune-mediated sequela that are manifestations of immune dysregulation induced by the organism and/or the vector [7]. Many of the CVBDs are characterized by serum hypergammaglobulinaemia and the production of circulating immune complexes or autoantibodies (e.g. antierythrocyte and antiplatelet antibodies, antinuclear antibodies) that play a role in disease pathogenesis. Immune complex deposition and autoantibody formation is widely recognized in the pathogenesis of canine leishmaniosis [63-65] and monocytic ehrlichiosis [66,67]. In the latter disease, both platelet-bound and serum platelet-bindable antibodies have been demonstrated [68,69], in addition to antinuclear antibodies and antierythrocyte antibodies [70]. Dogs with A. phagocytophilum infection have also been reported as being Coombs positive and having platelet-bound antibodies [71,72]. Similarly, 11/16 dogs with Rocky Mountain spotted fever had serum antiplatelet antibodies and all 15 dogs infected experimentally with Rickettsia rickettsii developed such antibodies by day 26 post infection [67].
The role of the immune system in the pathogenesis of the haemolytic anaemia that characterizes canine Babesia infection has been investigated. Studies of Babesia gibsoni-infected dogs in Japan demonstrated the presence of IgG and IgM red cell-associated antibodies and the specificity of these antibodies for erythrocyte membrane antigens [73]. A recent European study has suggested that Coombs test positivity is more likely to be associated with Babesia vogeli infection rather than that caused by Babesia canis [74], although an earlier study from North America reported Coombs positivity in 25/28 cases of B. gibsoni infection and 6/9 cases of B. canis infection [75]. In contrast, canine haemoplasma infections do not appear to act as a trigger for immune-mediated haemolytic anaemia in this species [76]. The thrombocytopenia that occurs in canine babesiosis may also in part have an immune-mediated pathogenesis and platelet-bound antibodies have been demonstrated in B. gibsoni-infected dogs [77].
Dogs infected experimentally with Bartonella vinsonii subsp. berkoffii developed mild cyclical or sustained immunosuppression related to a reduction in circulating CD8+ T lymphocytes, but had elevation of CD4+ T cells and reduced B cell expression of MHC class II within lymph nodes [78,79]; however, there remains little known of the immune response to Bartonella in the dog.
A recent study of Bernese Mountain dogs, a breed predisposed to borreliosis and the proposed associated glomerulopathy; has shown that deficiency of the third component of complement does not appear to underlie either predisposition [80]. The immune response occurring within the synoviae of dogs with borreliosis has not yet been well-characterized, but IL-8 expression has been defined [81].
Vaccination for canine vector-borne diseases
This section summarizes the current commercially-produced vaccines designed to limit these infections in the dog, but does not generally review the numerous developmental studies of vaccine candidates. Perhaps the most widely available are the Borrelia vaccines that are sold in North America and Europe [82]. These are either adjuvanted whole cell lysates (e.g. Merilyme, Merial; LymeVax, Fort Dodge) or vaccines containing a recombinant version of the outer surface protein (Osp) A of the organism that are adjuvanted (e.g. ProLyme, Intervet-Schering Plough) or non-adjuvanted (e.g. Recombitek Lyme, Merial). Most whole cell bacterins are based on Borrelia burgdorferi sensu stricto, but one European vaccine includes Borrelia garinii and Borrelia afzelii which are more relevant species in that area (Biocan B, Bioveta). The major serological response to the whole cell vaccines is to the OspA and OspC proteins. The OspA antibodies are bactericidal and prevent re-infection by killing the spirochaetes in the gut of the fed tick via a complement-dependent mechanism. However, these vaccines fail to protect 20-40% of vaccinated dogs from Borrelia infection, which is suggested to reflect the possibilities that: (1) the organism down-regulates OspA expression when a tick commences feeding, (2) the borreliacidal anti-OspA antibodies may be genospecies specific, or (3) that the tick may carry an OspA-negative Borrelia [83].
Recombinant OspC vaccines are not licensed, but have been shown experimentally to inhibit colonization of the tick salivary gland, thereby blocking transmission to the vertebrate host. OspC is expressed both in the tick midgut and salivary gland and in the early stages of infection in the host. A bivalent B. burgdorferi bacterin (Nobivac Lyme, Intervet-Schering Plough) containing isolates that engender both OspA and OspC antibodies has recently been tested in dogs challenged 1 year post vaccination with Borrelia-infected ticks. Compared with unvaccinated controls, vaccinates remained free of joint infection, lameness and synovitis, did not seroconvert to infection-specific antigens (determined by western blotting and use of the Idexx SNAP 4Dx® test kit) and cleared Borrelia organisms from the skin adjacent to tick attachment sites by 2 months post exposure [83].
The major consideration related to these non-core Borrelia vaccines is that of when their administration might be appropriate; in a situation where exposure (seropositivity) is far more common than clinically significant disease [84]. The decision to use such products in an individual dog should be based upon knowledge of the geographical distribution of the causative organism, the particular species of Borrelia present in that region and whether there is vaccinal cross-protection, and the lifestyle and exposure risk (e.g. exercise in wooded areas that are home to Ixodes ticks) of that animal [85]. The products all have 1 year licensed duration of immunity and should not be considered an alternative to rigorous control of exposure to ectoparasites.
In Europe, two commercially produced vaccines against canine babesiosis are available. The first is a saponin-adjuvanted vaccine containing soluble parasite antigens (SPA) produced by B. canis (Pirodog, Merial) with a licensed duration of immunity of 1 year. The vaccine is unlikely to cross-protect against other Babesia species. A saponin adjuvanted bivalent vaccine containing SPA produced by B. canis and Borrelia rossi (Nobivac Piro, Intervet-Schering Plough) has been shown to provide protection against homologous and heterologous challenge. Vaccinated beagle dogs challenged with B. rossi shortly after the last of a series of vaccines had reduction in clinical signs, parasitaemia and plasma concentrations of SPA compared with unvaccinated controls [86]. In contrast, vaccinated dogs challenged with B. canis have reduction in clinical signs and plasma SPA, but not parasitaemia [87]. This suggests that the vaccine may have different protective effects - inhibiting infection and disease in the case of B. rossi challenge, but inhibiting severity of clinical disease without reducing parasitaemia following challenge with B. canis. The latter may occur if the vaccine-induced antibodies were able to prevent the initial vasodilatory shock that leads to microvascular agglutination and hypercoagulation in infected dogs. This pathogenesis is proposed to underlie B. canis, but not B. rossi infection [88,89]. The vaccine has a licensed duration of immunity of 6 months and is also available in South Africa. There are few available field efficacy data for these vaccines and any risk-benefit analysis for an individual dog should consider the necessity for biannual administration of an adjuvanted non-core vaccine. Again, tick control is of much greater importance than administration of a vaccine for this disease.
The most interesting vaccines in this group are those licensed for the protection of dogs from Leishmania infection in Brazil [90]. Although numerous vaccine candidates have been tested over many years only two products are currently available commercially [91]. There have been numerous published studies evaluating the saponin-adjuvanted vaccine incorporating the fucose mannose ligand (FML) enriched for the surface glycoprotein 63 of the parasite (Leishmune®, Fort Dodge Animal Health). This product induces protective immunity with IgG seroconversion and development of a robust response to intradermal administration of Leishmania lysates. Vaccinated dogs also have a specific Leishmania-specific IgG subclass profile [92]. Discrimination between vaccinated and infected dogs is important in a country where serological screening and culling of dogs is undertaken by the Ministry of Health [93]. It has been suggested that the potential for misidentification of vaccinates has led to reluctance of veterinarians in Brazil to offer the vaccine, but in reality it appears that the current serodiagnostic test rarely detects vaccinates [94]. After vaccination, cultures of blood lymphocytes stimulated with Leishmania antigen or FML have higher expression of IFN-γ and a reduced proportion of CD4+CD25+ putative Treg cells [95]. Similarly, there are more CD4+ T cells in the blood of vaccinated dogs that co-express IFN-γ protein as determined by dual-colour flow cytometry [96]. There is excellent reported clinical efficacy and duration of immunity of 1 year. One large trial was conducted of 550 vaccinates and 588 unvaccinated controls subjected to natural challenge by living in a Leishmania endemic area. Two years post vaccination, only 1% of vaccinates died from leishmaniosis (compared with 39% of controls) and only 1.2% of the vaccinates developed clinical signs of the disease (compared with 20.6% of controls) [97]. Most excitingly, where the product has been used it has had an impact on the prevalence of both canine and human infection in the same area, presumptively due to the effect of the vaccine in blocking transmission of the parasite [94].
When enriched with a double dose of saponin adjuvant, the vaccine has also been used successfully as an adjunct immunotherapeutic agent in dogs being treated medically with allopurinol or allopurinol in combination with amphoteracin B. The effect of combined medical and immunotherapy was to reduce clinical and parasitological signs 3 months after initiating therapy and at 8 months to significantly reduce the proportion of treated dogs that remained PCR-positive [98]. A second vaccine, under development for human use, has also been evaluated for immunotherapeutic purposes in affected dogs. The multicomponent protein vaccine Leish-111f formulated with monophosphoryl lipid A in stable emulsion (MPL-SE) had greater therapeutic efficacy in dogs with less severe clinical disease, but treatment with the MPL-SE adjuvant alone also led to clinical benefit [99].
The second canine Leishmania vaccine available in Brazil is Leishtec® (Hertape Calier Saúde Animal SA), which is a saponin-adjuvanted vaccine containing a recombinant version of the amastigote-specific A2 antigen of L. donovani. The vaccine has a 1-year duration of immunity [100]. Beagle dogs receiving this vaccine seroconvert to the A2 protein but not to entire Leishmania promastigote extract, enabling distinction between vaccinated and infected dogs. Cultured blood lymphocytes from vaccinated dogs express elevated levels of IFN-γ, but not IL-10 protein as detected by capture immunoassay. Fewer vaccinated dogs (28.5% of 7 dogs) developed clinical signs post experimental challenge than unvaccinated dogs (71/5% of 7 dogs), and in vaccinates these signs developed later (12 months) than in the unvaccinated controls (3-6 months) [100].
The first European canine Leishmania vaccine is due for release in 2011. This product (CaniLeish®; Virbac S.A.) consists of excreted secreted proteins (ESP) from Leishmania infantum - the dominant antigen of which is the promastigote surface antigen (PSA). The vaccine is indicated for the active immunization of Leishmania-negative dogs from 6 months of age and claims to reduce the risk of developing active infection and clinical disease. The product has a 1-year duration of immunity. Other European investigations have examined the LiESAp-MDP vaccine, which contains the 54 kDa excreted protein of L. infantum adjuvanted with muramyl dipeptide. In a field trial of spontaneous infection in and endemic area of France, the incidence of infection in 165 vaccinated dogs (2 years post vaccination) was 0.6% versus 6.9% in 175 unvaccinated controls [101].
Although these Leishmania vaccines are adjuvanted and administered annually, as non-core vaccines there is much to recommend their use in endemic areas of disease with a high rate of infection in the human population. There are excellent field data to support their efficacy and serological discrimination between vaccinated and infected animals appears feasible. Again, vaccination should be regarded as one of multiple strategies (including control of sandfly exposure and control of stray dogs) in the management of this disease within the population.
Experimental studies have also addressed the possibility of producing vaccines against arthropods for the dog, but these are far from a commercial reality. For example, naïve dogs vaccinated with extracts of salivary gland or midgut from R. sanguineus and challenged experimentally 7 and 21 days post vaccination, showed reduced tick attachment (for both vaccine extracts), feeding period and engorgement weight (for salivary vaccine) and fecundity (for midgut vaccine). In the same study, a control group of dogs repeatedly exposed to R. sanguineus also showed transient reductions in these parameters, suggesting development of a degree of spontaneous immunity to the tick [102].
It is clear that our understanding of the pathology and immunology of the CVBDs lags behind the recent rapid advances made in the molecular characterization of the causative organisms, their diagnosis and the epidemiology of infection. The tools to accomplish such studies are now generally available and the development of new vaccines and immunotherapeutics will require their application to expand our fundamental knowledge base.
Competing interests
Publication of the CVBD6 thematic series has been sponsored by Bayer Animal Health GmbH. The author is a member of the Bayer CVBD World Forum.
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The Hateful Life And Spiteful Death Of The Man Who Was Vigo The Carpathian
You've seen a painting of Norbert Grupe. A heavy, creased brow and shoulder-length hair framing a frightening scowl, the massive work hung in the fictional Manhattan Museum of Art in Ghostbusters II. When the medieval sorcerer pictured within the painting begins to physically manifest, it is on the Ghostbusters to… »


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We created Pandora to put the Music Genome Project directly in your hands
It's a new kind of radio –
stations that play only music you like
Read my bio it says everything about me.
- Hometown: Why do yu wanna know,bruh?
- | School: The Place of Jelly Beans!!!!!
- | Employer: Krusty krab


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- The Big Picture - http://www.ritholtz.com/blog -
Chart Attack: Mutual Fund Outflows
Posted By Barry Ritholtz On July 15, 2013 @ 6:30 am In Media,Technical Analysis,Video | Comments Disabled
I forgot to publish this Bloomberg appearance from last week — here is the last segments, looking at monthly mutual fund outflows on Bloomberg Television's "Street Smart."
on retail and obsolescence:
On today's "Chart Attack, Fusion IQ CEO Barry Ritholtz and Bloomberg's Adam Johnson
Chart Bill Gross Doesn't Want You to See
Source: July 9 2013 Bloomberg
Article printed from The Big Picture: http://www.ritholtz.com/blog
URL to article: http://www.ritholtz.com/blog/2013/07/chart-attack-mutual-fund-outflows/
Click here to print.
Copyright © 2008 The Big Picture. All rights reserved.


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"Sawdust and diamonds": Joanna Newsom at the Opera House with the Sydney Symphony
If you do have tickets, don't be late! There's no support act. It's all Joanna.
(Joanna Newsom, photo: Pete Newsom)
As a buddy of Julia Zemiro's -- and a RocKwiz devotee -- I often ask myself how I'd answer her "first concert?" question. It's not that I'm embarrassed about the first few concerts I went to as a teen... it's just they're so unrepresentative. Or, rather, that they're representative of a tiny part of the music I was (and am) into. First concerts are about opportunism, about getting to the concert. (Maybe the question should be qualified... What was the first concert you made it to on your own? Now that would be a question worth asking!)
Anyway, without rummaging through The Archives, I reckon the first was Melanie Safka at Dallas Brooks Hall. (Either her or Fairport Convention at the same venue. Sandy Denny was still alive, but had left the band.) In those days, 'Melanie' was as unique and sufficient an ID as 'Madonna' became twenty years later. And the 'Safka' bit was about as well known as 'Ciccone'. She's best known to Gen-xers for the Boogie Nights "Roller Girl" song 'Brand New Key'.
When I first encountered Joanna Newsom's first release The Milk-Eyed Mender, the best I could say about it was that it reminded me -- once or twice -- of Melanie. (Bits also reminded me of Mazzy Star -- just the pedal steel-like glides -- and, inevitably, of Alan Stivell's Renaissance de la Harpe Celtique... and please note the name of the first song on that album!) That said, the bits of Melanie it reminded me of were the annoying 'Alexander Beetle' bits.
And, if I might digress one last time, Melanie -- in that first concert experience of mine -- called for requests. She ignored my pleas for 'Some Say' [I always was a B-side kinda guy... 'Some Say (I Got Devil)' was the brilliant flip of 'Brand New Key' ]. "I heard a child's voice," she said. The kid wanted to hear 'Alexander Beetle'. She was brow-beaten into playing it by the loud-mouth bloke who relayed the request. A nice bit of theatre... Which happened the next night. And the next night. No-one seems to have heard the kid's voice apart from Ms Safka herself. My first concert and my first taste of musical mendacity. Sigh!
Anyway, I bought The Milk-Eyed Mender "sight unseen" on the strength of the universal acclaim it was getting from the indie music press around the world.
And I hated it.
But, weirdly, when an advance copy of the follow-up release Ys fell into my hands, I couldn't wait to listen to it. I put it at the top of a pretty big pile.
Watching Newsom play the five song set live, with the Sydney Symphony, I vividly remembered the first time I heard Ys and, in particular, the anxiety I felt as the first song (the twelve minute-plus 'Emily') ended and the second song began. What if the rest of the album was crap? What if the genius of 'Emily' wasn't sustained? How could it be? Given that the first seconds of 'Monkey and Bear' are a throw-back to extremes and eccentricities of The Milk-Eyed Mender, my fears looked grounded.
Why the 'flashbad' during the concert? Cos of the people I was sitting with. I was in the midst of Sydney Festival patrons rather than Newsom fans. Behind me was a couple expecting a concert with a harp soloist. I kid you not! (I overheard several comments along the lines of: "I've never seen a harp soloist before.") On my right were a group of rather glamorous women who looked infinitely more at home at the Opera House than the legions of waif-like Newsom fans in the gods.
And, yes, once the orchestra departed -- at interval -- so did a good number of the classical music fans. (The glam girls to my right -- who chose which Festival shows to see with a pin -- were groovin' away, even more smitten with Newsom when they had heard her with her "band" -- Joanna's word for mandolin & banjo playing "Frenchie" Ryan Francesconi and percussionist/backing vocalist Neal Morgan.) So, my anxiety was only partly warranted.
Good as the first half was -- Ys in its lush entirety with a bantam-sized orchestra -- it lacked the "now we are alone" quality of the second set. The eight songs included the traditionally folky 'Colleen' from the recent EP Joanna Newsom and the Ys Street Band and two new songs... So new that they don't yet have titles. One even came with the caveat that the lyrics were still in a state of flux. But I'll say more about the concert (I typed 'convert' first... there were one or two!) some other time.
Joanna Newsom with the Sydney Symphony, part of the 2008 Sydney Festival. Concert Hall, Sydney Opera House, January 25, 2008. (Final concert tonight, January 26.) Also Howard Gilman Opera House at the Brooklyn Academy of Music, with the Brooklyn Philharmonic conducted by Michael Christie, January 31 & February 1, 2008.
Labels: Alan Stivell, BAM, Brooklyn Philharmonic, Joanna Newsom, Melanie Safka, Neal Morgan, Ryan Francesconi, Sydney Festival, Sydney Symphony, Ys Street Band
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New Stroke Approach Video
This medical video looks into the approach to stroke victims and their treatments.
Read the full transcript
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CEO Yancey Strickler says the crowdfunding site's new status as a public benefit corporation will further its goal to be a "place of empowerment for artists," even if the decision puts a pinch on profits.
With crowdfunding becoming a more viable option for people to finance their passion projects, an in-depth look at raw numbers lays out the path to success.
You might not be able to stomach ground crickets as a snack, even if they are good for your health and the planet. But Fido? What does he know?
In this Tech Minute, CNET's Sharon Profis finds three gadgets on the crowdfunding site that are a new take on old tech.
The Buccaneer 3D printer was a major crowdfunding success in 2013 but two years on, the company has owned up to having bitten off more than it could chew.
A shed-building company plans to build its zombie-proof cabin on the site of a Zombie Infection attraction, with help from backers willing to settle for temporary security from the undead hordes.
A futuristic razor that promises to shave with lasers and raised millions on Kickstarter gets kicked off the site for not having a fully functional prototype. But it's found a new home on Indiegogo.
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The Audiophiliac considers this Kickstarter project for a craftily designed turntable, audio equipment, or LP vinyl-file storage rack.
Pugz wireless earbuds are new dogs with a new charging trick that lets you groove out while you charge them up.


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Carolina Club
Main Number: 919.962.1101
Our Story
UNC vs Maryland Tailgate[ X ]
Date: Sat, Nov 24, 2012
Time: All Day
Add to your Calendar: Download Now
TIME: 12:00 PM (3:00 PM Kickoff)
Carolina Football 2012… Let's Tailgate!
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Maryland November 24


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Originally posted by stevcolx
reply to post by danj3ris
It's not nice to kill without a reason. He didn't have a viable reason. He did it out of spite.
I have horses at home and they are lovely animals. They have a brain, a heart and if your religious a soul. They even have feelings. Strange that the guy doesn't feel any empathy for the horse he shot in cold blood. Do u think he'd feel empathy for people?
Maybe later we will see a youtube video of him being shot in the head. Hopefully!
We are all animals. Horses are limited by their bodies for how they move and communicate but they are not dumb animals. Some people are dumber than horses.
This guy is just cruel! Plain and simple.
Tim Sappington, an employee at the Valley Meat Company out of Roswell, NM posted a video on youtube of him bringing out a horse and saying "To all you animal activists, !**# you" and proceeds to shoot the horse in the head


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While the American Psychological Association has not identified playing video games as an addiction or obsession, it has been researching it.
- Filed Under
Q. My husband and I have been having difficulties lately, and I believe it is due to the amount of time he spends playing video games. We are always arguing about this, and he just tells me that I am crazy. I do not understand anything about these games, so maybe I am wrong. I just think that this is an obsession for him. Am I the crazy one?
A. No! You are not crazy. Husbands, wives and parents are all concerned about the impact excessive video-gaming is having on their loved ones. Parents are complaining that their children are withdrawing from activities to play their games, are flunking out of college ...


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Fitday for yesterday was only 2519
Today isn't looking much better.
Should I just look at the foods with the highest cals in my diet and double those? I'm trying to clean bulk, but "clean" food doesn't have that many cals it seems so i have to eat triple amounts sometimes.
I'm broke right now, or i would buy supplements to compensate...
I'm 6'0 180 right now, but carry the most weight in my mid section. In other words I am skinny cept for the brown fat in the lower stomach and sides.
I also have scoliosis (sp) of the spine (my spine is a bit crooked) and my back sways inward making it look like my stomach sticks out farther than it should if I don't concentrate on standing up straight all the time.
I'm sure the responses to this will be eat more and lift and it will all "even out", but I just want to make sure i'm getting the cals to actually grow. And 2500 isn't going to do jack for me...I would think minimum should be 3k


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Transcriptional programs activated by exposure of human prostate cancer cells to androgen
1 Department of Urology, Room S 287, Stanford University School of Medicine, Stanford, CA 94305, USA
2 Department of Biochemistry and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
3 Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
4 Department of Urology, UCLA School of Medicine, Los Angeles, CA 90095, USA
5 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
6 Department of Statistics, Stanford University School of Medicine, Stanford, CA 94305, USA
7 SUGEN, Inc., South San Francisco, CA 94080, USA
Genome Biology 2002, 3:research0032-research0032.12 doi:10.1186/gb-2002-3-7-research0032Published: 14 June 2002
Androgens are required for both normal prostate development and prostate carcinogenesis. We used DNA microarrays, representing approximately 18,000 genes, to examine the temporal program of gene expression following treatment of the human prostate cancer cell line LNCaP with a synthetic androgen.
We observed statistically significant changes in levels of transcripts of more than 500 genes. Many of these genes were previously reported androgen targets, but most were not previously known to be regulated by androgens. The androgen-induced expression programs in three additional androgen-responsive human prostate cancer cell lines, and in four androgen-independent subclones derived from LNCaP, shared many features with those observed in LNCaP, but some differences were observed. A remarkable fraction of the genes induced by androgen appeared to be related to production of seminal fluid and these genes included many with roles in protein folding, trafficking, and secretion.
Prostate cancer cell lines retain features of androgen responsiveness that reflect normal prostatic physiology. These results provide a broad view of the effect of androgen signaling on the transcriptional program in these cancer cells, and a foundation for further studies of androgen action.


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Debut author McQuiston delights with a unique take on The Hangover that is destined to have readers laughing out loud, cheering on the confused lovers and enjoying every moment of this love and laughter-filled treat. McQuiston creates a plot that captivates.
Widow Georgette Thorold has a dislike of marriage, so when she wakes up next to a handsome Scotsman she doesn't remember, with a wedding ring on her finger, she hits him over the head with a chamber pot and bolts. James McKenzie is determined to make his own way in the world. But one night might destroy his chances at redeeming his reputation. He does recall trying to protect a very drunk young woman from the randy men in town, but he can't quite wrap his mind around his sudden marriage. While Georgette is reunited with her scheming cousin and James searches for her, each begins remembering snippets of the night they shared. When they finally meet, Georgette wants an annulment and James believes she's a con artist. Have they made the biggest mistake of their lives, or stumbled into the best thing they have ever done? (AVON, Mar., 380 pp. $7.99)


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Basal Joint Reconstruction Treatment & Surgery
Basal joint reconstruction surgery is a procedure for people with advanced "wear and tear" arthritis in the basal joint of their thumb that has not improved with nonsurgical approaches. In these more severe cases, surgery is the most successful treatment. Also known as arthroplasty, reconstruction surgery on the basal joint relieves pain and restores functionality to the thumb. The basal joint is the joint that allows you to move your thumb into the palm of your hand, a motion called opposition. Repetitive motions can weaken the basal joint, wear down the articular cartilage surrounding the joint and make it more susceptible to degenerative arthritis.
In a healthy thumb, cartilage forms a slick and spongy protective covering for the ends of the bones and allows them to glide smoothly on each other at the joint. When the cartilage is damaged, the raw bone starts to rub against each other and arthritis sets in. Basal joint arthritis symptoms , such as debilitating hand pain, swelling, decreased strength and hindered range of motion, can make even the simplest daily activities difficult to do. Most arthritic conditions unfortunately tend to be progressive.
During basal joint reconstruction surgery, your orthopaedic hand surgeon removes the degenerated trapezium bone or a portion of the trapezium bone, one of the bones that form the thumb's basal joint, also known as the CMC joint, or carpometacarpal joint. The basal joint is made up by the trapezium bone and the first metacarpal bone. This joint is located at the base of the thumb, in the palm where the thumb meets the wrist There are several acceptable variations of the surgery used to treat basal joint arthritis. In the most commonly done operation, the surgeon replaces the trapezium with a piece of tendon that fills the space left by removing the trapezium, and that serves as a cushion for the first metacarpal bone. The surgeon also uses more of the tendon to secure the first metacarpal in place.. A very common procedure with long-lasting results, basal joint surgery removes the arthritis and is very effective in eliminating the pain.
After basal joint reconstruction surgery, your thumb and hand are placed in a splint to provide support, to control postop pain, and to promote healing. Rehabilitation consists of hand exercises and physical therapy or occupational therapy to help you strengthen your thumb and regain motion and coordination. Recovery takes an average of three to six months. After the reconstruction patients are able to do many of the activities that they were unable to do because of the arthritis.
The multidisciplinary team of orthopaedic experts at North Shore-LIJ Orthopaedic Institute's Hand and Wrist Services in New York treat basal joint arthritis as well as a broad range of conditions affecting the hand and wrist areas.
Rehabilitation Services
The Rehabilitation Network of the North Shore-LIJ Health System is dedicated to providing you and your family with result-oriented, comprehensive rehabilitation services. Our goal is to help you and your loved ones find relief from pain and get moving again after an accident, illness, injury or surgery. We're your partner in a safe, healthy, more rapid recovery.
Why Customers Choose North Shore-LIJ Orthopaedic Institute


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It's great to be a Bama Fan!
It's great to be a Bama Fan!
we didn't play our best and they did, but if the refs make the right call on the helmet hit to aj, we win. that's the truth
Assuming that we were all surprised by the reliance on the pass, I would imagine that A&M was probably caught off guard as well. It then begs the question, why were we unable to consistently complete a pass when we needed it?
AJ's injury.It then begs the question, why were we unable to consistently complete a pass when we needed it?
"I don't know what class is but I can tell when one has it, you can tell from a mile away"
Coach Bryant
Rasuputin's response to my question "What benefit do tablets provide students?"
(In an old southern trailer park redneck beer in hand marlboro light in other and camoflauge cutoff shorts man's voice) If a tablet was good enough for Moses and the 10 Commandments then by god they are good enough for my children in school today!!!!!!!
In fact the Nebaska games against UT & UF in the 90's are a prime example. UF and UT knew they were going to run and they couldn't stop it. The same with UF vs LSU this year.
The only time teams rely on the "unexpected" is when the offense wouldn't be succesful any other way. That wasn't the case in either the LSU or the TAMU game.
Last edited by JeffAtlanta; November 11th, 2012 at 01:51 PM.
We just were not prepared for Johnny Football and made to many mistakes early in the first half. Props to JM for his pefromance.
"If the public are bound to yield obedience to laws to which they cannot give their approbation, they are slaves to those who make such laws and enforce them." - As Candidus in the Boston Gazette, January 20, 1772


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Price: $18.00 direct from the winery
What They Said:
Per the winery "The youngest of our Old Vine Zins from vines 50 to 60 years old, this wine distinguishes itself with aromas of blackberry, cherry and nutmeg. With fruit forward flavors that pair nicely with creamy cheese pastas."
What I Think:
Talk about starting behind the 8 ball. We opened this one the same night we opened the Ridge. In hindsight it would have been more intelligent to base line that wine (and later this one too) against a more moderately priced Zinfandel, say the old faithful Cline from TJ's. That being said this was a very good wine, it certainly came into its own towards the end of the bottle. It was very full bodied with deep, dark fruit and well integrated tannins. The structure was round and polished in the mouth. Had I been more intelligent I would have saved myself a glass or more to taste sans the Ridge. Don't have many specifics for you but this was a very good, not spectacular or remarkable in comparison. In the interest of full disclosure I am a member of the Wine Club at Sausal . They are known for their old vine Zinfandels and find me as a fan due to their reasonable pricing. This is the second to last tier on their later. The make a low cost, Cellar Cats ($12), followed by this one before the Family Reserve ($24) and the Ancient Vines ($30). I have enjoyed all of this and it is a great place to taste if you find yourself in Sonoma. On an interesting side note, I wasn't aware that this wine was available retail until I randomly saw it on the shelf at the Bell Market near my house on the 24th Street. I would prefer not to rate this based on the lack of attention I paid to it, forced to I say, Wow! Why did I open it again! Disappointed in myself there.
Rating: Wow!


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FootprintWire 04.04.13
Today's green news: New York Whole Foods to grow rooftop produce
BASF launches sustainable construction "ideas exchange" website, here.
Local opposition to solar farm in the Cotswolds, in The Telegraph.
South African supplier promotes the use of thatched roofs in the Middle East, on AMEinfo.
And finally… An NYC Whole Foods store is to have a Gotham Greens farm on its roof, on Sustainable Business.
Have your say
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The latest advances in skin care promise to treat, refine and nourish the...
The latest advances in skin care promise to treat, refine and nourish the complexion. ESSENCE magazine Beauty and Cover Director Mikki Taylor shows you how to protect the skin you're in.
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text: Deming Elks Lodge: Members of the Deming Elks Lodge recently presented a check to the American Red Cross in Southwestern New Mexico. The $500 check will be used for Disaster Relief. Pictured here, from left, Ollie Cooper, Deming Elks; Renee Carkin, Red Cross Volunteer Deming; Renee Mackey, Red Cross Volunteer Deming; Fred Kent Deming Elks; Sue Cooper Deming Elks; Lori Sharp Red Cross Board Vice-Chair; and Tina Rhodes Red Cross Volunteer Deming.


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- School of Engineering
- About Us
- Academics
- Undergraduate
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- More...
SCU NSBE membership is mainly for Black students in the fields of engineering and sciences, but is also open to all Santa Clara University students, who are interested. Membership allows members to refreshments that meetings, exclusive access to both national and regional coventions not to mention companies, apparel, amongst others. For students to have access to all of SCU NSBE activities, they must pay both chapter, and national dues.
Chapter Dues:TBD
National Dues:$15 annually by registering with Santa Clara University on www.nsbe.org


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Conference battles in full force midway through Season
A cursory glance of the NHL Conferences reveals some interesting trends and sets up the 2nd half for what will be some amazing hockey. As always…it is time for the cream to rise to the top. Here are my opinions on who is rising up and who is going down.
Look at the Western Conference and you see 12 teams with realistic playoff aspirations. The battle for playoff spots and positioning will be fierce! Whoever rises to the top, has to be given extra credit for the sheer competitiveness of the Conference and it's Divisions. Additionally, due to the focus on interdivisional and interconference play, many of the remaining games will be 4 point games and the battles will be far more intense. Expect a playoff like atmosphere to most games from here on in.
Only 11 points separates 1st from 8th and San Jose, currently in the 12th spot, sit 8 pts out and have 3 or more games in hand on the teams ahead of them. Here is how the conference should shake down.
Detroit and Nashville look like locks to make the playoffs, as they each play 15 more games against teams in the bottom 5 of the division. Eight of Nashville's last 9 games come against the Blues, Blue Jackets, Blackhawks, Wild and the Ducks. Teams that will be playing more for pride, and spots on the team next year, than anything else.
Even if Nashville stumbles again, they should be able to collect enough points against weak competition to secure a playoff berth. I like their lineup and see them as being poised to take the next step. Solid, but not flashy, in every position except goaltending where Vokoun has emerged as a big time goalie. A team loaded with the zest and speed of youth. They seem to be destined for greater things, just maybe not this year.
Detroit has been consistent, if not great, all season long. They seem to be strong in just about every position and boast a lineup oozing with veteran leadership (Yzerman, Shanahan, Chelios, Lidstrom et al). The question mark seems to be whether Manny Legace can assert himself as a top flight goaltender in the playoffs.
The poor teams in the Northwest Division are going to be beating each other to a pulp for the remainder of the season. Calgary, Colorado, Edmonton, and Vancouver all seem to be teams missing a key ingredient to go far in the playoffs. The battle in this division might be so intense that two teams might be on the outside looking in with points totals in the 90's.
Calgary wants to prove 2003-04 wasn't a fluke and should stay in the playoff picture and possibly win the division. Calgary has what every other team in this division wants so badly…a star goalie with proven playoff success. They have depth and know what it takes to get there. This should give them the consistency to hold off the other teams in the division. Kiprusoff has wisely opted out of playing in the Olympics. Choosing to rest a sore hip and gear up for what is hoped to be a long playoff campaign. All this bodes well for Calgary's playoff hopes.
Edmonton is sorely in need of a goaltender who can make the key saves for them. The rest of the team seems to be playing well and they possess enough character and leadership to make a run at the playoffs. They desperately need to keep winning games, as even a short 4-5 game skid can be enough to put them behind the proverbial 8-ball. Kevin Lowe might have picked up a couple of extra d-men to facilitate a trade for a quality goaltender. Rumours continue to swirl around the goaltending situation and this needs to be resolved soon or they could find themselves on the outside looking in come late April.
Vancouver has finally found a 2nd line that can score on a regular basis. Now they need the top line of Bertuzzi, Naslund and Morrison to get hot heading into the late part of the season. If this occurs, the Canucks will make the playoffs. If it doesn't, they will probably still be there. Is it just me or does Mark Crawford sound like a man who is losing his team? I am not sold on him as a coach as I think players tire of his message and this might already be the case with his current squad. Still, the team is firmly entrenched in the playoff picture. They have decent depth and a mobile defensive rotation. Their GAA is high and goaltending is, of course, the main weakness on an above average NHL team. Can Alex Auld handle the load? He seems to be answering that question with a capable, but not spectacular: "yes".
Colorado is still in the mix and boast the 2nd best record vs their division. They play a lot of tough games down the road and might struggle if Aebischer starts playing like…well, David Aebischer again. I don't think team management is sold on him as their go-to-guy and wouldn't be surprised if they dealt for a goalie. Pierre Lacroix is always working the phones seeing what is being shopped around. I still think they lack 3rd and 4th line depth. The injury to Konowalchuk deepened this problem. Not a lock to make the playoffs but I think they will have to fight every step of the way to get there. Lastly, will the real Joe Sakic please stand up?
I have trouble picturing Dallas missing the playoffs this year. They have an awesome netminder in Turco who also doubles as a 3rd defenseman. They have veteran leadership and Modano seems to have put his troubles with the taxman behind him and is focusing on hockey. This team could go deep in the playoffs if they get hot at the right time.
Something about the LA sun, must make players more prone to injury, as LA has been bit by the injury bug. Once Demitra gets hurt he seems to stay that way. A solid, well coached squad that tries hard almost every night. Young goaltending has proven to be okay for the regular season. Will it be enough come playoff time? Have hit a lull in play lately, and this might be the sign of a team about to falter. San Jose and others are coming at them. So they can't afford to lay off the pedal for a second. I can see LA missing the playoffs. They will be knocking heads with 3-4 teams for the final spot.
Forgive me Duck fan. But, I have a feeling Scott Niedermayer will opt to have surgery if your team so much as stumbles in the next few weeks, and this will impact the team hugely. I have also heard J.S. Giguere being mentioned in the papers as being on the trading block. I see Goaltending woes, rookie coaching and lack of consistent offense will keep them from continuing to challenge for a playoff spot.
Phoenix is just there. Gretzky has been a better coach than many envisioned, but, this team still needs key pieces in order to be successful. I would be shocked if they battled through a mucky lower division to make the playoffs. Cujo might be heading to greener pastures and Gretzky doesn't seem to be done tinkering, so you never know what might transpire.
San Jose is coming! They are making a run for one of the final playoff spots. They will need to continue their improved recent play. What is deceiving is the games in hand that San Jose is sitting on. If those games turn into wins, by seasons end, they can definitely be in the playoffs. Inspired by the Thornton trade, both Joe and the team have really changed gears and are playing serious hockey. I see them doing just that and joining the top 8 in the conference at either LA, Edmonton, or Colorado's expense.
I can't discount the Wild as Lemaire seems to get the most out of that mediocre looking lineup. I just can't see them in the playoffs, and predict they slide a little further down the totem pole as the season progresses.
All the rest in the division are pretenders. Fodder for the rest of the league with, maybe, a late spoiler role to play.
This should all add up for some amazing matchups and key games late in the season. It will be a battle to remember and 3 or 4 teams will miss the playoffs with records well over .500 . Edmonton missed in 03-04 with 89 points. This year might take even more points, as the playing field has been levelled drastically since then.
What are your thoughts?