Biomedical subjects

Yu Zhao

Publications and source records attributed to Yu Zhao.

At least 73 records · Page 4Linked to original sources

PubMed2006

[Clinical study on pulmonary complications after allogeneic peripheral blood stem cell transplantation].

OBJECTIVE: To explore the incidence, pathogenesis, risk factors and effective treatment of pulmonary complications after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: Pulmonary complications in 70 patients received allo-PBSCT were analyzed. RESULTS: Thirty one episodes were observed in 26 patients. Among them episodes were infectious complications, including bacteria pneumonia, pulmonary fungus disease, CMV interstitial pneumonia and tuberculosis, some cases were caused by two pathogens, and 11 episodes were noninfectious complications, including late-onset noninfectious pulmonary complications (LONIPCs) (n=9), pulmonary edema (n=1) and interstitial pneumonia (n=1). The overall mortality was 12.9%. Graft-versus-host disease (GVHD) prophylaxis without MTX, severe acute GVHD and extensive chronic GVHD were high risk factors for pulmonary complications and advanced disease at transplantation, extensive chronic GVHD were significantly associated with the incidence of LONIPCs. CONCLUSION: Pulmonary disease is the main complication occurred in patients undergoing allo-PBSCT. It is of greatly importance to treat pathogens specifically and diagnose LONIPCs in its early stage.

Adolescent↗

PubMed2005

CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in the Complement Factor H (CFH) gene increases the risk for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD--or the relationship between them--is unclear. METHODS AND FINDINGS: We genotyped 581 Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with mixed neovascular AMD/GA), and 435 with early AMD (of whom 220 had soft drusen). A second cohort of 431 US patients from Utah, 322 with advanced AMD (244 neovascular AMD and 78 GA) and 109 early-AMD cases with soft drusen, were analyzed. We confirmed that the CFH Y402H variant shows significant association to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 x 10(-12)) and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 10(-9)) with advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of soft drusen and both forms of advanced AMD (GA or neovascular AMD). CONCLUSION: Soft drusen occur prior to progression to advanced AMD and represent a histological feature shared by neovascular AMD and GA. Our results suggest that CFH is a major risk factor of soft drusen, and additional genetic factors and/or environmental factors may be required for progression to advanced AMD.

Complement Factor H↗

PubMed2005

Purification of a lysozyme from skin secretions of Bufo andrewsi.

A novel toad lysozyme (named BA-lysozyme) was purified from skin secretions of Bufo andrewsi by a three-step chromatography procedure. BA-lysozyme is a single chain protein and the apparent molecular weight is about 15 kDa as judged by SDS-PAGE. The specific lytic activity against Micrococcus lysodeikticus of BA-lysozyme is 2.7 x 10(5) units/mg, indicating that it is a potent lysozyme. It displayed potent bactericidal activity against Staphylococcus aureus and Escherichia coli with minimal inhibitory concentrations (MIC) of 1 and 8 microM, respectively. The deduced primary structure of BA-lysozyme from cloned cDNA was confirmed by N-terminal sequencing and peptide mass fingerprinting. Its amino acid sequence shares 56.5% identity with that of chicken egg-white lysozyme. Phylogenetic analysis indicates that B. andrewsi lysozyme is closely related to that of turtle. This is the first report on the isolation and primary structure determination of amphibian lysozyme.

Amino Acid Sequence↗

PubMed2005

Design, synthesis, and SAR analysis of cytotoxic sinapyl alcohol derivatives.

Five series totalling 51 of sinapyl alcohol derivatives were designed and synthesized. Their cytotoxicity analyses were performed on six human tumor cell lines such as PC-3, CNE, KB, A549, BEL-7404, and HeLa. Certain sinapyl alcohol derivatives showed significant cytotoxic activities. Compound 14d exhibited especially potent cytotoxicity against the BEL-7404 cell line with an IC50 value of 0.7 microM, which showed more cytotoxic activity than the positive control, cisplatin. The structure-cytotoxicity relationships were discussed and the CoMFA analysis was performed using the cytotoxic data against HeLa cells as a template.

Antineoplastic Agents↗

PubMed2005

A novel heme-containing protein with anti-HIV-1 activity from skin secretions of Bufo andrewsi.

A novel protein, named BAS-AH, was purified and characterized from the skin of the toad Bufo andrewsi. BAS-AH is a single chain protein and the apparent molecular weight is about 63 kDa as judged by SDS-PAGE. BAS-AH was determined to bind heme (0.89 mol heme/mol protein) as determined by pyridine haemochrome analysis. Fifty percentage cytotoxic concentration (CC50) of BAS-AH on C8166 cells was 9.5 microM. However, at concentrations that showed little effect on cell viability, BAS-AH displayed dose dependent inhibition on HIV-1 infection and replication. The antiviral selectivity indexes (CC50/EC50) were 14.4 and 11.4, respectively, corresponding to the measurements of syncytium formation and HIV-1 p24 antigen expression. BAS-AH also showed an inhibitory effect on the activity of recombinant HIV-1 reverse transcriptase (IC50 = 1.32 microM). The N-terminal sequence of BAS-AH was determined to be NAKXKADVIGKISILLGQDNLSNIVAAM, which exhibited little identity with other known anti-HIV-1 proteins. BAS-AH is devoid of antibacterial, proteolytic, trypsin inhibitory activity, l-amino acid oxidase activity and catalase activity.

Amino Acid Sequence↗

PubMed2005

Purification and characterization of an irreversible serine protease inhibitor from skin secretions of Bufo andrewsi.

Amphibian skin secretions contain many bioactive compounds. In the present work, an irreversible serine protease inhibitor, termed baserpin, was purified for the first time from the skin secretions of toad Bufo andrewsi by successive ion-exchange and gel-filtration chromatography. Baserpin is a single chain glycoprotein, with an apparent molecular weight of about 60 kDa in SDS-PAGE. Baserpin is an irreversible inhibitor and effectively inhibits the catalytic activity of trypsin, chymotrypsin and elastase. SDS-stable baserpin-trypsin complex could be seen in SDS-PAGE indicates that it possibly belongs to the serpin superfamily. According to the association rates determined, baserpin is a potent inhibitor of bovine trypsin (4.6 x 10(6) M(-1) s(-1)), bovine chymotrypsin (8.9 x 10(6) M(-1) s(-1)) and porcine elastase (6.8 x 10(6) M(-1) s(-1)), whereas it shows no inhibitory effect on thrombin. The N-terminal sequence of baserpin is HTQYPDILIAKPXDK, which shows no similarity with other known serine protease inhibitors.

Amino Acid Sequence↗

PubMed2005

Isolation and preliminary characterization of a 22-kDa protein with trypsin inhibitory activity from toad Bufo andrewsi skin.

A novel trypsin inhibitor termed BATI was purified to homogeneity from the skin extracts of toad Bufo andrewsi by successive ion-exchange, gel-filtration and reverse-phase chromatography. BATI is basic single chain glycoprotein, with apparent molecular weight of 22 kDa in SDS-PAGE. BATI is a thermal stable competitive inhibitor and effectively inhibits trypsin's catalytic activity on peptide substrate with the inhibitor constant (K(i)) value of 14 nM and shows no inhibitory effect on chymotrypsin, thrombin and elastase. The N-terminal sequence of BATI is EKDSITD, which shows no similarity with other known trypsin inhibitors.

Animals↗

PubMed2005

Loss of ER retention and sequestration of the wild-type ELOVL4 by Stargardt disease dominant negative mutants.

PURPOSE: Mutations in ELOVL4, a member of the fatty acid elongase (ELO) family, are responsible for autosomal dominant Stargardt-like macular degeneration. The specific role of ELOVL4 in photoreceptors and the degenerative events induced by dominant ELOVL4 mutations are not well understood. As a first step to identifying possible mechanisms contributing to cellular dysfunction, we transfected HEK293 and COS cells with fluorescent-labeled wild-type and mutant ELOVL4 constructs. Effects of mutant ELOVL4 on interaction with wild-type protein were examined in this in vitro model. METHODS: Wild-type and mutant ELOVL4 proteins including ELOVL4 truncation (270X, a truncated ELOVL4 protein at amino acid position 270) and ELOVL4 5 bp deletion (5bp-del) and ELOVL4 (5A, substituting the ER retention signal, KAKGD, with a five alanine amino acid tract) were expressed as EGFP or DsRed fusion proteins. Cellular localization of these proteins was examined by fluorescence microscopy. ELOVL4 protein aggregates were measured by co-immunoprecipitation and by sucrose gradient centrifugation followed by immunodetection with western blots. To study cellular status of cells expressing mutant ELOVL4 proteins, transfected cells were examined for upregulation of Bip and CHOP, markers for the unfolded protein response (UPR) by western blotting. RESULTS: ELOVL4 mutants were not retained within the ER but were rather mislocalized and formed aggregates. Importantly, when cotransfected with wild-type ELOVL4, the mutants bound to and sequestered the wild-type protein into the aggregates. Expression of ELOVL4 mutants also induced UPR as evidenced by Bip and CHOP expression. CONCLUSIONS: Using this in vitro cell system, we have identified alterations in wild-type ELOVL4 protein localization, aggregate formation, and the induction of cellular stress by the ELOVL4 mutants. We propose that "inactivation" of the wild-type ELOVL4 protein through sequestration to a non-ER compartment by ELOVL4 mutants may play a role in cellular dysfunction.

Animals↗

PubMed2005

Carbonic anhydrase-related protein VIII deficiency is associated with a distinctive lifelong gait disorder in waddles mice.

The waddles (wdl) mouse is a unique animal model that exhibits ataxia and appendicular dystonia without pathological abnormalities of either the central or the peripheral nervous systems. A 19-bp deletion in exon 8 of the carbonic anhydrase-related protein VIII gene (Car8) was detected by high-throughput temperature-gradient capillary electrophoresis heteroduplex analysis of PCR amplicons of genes and ESTs within the wdl locus on mouse chromosome 4. Although regarded as a member of the carbonic anhydrase gene family, the encoded protein (CAR8) has no reported enzymatic activity. In normal mice, CAR8 is abundantly expressed in cerebellar Purkinje cells as well as in several other cell groups. Compatible with nonsense-mediated decay of mutant transcripts, CAR8 is virtually absent in mice homozygous for the wdl mutation. These data indicate that the wdl mouse is a Car8 null mutant and that CAR8 plays a central role in motor control.

Amino Acid Sequence↗

PubMed2005

Proline-based N-oxides as readily available and modular chiral catalysts. Enantioselective reactions of allyltrichlorosilane with aldehydes.

[reaction: see text]. A proline-based N-oxide is identified that serves as an effective catalyst for the reaction of allyltrichlorosilane with aryl and alpha,beta-unsaturated aldehydes at room temperature to afford the desired homoallylic alcohols in up to 92% ee. The chiral catalyst can be easily prepared from optically pure proline in three simple steps and 60% overall yield.

Alcohols↗

PubMed2005

Cerebral cortical control of orbicularis oculi motoneurons.

Cerebral cortical neural networks associated with eyelid movement play a critical role in facial animation, contribute to the regulation of blink frequency, and help prevent ocular injury. Eyelid closure depends, in part, on motoneurons that innervate the orbicularis oculi (OO) muscles. In this study, OO motoneuron cortical afferents were identified in rhesus monkeys with rabies virus, a retrograde transneuronal tracer. Virus was injected into the right OO muscle and immunohistochemically localized after 4-6 day transport intervals. Labeled motoneurons were limited to dorsal portions of the ipsilateral facial motor nucleus. After 4- and 4.5-day transport intervals, most labeled cortical neurons were localized to ventrolateral premotor (LPMCv), dorsolateral premotor (LPMCd), and motor (M1) cortices. Labeled neurons were more sparsely distributed in supplementary (M2), caudal (M4), and rostral (M3) cingulate motor cortices; the frontal eye fields (FEF); pre-supplementary motor cortex (pre-SMA); somatosensory cortices (areas 3a, 3b, and 1); and prefrontal cortex. At longer transport intervals (5-6 days), labeled neurons increased substantially in LPMCv, LPMCd, M2, M3, M4, pre-SMA, and FEF. Concentrations of labeled neurons also appeared in cortices along the lateral fissure and intraparietal sulcus. Overall, the densest collection of labeled neurons was localized to the caudal junction of LPMCd and LPMCv with M1. Rostral M3 was another focus of OO premotor neurons. Labeled neurons were distributed bilaterally in all motor cortical areas with a modest contralateral predominance for M2, LPMC, and M1. Thus, the cortical control of OO motor activity is distributed bilaterally among multiple motor areas.

Animals↗

PubMed2005

A new operative classification of idiopathic scoliosis: a peking union medical college method.

STUDY DESIGN: A retrospective radiographic study on the type of surgically treated idiopathic scoliosis, with a prospective study on the reliability of the type-related fusion guide. OBJECTIVES: To identify and classify surgically treated idiopathic scoliosis, and define its related fusion levels by a new classification system. SUMMARY OF BACKGROUND DATA: Some classification methods for idiopathic scoliosis have been suggested. However, poor intraobserver reproducibility and interobserver reliability were experienced in these studies, and were not appropriate for guiding surgical planning. METHODS: A total of 427 surgically treated idiopathic scoliosis cases were reviewed. Preoperative and postoperative standing anteroposterior, lateral, and preoperative supine side-bending radiograph were analyzed using the Scoliosis Research Society definition of scoliosis and curve apex. The resulting classification was tested for intraobserver reliability and interobserver reliability, and by 6 surgeons. Apical frequencies were determined for each type, and prospective surgical testing of the new type and its related fusion guide was performed. RESULTS: Three major types and 13 subtypes were identified, of which the Peking Union Medical College type I accounted for 56.62%, type II 42.16%, and type III 1.22%. The interobserver reliability testing was 85% (kappa coefficient 0.832), while intraobserver reproducibility was 91% (kappa coefficient 0.898). Each type had its corresponding fusion levels. A prospective study of 152 cases was performed according to the classification. All of these cases were followed over 18 months, and no postoperative decompensation was noted. CONCLUSION: The Peking Union Medical College classification of idiopathic scoliosis is one system to combine each type with its corresponding fusion level, and it had much higher interobserver reliability and intraobserver reproducibility than the King system. Further prospectivestudies would help to clarify and expand this system.

Adolescent↗

PubMed2005

Examination of ELN as a candidate gene in the Utah intracranial aneurysm pedigrees.

BACKGROUND AND PURPOSE: A study of intracranial aneurysm (IA) sibpairs suggested association of an ELN haplotype with IA risk. Subsequent linkage analysis of the ELN region on chromosome 7q11 in high-risk Utah IA pedigrees significantly confirmed linkage between IA and the ELN region. METHODS: We have investigated the ELN gene as a potential candidate gene for IA in Utah pedigrees. One IA case from each pedigree, who shared an ELN region haplotype segregating in the pedigree, was screened for mutation. The promoter region, 34 exons, and the 3'UTR (UnTranslated Region) of the ELN gene were screened for variants using DHPLC. RESULTS: Variants were observed in the promoter region, exons 4 and 6, and the 3'UTR. Variants in exon 6 and in one 3'UTR position were unique to Utah. The remaining variants were absent in the controls. There was no evidence for segregation of the ELN variants found in IA cases with the hypothesized chromosome 7 haplotypes segregating in pedigrees. CONCLUSIONS: Our analysis does not support ELN as the gene responsible for familial IA in the linked Utah IA pedigrees.

3' Untranslated Regions↗

PubMed2005

Simultaneous determination of abietane-type diterpenes, flavonolignans and phenolic compounds in compound preparations of Silybum marianum and Salvia miltiorrhiza by HPLC-DAD-ESI MS.

A gradient HPLC-DAD-ESI MS method has been developed for simultaneous determination of multiple bioactive compounds such as abietane-type diterpenes, flavonolignans and phenolic compounds in compound preparations of Silybum marianum and Salvia miltiorrhiza. The separation was completed on an ODS column using 0.5% (v/v) formic acid aqueous solution and methanol as gradient mobiles. Fourteen components can be identified by ESI MS working on ESI(-) and ESI(+) switching mode, respectively. Ten components can be quantified by using external standard method with UV detecting at 254 and 280 nm, respectively. The correlation coefficients of all the calibration curves were found to be higher than 0.992. The recoveries of the standards were about 96-101%. Besides quantification of the components, the chromatograms acquired by this method can be used as the bioactive components fingerprints for the quality control of compound preparations of S. marianum and S. miltiorrhiza.

Abietanes↗

PubMed2005

Autosomal dominant cone dystrophy caused by a novel mutation in the GCAP1 gene (GUCA1A).

PURPOSE: To describe the clinical features and genetic analysis of a family with an autosomal dominant cone dystrophy (adCD). METHODS: Selected members of a family with an autosomal dominant cone dystrophy underwent ophthalmic evaluation. Blood samples were obtained, genomic DNA was isolated, and genomic fragments were amplified by PCR. Linkage to locus D6S1017 was established. DHPLC mutational analysis and direct sequencing were used to identify a mutation in GUCA1A, the gene encoding the guanylate cyclase activating protein 1 (GCAP1). RESULTS: Of 24 individuals who are at risk of the disease in a five generation family, 11 members were affected. Clinical presentations included photophobia, color vision defects, central acuity loss, and legal blindness with advanced age. The disease phenotype was observed in the second and third decades of life and segregated in an autosomal dominant fashion. An electroretinogram performed on one proband revealed profoundly subnormal and prolonged photopic and flicker responses, but preserved scotopic ERGs, consistent with a cone dystrophy. Mutational analysis and direct sequencing revealed a C451T transition in GUCA1A, corresponding to a novel L151F mutation in GCAP1. Like the E155G mutation, this mutation occurs in the EF4 hand domain, a region of GCAP1 critical in conferring calcium sensitivity to the protein. The leucine at this position is highly conserved among vertebrate guanylate cyclase activating proteins. CONCLUSIONS: A novel L151F missense mutation in the EF4 high affinity Ca2+ binding site of GCAP1 is linked to adCD in a large pedigree. The cone dystrophy in this family shares clinical and electrophysiologic characteristics with other previously described adCD caused by mutations in GUCA1A.

Adult↗

PubMed2005

Combined influence of membrane surface properties and feed water qualities on RO/NF mass transfer, a pilot study.

The impact of membrane surface characteristics and NOM on membrane performance has been investigated for varying pretreatment and membranes in a field study. Surface charge, hydrophobicity and roughness varied significantly among the four membranes used in the study. The membranes were tested in parallel following two different pretreatment processes, an enhanced Zenon ultrafiltration process (ZN) and a compact CSF process (Superpulsator (SP)) prior to RO membrane treatment for a total of eight integrated membrane systems. All membrane systems were exposed to the similar temperature, recovery and flux as well as chemical dosage. The membrane feed water qualities were statistically equivalent following ZN pretreatment and SP pretreatment except for NOM and SUVA. Membrane surface characteristics, NOM and SUVA measurements were used to describe mass transfer in a low-pressure RO integrated membrane system. Solute and water mass transfer coefficients (MTCs) were investigated for dependence on membrane surface properties and NOM mass loading. Inorganic MTCs were accurately described by a Gaussian distribution curve. Water productivity decreased with NOM loading and increased with contact angle and roughness. The negative effects of NOM loading on productivity were reduced as the negative charge on the membrane surface increased. Inorganic MTCs were also correlated to surface hydrophobicity and surface roughness. The permeability change of identical membranes was related to NOM loading, hydrophobicity and roughness. Organic fouling as measured by water, organic and inorganic mass transfer was less for membranes with higher hydrophilicity and roughness.

Flocculation↗

PubMed2005

Central role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteins.

The 138 genes encoding the 79 ribosomal proteins (RPs) of Saccharomyces cerevisiae form the tightest cluster of coordinately regulated genes in nearly all transcriptome experiments. The basis for this observation remains unknown. We now provide evidence that two factors, Fhl1p and Ifh1p, are key players in the transcription of RP genes. Both are found at transcribing RP genes in vivo. Ifh1p, but not Fhl1p, leaves the RP genes when transcription is repressed. The occupancy of the RP genes by Ifh1p depends on its interaction with the phospho-peptide recognizing forkhead-associated domain of Fhl1p. Disruption of this interaction is severely deleterious to ribosome synthesis and cell growth. Loss of functional Fhl1p leads to cells that have only 20% the normal amount of RNA and that synthesize ribosomes at only 5-10% the normal rate. Homeostatic mechanisms within the cell respond by reducing the transcription of rRNA to match the output of RPs, and by reducing the global transcription of mRNA to match the capacity of the translational apparatus.

Cell Division↗

PubMed2005

Design, synthesis, and biological evaluation of new territrem B analogues.

Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined.

Antineoplastic Agents↗