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R. A. Sinico N. Mezzina B. Trezzi GM. Ghiggeri A. Radice 《Clinical and experimental immunology》2016,183(2):157-165
Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M‐type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement‐mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti‐PLA2R. Some evidence suggests that IgG4 anti‐PLA2R autoantibodies can bind mannan‐binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome‐wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)‐DQA1 loci with iMN. In addition to their diagnostic value, anti‐PLA2R antibodies may be useful to monitor disease activity and predict response to treatment. 相似文献
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Janneke AL van Kempen Henk J Schers Anne Jacobs Sytse U Zuidema Franca Ruikes Sarah HM Robben René JF Melis Marcel GM Olde Rikkert 《The British journal of general practice》2013,63(608):e225-e231
Background
Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.Aim
This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.Design and setting
Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.Method
The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.Results
The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.Conclusion
The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care. 相似文献46.
Early transvaginal ultrasound following an accurately dated pregnancy: the importance of finding a yolk sac or fetal heart motion 总被引:1,自引:2,他引:1
Deaton JL; Honore GM; Huffman CS; Bauguess P 《Human reproduction (Oxford, England)》1997,12(12):2820-2823
Our goals were to determine the prognostic value of a yolk sac or fetal
heart motion seen during an early accurately dated transvaginal ultrasound
(TVU). We reviewed 225 consecutive pregnancies for fetal heart motion data.
Furthermore, 63 pregnancies following in-vitro fertilization were reviewed
for yolk sac information. The TVU was performed between 5 and 6 weeks
following presumed conception (heart motion data) and between 22 and 32
days following in-vitro fertilization (yolk sac data). Pregnancies were
followed until an ongoing pregnancy or spontaneous abortion was documented.
The presence of a yolk sac between 22 and 32 days from fertilization was
associated with the development of fetal heart motion in 94% of cases. The
absence of the yolk sac by 32 days after fertilization was always
associated with a poor outcome. In women < 36 years of age, the presence
of fetal heart motion was associated with a spontaneous abortion in only
4.5% of the cases. However, the incidence of spontaneous abortion following
fetal heart motion increased to 10% in women 36-39 years and 29% in women
> or = 40 years of age. The presence of heart motion should not be
considered a reassuring sign in the older woman. These data have
implications regarding early embryology and the counselling of infertility
patients.
相似文献
47.
Warnes GM; Payne D; Jeffrey R; Hourigan L; Kirby C; Kerin J; Matthews C 《Human reproduction (Oxford, England)》1997,12(7):1525-1530
Over a 26 month period 17% of couples having treatment in our clinical
programmes selected a commercially available protein (normal serum albumin,
NSA) prepared from pooled human sera instead of using their own serum as a
supplement for their embryo culture media. In a retrospective analysis of
>2000 gonadotrophin-stimulated cycles and 1000 cycles where
frozen/thawed embryos were transferred, fertilization, embryo quality and
pregnancy rates following in-vitro fertilization (IVF), gamete
intra-Fallopian transfer (GIFT) or intracytoplasmic sperm injection (ICSI)
were unaffected by the type of protein used to supplement the culture
medium. When embryos were thawed in medium containing NSA, both pregnancy
(PR) and implantation rates (IR) were significantly lower (P <0.05) than
if the medium was supplemented with serum (PR 8.3% and 17.5%; IR 4.6% and
10.5%). Inclusion of NSA before freezing reduced the IR of thawed embryos.
To further test this observation all cycles where embryos were cultured and
frozen in medium containing NSA (173 cycles) were matched to cycles where
serum was used and the outcome was compared. At the end of 1995 just over
half of the embryos in both groups had been thawed. No statistical
difference was noted in the pregnancy rates (NSA, 5.6% versus serum, 11.3%)
but the IR per embryo was significantly lower when embryos were cultured
and frozen in medium supplemented with NSA (2.2%) than when serum was used
as the supplement (6.6%).
相似文献
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Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation. 相似文献
50.
Aimée E van Dijk Manon van Eijsden Karien Stronks Reinoud JBJ Gemke Tanja GM Vrijkotte 《BMC public health》2010,10(1):251