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Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 91 records · Page 5Linked to original sources

Molecular cloning and characterization of a novel peptidylprolyl isomerase (cyclophilin)-like gene (PPIL3) from human fetal brain.

During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated two cDNA clones encoding two novel proteins, which show 52% and 72% identity to the cyclophilin isoform 10 of C. elegans, respectively. Sequence analysis revealed these two cDNA clones are two different splicing variants of a novel cyclophilin-like gene (PPIL3). The PPIL3 gene was identified on a completely sequenced BAC (GenBank accession AC005037) from chromosome 2q33 between STS markers stSG2762 (proximal) and SHGC-3074 (distal), oriented toward the telomere. The PPIL3 gene consisted of eight exons spanning more than 18 kb of genomic DNA. RT-PCR analysis indicated that PPIL3 was ubiquitously expressed in adult human tissues.

5' Untranslated Regions↗

Molecular cloning, structure and expression of a novel nuclear RNA-binding cyclophilin-like gene (PPIL4) from human fetal brain.

The cyclophilins are members of a highly conserved, ubiquitous family, and play an important role in protein folding, immunosuppression by cyclosporin A (CsA), and infection of HIV-1 virions. Here we report that a novel member of the cyclophilin family, PPIL4, was cloned and identified during the large-scale sequencing analysis from a human fetal brain cDNA library. The PPIL4 gene encodes a protein which shares 96% amino acid identity with a protein encoded by a putative gene recently cloned from several different early stages of mouse embryo, and its homologues are found in several other organisms. According to bioinformatics analysis, the PPIL4 gene was found to be located in chromosome 6q24-->q25. Besides the PPIase motif, PPIL4 also has an RNA recognition motif (RRM), a pair of bipartite nuclear targeting sequences, and a lysine rich domain. RT-PCR analysis indicated that PPIL4 gene expression is abundant in kidney but has a ubiquitously low expression pattern in other human adult tissues.

Amino Acid Motifs↗

Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window.

BACKGROUND AND PURPOSE: We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. METHODS: Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. RESULTS: Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%). CONCLUSIONS: Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.

Acute Disease↗

Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice.

It has been suggested that increased collagenase-3 (MMP-13) activity plays a pivotal role in the pathogenesis of osteoarthritis (OA). We have used tetracycline-regulated transcription in conjunction with a cartilage-specific promoter to target a constitutively active human MMP-13 to the hyaline cartilages and joints of transgenic mice. Postnatal expression of this transgene resulted in pathological changes in articular cartilage of the mouse joints similar to those observed in human OA. These included characteristic erosion of the articular cartilage associated with loss of proteoglycan and excessive cleavage of type II collagen by collagenase, as well as synovial hyperplasia. These results demonstrate that excessive MMP-13 activity can result in articular cartilage degradation and joint pathology of the kind observed in OA, suggesting that excessive activity of this proteinase can lead to this disease.

Animals↗

The novel gene locus for agenesis of permanent teeth (He-Zhao deficiency) maps to chromosome 10q11.2.

He-Zhao deficiency has been recently characterized with a distinct form of agenesis of permanent teeth that is different from other previously reported disorders of tooth agenesis. This inherited abnormality suggests that some gene(s) associated with the development of permanent teeth may mutate. In this study, we map the gene locus to chromosome 10q11.2. The DNA pooling method combined with two-point and multi-point linkage analysis has been successfully applied. The maximum LOD (Zmax) scores for two-point and multi-point analyses are 13.29 (on marker D10S196) at recombination fraction (theta) = 0 and 18.09 (between markers D10S1772 and D10S1766), respectively. Haplotype analysis confined the locus within an interval of 5.5 cM flanked by markers D10S604 and D10S568. This study has demonstrated a novel gene locus responsible for He-Zhao deficiency and provides a good likelihood for the discovery of one of the genes determining permanent tooth formation and development.

Alleles↗

The role of the tubulointerstitium in radiation-induced renal fibrosis.

The functional and morphological response of the remaining hypertrophied kidney in unilaterally nephrectomized rats to single doses of 0-20 Gy X rays was investigated. Functional and histological end points were assessed serially 4-24 weeks postirradiation. Renal irradiation led to time- and dose-dependent reductions in renal function, seen in terms of a decreased glomerular filtration rate, increased blood urea nitrogen, and reduced hematocrit. These changes were accompanied by morphological changes in the glomerular, tubular and interstitial portions of the kidney. However, dose-dependent changes were observed only in terms of tubulointerstitial lesions. Significant increases in the degree of interstitial staining for collagen type III and fibronectin were observed 24 weeks postirradiation. These increases in extracellular matrix components were accompanied by a significant increase in interstitial alpha smooth muscle actin, suggesting activation of interstitial fibroblasts into myofibroblasts. There was no evidence of glomerular Tgfb after renal irradiation. A significant increase in tubular Tgfb staining was only seen 8 weeks postirradiation. In contrast, there was a shift of staining to the interstitium such that by 24 weeks postirradiation interstitial Tgfb staining was significantly greater than that seen in controls. These findings suggest that the tubule epithelial cell and the interstitial fibroblast are both active participants in the development and/or progression of radiation-induced renal fibrosis.

Animals↗

Diminution of metabolism/blood flow uncoupling following traumatic brain injury in rats in response to high-dose human albumin treatment.

OBJECT: The authors have recently demonstrated that high-dose human albumin is markedly neuroprotective in experimental traumatic brain injury (TBI) and cerebral ischemia. The pathophysiology of TBI involves acute uncoupling of cerebral glucose utilization and blood flow. The intent of this study was to establish whether the use of human albumin therapy in a model of acute TBI would influence this phenomenon. METHODS: Anesthetized, physiologically regulated rats received moderate (1.5-2 atm) fluid-percussion injury to the parietal lobe. Fifteen minutes after trauma or sham injury, rats in one group received human albumin (2.5 g/kg) administered intravenously and those in another group received 0.9% saline vehicle. At 60 minutes and 24 hours posttrauma, autoradiographic studies of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) were conducted, and the LCMRglu/LCBF ratio was determined. Sham-injured rats had normal levels of LCBF and LCMRglu, and no differences between vehicle- and albumin-treated rats were evident. Sixty minutes after TBI, LCBF was moderately reduced bilaterally in vehicle-treated rats, whereas in albumin-treated animals, the LCBF contralateral to the side of injury was generally normal. Despite acutely depressed LCBF, LCMRglu in vehicle-treated rats at 60 minutes was paradoxically normal bilaterally, and foci of elevated LCMRglu were noted in the ipsilateral hippocampus and thalamus. By contrast, in albumin-treated rats studied 60 minutes post-TBI, reduced LCMRglu values were measured in the ipsilateral caudoputamen and parietal cortex, whereas LCMRglu in other ipsilateral and contralateral sites did not differ from that measured in sham-injured animals. The metabolism/blood flow ratio was normal in sham-injured rats, but became markedly elevated in vehicle-treated rats 60 minutes post-TBI (on average, by threefold ipsilaterally and 2.1-fold contralaterally). By contrast, the mean metabolism/blood flow ratio in albumin-treated animals was elevated by only 1.6-fold ipsilaterally and was normal contralaterally. Twenty-four hours after TBI, LCBF contralateral to the side of injury had generally returned to normal levels in the albumin-treated group. CONCLUSIONS: These results demonstrate that human albumin therapy benefits the posttraumatic brain by diminishing the pronounced metabolism > blood flow dissociation that would otherwise occur within the 1st hour after injury. Viewed together with our previous evidence of histological neuroprotection, these findings indicate that human albumin therapy may represent a desirable treatment modality for acute TBI.

Acute Disease↗

Shifting-sand control in central Tibet.

The middle reaches of the Yarlung Zangbo, the Lhasa, and the Nianchu rivers form the center of politics, economy, and culture in the Tibetan Autonomous Region. Due to the fragility of the natural environment and overexploitation of land by the local people, desertification is becoming a serious problem in the valleys. Shifting sands cover an area of 578 km2 and have caused problems such as damage to farmland and grassland, traffic blockage and burying of water projects. This paper discusses strategies and techniques for combating shifting sands, including reformation of the agricultural structure, exploitation of new sources of energy, and combinations of mechanical and biotic measures. Using mechanical measures, straw barriers, and gravel layer covers, artificial vegetation can be established on the mobile sand dune by sowing and planting introduced species.

Agriculture↗

[Effect of silver carp stocking and fertilization on plankton community in enclosures in saline-alkaline ponds].

The effect of silver carp (Hypophthalmichthys molitrix) stocking and fertilization on plankton community of enclosures ecosystem in saline-alkaline ponds were studied. After stocking silver carp in enclosures, the abundance, chlorophyll-a content and primary productivity of phytoplankton increased, and the biomass of phytoplankton was mainly composed by small species, such as diatom and green algae. Moreover, Euglnophyta and Chrysophyta were also subdominant species. The biomass of zooplankton decreased with fish stocking, and that of Cladocera was greater in control than in fish-culture enclosures. Zooplankton community was dominated by larger species such as Daphnia carinata in control enclosures. Fertilization, especially applying inorganic fertilizer, significantly increased the abundance and primary productivity of phytoplankton and the biomass of zooplankton. Although the biomass of plankton in the enclosures applied organic fertilizer was greater than that of control enclosures, the primary productivity and chlorophyll-a content of phytoplankton, the diversity index of plankton, and the P/R ratio were very low, and thus, silver carp grew slowly. The effect of filter feeding fish and applying fertilizer on the structure of plankton community was also discussed.

Animals↗

Effect of all-trans retinoic acid and arsenic trioxide on tissue factor expression in acute promyelocytic leukemia cells.

OBJECTIVE: To study the effect of all-trans retinoic acid (ATRA) and arsenic troxide (As2O3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. METHODS: PCA from freshly isolated APL blasts from APL patients treated with ATRA or As2O3 was detected using a one-stage clotting assay. TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitive (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line, as well as U937 cells infected with pMSCV-PML-RARa treated with or without ATRA or As2O3, were also examined. RESULTS: Both ATRA and As2O3 can down-regulate the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro, in a time-dependent manner. The TF antigen level in PML-RARa + U937 cells was significantly higher than that in U937 cells infected with retrovirus vector. Both ATRA and As2O3 can also down-regulate the TF antigen in U937 cells transfected with or without PML-RARa. CONCLUSION: Tissue factor expression and PCA in APL cells may be down-regulated by ATRA and As2O3. By down-regulating TF expression, As2O3 might also be used to improve the DIC-related hemorrhage in APL. Our data indicate that elevated TF antigen in PML-RARa + U937 may be related to the fusion protein PML-RARa. The down-regulating effect of ATRA and As2O3 on TF expression in U937 cells might not involve this fusion protein.

Adolescent↗

[Correlation between the biological behavior and invasion potential in three mouse melanoma cell lines].

OBJECTIVE: To study the correlation between biological behavior and invasion potential in three homologous mouse melanoma cell lines (B16, B16F10, B16BL6). METHODS: The invasion potential of melanoma cells was assayed in a Transwell cell culture chamber. Melanin content was determined by the A value (optical density) at 470 nm in spectrophotometry. Tumor cells migration within the 3-D collagen matrix was microscopically recorded with a time-lapse video recorder and computer-assisted cell tracking system. Gelatin zymography was adopted to assay the type IV collagenase secretion. A PCR-based telomeric repeat amplification protocol (TRAP) was used for assaying telomerase activity. RESULTS: B16BL6 and B16F10 cells showed higher invasion potential than B16, but the melanin content in B16F10 was very low. B16F10 and B16BL6 possessed a higher migration ability, secreting much more type IV collagenase than the B16 though without significant difference as discovered in telomerase activity of the three melanomas cell lines. CONCLUSION: Invasion capability of mouse melanoma is closely correlated to tumor cells migration ability and secretion of type IV collagenase. Melanin content and telomerase activity are not related to the invasion ability of mouse melanoma cells.

Animals↗

[Correlation of the metabolism of oxygen free radical in ovary, uterine muscle and vein blood with the pathogenesis of endometriosis or endometrioma].

OBJECTIVE: To investigate the correlation of metabolism disturbance of oxygen free radical (OFR) with endometriosis and endometrioma, to provide an evidence for the diagnosis and treatment. METHODS: (1) The lipid peroxide (LPO), selenium (Se), superoxide dismutase (SOD) and vitamin E (VE) levels were respectively in the vein blood, ovary tissue of the chocolate cyst wall and chocolate cyst fluid in 32 operated patients with endometriosis (endometriosis group). (2) The levels above were determined separately in 23 operated patients with endometrioma (endometrioma group) and 30 cases of hysteroma (control group). RESULTS: (1) The LPO levels in vein blood and ovary tissue of endometriosis group were (6.357 +/- 1.251) mumol/L and (3.735 +/- 1.546) nmol/g protein. Which significantly higher than those of control group (P < 0.01). On the other hand, the Se. SOD. VE levels in endometriosis group were significantly lower than those in control group (P < 0.01-< 0.05). (2) The LPO level in ovary chocolate cyst fluid was higher than that in vein blood itself and control group. (P < 0.01). (3) The LPO levels in vein blood and uterine muscle of endometrioma was (5.882 +/- 1.711) mumol/L and (2.937 +/- 1.577) nmol/g protein, they were higher-than these in control group (3.547 +/- 1.640) mumol/L, (1.754 +/- 0.833) nmol/g protein, (P < 0.01). While, the Se. VE. SOD level tween the SOD level in uterine muscle tissue of endometriomin vein blood is significantly higher than those in control group (P < 0.01). There is no difference bea and control group (P > 0.05). CONCLUSION: The endome triosis and endometrioma is related to the produce or metabolistic imbalance of oxygen free radical, and so to the increasing of lipid peroxide.

Endometriosis↗

Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension.

OBJECTIVE: To determine whether the polymorphism A1166C in the angiotensin II type 1 receptor (AT1R) gene is associated with essential hypertension. METHODS: A case-control study was carried out using 125 hypertensive and 103 normotensive subjects. The A-->C variant at position 1166 (A1166C) of the AT1R gene was identified by polymerase chain reaction (PCR) and PCR/restriction fragment length polymorphism (PCR/RFLP) analysis. The digestion products were separated on 2% agarose gels and visualized with ethidium bromide under ultraviolet ray. RESULTS: The differences in C1166 allele frequency and in the AC genotype distribution of the AT1R gene between the hypertensive and normotensive groups were statistically significant (C allele: 0.092 vs 0.034, chi 2 = 6.186, P < 0.05; AC genotype: 0.184 vs 0.068, chi 2 = 6.654, P < 0.05). CONCLUSION: The AC genotype is associated with essential hypertension, and the C allele may be a marker for predisposition to hypertension in Chinese Han population.

Alleles↗

[A study of tissue factor expression and hemostatic molecular markers in patients with acute promyelocytic leukemia].

OBJECTIVES: To study the changes of tissue factor expression and hemostatic molecular markers in acute promyelocytic leukemia during all-trans retinoic acid (ATRA) or arsenic trioxide (AS(2)O(3)) treatment. METHODS: The plasma level of tissue factor (TF), tissue factor pathway inhibitor(TFPI), thrombin antithrombin complex(TAT), plasmin antiplasmin complex(PAP), urokinase type plasminogen activator(u-PA), urokinase type plasminogen activator receptor(u-PAR) and the TF level of bone marrow blasts lysate were measured by ELISA. Transcription of TF mRNA was detected by RT-PCR. RESULTS: The plasma levels of TF [(98.3 +/- 19.8) ng/L, (89.6 +/- 15.2) ng/L], TFPI [(94.4 +/- 37.0) mg/L, (93.5 +/- 36.4) mg/L], TAT [(21.9 +/- 9.6) microg/L, (18.2 +/- 9.7) microg/L[, PAP [(0.73 +/- 0.26) mg/L, (0.63 +/- 0.33) mg/L], u-PA [(0.63 +/- 0.23) microg/L, (0.57 +/- 0.01) microg/L] and u-PAR [(0.41 +/- 0.14) microg/L, (0.47 +/- 0.16) microg/L], the TF of bone marrow blasts lysate [(680.24 +/- 456.61) pg/10(7), (368.02 +/- 151.2) pg/10(7)] and transcription of mRNA were all remarkably elevated at the time of diagnosis. They all decreased after ATRA and AS(2)O(3) administration. CONCLUSIONS: There is over expression of TF, activation of coagulation system and hyperfibrinolysis, in patients with acute promyelocytic leukemia, these can be ameliorated with clinical improvement. All-trans retinoic acid and arsenic trioxide down-regulate the expression of TF mRNA and decrease the TF contents in APL blasts. However, there is also high plasma level of TF and TAT indicating the existence of hypercoagulability after remission.

Adult↗

[An experimental study on the relationship between early myocardial injury and the in situ expression of TNFalpha mRNA in burned rats with endotoxemia].

OBJECTIVE: To observe the in situ expression of TNF mRNA and protein in myocardial cell, so as to explore the possible mechanism of early myocardial injury in scalded rats with endotoxemia. METHODS: One hundred and seventy eight Wistar rats inflicted with 20% TBSA III degree napalm burn compound with endotoxemia and multiple organ injury were employed as the model and were randomly divided into four groups as follow. (1) burn and infusion group (BI): the rats were burned and infused with endotoxin. (2) simple burn group (S): the rats were burned only. (3) simple endotoxin infusion group (EI): the rats were only infused with endotoxin. (4) normal control (C). The observation time points were designed to be 0.5, 1, 3, 6, 12, 24 and 48 postburn hours (PBH). The morphological and functional changes in rat myocardium, the change in serum TNFalpha, the cellular location and distribution of TNFalpha mRNA and proteins were observed by light microscope (LM), electronic microscope (EM), ELISA, immunohistochemistry and in situ hybridization staining. RESULTS: There exhibited a series of pathomorphological changes in the myocardium at early postburn stage in rats of BI group, such as wavy degeneration of myocardial fibers, the formation of contractile bands, fragmentation of myocardial fibers and focal cytoplasmic lysis, etc. The left ventricular systolic pressure (LVSP) and the maximum change rate of intraventricular pressure (plus minus dp/dtmax) decreased significantly (P < 0.01). Serum TNFalpha level increased obviously at 1 PBH (P < 0.01) and peaked at 3 similar 6 PBH. It was found that TNFalpha mRNA was principally located in myocardial cells and in a part of inflammatory cells. But these milder pathomorphological changes in myocardial injury were found in rats of S and EI groups. In addition, there appeared elapsed TNFalpha peak values and relative weaker expression of myocardial TNFalpha mRNA. CONCLUSION: TNFalpha mRNA and protein could be expressed in myocardium in burned rats with endotoxemia which might be one of the origins of TNF in participating in the development of early postburn myocardial structural and functional injury.

Animals↗

[Study on endothelial cell injury in women with pregnancy induced hypertension].

OBJECTIVE: To investigate the mechanisms of endothelial cell injury in women with pregnancy induced hypertension (PIH). METHODS: Human umbilical endothelial cells were cultured in the serum from 10 women with severe PIH and 10 normal pregnant women, and co-cultured with neutrophils or not for 48 hrs. The morphology and cell cycles were studied. RESULTS: Without neutrophils, no apoptotic cells were observed, while neutrophils were added, apoptotic cells were obviously detected. The percentage of apoptotic cells in PIH was more than that in non-PIH. The percentage of cells in G2/M phase decreased in all the groups, but there were no significant differences among them. CONCLUSIONS: Endothelial cells were injured indirectly in PIH patients. Activated neutrophils induced apoptosis might be one of the answers.

Adult↗

[The effects of otitis media with effusion and hearing loss on the speech outcome after cleft palate surgery].

OBJECTIVE: To find out the exact effect of OME and hearing loss on the speech outcome post palatoplasty in cleft palate patients. METHODS: Otoscopy and tympanometry were performed in 18 cleft palate patients whose ages ranged from 5 to 23 years old and hearing thresholds were also tested before cleft palates repair. All patients were followed up from 3 to 18 months postoperatively. Articulation scores were evaluated and linear correlation analysis was performed between these results and their mean hearing thresholds for air conduction in speech frequencies before the palate closure. The incidences of the OME were compared among the groups with different articulation scores. RESULTS: The postoperative articulation scores correlate negatively (r = -0.504, P = 0.032 < 0.05) to the degrees of hearing loss. But the incidences of OME had no significant differences among the groups with different articulation scores. CONCLUSIONS: The hearing level preoperation is more important than tympanometric data on the foresight of the speech result postoperation in cleft palate patients.

Adolescent↗

[Studies of the resistance of the recombinant alphavirus RNAs containing dengue-2 PrM gene to virus infection].

The amplified PrM gene of dengue-2 virus was cloned into the downstream SP6 promoter-pSFV vector and the recombinant plasmid (pSF.rM2) DNA which contained sense- or antisense-PrM gene, was selected. pSF.rM2 DNA and helper DNA linearized by the enzyme SpeI digestion were both transcribed in vitro into recombinant RNAs which contained the capping analog on the 5'-end and contaansfected into BHK cells by electroportation. The the transfected host cells were challenged with dengue-2 virus and the resistant efficiency of recombinant virus RNAs containing sense- or antisense-PrM gene to virus infection were observed, respectively. The recombinant plasmids (pSFV-PrM) containing sense- or antisense-PrM gene were selected with determination of the nucleotide sequence. The recombinant virus particles were obtained with recombinant RNA and helper RNA co-transfected into BHK cells. Host cells transfected with antisense-PrM RNA derived complete resistance to dengue-2 virus replication and the efficiency was higher than that of the recombinant virus RNA containing sense-PrM gene.

Alphavirus↗