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D Sibley

Publications and source records attributed to D Sibley.

12 recordsLinked to original sources
PubMed2001

High-resolution typing of Toxoplasma gondii using microsatellite loci.

High-resolution typing of Toxoplasma gondii is essential to understand the effect of genetic differences among strains on the variation in disease manifestation and transmission patterns. Current typing methods discern 3 lineages with minimal within-lineage variation. Described here are 6 new variable loci. These loci, including a minisatellite and 5 microsatellites, were more polymorphic than allozymes, restriction fragment length polymorphisms, and sequence variation in introns. Most importantly, these loci revealed, for the first time, substantial within-lineage variation that was over 6-fold higher than that detected by other markers. Genotyping at these loci facilitates classification of isolates beyond the lineage level.

Animals↗
PubMed2000

Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid cells from the gut-associated lymphoid tissues and altered resistance to oral infections with Salmonella typhimurium.

Studies were done to test whether ethanol (ETOH) consumption alters resistance to mucosal and systemic infections by Salmonella typhimurium. S. typhimurium-immune and -nonimmune mice were fed 1 of 3 diets (an ETOH-containing liquid diet, an isocaloric liquid diet equal in volume to that of the ETOH-treated group, or laboratory chow) in a pair-feeding design and were infected orally or intravenously with S. typhimurium. The number of bacteria in spleen and liver and the effect of ETOH feeding and infection on the number of lymphoid cells in the gut-associated lymphoid tissues (GALT) were determined. ETOH feeding resulted in profound loss of GALT lymphoid cells and an increased number of Salmonella organisms in the intestines, liver, and spleen of infected nonimmune, but not of immune, mice. These data show that ETOH consumption in this model impairs host defense mechanisms that control mucosal infections and inhibits the mechanisms that control levels of bacteria in the central organs.

Alcohol Drinking↗
PubMed1999

Molecular parasitology goes cellular.

Application of molecular genetics is an increasingly feasible undertaking in parasitology; however, an understanding of the phenotypes of various mutants generated by this approach will ultimately rely on cellular approaches to resolve the function of various proteins. In addition to the advances in understanding the biology of parasitism, such studies probably will uncover fundamental aspects of how eukaryotic cells communicate and regulate their responses to the environment. Thus, parasites may one day provide useful biological tools, just as viruses and bacterial toxins have done in the past, towards probing the biology of mammalian cells.

Animals↗
PubMed1999

Replication of Toxoplasma gondii, but not Trypanosoma cruzi, is regulated in human fibroblasts activated with gamma interferon: requirement of a functional JAK/STAT pathway.

To study the role of tryptophan degradation by indoleamine 2, 3-dioxygenase (INDO) in the control of Trypanosoma cruzi or Toxoplasma gondii replication, we used human fibroblasts and a fibrosarcoma cell line (2C4). The cells were cultured in the presence or absence of recombinant gamma interferon (rIFN-gamma) and/or recombinant tumor necrosis factor alpha (rTNF-alpha) for 24 h and were then infected with either T. cruzi or T. gondii. Intracellular parasite replication was evaluated 24 or 48 h after infection. Treatment with rIFN-gamma and/or rTNF-alpha had no inhibitory effect on T. cruzi replication. In contrast, 54, 73, or 30% inhibition of T. gondii replication was observed in the cells treated with rIFN-gamma alone, rIFN-gamma plus rTNF-alpha, or TNF-alpha alone, respectively. The replication of T. gondii tachyzoites in cytokine-activated cells was restored by the addition of extra tryptophan to the culture medium. Similarly, T. gondii tachyzoites transfected with bacterial tryptophan synthase were not sensitive to the microbiostatic effect of rIFN-gamma. We also investigated the basis of the cytokine effect on parasite replication by using the three mutant cell lines B3, B9, and B10 derived from 2C4 and expressing defective STAT1alpha (signal transducer and activator of transcription), JAK2 (Janus family of cytoplasmic tyrosine kinases), or JAK1, respectively, three important elements of a signaling pathway triggered by rIFN-gamma. We found that rTNF-alpha was able to induce low levels expression of INDO mRNA in the parental cell line, as well as the cell line lacking functional JAK2. In contrast to the parental cell line (2C4), rIFN-gamma was not able to induce the expression of INDO mRNA or microbiostatic activity in any of the mutant cell lines. These findings indicate the essential requirement of the JAK/STAT pathway for the induction of high levels of INDO mRNA, tryptophan degradation, and the anti-Toxoplasma activity inside human nonprofessional phagocytic cells.

Animals↗
PubMed1995

Effects of ethanol on cellular immunity to facultative intracellular bacteria.

Alcohol abuse has been associated with an increase in infectious diseases caused by pathogenic and opportunistic microorganisms. Study results obtained from this laboratory and other laboratories have shown that consumption of large amounts of ethanol is associated with numerous changes in the immune system. The purpose of this article is to report findings obtained from this laboratory, as well as review those obtained from other laboratories, from experiments designed to evaluate the effects of ethanol on various components of antimicrobial host-defense mechanisms. The effects of ethanol on various aspects of immunity obtained with the use of in vivo and in vitro model systems are reviewed as they pertain to antimicrobial defenses. All current data would support the suggestion that ethanol affects both the development of an antigen-specific immune response and the effector mechanisms of the cellular immune response. Findings obtained from animal models show that ethanol prevents the formation of granulomas in infected tissues, perhaps by inhibiting the response of macrophages to T-cell cytokines. Data obtained from this laboratory also support the suggestion that the inability of the immune system to control the intracellular growth of microorganisms results in an exaggerated inflammatory response that is responsible for at least a part of the tissue damage.

Alcoholism↗
PubMed1994

Increased susceptibility of experimental animals to infectious organisms as a consequence of ethanol consumption.

It has been shown by a number of studies that chronic alcohol abuse is associated with an increased incidence of infections. The mechanism of this increased susceptibility to infectious agents is multifactorial and certainly includes abuse of other drugs, smoking, malnutrition and other factors. Recently, it has become apparent that consumption of alcohol by human beings and experimental animals is associated with changes in the immune system. The increased incidence of tuberculosis and opportunistic bacterial and fungal infections described in alcoholics has led to the suggestion that alcohol affects the cell-mediated arm of the immune response. The present report will review the data that shows the effects of alcohol on the immune system. We will also review the data from our laboratory and other laboratories that show the effects of alcohol on host defense mechanisms to infectious agents. Where possible, mechanisms of increased susceptibility will be discussed or postulated.

Alcohol Drinking↗