A 25-week placebo-controlled study of eptastigmine in patients with Alzheimer disease

Studies of Pneumocystis carinii have been limited by our inability to propagate it in continuous culture. In this context, studies of P. carinii antigens have provided significant insight into the biology of this organism. The mannose-rich surface major surface glycoprotein of P. carinii termed glycoprotein A (gpA) is the best studied of these P. carinii antigens. Significant genetic and immunologic diversity exists between the gpA molecules expressed by P. carinii derived from different mammalian sources. The molecular and biochemical nature of gpA and other P. carinii antigens including p55 are reviewed. In addition, available information concerning the role of P. carinii gpA and other antigens in host-organism interactions are also discussed.     

Attenuation of neomycin ototoxicity by iron chelation

Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential (CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.     

Morphological and molecular characterization of Giardia isolated from the straw-necked ibis (Threskiornis spinicollis) in Western Australia

Following the first report of avian Giardia infection in Australia, isolates of the parasite recovered from naturally infected straw-necked ibis (Theskiornis spinicollis) were characterized using median body morphology, scanning electron microscopy, multilocus enzyme electrophoresis, random amplified polymorphic DNA (RAPD), and small subunit ribosomal RNA (SSU-rRNA) analyses. Results were compared with Giardia from other birds and mammals, and the extent of genetic diversity between a range of ibis isolates collected in Western Australia was determined. The ibis isolates of Giardia were genetically relatively homogeneous, which is in contrast to the extensive genetic heterogeneity often displayed by mammalian Giardia isolates. Morphologically, Giardia from ibis were similar to Giardia ardeae although they differed genetically and by the fact that the ibis isolates could not be established in in vitro culture. Sequence data of the DNA coding for the SSU-rRNA found a 96% homology between the ibis isolates from Western Australia and G. ardeae, suggesting that they represent distinct strains of the same species. In contrast, the ibis isolates were genetically and morphologically very different than Giardia duodenalis and Giardia muris from mammals.     

An eukaryotic RuvB-like protein (RUVBL1) essential for growth

A human protein (RUVBL1), consisting of 456 amino acids (50 kDa) and highly homologous to RuvB, was identified by using the 14-kDa subunit of replication protein A (hsRPA3) as bait in a yeast two-hybrid system. RuvB is a bacterial protein involved in genetic recombination that bears structural similarity to subunits of the RF-C clamp loader family of proteins. Fluorescence in situ hybridization analysis demonstrated that the RUVBL1 gene is located at 3q21, a region with frequent rearrangements in different types of leukemia and solid tumors. RUVBL1 co-immunoprecipitated with at least three other unidentified cellular proteins and was detected in the RNA polymerase II holoenzyme complex purified over multiple chromatographic steps. In addition, two yeast homologs, scRUVBL1 and scRUVBL2 with 70 and 42% identity to RUVBL1, respectively, were revealed by screening the complete Saccharomyces cerevisiae genome sequence. Yeast with a null mutation in scRUVBL1 was nonviable. Thus RUVBL1 is an eukaryotic member of the RuvB/clamp loader family of structurally related proteins from bacteria and eukaryotes that is essential for viability of yeast.     

Separate jasmonate-dependent and salicylate-dependent defense-response pathways in Arabidopsis are essential for resistance to distinct microbial pathogens

The endogenous plant hormones salicylic acid (SA) and jasmonic acid (JA), whose levels increase on pathogen infection, activate separate sets of genes encoding antimicrobial proteins in Arabidopsis thaliana. The pathogen-inducible genes PR-1, PR-2, and PR-5 require SA signaling for activation, whereas the plant defensin gene PDF1.2, along with a PR-3 and PR-4 gene, are induced by pathogens via an SA-independent and JA-dependent pathway. An Arabidopsis mutant, coi1, that is affected in the JA-response pathway shows enhanced susceptibility to infection by the fungal pathogens Alternaria brassicicola and Botrytis cinerea but not to Peronospora parasitica, and vice versa for two Arabidopsis genotypes (npr1 and NahG) with a defect in their SA response. Resistance to P. parasitica was boosted by external application of the SA-mimicking compound 2, 6-dichloroisonicotinic acid [Delaney, T., et al. (1994) Science 266, 1247-1250] but not by methyl jasmonate (MeJA), whereas treatment with MeJA but not 2,6-dichloroisonicotinic acid elevated resistance to Alternaria brassicicola. The protective effect of MeJA against A. brassicicola was the result of an endogenous defense response activated in planta and not a direct effect of MeJA on the pathogen, as no protection to A. brassicicola was observed in the coi1 mutant treated with MeJA. These data point to the existence of at least two separate hormone-dependent defense pathways in Arabidopsis that contribute to resistance against distinct microbial pathogens.     

Recurrent unexplained syncope: the role of head-upright tilt table testing

Recurrent episodes of sudden unexplained syncope are a common complaint of patients referred to health care professionals for evaluation. Traditional evaluations are both time consuming and expensive and leave many patients without a diagnosis. Although vasovagally mediated episodes of hypotension and bradycardia have been thought to be a common cause of unexplained syncope, this was traditionally a diagnosis of exclusion. Head-upright tilt table testing has recently emerged as a valuable method for confirming the diagnosis of vasovagal syncope and has allowed a better understanding of this phenomena. This article reviews the pathophysiology of vasovagal syncope, the use of head-upright tilt table testing in its diagnosis, and potential therapies used to prevent recurrences.