Search

The morphology and genetic characterization of a new species of trypanosome infecting koalas (Phascolarctos cinereus) are described. Morphological analysis of bloodstream forms and phylogenetic analysis at the 18S rDNA and gGAPDH loci demonstrated this trypanosome species to be genetically distinct and most similar to Trypanosoma bennetti, an avian trypanosome with a genetic distance of 0.9% at the 18S rDNA and 10.7% at the gGAPDH locus. The trypanosome was detected by 18S rDNA PCR in the blood samples of 26 out of 68 (38.2%) koalas studied. The aetiological role of trypanosomes in koala disease is currently poorly defined, although infection with these parasites has been associated with severe clinical signs in a number of koalas. Based on biological and genetic characterization data, this trypanosome species infecting koalas is proposed to be a new species Trypanosome irwini n. sp.

Little is known of the prevalence and life-cycle of trypanosomes in mammals native to Australia. Native Australian trypanosomes have previously been identified in marsupials in the eastern states of Australia, with one recent report in brush-tailed bettongs (Bettongia penicillata), or woylie in Western Australia in 2008. This study reports a novel Trypanosoma sp. identified in blood smears, from 7 critically endangered Gilbert's potoroos (Potorous gilbertii) and 3 quokkas (Setonix brachyurus) in Western Australia. Trypanosomes were successfully cultured in vitro and showed morphological characteristics similar to members of the subgenus Herpetosoma. Phylogenetic analysis of 18S rRNA gene sequences identified 2 different novel genotypes A and B that are closely related to trypanosomes previously isolated from a common wombat (Vombatus ursinus) in Victoria, Australia. The new species is proposed to be named Trypanosoma copemani n. sp.

Predictive genetic testing for Huntington's disease (HD) has revealed early cognitive deficits in asymptomatic gene carriers, such as altered working memory, executive function and impaired recognition memory. The perirhinal cortex processes aspects of recognition memory and the underlying mechanism is believed to be long-term depression (LTD) of excitatory neurotransmission, the converse of long-term potentiation (LTP). We have used the R6/1 mouse model of HD to assess synaptic plasticity in the perirhinal cortex. We report here a progressive derailment of both LTD and short-term plasticity at perirhinal synapses. Layer II/III neurones gradually lose their ability to support LTD, show early nuclear localization of mutant huntingtin and display a progressive loss of membrane integrity (depolarization and loss of cell capacitance) accompanied by a reduction in the expression of D1 and D2 dopamine receptors visualized in layer I of the perirhinal cortex. Importantly, abnormalities in both short-term and long-term plasticity can be reversed by the introduction of a D2 dopamine receptor agonist (Quinpirole), suggesting that alterations in dopaminergic signalling may underlie early cognitive dysfunction in HD.

We have evaluated the performance of a novel line-blot immunoassay (LIA; Mikrogen) and compared results with those obtained by CIE (in-house), ELISA (Pharmacia Diagnostics), and FEIA (Pharmacia Diagnostics). Sera from systemic lupus erythematosus (SLE) patients (n = 123), systemic sclerosis patients (n = 25), and healthy controls (n = 40) were analyzed for the presence of antibodies to RNP, Sm, SSA, SSB, CENP-B, Scl-70, and Jo-1. Reading of LIA results, as compared with a cutoff control, was performed by automatic analysis of the test strips. Because LIA enables recognition of separate subunits of RNP (68, A, and C), Sm (B and D), and SSA (52 and 60), at least two of the RNP antigens and either one of the Sm or SSA antigens should be detected for considering the test RNP, Sm, or SSA-positive, respectively. LIA had the highest sensitivity in patients with autoimmune connective tissue diseases: 131 specificities (not PO, PCNA, or histones), as compared with ELISA (121), FEIA (119), and CIE (80). However, LIA revealed three positive reactions in healthy controls; other assays were completely negative. LIA is better than CIE, but similar to ELISA and FEIA, in terms of detecting systemic sclerosis-associated antibodies (CENP-B and Scl-70). Furthermore, LIA had the highest sensitivity (17.9%) for the SLE-specific anti-Sm antibodies, as compared with ELISA (11.4%), CIE (8.1%), and FEIA (5.7%). Finally, anti-SSA antibodies were far more prevalent by LIA in the systemic sclerosis samples because of anti-SSA52 reactivity. The clinical relevance of the latter finding remains to be determined. In conclusion, LIA is suitable for routine evaluation of autoantibodies to extractable nuclear antigens.

Both celiac disease and inflammatory bowel disease (IBD) are characterized by chronic diarrhea and the presence of distinct (auto)antibodies. In the present study we wanted to determine the prevalence of serological markers for inflammatory bowel disease, i.e., perinuclear antineutrophil cytoplasmic antibodies (pANCA) and/or anti-Saccharomyces cerevisiae antibodies (ASCA), in 37 patients with biopsy-confirmed celiac disease (Marsh IIIb/c). The majority of the patients was positive for IgA (auto)antibodies typically associated with celiac disease, i.e., antiendomysium antibodies (EMA) (86.5%), antigliadin antibodies (AGA) (73%), and antirecombinant human tissue transglutaminase antibodies (rh-tTGA) (86.5%). Four patients with selective IgA deficiency could be identified by analyzing EMA, AGA, and rh-tTGA for the IgG isotype. The prevalence of pANCA and ASCA, markers that are used for IBD, was unexpectedly high in our cohort of patients with celiac disease: 8 patients were positive for pANCA (IgG) and 16 patients were positive for ASCA (IgG and/or IgA). These results indicate that the presence of pANCA or ASCA in the serum of patients with chronic diarrhea does not exclude celiac disease. A prospective study is required to determine whether pANCA and/or ASCA identify patients at risk for developing secondary autoimmune disease.

Objective: To assess the efficacy and safety of fluvastatin in hypercholesterolemic, cyclosporine-treated, renal transplant recipients, and to determine whether concomitant steroid therapy in such patients alters the lipid-lowering effects of fluvastatin., Design: An open-label, prospective, parallel study was performed in 20 cyclosporine-treated renal transplant recipients with hypercholesterolemia defined by a low-density lipoprotein (LDL) concentration greater than 160 mg/dL or a total cholesterol/high-density lipoprotein (HDL) concentration ratio greater than 5.0. Lipid profiles were measured before and 1 month after treatment with fluvastatin 20 mg/d. Lipid profiles in a group of patients receiving concomitant therapy with prednisone (n = 12) were compared with those of patients who had not received steroids for at least 6 months (n = 8)., Setting: The Renal Transplant Clinic at University Hospitals of Cleveland., Main Outcome Measures: The main outcome measures were serum concentrations of total cholesterol, LDL, HDL, and triglycerides. Treatment failure was defined by LDL concentrations persistently above 160 mg/dL after 1 month of fluvastatin therapy. Safety was assessed clinically and by serial measurements of liver enzymes and creatine phosphokinase., Results: LDL concentrations decreased significantly in both the steroid-treated and steroid-free groups after 1 month of fluvastatin therapy. There was no significant change in HDL concentrations or serum triglycerides in either group. Treatment failure was more common in patients receiving steroids (4/12 patients) than in steroid-free patients (1/8 patients). After 1 month of therapy, LDL cholesterol was significantly lower in the steroid-free group (126 +/- 18 mg/dL) than in the steroid-treated group (147 +/- 23 mg/dL) (p < 0.05). There was no clinical or laboratory evidence of myonecrosis in either group., Conclusions: Low dosages of fluvastatin appear to be safe in cyclosporine-treated renal transplant recipients. Steroid-free patients exhibit a response to fluvastatin that is qualitatively similar to that of steroid-treated patients, consisting of a significant decrease in LDL concentrations and no change in HDL or serum triglyceride concentrations.

The mechanism of meso-tetra (p-sulfophenyl)porphine (TPPS4) localization was examined in Vero and HEp-2 cells in vitro. TPPS4 was found to be relatively nontoxic to both cell types at concentrations up to 200 microgram/ml. However, changes in cellular ultrastructure were observed by electron microscopy, consisting mainly of an increase in membrane-bound vacuoles. The nature of the new structures has not been determined. Both fluorescence microscopy and cellular fractionation indicate that TPPS4 is localized inside the cells studied. Considerable differences in the pattern of localization between the two cell types were found. The TPPS4 in the Vero cells was found to be mainly in the soluble fraction and the red fluorescence was found to be diffuse throughout the cytoplasm. The HEp-2 cells showed TPPS4 fluorescence associated with various cell organelles, predominatly the nucleolus. [14C]-TPPS4 was found in many cellular components but predominantly it was in the soluble and protein fractions. These differences may be significant in the understanding of in vivo localization of this porphyrin in neoplastic tissue.