Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

At least 271 records · Page 15Linked to original sources

PubMed2005

Follicular aspiration during the selection phase prevents severe ovarian hyperstimulation in patients with polycystic ovary syndrome who are undergoing in vitro fertilization.

OBJECTIVE: The objective was to assess the effectiveness of follicular aspiration in the selection phase of infertile women with polycystic ovary syndrome (PCOS) under controlled ovarian hyperstimulation (COH). STUDY DESIGN: In group A, 13 infertile patients with PCOS failed at previous IVF or intracytoplasmic sperm injection (ICSI) treatment due to ovarian hyperstimulation syndrome (OHSS; a total of 13 cycles). In group B, new IVF cycles with ultrasound-guided transvaginal follicular aspirations during the selection phase (a total of 13 cycles) were conducted using the same patients. No more than ten follicles remained in bilateral ovaries. Parameters monitored included ovarian size, number of dominant follicles, estradiol (E2) level on the day of human chorionic gonadotrophin (HCG) injection, maturation of oocytes, fertilization rate, cleavage rate, embryo implantation rate, pregnancy rate, and level of serum hormone. RESULTS: In group B, the average number of follicles>or=12 mm and average serum E2 level were 15.5+/-4.0 and 9899+/-1430 pmol/l, respectively, which were significantly lower than 29.1+/-8.4 (P<0.001) and 15,544+/-1766 pmol/l (P<0.001) in group A. No cycles with moderate or severe OHSS occurred in group B, while nine out of 13 (69.2%) cycles did have this problem in group A. Oocyte maturation rate, fertilization rate and cleavage rate in group B were 80.7%, 76.9%, and 80.3%, respectively; and all of them are significantly higher than 56.4% (P<0.01), 58.7% (P<0.01), and 70.2% (P<0.02) respectively in group A. CONCLUSION: Follicular aspiration during the selection phase can prevent severe OHSS and reduce OHSS prevalence in patients with PCOS undergoing COH.

Adult↗

PubMed2005

Carriers of three polymorphisms of cholesteryl ester transfer protein gene are at increased risk to coronary heart disease in a Chinese population.

BACKGROUND: The cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissue to the liver and the polymorphism in the CETP gene may therefore alter the susceptibility to coronary heart disease (CHD). The aim of the present study was to screen the CETP gene for new single nucleotide polymorphisms (SNPs) and to determine whether SNPs at important cholesterol metabolism gene loci might exert effects on the risk to CHD in Chinese. METHODS: Genomic DNA samples were collected from 203 Chinese patients with CHD and 209 age- and gender-matched controls. The coding region, adjacent intronic sequences and promoter region (totally 5501 bp) of the CETP gene were screened based on a combination of polymerase chain reaction, denaturing high performance liquid chromatography and DNA sequencing. The association of individual single nucleotide polymorphisms with CHD was assessed by univariate, multivariate analysis and haplotype analysis. RESULTS: Fifteen SNPs were identified in the CETP gene including 12 novel ones, of which, 3 were in promoter region, 1 in exon 10, and other 9 in introns. The frequencies of -644C, +13054T, 296Q, and 442G alleles were considerably higher, while the frequency of +9907A allele lower, in CHD patients than those in controls (p=0.016, p=0.043, p=0.006, p=0.006, and p=0.029, respectively). The results of individual polymorphism analyses were confirmed by haplotype analysis for the combination of these 5 SNPs. The -644A/C, L296Q, and D442G polymorphisms were found to be associated with CHD in this Chinese population by multivariate analysis (p=0.009, p=0.024, and p=0.007, respectively). The adjusted odds ratio for the development of CHD for the -644C allele carriers was 1.63 compared with -644AA genotype (95% CI 1.05-2.78; p<0.01), 1.71 for the 296Q allele carriers relative to 296LL genotype (95% CI 1.10-2.89; p<0.05), and 1.31 for the 442G allele carriers relative to 442DD genotype (95% CI 1.02-2.56; p<0.01), respectively. CONCLUSIONS: There is a significant relation between the polymorphisms in the CETP gene and the development of CHD, and individuals homozygous or heterozygous for the -644C, 296Q, and 442G alleles of the CETP gene are at increased risk to develop CHD in this Chinese population.

Asian People↗

PubMed2005

Donor lymphocyte infusion induces long-term donor-specific cardiac xenograft survival through activation of recipient double-negative regulatory T cells.

Previous studies have shown that pretransplant donor lymphocyte infusion (DLI) can enhance xenograft survival. However, the mechanism by which DLI induces xenograft survival remains obscure. Using T cell subset-deficient mice as recipients we show that CD4+, but not CD8+, T cells are necessary to mediate the rejection of concordant cardiac xenografts. Adoptive transfer of naive CD4+ T cells induces rejection of accepted cardiac xenografts in CD4-/- mice. This rejection can be prevented by pretransplant DLI in the absence of any other treatment. Furthermore, we demonstrate that DLI activates alphabeta-TCR+CD3+CD4-CD8- double-negative (DN) regulatory T (Treg) cells in xenograft recipients, and that DLI-activated DN Treg cells can inhibit the proliferation of donor-specific xenoreactive CD4+ T cells in vitro. More importantly, adoptive transfer of DLI-activated DN Treg cells from xenograft recipients can suppress the proliferation of xenoreactive CD4+ T cells and their ability to produce IL-2 and IFN-gamma in vivo. Adoptive transfer of DLI-activated DN Treg cells also prevents CD4+ T cell-mediated cardiac xenograft rejection in an Ag-specific fashion. These data provide direct evidence that DLI can activate recipient DN Treg cells, which can induce donor-specific long-term cardiac xenograft survival by suppressing the proliferation and function of donor-specific CD4+ T cells in vivo.

Adoptive Transfer↗

PubMed2005

Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI.

Using MRI, we investigated dynamic changes of brain angiogenesis after neural progenitor cell transplantation in the living adult rat subjected to embolic stroke. Neural progenitor cells isolated from the subventricular zone (SVZ) of the adult rat were labeled by superparamagnetic particles and intracisternally transplanted into the adult rat 48 h after stroke (n = 8). Before and after the transplantation, an array of MRI parameters were measured, including high resolution 3D MRI and quantitative T1, T1sat (T1 in the presence of an off-resonance irradiation of the macromolecules of brain), T2, the inverse of the apparent forward transfer rate for magnetization transfer (kinv), cerebral blood flow (CBF), cerebral blood volume (CBV), and blood-to-brain transfer constant (Ki) of Gd-DTPA. The von Willerbrand factor (vWF) immunoreactive images of coronal sections obtained at 6 weeks after cell transplantation were used to analyze vWF immunoreactive vessels. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. In the ischemic boundary regions, angiogenesis confirmed by an increase in vascular density and the appearance of large thin wall mother vessels was coincident with increases of CBF and CBV (CBF, P < 0.01; CBV, P < 0.01) at 6 weeks after treatment, and coincident with transient increases of K(i) with a peak at 2 to 3 weeks after cell therapy. Relative T1, T1sat, T2, and kinv decreased in the ischemic boundary regions with angiogenesis compared to that in the non-angiogenic ischemic region (T1, P < 0.01 at 6 weeks; T1sat, P < 0.05 at 2 to 6 weeks; T2, P < 0.05 at 3 to 6 weeks; kinvP < 0.05 at 6 weeks). Of these methods, Ki appear to be the most useful MR measurements which identify and predict the location and area of angiogenesis. CBF, CBV, T1sat, T1, T2, and kinv provide complementary information to characterize ischemic tissue with and without angiogenesis. Our data suggest that select MRI parameters can identify the cerebral tissue destined to undergo angiogenesis after treatment of embolic stroke with cell therapy.

Algorithms↗

PubMed2005

Role of integrin alpha1beta1 in the regulation of renal medullary osmolyte concentration.

The mechanism by which cells sense extracellular tonicity and trigger the accumulation of protective organic osmolytes is poorly understood. It has been proposed that changes in cell volume following alteration of extracellular toncity are important initiators of signaling events that lead to osmolyte accumulation. Because the extracellular matrix receptors integrins are linked to the cytoskeleton and can transduce signals that alter cell behavior, we investigated the role of these receptors in the modulation of osmolyte accumulation in the kidney medulla under different osmotic conditions. We show that integrin alpha1-null mice have impaired ability to accumulate organic osmolytes in the inner medulla due to altered signaling and decreased induction of osmolyte transporters or aldose reductase gene transcription. Utilizing inner medullary collecting duct cells, we demonstrate that the lack of integrin alpha1beta1 results in an impaired ability to induce the tonicity enhancer-binding protein TonEBP under hypertonic conditions. Furthermore, under the same conditions, integrin alpha1-null cells show prolonged ERK1/2 phosphorylation and decreased inositol uptake compared with control cells. The reduction of inositol uptake is significantly reversed by treatment with the MEK inhibitor PD-98059. Finally, integrin alpha1-null mice develop morphological changes of early tubular necrosis and increased apoptosis of renal medullary cells following dehydration. Together, these results show that integrin alpha1beta1 is an important mediator of the compatible osmolyte response in the medulla of the mammalian kidney.

Aldehyde Reductase↗

PubMed2005

Impact of inhibition of Qo site of mitochondrial complex III with myxothiazol on persistent sodium currents via superoxide and protein kinase C in rat hippocampal CA1 cells.

Inhibition of Qo site of mitochondrial complex III under hypoxia has received attention, but its downstream pathways remain unclear. We used Qo site inhibitor myxothiazol to mimic the inhibition of the Qo site of complex III and studied the effects of the inhibition of this site on persistent and transient sodium currents and neuron excitability in rat hippocampal CA1 cells. The results showed myxothiazol apparently increased persistent sodium currents but with a weak effect on transient sodium currents; the effect of myxothiazol on persistent sodium currents was blocked by protein kinase C inhibitor and superoxide scavengers, but not by hydrogen peroxide scavenger and hydroxyl radical formation inhibitor; myxothiazol could increase the activity of protein kinase C and neuron excitability. These results suggest that the inhibition of Qo site of mitochondrial complex III increases persistent sodium currents via superoxide production and protein kinase C activation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2005

HIV incidence and factors contributed to retention in a 12-month follow-up study of injection drug users in Sichuan Province, China.

HIV-1 seroconversion and subtype were evaluated, and factors associated with cohort retention were analyzed for subjects' baseline sociodemographic and behavioral characteristics in a 12-month follow-up study of injection drug users (IDUs). In November 2002, a community-based baseline survey was conducted to recruit 333 HIV-seronegative IDUs for a prospective cohort study in Xichang County of Sichuan Province, China. During the 12-month follow-up period, HIV incidence was 3.17 per 100 person-years (95% confidence interval [CI]: 0.98, 5.37), and all subtypes of 8 HIV-1 seroconversions were CRF_07BC. The retention rate at the 12-month follow-up visit was 70.3% (234 of 333 subjects). In a multiple logistic regression model, ethnicity (OR = 0.60, 95% CI: 0.34, 1.04) and appearing at the 6-month follow-up visit (OR = 9.03, 95% CI: 5.14, 15.89) were independently associated with retention. No drug-using or sexual behaviors were found to be associated with retention. This study confirmed one of drug-trafficking routes in mainland China, from Yunnan to Sichuan and then to Xinjiang. This study also suggested that HIV is spreading rapidly to more geographic areas along drug-trafficking routes in China, and a short-term follow-up rate may predict a long-term retention rate in this IDU cohort.

Adult↗

PubMed2005

Effects of Zn pre-exposure on Cd and Zn bioaccumulation and metallothionein levels in two species of marine fish.

Zinc is an essential trace metal but also a potential toxicant to aquatic organisms. In this study, two juvenile marine fish species, the black sea bream Acanthopagrus schlegeli and the grunt Teraponjarbua, were pre-exposed to Zn either from waterborne (0.74-170 microg L-1) or dietary (39-5926 microg g-1) Zn for 1 or 3 weeks. The concentrations of Zn and metallothionein (MT) in the whole body of the black sea bream and in the gills, viscera and carcass of the grunt were then measured during this pre-exposure. Following the pre-exposure, both fish species were then exposed to 109Cd and 65Zn labeled food or water to quantify the dietary assimilation efficiency (AE) and the uptake rate of dissolved Cd and Zn. Zn concentrations in both fish species were enhanced after pre-exposure, but the increases were much less than the increase of ambient Zn pre-exposure concentration. Following Zn pre-exposure, MT concentrations in the viscera and carcass were significantly elevated, whereas the MT levels were not significantly elevated in the gills. Waterborne and dietary Zn exposure enhanced the uptake rates of dissolved Cd and Zn in both fish. The maximum increases of uptake rate constants of dissolved Cd and Zn were up to 1.9-2.8 and 2.1-2.6 times, respectively, in the seabream and grunt. In contrast, dietary assimilation efficiency of Cd and Zn was not significantly enhanced following Zn pre-exposure. A positive linear relationship was found between the uptake rate constants of dissolved metals and Zn or MT concentrations in the fish. The results suggested that Zn pre-exposure increased the potential of metal uptake from ambient water, but had little effect on dietary metal uptake. Furthermore, the Zn body concentration and metal uptake from the dissolved phase were significantly dependent on the fish body size.

Analysis of Variance↗

PubMed2005

Assessing combination treatments in acute stroke: preclinical experiences.

BACKGROUND: Acute ischemic stroke is a complex disease. Treatment success may require combining different therapeutic approaches. An obvious treatment combination in acute ischemic stroke is a thrombolytic therapy, adjuvant with a neuroprotective agent to have better stroke recovery. SUMMARY OF REVIEW: Complete factorial designs can assess the synergy of combination treatments and distinguish them from supper-additive, additive or sub-additive effects. A factorial design, a two-way analysis of variance and a novel graphic technique can detect and illustrate interactions of two treatments, which were used to evaluate combination treatments to extend the therapeutic window for thrombolytic therapy in an embolic stroke model on rats. We hypothesized synergy or additive effects on stroke recovery when combining thrombolytic therapy with either an antagonist to the integrin CD11b/CD18 (UK-279,276) or a glycoprotein IIb/IIIa receptor inhibitor. CONCLUSIONS: Factorial designs offer an efficient approach to study synergistic effects of two treatments. Our graphical technique provides a powerful, intuitive and quantitative explanation of joint treatment effects. Combining thrombolytic therapy with a neuroprotectant yielded a super-additive or additive treatment effect for two preclinical experiments designed to extend the thrombolytic therapeutic window for stroke.

Analysis of Variance↗

PubMed2005

Relationship structures and semantic type assignments of the UMLS Enriched Semantic Network.

OBJECTIVE: The Enriched Semantic Network (ESN) was introduced as an extension of the Unified Medical Language System (UMLS) Semantic Network (SN). Its multiple subsumption configuration and concomitant multiple inheritance make the ESN's relationship structures and semantic type assignments different from those of the SN. A technique for deriving the relationship structures of the ESN's semantic types and an automated technique for deriving the ESN's semantic type assignments from those of the SN are presented. DESIGN: The technique to derive the ESN's relationship structures finds all newly inherited relationships in the ESN. All such relationships are audited for semantic validity, and the blocking mechanism is used to block invalid relationships. The mapping technique to derive the ESN's semantic type assignments uses current SN semantic type assignments and preserves nonredundant categorizations, while preventing new redundant categorizations. RESULTS: Among the 426 newly inherited relationships, 326 are deemed valid. Seven blockings are applied to avoid inheritance of the 100 invalid relationships. Sixteen semantic types have different relationship structures in the ESN as compared to those in the SN. The mapping of semantic type assignments from the SN to the ESN avoids the generation of 26,950 redundant categorizations. The resulting ESN contains 138 semantic types, 149 IS-A links, 7,303 relationships, and 1,013,876 semantic type assignments. CONCLUSION: The ESN's multiple inheritance provides more complete relationship structures than in the SN. The ESN's semantic type assignments avoid the existing redundant categorizations appearing in the SN and prevent new ones that might arise due to multiple parents. Compared to the SN, the ESN provides a more accurate unifying semantic abstraction of the UMLS Metathesaurus.

Semantics↗

PubMed2005

Role of intestinal first-pass metabolism of baicalein in its absorption process.

PURPOSE: The aim of the present study was to investigate the role of intestinal first-pass metabolism of baicalein (B) in its absorption process. METHODS: The intestinal absorption of B was characterized using Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model. In addition, preliminary metabolic kinetics of B was evaluated in both rat and human intestinal S9 fractions. RESULTS: B was well absorbed and extensively metabolized to baicalin (BG), baicalein-7-O-beta-glucuronide, in rat intestinal perfusion model, whereas less extent of metabolism was observed in the Caco-2 cell monolayer model. Moreover, BG generated in the intestinal epithelium during the absorption of B also rapidly transported to both the apical side (the apical chamber of Caco-2 model and the perfusate of the intestinal perfusion model) as well as the basolateral side of the small intestine (the basal chamber of Caco-2 model and the mesenteric vein of the intestinal perfusion model). From the preliminary metabolic studies, it was found that a higher loading dose of B resulted in a less extent of metabolism in intestine. In addition, the extent of metabolism of B was similar in jejunum and ileum when 50 microM of B was perfused through different sections of rat small intestine. CONCLUSION: The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability.

Animals↗

PubMed2005

Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA) derivatives: key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease.

(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.

Alkylation↗

PubMed2005

Fenvalerate modifies T-type Ca2+ channels in mouse spermatogenic cells.

Prior to fertilization sperm must undergo the acrosome reaction that is initiated by opening of T-type Ca(2+) channel. Hence, T-type Ca(2+) channels could be a potential target for agents affecting the acrosome reaction. Our previous data have suggested that fenvalerate, a type II pyrethroid, inhibited the acrosome reaction in mice. To elucidate its potential mechanism we investigated fenvalerate's effect on T-type Ca(2+) channels in mouse pachytene spermatocytes using a whole-cell patch clamp technique. Fenvalerate significantly inhibited T-type Ca(2+) currents in a concentration-dependent manner. The maximal inhibitory concentration was 1 microM. The inhibitory effect of fenvalerate was slow and irreversible after washout of the drug. The curves of activation and inactivation simultaneously shifted to hyperpolarization, about 14 mV, suggesting the open time of Ca(2+) channel was unchanged. Voltage-dependent gating of Ca(2+) channel indicated a change in permeability to ions that contributed to fenvalerate's inhibition on Ca(2+) current. Taken together with our previous findings, these data suggest that the changes of T-type Ca(2+) currents contribute to the suppression of acrosome reaction and fertilizing ability caused by fenvalerate.

Animals↗

PubMed2005

Phase II randomized study comparing the toxicity profile of gemcitabine plus cisplatin with gemcitabine plus oral etoposide in the treatment of advanced non-small cell lung cancer.

OBJECTIVE: This is a randomized phase II study designed to compare the toxicity profile of a non-platinum-based with a platinum-based regimen in the treatment of advanced non-small cell lung cancer. METHODS: Eighty-nine chemotherapy-naïve patients were randomized either to gemcitabine (1,000 mg/m2, 30-min infusion on days 1, 8 and 15) and oral etoposide (50 mg, days 1-14; GE group) or gemcitabine at the same schedule and cisplatin (75 mg/m2 on day 15; GP group). The primary endpoint is toxicity, and secondary endpoints include response rate, survival outcome and quality of life (QOL). RESULTS: The incidence of WHO grade 3 or 4 anemia, neutropenia and thrombocytopenia was 29, 44 and 22% (GE group), and 28, 49 and 23% (GP group), respectively (p = 0.75, 0.95 and 0.87, respectively). The rate of grade 2 or above nausea was numerically higher in the GP arm, but the difference was not statistically significant (GE 15.5%, GP 27.7%, p = 0.20). The rate of vomiting in the GE and GP arms was 20.0 and 20.5%, respectively (p = 0.96). However, subjective changes in QOL scores on nausea and vomiting were significantly higher in the GP arm (p = 0.001). Other symptoms including sore mouth and hair loss were significantly higher in the GE arm (p = 0.003 and 0.007, respectively). There were also significant differences observed in emotional (p = 0.014), cognitive (p = 0.028) and social functioning (p = 0.034) in favor of GP. The differences in tumor response (35.5 and 46.5% for GE and GP, respectively) were not significantly different. Median time to disease progression (33.8 and 40.7 weeks, respectively) and overall survival (41.4 and 57.3 weeks, respectively) were of borderline significance in favor of the GP arm (p = 0.055). CONCLUSION: This toxicity profile of GE is similar to GP, but the apparent inferior efficacy may discourage further investigation.

Adenocarcinoma↗

PubMed2005

Role of nitric oxide in Parkinson's disease.

As a signal molecule, nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of vascular, respiratory, immune, muscular, and nervous systems. NO and its derivatives are also involved in the pathogenic processes in various types of diseases including, but not limited to, neurodegenerative disorders. Although the molecular mechanisms of how NO contributes to diseases are not completely understood, studies have shown that NO may cause neuronal injury and death by mediation of excitotoxicity, damage of DNA, and/or modification of proteins. Understanding the pathogenic mechanisms of NO and its role in Parkinson's disease (PD) and other neurodegenerative diseases may help to develop novel neuroprotective therapies for these diseases.

Animals↗

PubMed2005

A specific role of integrin Mac-1 in accelerated macrophage efflux to the lymphatics.

In response to injury, monocytes migrate to the site of inflammation, where they differentiate into macrophages and participate in various biologic processes. However, their fate during the resolution of acute inflammation is not fully understood. Here, we show that inflammatory macrophages do not die locally by apoptosis; rather, they migrate across the peritoneal mesothelium to the lymphatics, through which they further migrate to the lymph nodes and to the blood circulation. Macrophage efflux is enhanced considerably on cell activation, and such accelerated macrophage migration is dependent specifically on integrin Mac-1, and can be blocked by addition of its antagonist. Thus, genetic inactivation of Mac-1 in mice inhibits the accelerated macrophage efflux from the inflammatory site to the lymphatics, but it does not compromise the accumulation of blood monocytes into the inflammatory site. Together, our study demonstrates that Mac-1 is involved specifically in the efflux of activated macrophages to the lymphatics, suggesting that Mac-1 may play an important role in the removal of local inflammatory macrophages and in their subsequent migration to the lymph nodes, a process that is critical to the development of the adaptive immunity.

Animals↗

PubMed2005

[The preparation, structure evaluation and preliminary application of biomimetic biphasic calcium phosphate scaffold].

OBJECTIVE: To fabricate biomimetic biphasic calcium phosphate BCP ceramic scaffolds using three-dimensional (3D) gel-lamination technology and evaluated their structure with 3D parameters and related method. METHODS: Series two-dimensional images of femoral head's specimen of dogs were obtained by micro-computed tomography (Micro-CT). According to these images, porous biomimetic biphasic calcium phosphate (BCP) ceramic scaffolds with oriented trabecular structure were fabricated by three-dimensional (3D) gel-lamination technology. And then, the three-dimensional structure of the scaffolds were reconstructed by computer according to Micro-CT images of these scaffolds and evaluated by three-dimensional parameters. These parameters included bone volume fraction (BVF, BV/TV), bone surface/bone volume (BS/BV) ratio, trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.Sp) and structure model index (SMI). The biomechanical properties and biocompatibility of these scaffolds were also evaluated in the study. Six scaffolds, which were combined with BMCs (bone mesenchymal cells, BMCs), were planted into the bone defect of six dogs' femoral head respectively. RESULTS: There was no significant difference between trabecular samples and BCP scaffolds in BV/TV, Tb.Th, Tb.N, and Tb.Pf (P > 0.05). The trabecular system of the scaffold, which had some orientation, represented plate-like model. With a micro-porous porosity of 62%, the average compressive modulus and ultimate strength along the axis of the scaffolds reached (464.0 +/- 36.0) MPa and (5.6 +/- 0.8) MPa respectively. The results of animal test indicated that the trabeculae of these scaffolds were covered by a layer of new bone after 10 weeks of operation. CONCLUSION: Porous BCP scaffolds have been produced with oriented microarchitectural features designed to facilitate vascular invasion and cellular attachment and with initial mechanical properties comparable to those of trabecular bone.

Animals↗

PubMed2005

Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.

Both homozygous (L166P, M26I, deletion) and heterozygous mutations (D149A, A104T) in the DJ-1 gene have been identified in Parkinson's disease (PD) patients. The biochemical function and subcellular localization of DJ-1 protein have not been clarified. To date the localization of DJ-1 protein has largely been described in studies over-expressing tagged DJ-1 protein in vitro. It is not known whether the subcellular localization of over-expressed DJ-1 protein is identical to that of endogenously expressed DJ-1 protein both in vitro and in vivo. To clarify the subcellular localization and function of DJ-1, we generated three highly specific antibodies to DJ-1 protein and investigated the subcellular localization of endogenous DJ-1 protein in both mouse brain tissues and human neuroblastoma cells. We have found that DJ-1 is widely distributed and is highly expressed in the brain. By cell fractionation and immunogold electron microscopy, we have identified an endogenous pool of DJ-1 in mitochondrial matrix and inter-membrane space. To further investigate whether pathogenic mutations might prevent the distribution of DJ-1 to mitochondria, we generated human neuroblastoma cells stably transfected with wild-type (WT) or mutant (M26I, L166P, A104T, D149A) DJ-1 and performed mitochondrial fractionation and confocal co-localization imaging studies. When compared with WT and other mutants, L166P mutant exhibits largely reduced protein level. However, the pathogenic mutations do not alter the distribution of DJ-1 to mitochondria. Thus, DJ-1 is an integral mitochondrial protein that may have important functions in regulating mitochondrial physiology. Our findings of DJ-1's mitochondrial localization may have important implications for understanding the pathogenesis of PD.

Blotting, Western↗