胆固醇结晶栓塞

着重介绍胆固醇结晶栓塞症的认识过程、病因、病理、发病机制、临床表现、治疗以及预后.以对胆固醇结晶栓塞症作出一个简单的总结,加深大家对胆固醇结晶栓塞症的认识.     

Crystal deposition disease

Calcium pyrophosphate dihydrate crystal deposition disease and HA crystal deposition disease are two common disorders that may come to the attention of a physician because of a variety of clinical symptomatology patterns. In CPPD crystal deposition disease, characteristic radiologic features include articular and periarticular calcification and an arthropathy consisting of joint space narrowing, bone sclerosis, often prominent subchondral cyst formation, occasional severe and progressive destructive bone changes, and variable osteophyte formation. These findings are often seen in a characteristic distribution with involvement of non-weight-bearing as well as weight-bearing joints and with involvement of distinctive intraarticular sites such as the patellofemoral compartment of the knee and the radiocarpal compartment of the wrist. In HA crystal deposition disease, characteristic radiologic features consist of calcific tendinitis and periarthritis as well as a more recently described arthropathy. Awareness of the distinctive roentgenographic appearance of these two diseases should allow a specific diagnosis to be made, and an understanding of their pathologic features should aid in appropriate therapy and guide future investigation of possible etiologic factors.     

Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site

Vascular endothelial growth factor (VEGF) is a homodimeric member of the cystine knot family of growth factors, with limited sequence homology to platelet-derived growth factor (PDGF) and transforming growth factor β2 (TGF-β). We have determined its crystal structure at a resolution of 2.5 Å, and identified its kinase domain receptor (KDR) binding site using mutational analysis. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended. The dimerization mode of VEGF is similar to that of PDGF and very different from that of TGF-β. Mutational analysis of VEGF reveals that symmetrical binding sites for KDR are located at each pole of the VEGF homodimer. Each site contains two functional “hot spots” composed of binding determinants presented across the subunit interface. The two most important determinants are located within the largest hot spot on a short, three-stranded sheet that is conserved in PDGF and TGF-β. Functional analysis of the binding epitopes for two receptor-blocking antibodies reveal different binding determinants near each of the KDR binding hot spots.     

Crystal structure of a disulfide-linked "trefoil" motif found in a large family of putative growth factors.

Porcine pancreatic spasmolytic polypeptide (PSP) belongs to a large family of homologous growth factor-like polypeptides characterized by a disulfide-linked "trefoil motif," duplicated and conserved in various family members. PSP contains two trefoil motifs, has several pharmacological actions on the gut, and has growth factor properties on epithelial cells in vitro. The human PSP analogue, human spasmolytic polypeptide, appears to be involved in many regenerative situations and, especially, in healing gastrointestinal ulcers. One member of the trefoil family, pS2, is secreted in approximately 50% of estrogen-dependent human breast carcinomas, which has led to its use as a tumor prognostic marker. Both pS2 and human spasmolytic polypeptide are also widely expressed in chronic gastrointestinal ulcerative conditions such as Crohn disease. Here we report the three-dimensional structure at 2.6-A resolution of a trefoil-containing protein, namely PSP, purified from porcine pancreas. The structure shows two homologous domains that share a supersecondary structure and disulfide bond pattern. The two domains pack asymmetrically giving rise to a number of protruding loops, exposed clefts, and an unusual electrostatic surface potential. Knowledge of the structure of PSP should allow the design of mutants to investigate further the function of PSP and other trefoil-containing peptides.     

Crystal deposition and osteoarthritis

Calcium-containing crystals are commonly found in osteoarthritic (OA) joints. Although most often found in advanced OA, some calcium pyrophosphate dihydrate and apatite can be present in early stages. These crystals could be factors in pathogenesis of OA and even more likely in the progression of disease. Calcium pyrophosphate dihydrate apatites and other calcium phosphates can be mitogenic, can stimulate the release of metalloproteases, and might have mechanical abrasive effects.     

Crystal Growth,Thermal and Spectral Properties of Er: LGGG Crystal

A high-quality Er³⁺-doped (Gd_1−xLu_x)₃Ga₅O₁₂ (Er: LGGG) laser crystal with a size of Φ 36 × 45 mm³ was successfully grown by the Czochralski (Cz) method for the first time. The effective segregation coefficient of Er³⁺ was determined to be 0.97, close to 1, and, thus, the uniform high-quality Er: LGGG crystal can be grown. In addition, the thermal and spectroscopic properties of Er: LGGG were investigated. Based on the measured characteristics, the Er: LGGG crystal has a huge potential for use in the 3.0 µm mid-infrared laser because of its outstanding optical quality, extraordinary thermal conductivity and stable structure.     

Ultra-Short Polarization Rotator Based on Flat-Shaped Photonic Crystal Fiber Filled with Liquid Crystal

In this study we demonstrate a high-performance polarization rotator (PR) based on flat-shaped photonic crystal fiber. The flat surfaces of the fiber are plated on gold films as electrodes, and the core of the structure is filled with liquid crystal. The polarization rotation characteristics of the flat-shaped fiber can be effectively adjusted by applying external voltage. The optical properties are analyzed using the finite element method (FEM). The results show that the magnitude of the modulation voltage is closely related to the thickness of the flat fiber. When the fiber thickness is 20 μm, only 100 V is required to achieve the highest PR performance. In the wavelength of the 1.55 μm band (~200 nm bandwidth), the conversion length of the PR is only 3.99 μm, the conversion efficiency is close to 100%, and the minimum crosstalk value is −26.2 dB. The presented PR, with its excellent performance, might enable promising applications in the communication system and the photonic integrated circuits.     

Crystal structure of prethrombin-1

Prothrombin is the zymogen precursor of the clotting enzyme thrombin, which is generated by two sequential cleavages at R271 and R320 by the prothrombinase complex. The structure of prothrombin is currently unknown. Prethrombin-1 differs from prothrombin for the absence of 155 residues in the N-terminal domain and is composed of a single polypeptide chain containing fragment 2 (residues 156–271), A chain (residues 272–320), and B chain (residues 321–579). The X-ray crystal structure of prethrombin-1 solved at 2.2-Å resolution shows an overall conformation significantly different (rmsd = 3.6 Å) from that of its active form meizothrombin desF1 carrying a cleavage at R320. Fragment 2 is rotated around the y axis by 29° and makes only few contacts with the B chain. In the B chain, the oxyanion hole is disrupted due to absence of the I16-D194 ion pair and the Na⁺ binding site and adjacent primary specificity pocket are highly perturbed. A remarkable feature of the structure is that the autolysis loop assumes a helical conformation enabling W148 and W215, located 17 Å apart in meizothrombin desF1, to come within 3.3 Å of each other and completely occlude access to the active site. These findings suggest that the zymogen form of thrombin possesses conformational plasticity comparable to that of the mature enzyme and have significant implications for the mechanism of prothrombin activation and the zymogen → protease conversion in trypsin-like proteases.     

Update on Oxalate Crystal Disease

Oxalate arthropathy is a rare cause of arthritis characterized by deposition of calcium oxalate crystals within synovial fluid. This condition typically occurs in patients with underlying primary or secondary hyperoxaluria. Primary hyperoxaluria constitutes a group of genetic disorders resulting in endogenous overproduction of oxalate, whereas secondary hyperoxaluria results from gastrointestinal disorders associated with fat malabsorption and increased absorption of dietary oxalate. In both conditions, oxalate crystals can deposit in the kidney leading to renal failure. Since oxalate is primarily renally eliminated, it accumulates throughout the body in renal failure, a state termed oxalosis. Affected organs can include bones, joints, heart, eyes, and skin. Since patients can present with renal failure and oxalosis before the underlying diagnosis of hyperoxaluria has been made, it is important to consider hyperoxaluria in patients who present with unexplained soft tissue crystal deposition. The best treatment of oxalosis is prevention. If patients present with advanced disease, treatment of oxalate arthritis consists of symptom management and control of the underlying disease process.     

Crystal structure of lignin peroxidase

The crystal structure of lignin peroxidase (LiP) from the basidiomycete Phanerochaete chrysosporium has been determined to 2.6 A resolution by usine multiple isomorphous replacement methods and simulated annealing refinement. Of the 343 residues, residues 3-335 have been accounted for in the electron density map, including four disulfide bonds. The overall three-dimensional structure is very similar to the only other peroxidase in this group for which a high-resolution crystal structure is available, cytochrome c peroxidase, despite the fact that the sequence identity is only approximately 20%, LiP has four disulfide bonds, while cytochrome c peroxidase has none, and LiP is larger (343 vs. 294 residues). The basic helical fold and connectivity defined by 11 helical segments with the heme sandwiched between the distal and proximal helices found in cytochrome c peroxidase is maintained in LiP. Both enzymes have a histidine as a proximal heme ligand, which is hydrogen bonded to a buried aspartic acid side chain. The distal or peroxide binding pocket also is similar, including the distal arginine and histidine. The most striking difference is that, whereas cytochrome c peroxidase has tryptophans contacting the distal and proximal heme surfaces, LiP has phenylalanines. This in part explains why, in the reaction with peroxides, cytochrome c peroxidase forms an amino acid-centered free radical, whereas LiP forms a porphyrin pi cation radical.     

Crystal structures of proline-derived enamines

The isolation and structural characterization of both aldehyde- and ketone-derived proline enaminones are reported and discussed. Crystal structures of 10 proline enamines provide information on stereochemical aspects, i.e., double bond configuration and syn- vs. anti-positioning of the carboxylate relative to the enamine double bond. Furthermore, the obtained crystal structures are compared with the density functional theory-calculated structures of the ground and transition state and the postulated Seebach-Eschenmoser transition state.