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101.
Kasper Lage Niclas Tue Hansen E. Olof Karlberg Aron C. Eklund Francisco S. Roque Patricia K. Donahoe Zoltan Szallasi Thomas Skt Jensen Sren Brunak 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(52):20870-20875
Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were systematically mapped to tissues they affect from disease-relevant literature in PubMed to create a disease–tissue covariation matrix of high-confidence associations of >1,000 diseases to 73 tissues. By retrieving >2,000 known disease genes, and generating 1,500 disease-associated protein complexes, we analyzed the differential expression of a gene or complex involved in a particular disease in the tissues affected by the disease, compared with nonaffected tissues. When this analysis is scaled to all diseases in our dataset, there is a significant tendency for disease genes and complexes to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also identified complexes in Parkinson disease, cardiomyopathies, and muscular dystrophy syndromes that are similarly tissue specific. Our method represents a conceptual scaffold for organism-spanning analyses and reveals an extensive list of tissue-specific draft molecular pathways, both known and unexpected, that might be disrupted in disease. 相似文献
102.
Catherine Dallemagne Sze‐Yuan Ooi Lindsay Brown Glenda Gob Zoltan Endre 《Nephrology (Carlton, Vic.)》2000,5(4):277-284
Summary: This study has compared renal function in deoxycorticosterone (DOCA)‐salt hypertensive Wistar rats (uninephrectomy followed by administration of DOCA 25 mg subcutaneously every fourth day and 1% NaCl in the drinking water) with various control rats using the isolated perfused kidney preparation. The systolic blood pressure of DOCA‐salt hypertensive rats was 180 ± 10 mmHg (uninephrectomy controls: 136 ± 9 mmHg) while normalization of calcium intake (DOCA‐Ca rats, 1% CaCl2 in water) attenuated this increase (systolic blood pressure, 146 ± 5 mmHg). Renal mass corrected for body weight increased by 25% after uninephrectomy, 55% in uninephrectomized rats given NaCl, 152% in DOCA‐salt rats and 147% in DOCA‐Ca rats. At a renal perfusion pressure of 135 mmHg, isolated perfused kidneys from DOCA‐salt rats showed decreases of 48% in glomerular filtration rate and 69% in sodium excretion with an increase of 44% in renal vascular resistance compared with uninephrectomized rats. There were no significant differences in renal function between DOCA‐salt and DOCA‐Ca rats. Histological assessment of renal pathology showed proximal tubular hypertrophy and hyperplasia, marked focal distal tubular atrophy, interstitial fibrosis and glomerular hypercellularity in DOCA rats compared with UNX rats. Lesions were less obvious in UNX‐salt or DOCA‐Ca rats. The lack of direct correlation between alterations in function and pathology may be explained by the compensatory effect of remaining healthy or hypertrophied nephrons. Thus, the DOCA‐salt model of hypertension in rats is associated with marked structural kidney damage and severely decreased kidney function. Marked attenuation of systemic hypertension by normalizing calcium intake in DOCA‐salt rats did not prevent impairment of kidney function. 相似文献
103.
Influence of storage on red blood cell rheological properties. 总被引:13,自引:0,他引:13
Tamara L Berezina Sergey B Zaets Claire Morgan Charles R Spillert Mikio Kamiyama Zoltan Spolarics Edwin A Deitch George W Machiedo 《The Journal of surgical research》2002,102(1):6-12
BACKGROUND: It is known that the age of transfused blood is a risk factor for the development of multiple organ failure in surgical patients. However, the character of hemorrheological changes in stored blood as well as the time when they appear remains disputable. We assumed that blood storage was accompanied by a progressive decrease of RBC deformability and rheological disorders. The degree of rheological disturbances should be directly proportional to the number of RBC with altered geometry. MATERIALS AND METHODS: Nine packages of RBC kept in adenine saline solution were examined from the 5th to the 42nd day of storage. RBC deformability index (DI) was determined by micropore filtration technique. RBC shape was estimated by means of scanning electron microscopy. Blood clotting time was measured by Sonoclot coagulation analyzer. RESULTS: Significant alterations of RBC shape started at the second week of storage and progressed during the rest of the storage period. RBC shape changes were accompanied by progressive decrease in DI and increase in hemolysis and acidosis. The correlation index between the percentage of abnormally shaped RBC and DI was -0.81 (P = 0.0258). Blood clotting progressively decreased after 2 weeks of storage, probably due to the exhaustion of some procoagulant plasma factors. CONCLUSIONS: Serious hemorrheological disorders, including the decrease in RBC deformability secondary to shape abnormalities, acidosis, and the decrease of blood clotting, start already at the second week of storage and progress up to the end of the storage period. Transfusion of packed RBC older than 7 days may contribute to hemorrheological disorders in critically ill patients. 相似文献
104.
105.
Zaets SB Berezina TL Morgan C Kamiyama M Spolarics Z Xu DZ Deitch EA Machiedo GW 《Shock (Augusta, Ga.)》2003,19(3):268-273
Previous work in our laboratory has demonstrated a decrease in red blood cell (RBC) deformability in sepsis. This has not been studied following hemorrhagic shock. We tested the hypotheses that hemorrhagic shock, associated with soft tissue trauma, leads to decreased RBC deformability and that this is related to alterations in the resting shape of the RBC. Elongation index (EI), a measure of RBC deformability, was determined over a range of shear stresses from 0.3 to 30 Pa in 26 male rats before and at various times after 90 min of hemorrhagic shock. RBC resting shape was determined by scanning electron microscopy. The data demonstrate that EI decreased significantly at the end of shock (before resuscitation), and remained below normal throughout the 6-h postshock period. Eight of the 26 animals decompensated during shock, requiring return of a portion of the shed blood to maintain a mean arterial pressure of 30-40 mmHg. Four of eight decompensated animals died before the end of the study period, compared with none of the compensated rats. The decompensated rats had significantly lower EI at 0.3 Pa by the end of the shock period (0.050 +/- 0.009) than the compensated shock group (0.058 +/- 0.006; P < 0.05). RBC shape alterations were first demonstrated at the end of the shock period and persisted throughout the 6-h postshock resuscitation period. These data indicate that trauma and hemorrhagic shock cause RBC shape alterations and a significant decrease in RBC deformability, which becomes manifested during the shock period and persists for at least 6 h postshock. Additionally, a direct relationship appears to exist between the magnitude of the physiologic insult and the degree of RBC damage. 相似文献
106.
Vesey DA Cheung C Cuttle L Endre Z Gobe G Johnson DW 《The Journal of laboratory and clinical medicine》2002,140(5):342-350
One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent. 相似文献
107.
108.
Csaba Papp Artur Beke Gabor Mezei Zsanett Szigeti Zoltán Bán Zoltan Papp 《Journal of ultrasound in medicine》2006,25(6):711-7; quiz 718-20
OBJECTIVE: This study was conducted to evaluate the diagnostic value of different sonographic signs of fetuses with Turner syndrome in the first and second trimesters of pregnancy. METHODS: Between 1990 and 2004, Turner syndrome was found in 69 of 22,150 fetal karyotypings. Congenital anomalies detected by sonography were analyzed. RESULTS: Of the 514 (2.3%; 514/22,150) chromosome aberrations that were diagnosed, 69 Turner syndrome cases were found (13.4%; 69/514). Twenty-four fetuses had a 45,X karyotype (34.8%), and 45 fetuses were mosaic (65.2%). Forty-seven fetuses (68.1%; 47/69) showed symptoms on sonography. A substantial proportion of fetuses with Turner syndrome showed early-onset signs that could be detected in the first trimester (29.8%;14/69). The most common findings with sonography were hygroma colli (26.1%; 18/69), fetal hydrops (11.6%; 8/69), cardiac defects (13%; 9/69), and increased nuchal translucency (13%; 9/69). Among heart defects, coarctation of the aorta was the most common (44.4% of all cardial defects). Soft markers were also detected with relatively high frequency (23.2%; 16/69). CONCLUSIONS: The diagnosis of severe Turner syndrome is possible in early pregnancy. A search for soft markers during second-trimester sonography and extensive use of echocardiography may increase the detection rate of Turner syndrome. 相似文献
109.
D’Antongiovanni Vanessa Pellegrini Carolina Benvenuti Laura Fornai Matteo Di Salvo Clelia Natale Gianfranco Ryskalin Larisa Bertani Lorenzo Lucarini Elena Di Cesare Mannelli Lorenzo Ghelardini Carla Nemeth Zoltan H. Haskó György Antonioli Luca 《Inflammation》2022,45(4):1829-1847
Inflammation - The pharmacological blockade of P2X4 receptors has shown potential benefits in the management of several immune/inflammatory diseases. However, data regarding the involvement of P2X4... 相似文献
110.
PROPERTIES OF GUINEA PIG 7S ANTIBODIES : I. ELECTROPHORETIC SEPARATION OF TWO TYPES OF GUINEA PIG 7S ANTIBODIES 总被引:14,自引:16,他引:14
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Baruj Benacerraf Zoltan Ovary Kurt J. Bloch Edward C. Franklin 《The Journal of experimental medicine》1963,117(6):937-949
Guinea pigs hyperimmunized with single protein antigens or hapten conjugates emulsified in complete adjuvants produced two types of precipitating antibodies with different electrophoretic mobilities. "Slow" migrating antibody generally appeared earlier and "fast" migrating antibody later in the course of immunization. Animals initially immunized by the intraperitoneal route with hapten conjugates without adjuvants produced primarily fast migrating antibody. Purified guinea pig antibodies were also separable into slow and fast migrating components by electrophoresis in supporting media. Using suitable antisera prepared in rabbits hyperimmunized with guinea pig serum, it was demonstrated that slow and fast antibodies have both common and distinct antigenic determinants. Analytical ultracentrifugation disclosed that both antibodies have sedimentation coefficients of approximately 7S. These antibodies have been designated guinea pig 7Sγ1 and 7Sγ2. 相似文献