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891.
Extent of Laminin-5 Assembly and Secretion Effect Junctional Epidermolysis Bullosa Phenotype 总被引:1,自引:0,他引:1 下载免费PDF全文
Chihiro Matsui Phyllis Pereira C. Kathy Wang Charlotte F. Nelson Timothy Kutzkey Caroline Lanigan David Woodley Masaaki Morohashi Elizabeth A. Welsh Warren K. Hoeffler 《The Journal of experimental medicine》1998,187(8):1273-1283
Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the α3β3γ2 heterotrimer assembles intracellularly via a β3γ2 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein–protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains needed for laminin-5 heterotrimer assembly. 相似文献
892.
893.
Arash Moghaddam Charlotte Elleser Bahram Biglari Andreas Wentzensen Gerald Zimmermann 《Archives of orthopaedic and trauma surgery》2010,130(1):71-76
Background
Non-unions of long bone fractures are a therapeutic and economic problem of increasing frequency. Aside from conservative treatment options such as ultrasound, impulse waves, and casts, the basic surgical options are autogenous cancellous bone grafting, rod dynamization, reamed nailing, plate fixation, and bone transport techniques. If these methods fail to work, there is a need for alternative treatment options.Methods
Since May 2001, treatment with recombinant human bone morphogenic protein 7 (BMP 7 or osteogenic protein 1) in combination with a type-one collagen carrier has been the subject of increasing interest. BMP 7 induces the formation of new bone by stem cell differentiation, thereby initiating the reaction cascade of osteogenesis. Non-unions over 9 months and unsuccessful bone grafting constitute the indication for this treatment.Results
We report our experience with 54 patients who had atrophic non-union of long bone fractures. Between May 2002 and May 2006, 57 units of BMP 7 were used. The localization of the non-unions included 21 in the femur, 26 in the tibia, 3 in the humerus and 7 in the forearm. In 36 cases, BMP 7 was used in combination with osteosynthesis revision and bone grafting; in 9 additional patients, BMP 7 was used with bone grafting alone. In 12 patients, BMP 7 was applied as a single procedure without any bone grafting or any change in osteosynthesis.Conclusions
There were no perioperative or postoperative complications. Follow-up was obtained for a minimum of 6 months. 47 of the 57 (82%) implantations were successful, with bony healing confirmed by clinical and radiological evaluation. In summary, our results support BMP 7 as an additional innovative therapy for long bone non-unions. 相似文献894.
Charlotte Grith Eriksen Helene Olsen Lise Bjerre Husted Lotte Sørensen Mette Carstens Kjeld Søballe Bente Lomholt Langdahl 《Calcified tissue international》2010,87(5):414-423
Increasing age is associated with reduced bone mineral content and increased risk of fractures. This is caused by a relative
insufficiency of osteoblasts compared with osteoclasts. We therefore wanted to examine the potential differences in proliferation,
differentiation, and expression of cytokines between human osteoblasts (hOBs) obtained from young and elderly individuals.
Cultures of hOBs were obtained from 11 elderly (73–85 years) and 15 young (21–27 years) healthy individuals. The cells were
stimulated with hGH, IGF-I, hGH + IGF-I, and TGF-β1. Proliferation was evaluated by thymidine incorporation, and differentiation
was evaluated by alkaline phosphatase, OPG, and PINP production. Expression of IL-6, TGF-β1, OPG, and RANKL was investigated
using real-time PCR and three carefully selected housekeeping genes. Combined stimulation with hGH and IGF-I increased proliferation
without differences between hOBs obtained from young and elderly individuals. hOBs from young individuals responded to stimulation
with vitamin D with a more pronounced increase in alkaline phosphatase: 107 ± 17% vs. 43 ± 5%, P < 0.01. Stimulation with TGF-β1 decreased OPG production by hOBs from elderly individuals but not from young individuals,
P < 0.05. hOBs from elderly individuals expressed significantly higher amounts of IL-6 mRNA (P < 0.05) and less OPG and TGF-β1 mRNA (P = 0.08 and P = 0.08, respectively) compared with hOBs from young individuals. In conclusion, hOBs from elderly individuals express more
IL-6 mRNA and less OPG and TGF-β1 mRNA than hOBs from young individuals. This could partly explain the reduced bone mass and
increased fracture risk seen in the elderly. hOBs from young and elderly individuals responded similarly to short-term stimulation
of proliferation and differentiation. 相似文献
895.
Julie Jarand Karen Shean Max O’Donnell Marian Loveday Charlotte Kvasnovsky Martie Van der Walt Shahieda Adams Paul Willcox Justin O’Grady Alimuddin Zumla Keertan Dheda 《Tropical medicine & international health : TM & IH》2010,15(10):1179-1184
Objective To determine the clinical profile and outcomes of health care workers (HCWs) with extensively drug resistant tuberculosis (XDR‐TB) in the Eastern and Western Cape Provinces of South Africa. Method Retrospective case record review of 334 patients with XDR‐TB reported during the period 1996–2008 from Western and Eastern Cape Province, Cape Town, South Africa. Case records of HCWs with XDR‐TB were analysed for clinical and microbiological features, and treatment outcomes. Results From 334 case records of patients with XDR‐TB, 10 HCWs were identified. Eight of ten were HIV‐uninfected, and four of 10 had died of XDR‐TB despite treatment. All 10 HCWs had received an average of 2.4 courses of TB treatment before being diagnosed as XDR‐TB. Conclusions In the Eastern and Western Cape provinces of South Africa XDR‐TB affects HCWs, is diagnosed rather late, does not appear to be related to HIV status and carries a high mortality. There is an urgent need for the South African government to implement WHO infection control recommendations and make available rapid drug susceptibility testing for HCWs with suspected multidrug‐resistant (MDR)/XDR‐TB. Further studies to establish the actual risk and sources of infection (nosocomial or community) are required. 相似文献
896.
Zelee Hill Charlotte Tawiah‐Agyemang Alexander Manu Eunice Okyere Betty R. Kirkwood 《Tropical medicine & international health : TM & IH》2010,15(10):1118-1124
Objectives This study aimed to collect data on thermal care practices in rural Ghana to inform the design of a community newborn intervention. Methods All 635 women who delivered in six districts in Ghana in the first 2 weeks of December 2006 were interviewed about immediate newborn care. Qualitative data on thermal care practices and barriers and facilitators to behaviour change were collected from recently delivered/pregnant women, birth attendants/grandmothers, and husband through birth narratives, in‐depth interviews and focus group discussion. Results Respondents knew that keeping the baby warm was essential for health but 71% of babies born at home had delayed drying, 79% delayed wrapping, 93% early bathing and 10% were placed skin‐to‐skin. Birth attendants were usually in charge of mother and baby immediately after birth. Delays in drying/wrapping were linked to leaving the baby unattended until the placenta was delivered. Early bathing was linked to reducing body odour in later life, shaping the baby’s head, and helping the baby sleep and feel clean. Respondents thought that changing bathing behaviours would be difficult, especially as babies are bathed early in facilities. The concept of skin‐to‐skin care was easily understood and most women said they would try it if it was good for the baby. Conclusion Thermal care is a key component of community newborn interventions, the design of which should be based on an understanding of current behaviours and beliefs. Formative research can help select focus behaviours, decide who to include in interventions, ensure consistent messages and determine what messages and approaches are needed to overcome behaviour change barriers. 相似文献
897.
Marqueurs de lymphome B au cours des vascularites cryoglobulinémiques liées au virus de l’hépatite C
898.
899.
Schepers E Glorieux G Dou L Cerini C Gayrard N Louvet L Maugard C Preus P Rodriguez-Ortiz M Argiles A Brunet P Cohen G Jankowski J Jankowski V Massy Z Rodriguez M Vanholder R;European Uremic Toxin Work Group 《Blood purification》2010,30(4):277-287
Chronic kidney disease is considered a major cause of cardiovascular risk and non-traditional risk factors remain largely unknown. The in vitro toxicity of 10 guanidino compounds (GCs) was evaluated via a standardized approach on different cell systems of relevance in cardiovascular disease. The parameters evaluated were production of reactive oxygen species, expression of surface molecules, cell proliferation, cytotoxicity and calcification. Several GCs had a stimulatory effect on monocytes and granulocytes (SDMA, creatine and guanidinobutyric acid (GBA)). Some GCs (guandine (G), guanidinosuccinic acid (GSA) and SDMA) inhibited endothelial cell proliferation or reduced calcification in osteoblast-like human VSMC (ADMA, GSA and SDMA). Stimulation of osteoclastogenesis could be demonstrated for ADMA, G, guanidinoacetic acid and GBA in a RAW264.7 cell line. No compounds were cytotoxic to AoSMC or endothelial cells, nor influenced their viability. GCs, especially SDMA, likely contribute to cardiovascular complications in uremia, mainly those related to microinflammation and leukocyte activation. 相似文献
900.