Constitutive Model for Time-Dependent Flows of Shear-Thickening Suspensions.

We develop a tensorial constitutive model for dense, shear-thickening particle suspensions subjected to time-dependent flow. Our model combines a recently proposed evolution equation for the suspension microstructure in rate-independent materials with ideas developed previously to explain the steady flow of shear-thickening ones, whereby friction proliferates among compressive contacts at large particle stresses. We apply our model to shear reversal, and find good qualitative agreement with particle-level, discrete-element simulations whose results we also present.

Effects of tail docking and tail biting on performance and welfare of growing-finishing pigs in a confinement housing system.

A study was conducted to evaluate the effect of tail docking on the welfare and performance of victimized pigs by tail biting and tail biters. Pigs ( = 240; 25.7 ± 2.9 kg average weight), including 120 pigs that were tail docked at birth and 120 pigs that remained with intact tails, were used. Pigs were housed in 8 pens of 30 pigs in a confinement barn for 16 wk, with 4 pens each housing pigs of both sexes with docked or intact tails. Tail biters and victimized pigs with damaged tails were identified during outbreaks of tail biting. Growth performance was monitored, and skin lesions on the tail, ears, and body were assessed. Blood samples were collected from focal tail biters, victimized pigs, and nonvictimized pigs for analysis of total serum protein, IgG, and substance P concentrations. When pigs were marketed, carcass weights and the number of pigs with carcass trim loss were recorded. During the growing-finishing period, 48% of pigs with docked tails and 89% of pigs with intact tails experienced lesions on their tails, including 5% of docked pigs and 30% of intact pigs identified as victimized pigs that experienced puncture wounds with signs of infection on their tails or loss of tails ( < 0.001). Victimized pigs tended to gain less weight ( = 0.07) between 17 and 21 wk of age than other pigs when tail biting prevailed in this study. Victimized pigs were more frequently ( = 0.04) sold for less than full value and had a lower dressing percentage ( < 0.001) compared with nonvictimized pigs. For victimized pigs, total serum protein and IgG concentrations were elevated 5 d after tails were injured, suggesting that tail damage can cause inflammation, which may lead to carcass abscesses and trim loss. Compared with victimized pigs and nonvictimized pigs, tail biters had lower total serum protein ( = 0.01) and IgG ( = 0.01) concentrations, indicating that tail biters may experience poor immune functions. Results of this study demonstrated that tail docking reduced tail damage in pigs kept in a confinement system. Tail damage can cause inflammation and reduce the value of market pigs. More research is needed to test whether compromised immune functions predispose pigs to tail biting.

An investigation of side-effects and efficacy of foam-based sclerotherapy with carbon dioxide or room air in the treatment of reticular leg veins: a pilot study.

OBJECTIVES: In sclerotherapy, carbon dioxide (CO(2)) or room air can be employed by phlebologists for foam creation. We compared room air (RA) and carbon dioxide in treating reticular leg veins with foam sclerotherapy. METHODS: Twenty patients were randomly treated with RA- or CO(2)-created sodium tetradecyl sulphate (STS) foam. Concentration and volume of STS, side-effects and efficacy were determined. RESULTS: There was no difference in the efficacy, local side-effects or distant side-effects between RA and CO(2) foam in the treatment of reticular leg veins. The total volume of foam sclerosant required for treatment was greater with CO(2) compared with RA (P value = 0.01). CONCLUSION: No differences were found in efficacy or side-effects between RA- and CO(2)-foam sclerotherapy for reticular leg veins. CO(2) foam's shorter half-life was hypothesized to be responsible for larger total volumes of CO(2) foam sclerosant.

An investigation on the influence of glycerin on sclerosant foam stability.

BACKGROUND: Foam sclerotherapy is an increasingly popular modality in the treatment of varicose veins. Foam stability varies according to foam composition, volume and injection technique. MATERIALS AND METHODS: A disposable plastic connector was used to create foam from 0.50% sodium tetradecyl sulphate (STS) mixed with varying volumes of glycerin. As a measure of foam stability, the half liquid time was defined as the time required for half of the original volume of sclerosing solution to settle. Three recordings were determined for each of the three mixtures of sclerosant foam. RESULTS: The time for sclerosing solution to settle to half of its initial volume was found to be 89 seconds for 0.50% STS alone, 117.7 seconds with the addition of 0.1 mL of 72% glycerin, and 114.7 seconds with the addition of 0.2 mL of 72% glycerin. CONCLUSION: The small volumes of glycerin added to STS prolonged the half liquid time of STS foam up to 35%. As glycerin alone is unable to be foamed with the double-syringe system technique there may be a point at which further addition of glycerin has a negative effect on the half-life of foam.

Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells.

Epidermolysis bullosa acquisita is an autoimmune blistering disease characterized by circulating and skin basement membrane-bound IgG autoantibodies to type VII collagen, a major structural protein of the dermal-epidermal junction. Regulatory T cells (T(reg)) suppress self antigen-mediated autoimmune responses. To investigate the role of T(reg) in the the autoimmune response to type VII collagen in a mouse model, a monoclonal antibody against mouse CD25 was used to deplete T(reg). A recombinant mouse type VII collagen NC1 domain protein and mouse albumin were used as antigens. SKH1 mice were used as a testing host. Group 1 mice received NC1 immunization and were functionally depleted of T(reg); group 2 mice received NC1 immunization and rat isotype control; and group 3 mice received albumin immunization and were functionally depleted of T(reg). Results demonstrated that anti-NC1 IgG autoantibodies with high titres, as determined by enzyme-linked immunosorbent assay and Western blotting, developed in all mice immunized with NC1 (groups 1 and 2), but were undetected in group 3 mice. The predominant subclasses of anti-NC1 autoantibodies were IgG1, IgG2a and IgG2b; furthermore, these antibodies carried only the kappa light chain. IgG autoantibodies in the sera of NC1-immunized mice reacted with mouse skin basement membrane in vitro and deposited in skin basement membrane in vivo as detected by indirect and direct immunofluorescence microscopy, respectively. Our data suggest that the development of autoimmunity against type VII collagen in mice is independent of T(reg) function and the autoimmune response is mediated by both Th1 and Th2 cells. We speculate that the basement membrane deposition of IgG may eventually lead to blister development.

Complete genome sequence of a virulent isolate of Streptococcus pneumoniae.

The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.

The Comprehensive Microbial Resource.

One challenge presented by large-scale genome sequencing efforts is effective display of uniform information to the scientific community. The Comprehensive Microbial Resource (CMR) contains robust annotation of all complete microbial genomes and allows for a wide variety of data retrievals. The bacterial information has been placed on the Web at http://www.tigr.org/CMR for retrieval using standard web browsing technology. Retrievals can be based on protein properties such as molecular weight or hydrophobicity, GC-content, functional role assignments and taxonomy. The CMR also has special web-based tools to allow data mining using pre-run homology searches, whole genome dot-plots, batch downloading and traversal across genomes using a variety of datatypes.

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment.

Using in vivo extracellular single-cell recording and microiontophoresis, we compared the responsiveness of medial prefrontal cortex (mPFC) neurons (layers V-VI) to dopamine and glutamate in rats that had received repeated amphetamine or saline injections. Neurons from amphetamine-pretreated rats showed increased responsiveness to glutamate and decreased responsiveness to dopamine after three days of withdrawal, suggesting that the mPFC is transiently hyperexcitable during amphetamine withdrawal. Published 2000 Wiley-Liss, Inc.

Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284, 156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Analysis of leukocytes recruited to the pancreas by diabetogenic T cell clones.

To investigate host leukocytes recruited to the pancreas by diabetogenic T cells, we administered islet-specific CD4(+) T cell clones to 2-week-old nonobese diabetic (NOD) mice and examined the resulting pancreatic infiltrate by flow cytometry. Two different Vbeta4(+)CD4(+) T cell clones, BDC 2.5 and BDC 6.9, were found to recruit a heterogeneous T cell population as determined by staining with a panel of anti-TCR Vbeta monoclonal antibodies. The majority of the diabetes-initiating, Vbeta4(+) T cell clones migrated to the spleen whereas only 5-8% of the T cell population infiltrating the pancreas was Vbeta4(+). Anti-IL-2 receptor staining indicated that fewer than 10% of the total population of infiltrating lymphocytes within the pancreas were in a highly activated state. We have further found that normal splenic T cells from the NOD mouse proliferate poorly to IL-2 in vitro, yet secrete IFN-gamma in response to IL-2 stimulation. These results suggest that the recruited host T cells in our disease transfer system are not directly pathogenic but, rather, are responding to the small numbers of inflammatory T cell clones by providing cytokines that facilitate the disease process.

Inhibition of angiogenesis by interleukin 4.

Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose-response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (TH0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.

Alcohol consumption alters antigen-specific Th1 responses: mechanisms of deficit and repair.

Among the physiological effects associated with excessive alcohol consumption are alterations in immune function. Alcohol impairs T-helper 1 lymphocyte (Th1) regulated, cell-mediated immune responses. Antibody responses, regulated by T-helper 2 lymphocyte (Th2), are either unimpaired or enhanced. Antigen presenting cells are central to the development of both Th1 and Th2 regulated immune responses. We used both T-cell receptor transgenic and conventionally immunized mice to demonstrate that ethanol consumption directly affects antigen presenting cells that, in turn, determines whether Th1 or Th2 response patterns predominate. Ethanol consumption inhibits Th1-associated interleukin-12 and interferon-gamma cytokine production and delayed-type hypersensitivity. Administration of exogenous recombinant interleukin-12 both restores interferon-gamma levels and delayed-type hypersensitivity responses in ethanol-consuming mice.

Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns.

Current thinking attributes the balance between T helper 1 (Th1) and Th2 cytokine response patterns in immune responses to the nature of the antigen, the genetic composition of the host, and the cytokines involved in the early interaction between T cells and antigen-presenting cells. Here we introduce glutathione, a tripeptide that regulates intracellular redox and other aspects of cell physiology, as a key regulatory element in this process. By using three different methods to deplete glutathione from T cell receptor transgenic and conventional mice and studying in vivo and/or in vitro responses to three distinct antigens, we show that glutathione levels in antigen-presenting cells determine whether Th1 or Th2 response patterns predominate. These findings present new insights into immune response alterations in HIV and other diseases. Further, they potentially offer an explanation for the well known differences in immune responses in "Th1" and "Th2" mouse strains.

Human antibody responses to Trypanosoma cruzi 70-kD heat-shock proteins.

Heat-shock proteins of the 70-kD (hsp70) family are targets of humoral and cellular immune responses following bacterial or parasitic infections, including Chagas' disease. In the present study, we measured antibodies in human sera reactive with hsp70s from the cytoplasm (cy-hsp70), mitochondrion (mt-hsp70), and endoplasmic reticulum (grp78) of Trypanosoma cruzi. Of the three hsp70s tested, only grp78 detected T. cruzi infection in more than 90% of nontreated (NT) patients, with cy-hsp70 and mt-hsp70 detecting only 78% and 25% of NT patients, respectively. Reactivity of leishmanial sera was 77% with cy-hsp70, 13% with grp78, and 5% with mt-hsp70. Therefore, considering sensitivity and specificity, the best candidate for T. cruzi serodiagnosis is grp78. Combination of grp78 with a T. cruzi 24-kD flagellar calcium binding protein (FCaBP) increased the diagnostic sensitivity from 90% to 97% but increased leishmanial reactivity from 3% to 8%. To determine whether hsp70s are useful for discriminating between cured and noncured patients treated with trypanocidal drugs, we tested sera from treated noncured (TNC) patients and cured patients who have positive conventional serology, termed treated dissociated (TD). The cy-hsp70 and grp78 reacted with 74% and 68% of TNC patient sera, respectively, but these antigens did not discriminate TNC from TD patients (52% and 45% positive, respectively). The mt-hsp70 was detected by sera from few TNC patients (18%) and no TD patients. Although individual hsp70s were not useful for determining the effect of trypanocidal drugs on T. cruzi infection in individual patients, the majority of TNC patient sera (70-80%) reacted with two or three of the hsp70s. In contrast, no TD sera reacted with all three hsp70s, and 40% did not react with any of the hsp70s, indicating that the number of hsp70s detected decreases following successful treatment. Considered together, these results show that grp78 has potential as a diagnostic antigen and that absence of reactivity to all three hsp70s may be indicative of effective treatment.

Interleukin-12 therapy restores cell-mediated immunity in ethanol-consuming mice.

Previous studies from our laboratory show that ethanol consumption impairs antigen-specific, cell-mediated, but not, humoral immune responses of C57BL/6, BALB/c, and DO11.10 T-cell receptor transgenic mice. This ethanol-associated deficit is associated with decreased interleukin (IL)-12 and interferon-gamma (IFN-gamma) production, but not IL-2 or antigen-specific T-cell proliferation by explanted leukocytes from ethanol-consuming mice. IL-12 expression by macrophage/monocytes is viewed as a requirement for the production of IFN-gamma by Th1 lymphocytes that mediate cellular immunity. In this study, we restored antigen-specific, cell-mediated immunity, delayed hypersensitivity, to ethanol-consuming C57BL/6 or BALB/c mice with a single 100 ng of intravenous injection of recombinant IL-12 at the time of immunization. The addition of exogenous recombinant IL-12 to co-cultures of antigen-presenting cells derived from ethanol-consuming mice and purified T cells derived from ethanol-nonconsuming DO11.10 repairs the ability of Th1 cells to make IFN-gamma in response to antigen. Administration of recombinant IL-12 opens a potential for restoring cell-mediated immune function to ethanol-consuming individuals.