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51.
We have investigated the morphological effects of a genetic locus, Pgm1- t,
that affects the expression of a phosphoglucomutase locus (Pgm1) in liver
of rainbow trout (Salmo gairdneri). We have previously shown that embryos
with liver Pgm1 expression hatch earlier than those without liver Pgm1
expression. We predicted that this difference in developmental rate should
cause a reduction in meristic counts in the more rapidly developing fish
with liver Pgm1 expression. Eight meristic (countable) characters in nine
full-sib groups segregating for the presence or absence of liver Pgm1
expression are in agreement with this prediction. In eight of the nine
families, there is a significant difference in the multivariate
distribution of the eight meristic counts between full sibs with and
without liver Pgm1 expression. This separation in multivariate space is
based on a tendency for lower meristic counts in fish with liver Pgm1
expression. The magnitude of these morphological differences is similar to
that between two subspecies of cutthroat trout (Salmo clarki) that show
substantial genetic divergence at structural loci encoding enzymes (Nei's D
= 0.34). These data support the view that small changes in the
developmental process caused by genetic differences at regulatory genes can
have large effects on morphology.
相似文献
52.
Preincubation of quiescent Swiss 3T3 cells in fresh synthetic medium caused a reduction of the lag period prior to bradykinin-stimulated DNA synthesis as well as a leftward shift in the dose-response curve (half-maximum effect at 2 nM and 8 nM for preincubated cells and control cells, respectively). These enhancing effects were selective for bradykinin since vasopressin-stimulated DNA synthesis was not affected by preincubation in synthetic medium. Preincubation in synthetic medium also caused a marked enhancement (five- to sixfold increase) of bradykinin-induced Ca2+ mobilization from intracellular stores. This enhancement was time-dependent, peaked after 12 h of preincubation, and was prevented by inhibition of RNA or protein synthesis. Furthermore, preincubation in synthetic medium did not enhance the Ca2+ mobilization by bombesin, vasopressin, or PDGF. Additionally, bradykinin-induced tyrosine phosphorylation was also enhanced by prior incubation in fresh medium. Scatchard analysis of [3H]bradykinin binding revealed a doubling of the number of bradykinin receptors without any significant change of affinity after preincubation, thus providing an explanation for the increased cellular responsiveness to bradykinin. This enhancement of responsiveness to bradykinin was caused by the removal of an inhibitory factor present in conditioned medium which is produced by the cells and accumulates gradually in the medium. Addition of tumor necrosis factor α or interferon β to synthetic medium substituted for conditioned medium in preventing the increase in responsiveness to bradykinin. These findings demonstrate a novel mechanism that regulates cellular sensitivity to bradykinin via an autocrine factor(s). © 1995 Wiley-Liss, Inc. 相似文献
53.
54.
Kazuhisa?Nozawa Carlos?A?Casiano John?C?Hamel Christine?Molinaro Marvin?J?Fritzler Edward?KL?ChanEmail author 《Arthritis research & therapy》2002,4(4):R3
Anti-Golgi complex autoantibodies are found primarily in patients with Sjögren's syndrome and systemic lupus erythematosus, although they are not restricted to these diseases. Several Golgi autoantigens have been identified that represent a small family of proteins. Common features of all Golgi autoantigens appear to be their distinct structural organization of multiple α-helical coiled-coil rods in the central domains flanked by non-coiled-coil N-termini and C-termini, and their localization to the cytoplasmic face of Golgi cisternae. Many autoantigens in systemic autoimmune diseases have distinct cleavage products in apoptosis or necrosis and this has raised the possibility that cell death may play a role in the generation of potentially immunostimulatory forms of autoantigens. In the present study, we examined changes in the Golgi complex and associated autoantigens during apoptosis and necrosis. Immunofluorescence analysis showed that the Golgi complex was altered and developed distinctive characteristics during apoptosis and necrosis. In addition, immunoblotting analysis showed the generation of antigenic fragments of each Golgi autoantigen, suggesting that they may play a role in sustaining autoantibody production. Further studies are needed to determine whether the differences observed in the Golgi complex during apoptosis or necrosis may account for the production of anti-Golgi complex autoantibodies. 相似文献
55.
56.
Yamasaki Y Narain S Hernandez L Barker T Ikeda K Segal MS Richards HB Chan EK Reeves WH Satoh M 《Arthritis research & therapy》2006,8(4):R111-10
Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of 35S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset. 相似文献
57.
Background
To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH).Methods
Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test.Results
We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase.Conclusion
Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively. 相似文献58.
Introduction
Classic anti-nucleolar antibodies anti-Th/To and U3 ribonucleoprotein (-U3RNP) can help in the diagnosis, prediction of organ involvement and prognosis in systemic sclerosis (SSc); however, no validated commercial assay is available. We aimed at establishing a novel quantitative real time PCR (qPCR) method to detect these antibodies.Methods
Standard immunoprecipitation (IP) was performed using K562 cell extract and RNA components were extracted. cDNA was reverse transcribed from RNA components and Th RNA and U3 RNA were detected by qPCR using custom primers. Cycle threshold (Ct) values were compared in a titration experiment to determine the assay efficacy. The new assay was evaluated by testing 22 anti-Th/To and 12 anti-U3RNP positive samples in addition to 88 controls, and the results were compared with IP as a gold standard.Results
By testing serial 1:8 dilutions of cell lysate as the substrate in the IP step, RNA extracted after IP, and its derived cDNA, linear dose response curves were noted for both anti-Th/To and -U3RNP. With every dilution, Ct values changed approximately three as expected, reflecting the eight-fold difference of cDNA. The Ct difference between positive and negative samples was 8 to 13, which was similar throughout the dilutions. In the specificity analysis, the Ct values of positive samples were clearly different from the negative groups and the results by qPCR had a near perfect correlation with IP.Conclusions
Our new method readily detects these two clinically important antibodies in SSc. Making tests for anti-Th/To and -U3RNP antibodies widely available to clinicians should be helpful in the diagnosis and follow-up of SSc patients. 相似文献59.
Kelvin KL Wong Pongpat Thavornpattanapong Sherman CP Cheung Zhonghua Sun Jiyuan Tu 《BMC cardiovascular disorders》2012,12(1):1-18
Background
This study characterizes the distribution and components of plaque structure by presenting a three-dimensional blood-vessel modelling with the aim of determining mechanical properties due to the effect of lipid core and calcification within a plaque. Numerical simulation has been used to answer how cap thickness and calcium distribution in lipids influence the biomechanical stress on the plaque.Method
Modelling atherosclerotic plaque based on structural analysis confirms the rationale for plaque mechanical examination and the feasibility of our simulation model. Meaningful validation of predictions from modelled atherosclerotic plaque model typically requires examination of bona fide atherosclerotic lesions. To analyze a more accurate plaque rupture, fluid-structure interaction is applied to three-dimensional blood-vessel carotid bifurcation modelling. A patient-specific pressure variation is applied onto the plaque to influence its vulnerability.Results
Modelling of the human atherosclerotic artery with varying degrees of lipid core elasticity, fibrous cap thickness and calcification gap, which is defined as the distance between the fibrous cap and calcification agglomerate, form the basis of our rupture analysis. Finite element analysis shows that the calcification gap should be conservatively smaller than its threshold to maintain plaque stability. The results add new mechanistic insights and methodologically sound data to investigate plaque rupture mechanics.Conclusion
Structural analysis using a three-dimensional calcified model represents a more realistic simulation of late-stage atherosclerotic plaque. We also demonstrate that increases of calcium content that is coupled with a decrease in lipid core volume can stabilize plaque structurally. 相似文献60.
In the previous issue of Arthritis Research & Therapy, Muro and colleagues reported a detailed epidemiologic analysis in central Japan on one of the new myositis-specific autoantibodies
to MDA-5 (melanoma differentiation-associated gene 5), which is associated with clinically amyopathic dermatomyositis accompanying
interstitial lung disease. The increasing prevalence of anti-MDA-5, higher prevalence in small rural towns, and geographical
clustering in two areas along the Kiso River suggest a role of environmental factors associated with rural communities or
the river/water system or both. A detailed analysis of a small cohort may offer clues, which is ignored in multi-center studies,
to the pathogenesis of systemic rheumatic diseases and autoantibody production. 相似文献