Blastocystis hominis: pathogenic potential in human patients and in gnotobiotes.
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Despite years of intensive work, the biochemical defect responsible for the pathogenesis of inherited muscular dystrophy has not been identified either in humans or animal models. This review examines evidence in support of the hypothesis that free radicals may be responsible for muscle degeneration in this disorder. A variety of cellular abnormalities noted in dystrophic muscles can be accounted for by free radical mediated damage. In addition, chemical by-products associated with free radical damage are found in dystrophic muscle tissue from humans and animals with this disease. Various enzymatic antioxidant systems can be enhanced as a normal cellular response to oxidative stress, and such changes are seen both in dystrophic muscle cells and certain other tissues of dystrophic animals. An increased level of free radical damage would follow from either: enhanced production of free radical species, or a deficient component of the cellular antioxidant system, such as vitamin E. The free radical hypothesis of muscular dystrophy can account for data supporting several alternative theories of the pathogenesis of this disease, as well as other observations which have not previously been explained.
The various microbial species present in different areas of the oral cavity are described. A few streptococcal species, whose only known habitat is the mouth, have been associated with subacute bacterial endocarditis, and it would therefore seem that the oral cavity can serve as a reservoir for at least one type of focal infection. However, the role of oral bacteria in other types of focal infection is obscure.
Pathogens were recovered from the contents of 41 out of 50 feeding bottles and from 32 teats in a survey in Zaria, Nigeria. 39 bottle contents and 30 teats yielded enteric pathogens. Traditional weaning gruels were more contaminated than were commercial feeds. Koko bottles yielded more pathogens than Akamu bottles. Enteropathogenic Escherichia coli was the most common pathogen recovered, seen more in bottle contents than teats. Bottle hygiene was poor and cleaning methods and feeding practices were not satisfactory. Lack of facilities in the home prevented better hygiene. Prolonged pre-cooking preparation, storage of gruels in bulk for the whole day in thermos flasks or enamel bowls, and inadequate hygiene in the preparation of commercial feeds resulted in the large recovery of pathogens. Alternate feeding methods were suggested and the need for the practice of good hygiene by all who are involved in the preparation of infant feeds was emphasized.
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Thymomas associate strongly with myasthenia gravis (MG). We now show that cultured thymoma epithelial cells can present synthetic acetylcholine receptor (AChR) peptides to HLA-sharing responder T cell lines/clones nearly as efficiently as blood mononuclear cells. Responses depended strictly on the specific antigen added. Processing of longer recombinant AChR polypeptides was clearly less efficient than by blood mononuclear cells, and was selectively abolished by preculture with chloroquine. The T cell responses depended on the presence of LFA-3 on the thymoma cells. This study demonstrates that thymoma epithelial cells have the capacity to stimulate T cells and perhaps, therefore, to autosensitize against AChR in vivo.
Different oral vaccines intended to control fox rabies were administered to 271 wild rodents. Vaccines were administered orally or by the mucosal route to four different European species belonging to the genera Apodemus, Arvicola, Clethrionomys and Microtus. These rodents are likely to consume baits and to have contact with the vaccine. Two genetically engineered vaccines were tested: SAG1 (an avirulent mutant of the rabies virus) and V-RG (vaccinia recombinant virus expressing the rabies glycoprotein gene). Both were found to be completely innocuous when administered orally or by the mucosal route. The residual pathogenicity of conventional modified live vaccines derived from the SAD strain was confirmed.
Microtubular and actin cytoskeletons were investigated in the lipophilic yeast Malassezia pachydermatis by fluorescence and electron microscopy. To detect microtubules by indirect immunofluorescence using monoclonal anti-tubulin antibody, a prolonged incubation with lysing enzymes was necessary due to its very thick cell wall. Cytoplasmic microtubules were detected in interphase and a spindle with astral microtubules was seen in M-phase. The disintegration of cytoplasmic microtubules and migration of the nucleus to the bud before mitosis were characteristic features of the basidiomycetous yeast Malassezia pachydermatis. The visualisation of F-actin structures (patches, cables and cytokinetic rings) by fluorescence microscopy using both monoclonal anti-actin antibody and rhodamine-phalloidin failed, but actin was detected by electron microscopy with immunogold labelling. Clusters of gold particles indicating actin structures were detected at the plasma membrane of cells with unique cortical ultrastructural features characteristic of the genus Malassezia. A possible association of these with the actin cytoskeleton is suggested.
A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. The disadvantage of the compounds is in their low solubility in water. The antimycobacterial activity of N-benzylsalicylamides correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on the partition coefficients and electronic indexes.
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Thermophilic amoeboflagellates in the genus Naegleria include both virulent and benign species. One of the less studied species, N. italica, has not been detected in the environment since the first reports from Italy in the 1980s; its virulence is known only from infection of laboratory mice. Two recent strains from recreational water in Western Australia (AWQC NG960, NG961) were tentatively identified as N. italica from the characteristic mobilities of seven isozymes. Sequences of the 5.8S rRNA gene and its flanking ITS aligned with a 380+bp length of the published sequence for N. italica with 98% identity. Differences from the type strain were confined to ITS2. Shorter alignments (<320 bp) were observed with other Naegleria species, corresponding to conserved regions of the 5.8S gene and ITS. Unlike the European type strain of N. italica, the Australian isolates failed to infect laboratory mice intranasally, confirming that infectivity of this species is variable and often lower than in N. fowleri.
The amoeboflagellate genus Naegleria includes a few species that are virulent in experimental animals. One of these species, Naegleria italica, has been isolated from the environment only in Italy and Australia. I report here the isolation of a strain of N. italica from a water sample collected in Peru. This broadens the occurrence of this species to encompass three different continents. This new N. italica isolate from Peru has the same ITS1, 5.8S rDNA and ITS2 sequence as that of the type strain from Italy and the isolate from Australia. From the same water body in Peru a Naegleria strain was isolated that differs from N. italica by only one additional base pair in the ITS2 sequence. The maximum growth temperature tolerated by this particular isolate is 40 degrees C, which is different from that of N. italica, which is 42 degrees C.
We surveyed live-poultry markets in Korea in 2003 and isolated 9 H9N2, 6 H3N2, and 1 H6N1 influenza viruses. Antigenic and phylogenetic analyses showed that all 9 H9N2 isolates were of A/Chicken/Korea/25232-96006/96-like lineage (which caused disease in chickens in Korea in 1996) but were different from H9N2 viruses of southeastern China. They had at least 4 genotypes and replicated in chickens but not in mice. The H3N2 and H6N1 viruses were new to Korea and were probably reassortants of avian influenza viruses from southeastern China and recent Korean H9N2 viruses. All 8 segments of the H3N2 viruses formed a single phylogenetic cluster with 99.1 to 100% homology. The H3N2 viruses replicated in chickens and mice without preadaptation, but the H6N1 virus did not. Our results show an increasingly diverse pool of avian influenza viruses in Korea that are potential pandemic influenza agents.
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The ATP-binding cassette transporter A1 (ABCA1) modulates the transbilayer distribution of phosphatidylserine at the outer leaflet of the plasma membrane. This external exposure of phosphatidylserine is a hallmark of microparticle production and is impaired in ABCA1(-/-) mice. In this study, we report about the complete resistance to cerebral malaria of these mice. On analysis of histological and systemic parameters we evidenced an impairment of cellular responses to Plasmodium berghei ANKA infection in ABCA1(-/-) mice, as shown by lower plasma tumor necrosis factor levels, a weaker up-regulation of endothelial adhesion molecules in brain microvessels, a reduced leukocyte sequestration, as well as an ablated platelet accumulation. Besides, the number and the procoagulant activity of microparticles were dramatically reduced in the plasma of ABCA1(-/-) compared to ABCA1(+/+) mice. Moreover, microparticles derived from Plasmodium berghei ANKA-infected ABCA1(+/+) mice induced a significant increase of tumor necrosis factor release by noninfected macrophages. In ABCA1(-/-) mice platelet and macrophage responses to vesiculation agonists were ablated and reduced, respectively. Altogether, by pointing out the ABCA1 transporter as a major element controlling cerebral malaria susceptibility, these data provide a novel insight into its pathophysiological mechanisms and are consistent with a pathogenic role of microparticles in this neurological syndrome.
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