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ABSTRACT: To analyze the clinical data and result of voiding cystourethrography (VCUG) in high-risk children with vesicoureteral reflux (VUR) for better awareness of VUR, and to assess the usefulness of non-radioactive voiding ultrasonography (VUS) in the diagnosis of VUR.
Ninety-three high-risk children with VUR who were hospitalized from July 2007 to April 2010 were studied. The study included 58 cases of urinary tract infection (UTI) and 35 cases of fetal or postnatal hydronephrosis detected on a B ultrasound scan. The results of urinalysis, urine culture, renal function, B ultrasound and VCUG were evaluated. Part of patients underwent VUS followed by VCUG immediately.
(1) Sixty-two boys and 31 girls (aged 1 month to 11.5 years, mean age 2 years) were included. VUR was detected in 26 patients (28%) by VCUG. In terms of kidney-ureter units, VUR was detected in 36 of 186 kidney-ureter units, including 6 grade I, 3 grade II, 6 grade III, 15 grade IV and 6 grade V. (2) VUR was detected in 20 of 58 UTI patients (34.5%) by VCUG. The proportion of VUR in recurrent UTI group was 61.1%, much higher than that in first UTI group (22.5%). Thirteen of 20 VUR (65%) occurred in UTI patients under 1 year of age (M/F 10/3), with more bilateral VUR and severe grades of VUR than the older group. VUR was detected in 6 of 35 fetal or postnatal hydronephrosis patients (17.1%) by VCUG. (3) Twenty-two patients underwent both VUS and VCUG. VUR was detected in 4 patients and 6 kidney-ureter units by VCUG, while in 6 patients and 9 kidney-ureter units by VUS. Taking VCUG as the reference standard, VUS had a sensitivity of 100%, specificity of 92.1%, positive predictive value of 66.7%, and negative predictive value of 100%. There was a concordance rate of 93.2% between VUS and VCUG.
It is important to early screen VUR in UTI, fetal or postnatal hydronephrosis patients. There are more VUR, especially more bilateral VUR and severe grades of VUR, occurred in UTI patients under 1 year of age compared to older children. The incidence of VUR in recurrent UTI group was much higher than that in first UTI group. VUS is an accurate, reliable and radiation-free technique for the detection of VUR. It could be used to screen high-risk children for VUR and do the evaluation in the follow-up of VUR.
Zhonghua er ke za zhi. Chinese journal of pediatrics 04/2011; 49(4):282-6.
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ABSTRACT: α-Synuclein (α-Syn) fibrils are the major component of Lewy bodies that are closely associated with the pathogenesis of Parkinson’s disease, but the mechanism for the fibril assembly remains poorly understood. Here we report using a combination of peptide truncation and atomic force microscopy (AFM) to elucidate the self-assembly and morphology of the α-Syn fibrils. The results show that protease K significantly slims the fibrils from the mean height of ∼6.6 to ∼4.7 nm, whereas chaotropic denaturant urea completely breaks down the fibrils into small particles. The in situ enzymatic digestion also results in thinning of the fibrils, giving rise to some nicks on the fibrils. Moreover, N- or C-terminally truncated α-Syn fragments assemble into thinner filaments with the heights depending on the peptide lengths. A nine-residue peptide corresponding to the homologous GAV-motif sequence can form very thin (∼2.2 nm) but long (>1 μm) filaments. Thus, the central sequence of α-Syn forms a fibrillar core by cross-β-structure that is flanked by two flexible termini, and the orientation of the fibril growth is perpendicular to the β-sheet structures.
Biochemical and Biophysical Research Communications 05/2008; · 2.48 Impact Factor
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ABSTRACT: alpha-Synuclein (alpha-Syn), amyloid beta-protein and prion protein are among the amyloidogenic proteins that are associated with the neurodegenerative diseases. These three proteins share a homologous region with a consensus sequence mainly consisting of glycine, alanine and valine residues (accordingly named as the GAV motif), which was proposed to be the critical core for the fibrillization and cytotoxicity. To understand the role of the GAV motif in protein amyloidogenesis, we studied the effects of the homologous peptides corresponding to the sequence of GAV motif region (residues 66-74) on alpha-Syn aggregation. The result shows that these peptides can promote fibrillization of wild-type alpha-Syn and induce that of the charge-incorporated mutants but not the GAV-deficient alpha-Syn mutant. The acceleration of alpha-Syn aggregation by the homologous peptides is under a sequence-specific manner. The interplay between the GAV peptide and the core regions in alpha-Syn may accelerate the aggregation process and stabilize the fibrils. This finding provides clues for developing peptide mimics that could promote transforming the toxic oligomers or protofibrils into the inert mature fibrils.
FEBS Letters 07/2006; 580(15):3657-64. · 3.54 Impact Factor
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Feng Zhang,
Hai-Ning Du,
Zhi-Xiang Zhang, Li-Na Ji,
Hong-Tao Li,
Lin Tang,
Hua-Bin Wang,
Chun-Hai Fan,
Hong-Jie Xu,
Yi Zhang,
Jun Hu,
Hong-Yu Hu,
Jian-Hua He
Angewandte Chemie International Edition 06/2006; 45(22):3611-3. · 13.45 Impact Factor
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ABSTRACT: Fibrillization of alpha-synuclein (alpha-Syn) is closely associated with the formation of Lewy bodies in neurons and dopamine (DA) is a potent inhibitor for the process, which is implicated in the causative pathogenesis of Parkinson's disease (PD). To elucidate any molecular mechanism that may have biological relevance, we tested the inhibitory abilities of DA and several analogs including chemically synthetic and natural polyphenols in vitro. The MS and NMR characterizations strongly demonstrate that DA and its analogs inhibit alpha-Syn fibrillization by a mechanism where the oxidation products (quinones) of DA analogs react with the amino groups of alpha-Syn chain, generating alpha-Syn-quinone adducts. It is likely that the amino groups of alpha-Syn undergo nucleophilic attack on the quinone moiety of DA analogs to form imino bonds. The covalently cross-linked alpha-Syn adducts by DA are primarily large molecular mass oligomers, while those by catechol and p-benzoquinone (or hydroquinone) are largely monomers or dimers. The DA quinoprotein retains the same cytotoxicity as the intact alpha-Syn, suggesting that the oligomeric intermediates are the major elements that are toxic to the neuronal cells. This finding implies that the reaction of alpha-Syn with DA is relevant to the selective dopaminergic loss in PD.
FEBS Journal 08/2005; 272(14):3661-72. · 3.79 Impact Factor
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ABSTRACT: Accumulating evidence shows that some amyloidogenic proteins contain core sequences, which are critical for their fibrillization. Core sequences of alpha-synuclein, beta-amyloid peptide and prion protein usually reside in their unfolded regions and share a conserved consensus (VGGAVVAGV) designated as GAV homologue. Here we investigate the role of unfolded regions in fibrillization after GAV homologue is attached to the C-terminus or inserted into the loop regions of different host proteins, namely alpha -Syn1-65, gamma-synuclein, E. coli thioredoxin and immunoglobulin G binding B1 domain of streptococcal protein G. The results imply that an unstructured region is required by GAV homologue for the fibrillization of host proteins. A number of amyloidogenic proteins with core sequences located in unstructured regions are summarized and discussed in details. The finding may provide further insight into the elucidating of the molecular mechanism underlying the fibrillization of alpha-Syn, Abeta and PrP as well as other amyloidogenic proteins.
The Protein Journal 06/2005; 24(4):209-18. · 1.04 Impact Factor
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ABSTRACT: Human alpha-synuclein is a presynaptic terminal protein and can form insoluble fibrils that are believed to play an important role in the pathogenesis of several neurodegenerative diseases such as Parkinson's disease, dementia with Lewy bodies and Lewy body variant of Alzheimer's disease. In this paper, in situ atomic force microscopy has been used to study the structural properties of alpha-synuclein fibrils in solution using two different atomic force microscopy imaging modes: tapping mode and contact mode. In the in situ contact mode atomic force microscopy experiments alpha-synuclein fibrils quickly broke into fragments, and a similar phenomenon was found using tapping mode atomic force microscopy in which alpha-synuclein fibrils were incubated with guanidine hydrochloride (0.6 M). The alpha-synuclein fibrils kept their original filamentous topography for over 1 h in the in situ tapping mode atomic force microscopy experiments. The present results provide indirect evidence on how beta-sheets assemble into alpha-synuclein fibrils on a nanometer scale.
Acta Biochimica et Biophysica Sinica 03/2005; 37(2):113-8. · 1.38 Impact Factor
