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51.
Gilaad G. Kaplan Elijah Dixon Remo Panaccione Andrew Fong Li Chen Mieczyslaw Szyszkowicz Amanda Wheeler Anthony MacLean W. Donald Buie Terry Leung Steven J. Heitman Paul J. Villeneuve 《CMAJ》2009,181(9):591-597
Background
The pathogenesis of appendicitis is unclear. We evaluated whether exposure to air pollution was associated with an increased incidence of appendicitis.Methods
We identified 5191 adults who had been admitted to hospital with appendicitis between Apr. 1, 1999, and Dec. 31, 2006. The air pollutants studied were ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and suspended particulate matter of less than 10 μ and less than 2.5 μ in diameter. We estimated the odds of appendicitis relative to short-term increases in concentrations of selected pollutants, alone and in combination, after controlling for temperature and relative humidity as well as the effects of age, sex and season.Results
An increase in the interquartile range of the 5-day average of ozone was associated with appendicitis (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.03–1.25). In summer (July–August), the effects were most pronounced for ozone (OR 1.32, 95% CI 1.10–1.57), sulfur dioxide (OR 1.30, 95% CI 1.03–1.63), nitrogen dioxide (OR 1.76, 95% CI 1.20–2.58), carbon monoxide (OR 1.35, 95% CI 1.01–1.80) and particulate matter less than 10 μ in diameter (OR 1.20, 95% CI 1.05–1.38). We observed a significant effect of the air pollutants in the summer months among men but not among women (e.g., OR for increase in the 5-day average of nitrogen dioxide 2.05, 95% CI 1.21–3.47, among men and 1.48, 95% CI 0.85–2.59, among women). The double-pollutant model of exposure to ozone and nitrogen dioxide in the summer months was associated with attenuation of the effects of ozone (OR 1.22, 95% CI 1.01–1.48) and nitrogen dioxide (OR 1.48, 95% CI 0.97–2.24).Interpretation
Our findings suggest that some cases of appendicitis may be triggered by short-term exposure to air pollution. If these findings are confirmed, measures to improve air quality may help to decrease rates of appendicitis.Appendicitis was introduced into the medical vernacular in 1886.1 Since then, the prevailing theory of its pathogenesis implicated an obstruction of the appendiceal orifice by a fecalith or lymphoid hyperplasia.2 However, this notion does not completely account for variations in incidence observed by age,3,4 sex,3,4 ethnic background,3,4 family history,5 temporal–spatial clustering6 and seasonality,3,4 nor does it completely explain the trends in incidence of appendicitis in developed and developing nations.3,7,8The incidence of appendicitis increased dramatically in industrialized nations in the 19th century and in the early part of the 20th century.1 Without explanation, it decreased in the middle and latter part of the 20th century.3 The decrease coincided with legislation to improve air quality. For example, after the United States Clean Air Act was passed in 1970,9 the incidence of appendicitis decreased by 14.6% from 1970 to 1984.3 Likewise, a 36% drop in incidence was reported in the United Kingdom between 1975 and 199410 after legislation was passed in 1956 and 1968 to improve air quality and in the 1970s to control industrial sources of air pollution. Furthermore, appendicitis is less common in developing nations; however, as these countries become more industrialized, the incidence of appendicitis has been increasing.7Air pollution is known to be a risk factor for multiple conditions, to exacerbate disease states and to increase all-cause mortality.11 It has a direct effect on pulmonary diseases such as asthma11 and on nonpulmonary diseases including myocardial infarction, stroke and cancer.11–13 Inflammation induced by exposure to air pollution contributes to some adverse health effects.14–17 Similar to the effects of air pollution, a proinflammatory response has been associated with appendicitis.18–20We conducted a case–crossover study involving a population-based cohort of patients admitted to hospital with appendicitis to determine whether short-term increases in concentrations of selected air pollutants were associated with hospital admission because of appendicitis. 相似文献52.
Sexual reproduction and the evolution of microbial pathogens 总被引:1,自引:0,他引:1
Heitman J 《Current biology : CB》2006,16(17):R711-R725
Three common systemic human fungal pathogens--Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus--have retained all the machinery to engage in sexual reproduction, and yet their populations are often clonal with limited evidence for recombination. Striking parallels have emerged with four protozoan parasites that infect humans: Toxoplasma gondii, Trypanosoma brucei, Trypanosoma cruzi and Plasmodium falciparum. Limiting sexual reproduction appears to be a common virulence strategy, enabling generation of clonal populations well adapted to host and environmental niches, yet retaining the ability to engage in sexual or parasexual reproduction and respond to selective pressure. Continued investigation of the sexual nature of microbial pathogens should facilitate both laboratory investigation and an understanding of the complex interplay between pathogens, hosts, vectors, and their environments. 相似文献
53.
54.
Kennio Ferreira-Paim Thatiana Bragine Ferreira Leonardo Andrade-Silva Delio Jose Mora Deborah J. Springer Joseph Heitman Fernanda Machado Fonseca Dulcilena Matos Márcia Souza Carvalho Melhem Mario León Silva-Vergara 《PloS one》2014,9(9)
Background
Although Cryptococcus laurentii has been considered saprophytic and its taxonomy is still being described, several cases of human infections have already reported. This study aimed to evaluate molecular aspects of C. laurentii isolates from Brazil, Botswana, Canada, and the United States.Methods
In this study, 100 phenotypically identified C. laurentii isolates were evaluated by sequencing the 18S nuclear ribosomal small subunit rRNA gene (18S-SSU), D1/D2 region of 28S nuclear ribosomal large subunit rRNA gene (28S-LSU), and the internal transcribed spacer (ITS) of the ribosomal region.Results
BLAST searches using 550-bp, 650-bp, and 550-bp sequenced amplicons obtained from the 18S-SSU, 28S-LSU, and the ITS region led to the identification of 75 C. laurentii strains that shared 99–100% identity with C. laurentii CBS 139. A total of nine isolates shared 99% identity with both Bullera sp. VY-68 and C. laurentii RY1. One isolate shared 99% identity with Cryptococcus rajasthanensis CBS 10406, and eight isolates shared 100% identity with Cryptococcus sp. APSS 862 according to the 28S-LSU and ITS regions and designated as Cryptococcus aspenensis sp. nov. (CBS 13867). While 16 isolates shared 99% identity with Cryptococcus flavescens CBS 942 according to the 18S-SSU sequence, only six were confirmed using the 28S-LSU and ITS region sequences. The remaining 10 shared 99% identity with Cryptococcus terrestris CBS 10810, which was recently described in Brazil. Through concatenated sequence analyses, seven sequence types in C. laurentii, three in C. flavescens, one in C. terrestris, and one in the C. aspenensis sp. nov. were identified.Conclusions
Sequencing permitted the characterization of 75% of the environmental C. laurentii isolates from different geographical areas and the identification of seven haplotypes of this species. Among sequenced regions, the increased variability of the ITS region in comparison to the 18S-SSU and 28S-LSU regions reinforces its applicability as a DNA barcode. 相似文献55.
Sexual reproduction is a nearly universal feature of eukaryotic organisms. Given its ubiquity and shared core features, sex is thought to have arisen once in the last common ancestor to all eukaryotes. Using the perspectives of molecular genetics and cell biology, we consider documented and hypothetical scenarios for the instantiation and evolution of meiosis, fertilization, sex determination, uniparental inheritance of organelle genomes, and speciation.The transition from prokaryote to protoeukaryote to the last eukaryotic common ancestor (LECA) entailed conservation, modification, and reconfiguration of preexisting genetic circuits via mutation, horizontal gene transfer (HGT), endosymbiosis, and selection, as detailed in previous articles of this collection. During the course of this evolutionary trajectory, the LECA became sexual, reassorting and recombining chromosomes in a process that entails regulated fusions of haploid gametes and diploid → haploid reductions via meiosis. That the LECA was sexual is no longer a matter of speculation/debate as evidence of sex, and of genes exclusively involved in meiosis, has been found in all of the major eukaryotic radiations (Brawley and Johnson 1992; Ramesh et al. 2005; Kobiyama et al. 2007; Malik et al. 2008; Phadke and Zufall 2009; Fritz-Laylin et al. 2010; Lahr et al. 2011; Peacock et al. 2011; Vanstechelman et al. 2013).We propose that the transition to a sexual LECA entailed four innovations: (1) alternation of ploidy via cell–cell fusion and meiosis; (2) mating-type regulation of cell–cell fusion via differentiation of complementary haploid gametes (isogametic and then anisogametic), a prelude to species-isolation mechanisms; (3) mating-type-regulated coupling of the diploid/meiotic state to the formation of adaptive diploid resting spores; and (4) mating-type-regulated transmission of organelle genomes. Our working assumption is that the protoeukaryote → LECA era featured numerous sexual experiments, most of which failed but some of which were incorporated, integrated, and modified. Therefore, this list is not intended to suggest a sequence of events; rather, the four innovations most likely coevolved in a parallel and disjointed fashion.Once these core sexual-cycle themes were in place, the evolution of eukaryotic sex has featured countless prezygotic and postzygotic variations, the outcome being the segregation of panmictic populations into distinct species with distinctive adaptations.For additional reviews on the evolution of sex, the interested reader is referred to Goodenough (1985), Dacks and Roger (1999), Schurko et al. (2009), Wilkins and Holliday (2009), Gross and Bhattacharya (2010), Lee et al. (2010), Perrin (2012), and Calo et al. (2013). 相似文献
56.
A study of 310 patients with prostatism who were not operated upon within a month following the first examination, was made in an effort to determine indications for operation in the patient with mild symptoms of prostatism. This study showed that long duration of symptoms, residual urine of more than 60 cc. and enlargement of the gland beyond Grade I are criteria for the necessity of operation. Palliative treatment is not always indicated. Patients with a soft, boggy prostate and those with more than a slight amount of infection in the prostate are benefited by light prostatic massage once weekly and stilbestrol given in doses of 1 mg. twice daily. Severe infection is treated by chemotherapy and bladder irrigations. 相似文献
57.
FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. 总被引:16,自引:1,他引:15
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In complex with the immunophilin FKBP12, the natural product rapamycin inhibits signal transduction events required for G1 to S phase cell cycle progression in yeast and mammalian cells. Genetic studies in yeast first implicated the TOR1 and TOR2 proteins as targets of the FKBP12-rapamycin complex. We report here that the TOR2 protein is membrane associated and localized to the surface of the yeast vacuole. Immunoprecipitated TOR2 protein contains readily detectable phosphatidylinositol-4 (PI-4) kinase activity attributable to either a TOR2 intrinsic activity or to a PI-4 kinase tightly associated with TOR2. Importantly, we find that rapamycin stimulates FKBP12 binding to wild-type TOR2 but not to a rapamycin-resistant TOR2-1 mutant protein. Surprisingly, FKBP12-rapamycin binding does not markedly inhibit the PI kinase activity associated with TOR2, but does cause a delocalization of TOR2 from the vacuolar surface, which may deprive the TOR2-associated PI-4 kinase activity of its in vivo substrate. Several additional findings indicate that vacuolar localization is important for TOR2 function and, conversely, that TOR2 modulates vacuolar morphology and segregation. These studies demonstrate that TOR2 is an essential, highly conserved component of a signal transduction pathway regulating cell cycle progression conserved from yeast to man. 相似文献
58.
59.
A. Dutour P. Giraud J. Y. Maltese D. Becquet G. Pesce P. Salers LH. Ouafik M. Renard C. Oliver 《Peptides》1990,11(6):1081-1085
The TRH secretory responsiveness of the pancreatic islet cell clusters from newborn rat in organ culture was studied. Basal TRH secretion was stable over a 9-day period. The response to various secretagogues was tested on day 4. TRH secretion was stimulated by high potassium-induced depolarization and also through both cAMP and protein kinase-C dependent pathways. Like insulin, TRH release was stimulated by glucose and arginine and inhibited by somatostatin. These data suggest the existence of a common mechanism for TRH and insulin secretion by the pancreatic β-cells. 相似文献
60.
Xiaorong Lin Sweta Patel Anastasia P. Litvintseva Anna Floyd Thomas G. Mitchell Joseph Heitman 《PLoS pathogens》2009,5(1)
The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the α mating type is overwhelmingly predominant over a. How genetic diversity is generated and maintained by this heterothallic fungus in a largely unisexual α population is unclear. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions generating both diploid intermediates and haploid recombinant progeny. Same-sex mating (α-α) also occurs in nature as evidenced by the existence of natural diploid αADα hybrids that arose by fusion between two α cells of different serotypes (A and D). How significantly this novel sexual style contributes to genetic diversity of the Cryptococcus population was unknown. In this study, ∼500 natural C. neoformans isolates were tested for ploidy and close to 8% were found to be diploid by fluorescence flow cytometry analysis. The majority of these diploids were serotype A isolates with two copies of the α MAT locus allele. Among those, several are intra-varietal allodiploid hybrids produced by fusion of two genetically distinct α cells through same-sex mating. The majority, however, are autodiploids that harbor two seemingly identical copies of the genome and arose via either endoreplication or clonal mating. The diploids identified were isolated from different geographic locations and varied genotypically and phenotypically, indicating independent non-clonal origins. The present study demonstrates that unisexual mating produces diploid isolates of C. neoformans in nature, giving rise to populations of hybrids and mixed ploidy. Our findings underscore the importance of same-sex mating in shaping the current population structure of this important human pathogenic fungus, with implications for mechanisms of selfing and inbreeding in other microbial pathogens. 相似文献