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61.
Elsässer A Decker E Kostin S Hein S Skwara W Müller KD Greiber S Schaper W Klövekorn WP Schaper J 《Molecular and cellular biochemistry》2000,213(1-2):17-28
Recently, we proposed the hypothesis that a vicious cycle exists in human hibernating myocardium (HM) between the progression of myocyte degeneration and the development of fibrosis [1]. We now investigated the pathomechanism of this cycle in more detail and established a correlation between the severity of the morphological changes and the degree of postoperative functional recovery of HM.HM was diagnosed by dobutamine echocardiography, thallium-201 scintigraphy and radionuclide ventriculography. Functional recovery was present at 3 months after coronary bypass surgery but remained unchanged at 15 months. Forty patients were subdivided into 2 groups: A with complete and B with incomplete recovery. Biopsies taken during surgery and studied by electron microscopy, immunocytochemistry, rt-PCR, and morphometry revealed myocyte degeneration and inflammatory and fibrinogenic changes in a widened interstitial space. We report here for the first time an upregulation of TGF-1 evident by a 5-fold increase of fibroblasts and macrophages exhibiting a TGF-1 content 3-fold larger than in control, and a > 3-fold increase in TGF-1 mRNA by rt-PCR. The number of angiotensin converting enzyme (ACE) containing structures was increased (n/mm2: control - 11.4, A - 17.6, B - 19.2, control vs. A and B, p < 0.05). Fibrosis was more severe in group B than A or control (%: C - 10.1; A - 21.2; B - 40.6; p < 0.05). Capillary density was significantly reduced (n/mm2: C - 1152; A - 782; B - 579, p < 0.05) and intercapillary distance was widened (m: C - 29.5, A - 36.1, B - 43.3, p < 0.05). The number of CD 3 (n/mm2: C - 5.0; A - 9.6; B - 9.4, ns) and CD 68 positive cells (n/mm2: C - 37.2; A - 80.7; B - 55.0, C vs. A p < 0.05) was elevated in HM as compared to control indicating an inflammatory reaction. Cut-off points for functional recovery are fibrosis > 32%, capillary density < 660/mm2 and intercapillary distance > 39.0 m.In HM a self-perpetuating vicious cycle of tissue alterations leads to progressive replacement fibrosis and continuous intracellular degeneration which should be interrupted by early revascularization. 相似文献
62.
Nicolas Favre Claudia Daubenberger Jutta Marfurt Alberto Moreno Manuel Patarroyo G. Pluschke 《Immunogenetics》1998,48(4):253-259
We cloned and sequenced TcR alpha chain cDNA of three healthy Aotus nancymaae monkeys. Fifteen different TRAJ segments and 9 different TRAV genes were identified in the 29 rearrangements analyzed. As expected from the greater phylogenetic distance, A. nancymaae TRA gene sequences diverged more from the human sequences than those of the chimpanzee or the rhesus macaque. However, no Aotus TRAJ segment or TRAV gene was found which lacked a human counterpart. These counterparts were AJ02, AJ05, AJ09, AJ15, AJ22, AJ23, AJ28, AJ30, AJ32, AJ34, AJ37, AJ40, AJ42, AJ45, AJ52 and AV2S1, AV2S3, AV3S1, AV8S1, AV12S1, AV15S1, ADV21S1/DV5, AV22S1S and AV23S1, respectively. In most cases the identity of amino acid sequences between corresponding Aotus and human genes was greater than 80%. This marked conservation of TRA gene sequences indicates a close structural relationship of Aotus and human TcR and demonstrates that the TcR repertoire in primates is remarkably stable. The results support the concept
of using Aotus monkeys, which are susceptible to infection with the human malaria parasite Plasmodium falciparum, as an animal model for the evaluation of molecularly defined malaria vaccine candidates.
Received: 15 January 1998 / Revised: 23 March 1998 相似文献
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66.
Luning Wang Mikko J. Nissi Ferenc Tóth Jonah Shaver Casey P. Johnson Jinjin Zhang Michael Garwood Cathy S. Carlson Jutta M. Ellermann 《PloS one》2015,10(10)
Purpose
To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC) in goats.Methods
Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections.Results
All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG) loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues.Conclusions
Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions. 相似文献67.
68.
Rémy C. Lemoine Ann C. Petersen Lina Setti Jutta Wanner Andreas Jekle Gabrielle Heilek André deRosier Changhua Ji Pamela Berry David Rotstein 《Bioorganic & medicinal chemistry letters》2010,20(2):704-708
Replacement of a secondary amide with an N-acyl or N-sulfonyl gem-disubstituted azacyle in a series of CCR5 antagonists led to the identification of compounds with excellent in vitro HIV antiviral activity and increased intrinsic membrane permeability. 相似文献
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70.
Bindschedler LV Tuerck J Maunders M Ruel K Petit-Conil M Danoun S Boudet AM Joseleau JP Bolwell GP 《Phytochemistry》2007,68(21):2635-2648
Extractability and recovery of cellulose from cell walls influences many industrial processes and also the utilisation of biomass for energy purposes. The utility of genetic manipulation of lignin has proven potential for optimising such processes and is also advantageous for the environment. Hemicelluloses, particularly secondary wall xylans, also influence the extractability of cellulose. UDP-glucuronate decarboxylase produces UDP-xylose, the precursor for xylans and the effect of its down-regulation on cell wall structure and cellulose extractability in transgenic tobacco has been investigated. Since there are a number of potential UDP-glucuronate decarboxylase genes, a 490bp sequence of high similarity between members of the family, was chosen for general alteration of the expression of the gene family. Sense and antisense transgenic lines were analysed for enzyme activity using a modified and optimised electrophoretic assay, for enzyme levels by western blotting and for secondary cell wall composition. Some of the down-regulated antisense plants showed high glucose to xylose ratios in xylem walls due to less xylose-containing polymers, while arabinose and uronic acid contents, which could also have been affected by any change in UDP-xylose provision, were unchanged. The overall morphology and stem lignin content of the modified lines remained little changed compared with wild-type. However, there were some changes in vascular organisation and reduction of xylans in the secondary walls was confirmed by immunocytochemistry. Pulping analysis showed a decreased pulp yield and a higher Kappa number in some lines compared with controls, indicating that they were less delignified, although the level of residual alkali was reduced. Such traits probably indicate that lignin was less available for removal in a reduced background of xylans. However, the viscosity was higher in most antisense lines, meaning that the cellulose was less broken-down during the pulping process. This is one of the first studies of a directed manipulation of hemicellulose content on cellulose extractability and shows both positive and negative outcomes. 相似文献