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91.
Alison Severn Damo Xu Jacqueline Doyle Ludmila M. C. Leal Catherine A. O'Donnell Sara J. Brett David W. Moss Foo Y. Liew 《European journal of immunology》1993,23(7):1711-1714
Murine macrophages produce nitric oxide (NO) from L-arginine on stimulation with lipopolysaccharide (LPS), alone or with interferon-γ (IFN-γ). The effect of incubation of macrophages with low concentrations of LPS on NO synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, J774, and peritoneal macrophages from CBA mice. Cells which had been incubated with LPS produced significantly lower amounts of NO, and expressed lower levels of NO synthase activity, following stimulation with IFN-γ and LPS, or with a high concentration of LPS. This effect was not reversed by tumor necrosis factor-α. The ability of CBA macrophages to kill the intracellular parasite Leishmania major was markedly reduced by pre-incubation with LPS. Reduced NO production by macrophages previously exposed to LPS is a manifestation of endotoxin tolerance, and may represent an important means of regulation of NO synthesis and thus a survival mechanism for intracellular parasites. 相似文献
92.
Lucía Núñez Ruth A. Valero Laura Senovilla Sara Sanz-Blasco Javier García-Sancho Carlos Villalobos 《The Journal of physiology》2006,571(1):57-73
Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx pathway involved in control of multiple cellular and physiological processes including cell proliferation. Recent evidence has shown that SOCE depends critically on mitochondrial sinking of entering Ca2+ to avoid Ca2+ -dependent inactivation. Thus, a role of mitochondria in control of cell proliferation could be anticipated. We show here that activation of SOCE induces cytosolic high [Ca2+ ] domains that are large enough to be sensed and avidly taken up by a pool of nearby mitochondria. Prevention of mitochondrial clearance of the entering Ca2+ inhibited both SOCE and cell proliferation in several cell types including Jurkat and human colon cancer cells. In addition, we find that therapeutic concentrations of salicylate, the major metabolite of aspirin, depolarize partially mitochondria and inhibit mitochondrial Ca2+ uptake, as revealed by mitochondrial Ca2+ measurements with targeted aequorins. This salicylate-induced inhibition of mitochondrial Ca2+ sinking prevented SOCE and impaired cell growth of Jurkat and human colon cancer cells. Finally, direct blockade of SOCE by the pyrazole derivative BTP-2 was sufficient to arrest cell growth. Taken together, our results reveal that cell proliferation depends critically on mitochondrial Ca2+ uptake and suggest that inhibition of tumour cell proliferation by salicylate may be due to interference with mitochondrial Ca2+ uptake, which is essential for sustaining SOCE. This novel mechanism may contribute to explaining the reported anti-proliferative and anti-tumoral actions of aspirin and dietary salicylates. 相似文献
93.
Effect of ageing of serum on consumption of antibody by B1C-globulin determinants; evidence for circulating breakdown products in glomerulonephritis 下载免费PDF全文
C. D. West Sara Winter Judith Forristal N. C. Davis 《Clinical and experimental immunology》1968,3(1):57-62
Changes in antibody consumption by the A and D determinants of β1C-globulin were found to increase as serum aged in vitro. Consumption by the A determinant was 1·6 times and by the D determinant, 2·5–3 times greater in aged serum than in fresh EDTA plasma. The most likely explanation for the increased consumption with ageing is steric changes occurring as the β1C molecule fragments into β1A and α2D, resulting in exposure of additional antibody combining sites. In specimens from patients with hypocomplementemic nephritis, the increase in consumption with ageing was less than in normal subjects. The data add to the evidence presented in earlier studies of the presence in vivo, in certain nephritics, of breakdown products of β1C-globulin. The most abundant breakdown product would be α2D-globulin. 相似文献
94.
Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility 下载免费PDF全文
Lyons CR Lovchik J Hutt J Lipscomb MF Wang E Heninger S Berliba L Garrison K 《Infection and immunity》2004,72(8):4801-4809
Bioweapons are most often designed for delivery to the lung, although this route is not the usual portal of entry for many of the pathogens in the natural environment. Vaccines and therapeutics that are efficacious for natural routes of infection may not be effective against the pulmonary route. Pulmonary models are needed to investigate the importance of specific bacterial genes in virulence, to identify components of the host immune system that are important in providing innate and acquired protection, and for testing diagnostic and therapeutic strategies. This report describes the characteristics of host and Bacillus anthracis interactions in a murine pulmonary-infection model. The infective dose varied depending on the route and method of inoculation. The germination process in the lung began within 1 h of inoculation into the lung, although growth within the lung was limited. B. anthracis was found in the lung-associated lymph nodes approximately 5 h after infection. Minimal pneumonitis was associated with the lung infection, but significant systemic pathology was noted after dissemination. Infected mice typically succumbed to infection approximately 3 to 4 days after inoculation. The 50% lethal doses differed among inbred strains of mice, but within a given mouse strain, neither the age nor the sex of the mice influenced susceptibility to B. anthracis. 相似文献
95.
96.
Genetic requirements for salmonella-induced cytopathology in human monocyte-derived macrophages 下载免费PDF全文
Infection of human macrophages with Salmonella enterica serovar Typhimurium or Salmonella enterica serovar Dublin produces delayed cytotoxicity characterized by cell detachment and associated apoptosis. Using a site-specific mutant in the SpvB active site, we verify that the ADP-ribosylation activity of SpvB is required for delayed cytotoxicity in human macrophages infected with Salmonella: SipB and the type III protein secretion system (TTSS) encoded by Salmonella pathogenicity island 1 (SPI1) are not involved, whereas the SPI2 TTSS is absolutely required for SpvB-dependent cytotoxicity. Furthermore, we show that infection of macrophage cultures with wild-type or sipB mutant bacteria led to a complete loss of polymerized actin in over half of the cells after 24 h. In contrast, macrophages infected with the spvB or SPI2 (ssaV or ssaJ) mutant strain retained normal F-actin filaments, despite similar numbers of intracellular bacteria. We conclude that SpvB and a functional SPI2 TTSS are essential for Salmonella-induced delayed cytotoxicity of human macrophages. 相似文献
97.
Leigh J Beglinger Kevin Duff Sara Van Der Heiden Karen Parrott Douglas Langbehn Roger Gingrich 《Biology of blood and marrow transplantation》2006,12(9):928-935
Delirium has been associated with a high risk of mortality in medical patients. Despite the high incidence of delirium in patients who undergo hemapoietic stem cell transplantation (HSCT), delirium as a risk factor for death has not been examined in this population. Thirty adult patients undergoing HSCT who were admitted to the University of Iowa Blood and Marrow Transplantation Program inpatient unit were assessed prospectively from 1 to 2 weeks before transplantation, throughout their inpatient stay, and at 100 days after transplantation. The Delirium Rating Scale and Memorial Delirium Assessment Scale were used twice weekly during the inpatient period to assess delirium severity and occurence. Patients' self-reports of medical history, computerized medical records, and neuropsychological and psychiatric assessments were used to identify pretransplantation risk factors. The incidence of delirium (Delirium Rating Scale score >12 or Memorial Delirium Assessment Scale score >or=8) was 43% and occurred with highest frequency in the first 2 weeks after transplantion. The presence of delirium at any point during hospitalization after transplantation and transplant type (allogeneic) were highly predictive of mortality (p < .0005; odds ratios, 14.0 and 14.4). In conclusion, this study highlights the importance of monitoring for delirium during the acute recovery period after transplantation and suggests that early or even prophylactic treatment for delirium should be studied. Studies to determine the factors that connect delerium soon after transplantation to mortality are highly warranted. 相似文献
98.
Miksch S Lumsden A Guenther UP Foernzler D Christen-Zäch S Daugherty C Ramesar RK Lebwohl M Hohl D Neldner KH Lindpaintner K Richards RI Struk B 《Human mutation》2005,26(3):235-248
Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the elastic tissue in the skin, eye, and cardiovascular system. Mutations in the ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and detected 59 distinct mutations (32 missense, eight nonsense, and six likely splice-site point mutations; one small insertion; and seven small and five large deletions). Forty-three of these mutations are novel variants, which increases the total number of PXE mutations to 121. While most mutations are rare, three nonsense mutations, a splice donor site mutation, and the large deletion comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal haplotyping with two proximal and two distal polymorphic markers flanking ABCC6 demonstrated that most chromosomes that carry these relatively frequent PXE mutations have related haplotypes specific for these mutations, which suggests that these chromosomes originate from single founder mutations. The types of mutations found support loss-of-function as the molecular mechanism for the PXE phenotype. In 76 of the 81 families, the affected individuals were either homozygous for the same mutation or compound heterozygous for two mutations. In the remaining five families with one uncovered mutation, affected showed allelic compound heterozygosity for the cosegregating PXE haplotype. This demonstrates pseudo-dominance as the relevant inheritance mechanism, since disease transmission to the next generation always requires one mutant allelic variant from each parent. In contrast to other previous clinical and molecular claims, our results show evidence only for recessive PXE. This has profound consequences for the genetic counseling of families with PXE. 相似文献
99.
Amanda B. Spurdle Sara Shankman Michele Ramsay 《American journal of medical genetics. Part A》1995,55(1):53-56
A molecular investigation of 16 Bantu-speaking Black XX true hermaphrodites was undertaken in an attempt to determine the cause of the disorder. Y-specific sequences, including sequences mapping to the sexdetermining region of the Y, were shown to be absent from lymphocyte tissue of all 16 patients tested. Y chromosome sequences were also absent from the ovarian and testicular components of both ovotestes of a single XX true hermaphrodite, thus excluding gonadal mosaicism involving Y chromosome sequences. Since there is evidence for Xp genes involved in testis determination/differentiation, uniparental disomy of the X chromosome was investigated in 14 XXTH families. Uniparental disomy was excluded in 12 of the 14 families, and isodisomy was excluded in the remaining two cases. © 1995 Wiley-Liss, Inc. 相似文献
100.
The bone marrow is the site of neutrophil production, a process that is regulated by the cytokine granulocyte colony‐stimulating factor (G‐CSF). Mature neutrophils are continually released into the circulation, with an estimated 10 11 neutrophils exiting the bone marrow daily under basal conditions. These leucocytes have a short half‐life in the blood of ~6·5 hr, and are subsequently destroyed in the spleen, liver and indeed the bone marrow itself. Additionally, mature neutrophils are retained in the bone marrow by the stromal cell‐derived factor (SDF‐1α)/chemokine (C‐X‐C motif) receptor 4 (CXCR4) chemokine axis and form the bone marrow reserve. Following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated and this process is mediated by the co‐ordinated actions of cytokines and chemokines. In this review we discuss the factors and molecular mechanisms regulating the neutrophil mobilization and consider the mechanisms and functional significance of neutrophil clearance via the bone marrow. 相似文献