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61.
Plunkett FJ Franzese O Belaramani LL Fletcher JM Gilmour KC Sharifi R Khan N Hislop AD Cara A Salmon M Gaspar HB Rustin MH Webster D Akbar AN 《Mechanisms of ageing and development》2005,126(8):855-865
Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life. 相似文献
62.
In the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe replication factor C (RF-C) plays key roles both in chromosomal DNA replication and in DNA replication checkpoint function.
At the replication fork, the five-subunit RF-C complex functions to load the trimeric polymerase accessory factor PCNA onto
DNA. PCNA then acts as a sliding clamp, tethering Pol δ to the DNA to maximise its processivity. Here we describe the cloning
of the S. pomberfc3
+ gene, encoding a homologue of the S. cerevisiae Rfc3 and human hRFC36 proteins. The 1026 bp rfc3
+ ORF is interrupted by five introns, ranging in size from 49 to 165 bp. The spliced ORF is predicted to encode a 342 amino-acid
protein that is approximately 50% identical at the amino acid sequence level to the S. cerevisiae Rfc3 and human hRFC36 proteins. As expected, S. pomberfc3
+ is an essential gene, with rfc3Δ cells being defective for DNA replication. Loss of rfc3
+ function can be rescued by heterologous expression of either the S. cerevisiae Rfc3 or human hRFC36 proteins in S. pombe.
Received: 15 October 1999 相似文献
63.
Dendritic fibromyxolipoma (DFML) is an uncommon, recently described, benign soft tissue lesion that shares many clinical and pathological features with myxoid variants of spindle cell lipoma (SCL). As described, DFML is distinguished from SCL by the presence of dendritic cytoplasmic processes, abundant keloidal collagen and a prominent, often plexiform vascular pattern. We describe the first known reported case of an intramuscular DFML that occurred in the right shoulder region of a 73-year-old man. The tumor displayed the typical histopathological features of DFML but also included foci of chondroid metaplasia, a previously unreported finding. This report also discusses the differential diagnosis, particularly distinguishing DFML from SCL and myxoid liposarcoma. In view of the similarities in many clinical and pathological features between SCL and DFML, we speculate that DFML probably represents an unusual variant of myxoid SCL. 相似文献
64.
Roca A Quintó L Abacassamo F Loscertales MP Gómez-Olivé FX Fenwick F Cane PA Saiz JC Toms G Alonso PL 《Journal of medical virology》2003,69(4):579-587
Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group‐ and strain‐specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross‐reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains. J. Med. Virol. 69:579–587, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
65.
Deepika D'Cunha Burkardt Anna Zachariou Chey Loveday Clare L. Allen David J. Amor Anna Ardissone Siddharth Banka Alexia Bourgois Christine Coubes Cheryl Cytrynbaum Laurence Faivre Gerard Marion Rachel Horton Dieter Kotzot Guillermo Lay‐Son Melissa Lees Karen Low Ho‐Ming Luk Paul Mark Allyn McConkie‐Rosell Marie McDonald John Pappas Christophe Phillipe Deborah Shears Brian Skotko Fiona Stewart Helen Stewart I Karen. Temple Frederic T. Mau‐Them Ricardo A. Verdugo Rosanna Weksberg Yuri A. Zarate John M. Graham Katrina Tatton‐Brown 《American journal of medical genetics. Part A》2019,179(10):2049-2055
66.
Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice 总被引:22,自引:0,他引:22
Powrie Fiona; Leach Michael W.; Mauze Smita; Caddie Linda Barcomb; Coffman Robert L. 《International immunology》1993,5(11):1461-1471
CD4+ T cells in the mouse can be subdivided into two fractionsbased on the level of expression of the CD45RB determinant.Previous studies have shown that these subsets are functionallydistinct. We have further characterized the properties of thesesubpopulations in vivo by injecting them into C. B-17 scid mice.The animals restored with the CD45RBhighCD4+ T cell populationdeveloped a lethal wasting disease with severe mononuclear cellinfiltrates into the colon and elevated levels of IFN- mRNA.In contrast, animals restored with the reciprocal CD45RBlowsubset or with unfractionated CD4+ T cells did not develop thewasting or colitis. Importantly, the co-transfer of the CD45RBlowpopulation with the CD45RBhigh population prevented the wastingdisease and colitis. These data indicate that important regulatoryinteractions occur between the CD45RBhigh and CD45RBlowCD4+T cell subsets and that disruption of this mechanism has fatalconsequences. 相似文献
67.
The theory of planned behavior (TPB) and R. A. Karasek's (1979) job strain model were used to investigate the predictors of exercise in a group of employees. A total of 241 employees completed an initial questionnaire; 1 week later 213 employees responded to a questionnaire measuring behavior. Employees in high-strain jobs did significantly less exercise than those in low-strain jobs, although they did not intend to do less, suggesting that work may impede the intention implementation. Intenders who failed to exercise had significantly higher work demands and lower exercise self-efficacy than intenders who succeeded in exercising. Work also affected exercise indirectly through self-efficacy. Thus, work may be a target for behavior change intervention because of its impact at 2 stages of the TPB. 相似文献
68.
Gloyn AL Reimann F Girard C Edghill EL Proks P Pearson ER Temple IK Mackay DJ Shield JP Freedenberg D Noyes K Ellard S Ashcroft FM Gribble FM Hattersley AT 《Human molecular genetics》2005,14(7):925-934
Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro. 相似文献
69.
Modulation of immune responses to Mycobacterium bovis in cattle depleted of WC1(+) gamma delta T cells
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Kennedy HE Welsh MD Bryson DG Cassidy JP Forster FI Howard CJ Collins RA Pollock JM 《Infection and immunity》2002,70(3):1488-1500
It is accepted that cell-mediated immune responses predominate in mycobacterial infections. Many studies have shown that CD4(+) T cells produce Th1 cytokines, such as gamma interferon (IFN-gamma), in response to mycobacterial antigens and that the cytolytic activity of CD8(+) cells toward infected macrophages is important. However, the extent and manner in which gamma delta T cells participate in this response remain unclear. In ruminants, gamma delta T cells comprise a major proportion of the peripheral blood mononuclear cell population. We have previously shown that WC1(+) gamma delta T cells are involved early in Mycobacterium bovis infection of cattle, but their specific functions are not well understood. Here we describe an in vivo model of bovine tuberculosis in which the WC1(+) gamma delta T cells were depleted from the peripheral circulation and respiratory tract, by infusion of WC1(+)-specific monoclonal antibody, prior to infection. While no effects on disease pathology were observed in this experiment, results indicate that WC1(+) gamma delta T cells, which become significantly activated (CD25(+)) in the circulation of control calves from 21 days postinfection, may play a role in modulating the developing immune response to M. bovis. WC1(+)-depleted animals exhibited decreased antigen-specific lymphocyte proliferative response, an increased antigen-specific production of interleukin-4, and a lack of specific immunoglobulin G2 antibody. This suggests that WC1(+) gamma delta TCR(+) cells contribute, either directly or indirectly, toward the Th1 bias of the immune response in bovine tuberculosis--a hypothesis supported by the decreased innate production of IFN-gamma, which was observed in WC1(+)-depleted calves. 相似文献
70.
Aanesen Fiona Øiestad Britt Elin Grotle Margreth Løchting Ida Solli Rune Sowden Gail Wynne-Jones Gwenllian Storheim Kjersti Eik Hedda 《Journal of occupational rehabilitation》2022,32(2):306-318
Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on... 相似文献