Metabolite movement across the schistosome surface.

Intravascular schistosome parasites are covered by an unusual double lipid bilayer. Nutrients, such as glucose and amino acids, as well as other metabolites, are known to be transported across this surface via specific transporter proteins. For instance, the glucose transporter protein SGTP4 is found in the host-interactive tegumental membranes. A second glucose transporter, SGTP1, localizes to the tegumental basal membrane (and internal tissues). Following expression in Xenopus oocytes, SGTP1 and SGTP4 both function as facilitated-diffusion sugar transporters. Suppressing the expression of SGTP1 and SGTP4 in juvenile schistosomes using RNA interference (RNAi) impairs the parasite's ability to import glucose and severely decreases worm viability. Amino acids can also be imported into schistosomes across their surface and an amino acid transporter (SPRM1lc) has been localized in the parasite surface membranes (as well as internally). In Xenopus oocytes, SPRM1lc can import the basic amino acids arginine, lysine and histidine as well as leucine, phenylalanine, methionine and glutamine. To function, this protein requires the assistance of a heavy-chain partner (SPRM1hc) which acts as a chaperone. Water is transported across the tegument of schistosomes via the aquaporin protein SmAQP. Suppressing SmAQP gene expression makes the parasites less able to osmoregulate and decreases their viability. In addition, SmAQP-suppressed adult parasites have been shown to be impaired in their ability to excrete lactate. Analysis of tegumental transporter proteins, as described in this report, is designed to generate a comprehensive understanding of the role of such proteins in promoting parasite survival by controlling the movement of metabolites into and out of the worms.

High-throughput screening in suboptimal growth conditions identifies agonists of Giardia lamblia proliferation.

Giardia lamblia is one of the most prevalent parasites of mankind and is estimated to cause over 200 million infections per year. To screen chemical libraries for compounds that perturb trophozoite proliferation we adapted a conventional culture method to 384-well plates and identified numerous inhibitors. Here we used a modified assay to screen for compounds that promote trophozoite multiplication. Trophozoite growth was reduced by dilution of the culture medium and the growth period was extended to screen 2 compound libraries comprising 1500 compounds. A total of 4 agonists of trophozoite multiplication were identified. In the presence of one of these compounds, strychnine, enhanced growth was accompanied by unusual trophozoite morphology characterized by dividing trophozoites displaying more than the 2 nuclei per cell which are normally observed. The other agonists, although belonging to 2 distinct chemical groups, are known to affect isoprenylation, indicating a link between protein or lipid isoprenylation and growth in culture. Although inhibitors of isoprenylation are known to antagonize proliferation of mammalian cells, an agonistic effect of isoprenylation modulators has to our knowledge not been described previously. These observations illustrate the power of chemical genetics for identifying pathways controlling specific traits in G. lamblia.

Seroprevalence of brucellosis and risk factors related to high risk occupational groups in Kazeroon, South of Iran.

BACKGROUND: Brucellosis is a major zoonosis worldwide. Many people for their professions are at higher risk of contracting the disease. OBJECTIVE: To determine the seroprevalence of brucellosis and its risk factors in a group of high risk professions. METHODS: In a cross-sectional study, all personnel or students of veterinary schools, slaughters and butchers working in the city were invited to participate (n = 141). A comparison group (n = 44) randomly selected from patients who were selected at random from people attended our healthcare center for reasons other than the infectious diseases. RESULTS: 4 veterinarians, 15 veterinary assistants, 42 veterinarian students, 52 butchers, 17 slaughters, 8 slaughterhouse workers and 3 chefs made the first group and 14 storekeepers, 5 students of engineering, 11 clerks, 13 freelance workers, and 1 high school student made the comparison group. While the rate of consumption of most of the studied dairy products was almost similar in both groups, comparison group patients consumed more often milk (p<0.001) and cream (p<0.001) than the high risk group. 11 (7.8%; 95% CI: 3.4%-12.2%) cases from high risk group and none of the comparison group were found seropositive for Brucella. CONCLUSION: Profession is the main factor in seropositivity. Consumption of dairy products and raw milk is not associated with a higher risk of seropositivity.

L-Arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta) in Jurkat cells.

L-Arginine is a versatile amino acid that plays a central role in the normal function of several organ systems including the immune system. Its availability is tightly controlled and varies significantly in different organs and tissues in the body. L-Arginine plays an important role in supporting T-cell proliferation. Its depletion in certain disease states results in a diminished T-cell response. The main purpose of this study was to determine the effect of the depletion of L-arginine on the expression of the T-cell receptor (TCR) proteins. When the helper T-cell line Jurkat was cultured in arginine-free medium, there was a preferential decrease in the expression of the TCR zeta chain (CD3zeta). The reduced expression of CD3zeta was observed within 24 h of culture in L-arginine-free medium and was completely reversed with the replenishment of L-arginine. Furthermore, the absence of L-arginine blocked the normal re-expression of the TCR that had been internalized after antigen stimulation. There also was a significant decrease in proliferation of Jurkat cells in the absence of L-arginine; however, L-arginine depletion did not prevent the up-regulation of the interleukin 2 receptor chains upon stimulation, nor did it significantly diminish the production of interleukin 2. The changes in the expression of CD3zeta chain were not induced by apoptosis. Thus, the availability of L-arginine in the microenvironment may play a significant role in regulating the expression of the TCR.

Antibodies to cardiolipin and beta2-glycoprotein-1 in HTLV-1-associated myelopathy/tropical spastic paraparesis.

Anticardiolipin and anti-beta2GP1 antibodies were measured in 50 patients with HTLV-1-associated Myelopathy-Tropical Spastic Paraparesis (HAM-TSP) and the results were compared with those obtained for 34 HTLV-1-positive and 35 HTLV-1-negative controls, as well as 128 SLE patients. aCL but not anti-beta2GP1 was associated with HTLV-I infection. aCL was more prevalent than anti-beta2GP1 (32% vs. 8%) and was not associated with anti-beta2GP1 in HAM-TSP. IgA was the dominant isotype of aCL and anti-beta2GP1. The data suggest that tin HAM-TSP, IgA aCL are frequent and are associated with HTLV-1 infection.

Antibodies to cardiolipin and beta2-glycoprotein-1 in HTLV-1-associated myelopathy/tropical spastic paraparesis

Anticardiolipin and anti-beta2GP1 antibodies were measured in 50 patients with HTLV-1-associated Myelopathy-Tropical Spastic Paraparesis (HAM-TSP) and the results were compared with those obtained for 34 HTLV-1-positive and 35 HTLV-1-negative controls, as well as 128 SLE patients. aCL but not anti-beta2GP1 was associated with HTLV-I infection. aCL was more prevalent than anti-beta2GP1 (32 percent vs. 8 percent) and was not associated with anti-beta2GP1 in HAM-TSP. IgA was the dominant isotype of aCL and anti-beta2GP1. The data suggest that tin HAM-TSP, IgA aCL are frequent and are associated with HTLV-1 infection.(Au)

Significance of IgA antiphospholipid antibodies.

IgA anticardiolipin (IgA aCL) and IgA anti beta2-glycoprotein-I (IgA anti beta2GP1) antibodies are common in SLE and have been associated in some studies with thromboses and thrombocytopenia. Experimental work suggests that IgA aCL are as prothrombotic as the IgG-IgM isotypes. However, in SLE there appears to be less concordance between IgA aCL and IgA anti beta2GP1 as compared with the concordance between IgG and IgM isotypes, suggesting significant differences in their origins and specificities. For example, there may be a greater mucosal contribution to production of IgA antibeta2GP1 than IgA aCL. Infections may have a greater role in the presence of IgA aCL than IgA antibeta2GP1 antibodies.

Study of the association of HLA class I antigens with kala-azar.

HLA class I antigen frequencies were studied in 52 patients with kala-azar and compared with 222 unrelated healthy controls. The relative risk (RR) and etiologic or preventive fraction (EF/PF) were determined for each character, and statistical significance was evaluated with chi 2 with Yates' correction. Results showed that the only antigen with a statistically significant difference was HLA-A26 (15.38 vs. 1.35%; p = 0.004), with RR = 13.27 and EF = 0.142. This indicates a high risk of contracting the disease for HLA-A26-positive individuals and a relatively remarkable influence of this antigen on the prevalence rate of kala-azar.