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Biomedical subjects

X Zhang

Publications and source records attributed to X Zhang.

At least 163 records · Page 9Linked to original sources

Further evidence for a role of the anterior claustrum in epileptogenesis.

The anatomy of the claustrum (CLA) has been well characterized, but its functional role remains uncertain. The results of recent research suggest that the CLA may be part of a network of structures involved in seizure generalization, and we set out to test this idea. To test persistence, seizures were kindled in the anterior CLA. Following a 14-day suspension of kindling, all rats required only one stimulation to evoke a stage 5 seizure. In another experiment, groups of rats received bilateral lesions of the anterior CLA before and after amygdaloid kindling. We found that small lesions of the anterior CLA retard amygdaloid kindling, but do not block the expression of generalized seizures. Lesions produced after amygdaloid kindling resulted in a shorter seizure duration, but had no marked effect on seizure expression. Another group of rats was tested for transfer of kindling between the anterior CLA and contralateral amygdala. We found an asymmetrical transfer of kindling to the CLA from the amygdala wherein amygdaloid kindling facilitated subsequent kindling of the CLA but kindling of the anterior CLA failed to facilitate kindling of the amygdala. The results add support to the notion that the CLA contributes to the development of generalized limbic seizures.

Amygdala↗

Differential gene expression after complete spinal cord transection in adult rats: an analysis focused on a subchronic post-injury stage.

In an attempt to characterize changes in transcription after a sub-chronic spinal cord injury (SCI), we investigated gene expression profiles using cDNA microarray. Among 7523 genes and expressed sequence tags (ESTs) examined, 444 transcripts, including 218 genes and 226 ESTs, were identified to be either up-regulated (373 of 444) or down-regulated (71 of 444) greater than 2.0-fold in the spinal cord at 14 days after a complete spinal transection at the 11th thoracic level in adult rats. Based on their potential function, these differentially expressed genes were categorized into seven classes which include cell division-related protein, channels and receptors, cytoskeletal elements, extracellular matrix proteins, metalloproteinases and inhibitors, growth-associated molecules, metabolism, intracellular transducers and transcription factors, as well as others. Strong expressional changes were found in all classes revealing the complexity and diversity of gene expression profiles following SCI. We verified array results with RT-PCR for eight genes, Northern blotting for nine genes, and in situ hybridization for one gene and immunohistochemistry for four genes. These analyses confirmed, to a large extent, that the array results have accurately reflected the molecular changes occurring at 14 days post-SCI. Importantly, the current study has identified a number of genes, including annexins, heparin-binding growth-associated protein (HB-GAM), P9ka (S100A4), matrix metalloproteinases, and lysozyme, that may shed new light on SCI-related inflammation, neuroprotection, neurite-outgrowth, synaptogenesis, and astrogliosis. In conclusion, the identification of molecular changes using the large-scale microarray analysis may lead to a better understanding of underlying mechanisms, thus, the development of new repair strategies for SCI.

Animals↗

Regulation of matrix metalloproteinases (MMPS) and their inhibitors (TIMPS) during mouse peri-implantation: role of nitric oxide.

Nitric oxide (NO) is believed to play pivotal roles in embryo implantation. The purpose of this study was to investigate the effect of NO on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as the mechanism of NO during mouse implantation. Nitric oxide synthase (NOS) inhibitor, L-NAME was administered with or without sodium nitroprusside (SNP), NO donor, into one uterine horn on day 3 of pregnancy, and the contralateral uterine horn served as the control. We collected the uteri on days 5, 6, and 7 of pregnancy and examined the mRNA expression of MMP-2, -9, and TIMP-1, -2, -3, as well as the activities of MMP-2 and -9 by using in situ hybridization and gelatin zymography, respectively. The results showed that, compared with the control, the expression of MMP-2 and -9 mRNAs was decreased in L-NAME-treated uteri during peri-implantation. Treatment of mice with L-NAME had slight effect on the expression of TIMP-1 mRNA on day 5 of pregnancy, and no effect on TIMP-2 mRNA expression during peri-implantation. However, the expression of TIMP-3 mRNA was increased. The gelatin zymography results indicated that the activity of MMP-9 was decreased during peri-implantation, but the activity of MMP-2 did not change significantly in these time points examined. The L-NAME-mediated effect on MMPs and TIMPs were significantly reversed when SNP was co-administered with L-NAME. These data suggest that inhibition of NO production regulates the gene expression of MMP-2, -9, and TIMP-3, together with the activity of MMP-9 during peri-implantation, which may have serious consequence on embryo implantation.

Animals↗

Expression of Smad2 and Smad4 in mouse uterus during the oestrous cycle and early pregnancy.

SMAD2 and SMAD4 are intracellular transducers of TGF-beta superfamily. In situ hybridization and semi-quantitative RT-PCR were employed to determine the temporal and spatial expression of Smad2 and Smad4 mRNA in mouse uterus during the oestrous cycle and early pregnancy. Smad2 mRNA was predominantly present in the luminal and glandular epithelium at dioestrus and prooestrus, while Smad4 expression was at a steady level in the luminal and glandular epithelium throughout the oestrous cycle. During pre-implantation period, Smad2 hybridization signals were accumulated in the luminal and glandular epithelium at a basal level; Smad4 mRNA appeared in the epithelium with a little variation in hybridization signal intensity. After implantation, on day 5 of pregnancy, Smad2 signals were localized to the subluminal stroma surrounding the implanting blastocyst, and Smad4 mRNA were accumulated in the decidua near the luminal epithelium. Both Smads were present in the decidua on days 6-7 with a switch from the mesometrial pole to the antimesometrial pole. RT-PCR results showed that both Smad2 and Smad4 mRNA levels were rising during peri-implantatation. The results suggest that Smad2 and Smad4 might be involved in the cycling changes of mouse uterus during the oestrous cycle and embryo implantation.

Animals↗

No association between the PTGS2/PLA2G4A locus and schizophrenia in a Chinese population.

The present study was undertaken to replicate an association between the PTGS2/PLA2G4A locus and schizophrenia among a Chinese population. We recruited 168 Chinese parent-offspring trios of Han descent, consisting of fathers, mothers and affected offspring with schizophrenia. Of 3 informative SNPs genotyped, no one showed allelic association with schizophrenia; the haplotype analysis also failed to capture a haplotypic association with the illness. Because the frequencies of alleles and genotypes of SNPs analyzed differ in the Chinese population as compared with a British population that initially showed the genetic association between the PTGS2/PLA2G4A locus and schizophrenia, the ethnic background may be a major reason for poor replication of the initial finding.

Asian People↗

Combination therapy with peginterferon alpha-2B and ribavirin in liver transplant recipients with recurrent HCV infection: preliminary results of an open prospective study.

Allograft reinfection with hepatitis C virus (HCV) in transplant recipients occurs commonly and represents a major concern in the transplant setting. Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure. In this ongoing study, we present preliminary data from a prospective trial of standard interferon (IFN) alpha-2b (2 million units daily) for 3 months and subsequent peginterferon (PEG IFN) alpha-2b (1.5 microg/kg/week) for 9 months. IFN therapy was combined with ribavirin (10 to 12 mg/kg). So far, HCV has become undetectable by qualitative PCR in 33% of patients while 25% had a reduction of HCV RNA to undetectable by the bDNA assay and 42% had no virological response after 6 months of therapy. A biochemical response was detected in 42% of patients. Improvement of inflammatory activity was observed in 42% of patients after 6 months. In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor (G-CSF) due to leucopenia [corrected] In conclusion, we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavirin provides biochemical and virological benefits in transplant recipients with established recurrent HCV infection.

Adult↗

Comparison of some modeling and control issues for a flexible two link manipulator.

The nonlinear dynamics of a flexible two link manipulator presents a challenging modeling and control problem with its lumped actuator dynamics coupled with distributed link dynamics. Issues related to modeling uncertainty and control robustness as well as a good understanding of the experimental issues are essential for advanced modeling and control for such systems. This paper reports some of the advanced modeling, control, and experimental issues for a flexible two link manipulator, including some novel approaches developed by the authors.

Algorithms↗

GnRHa flare and IVF pregnancy rates.

OBJECTIVES: GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF 'poor responders'. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in 'poor responders'. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in 'poor responders'. METHODS: Seventy-three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age-matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. 'Poor responders' consisted of patients with peak E(2) less than 1000 pg/ml and/or less than five mature follicles with diameter >15 mm on the day of hCG administration. Student's t-test was used to analyze the data and the chi-squared test was used to compare fertilization and pregnancy rates. RESULTS: The flare protocol produced higher peak E(2) levels (1647+/-747 vs. 720+/-258 mIU/ml, P<0.05) and a larger number of mature follicles (5.8+/-2.2 vs. 4.0+/-1.0 P<0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P>0.05, NS). CONCLUSIONS: A comparison between the flare protocol group and the age-matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E(2) levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.

Adult↗

Anthropometric predictors of coronary heart disease in Chinese women.

OBJECTIVE: To evaluate the associations of body size and fat distribution with incidence of coronary heart disease (CHD) in Chinese women. DESIGN: Population-based, prospective cohort study. SUBJECTS: A total of 67 334 women aged 40-70 y, who had no prior history of CHD, stroke, and cancer at study recruitment. MEASUREMENTS: Weight, standing and sitting heights, circumferences of waist and hip, and ratios of the anthropometric measurements. OUTCOME: incidence of CHD (non-fatal myocardial infarction (MI) or fatal CHD). RESULTS: After a mean follow-up of 2.5 y (168 164 person-years), there were 70 incident cases of CHD (49 non-fatal MIs and 21 CHD deaths). Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-standing height ratio (WHtR), waist-to-sitting height ratio (WsHtR), and conicity index were all positively associated with the risk of CHD. With the exception of WHR, all other anthropometric indexes only predicted the risk of CHD among women </=55 y of age at enrollment. The relative risks (RRs) between extreme tertiles of BMI were 9.0 (95% CI, 2.0-41.5; P for trend=0.002) for younger women vs 1.3 (0.6-3.0; P for trend=0.83) for older women. Similarly, the RRs for WC, WHtR, WsHtR, and conicity index were 6.1 (1.8-21.4) vs 1.9 (0.6-5.4), 9.4 (2.6-33.8) vs 1.2 (0.5-3.1), 15.2 (3.3-69.1) vs 1.0 (0.4-2.5), and 7.8 (2.2-28.0) vs 0.9 (0.4-2.3) for the young and elderly, respectively. In contrast, the RR for WHR was 3.2 (1.1-9.1) for the young and 2.9 (1.0-8.4) for the elderly. CONCLUSIONS: WHR was positively associated with the risk of CHD in both younger and older women, while other anthropometrics, including BMI, were related to CHD risk primarily among younger women.

Adult↗

p97 and close encounters of every kind: a brief review.

The AAA (ATPase associated with various cellular activities) ATPase, p97, is a hexameric protein of chaperone-like function, which has been reported to interact with a number of proteins of seemingly unrelated functions. For the first time, we report a classification of these proteins and aim to elucidate any common structural or functional features they may share. The interactors are grouped into those containing ubiquitin regulatory X domains, which presumably bind to p97 in the same way as the p47 adaptor, and into non-ubiquitin regulatory X domain proteins of different functional subgroups that may employ a different mode of interaction (assuming they also bind directly to p97 and are not experimental artifacts). Future studies will show whether interacting proteins direct p97 to different cellular pathways or a common one and structural elucidation of these interactions will be crucial in understanding these underlying functions.

Animals↗

Neural regulation of tone in the oesophageal body: in vivo barostat assessment of volume-pressure relationships in the feline oesophagus.

Recent combined manometric-barostat studies demonstrated that the oesophageal body exhibits both peristaltic contractions and tone. This study further characterized the neural modulation of tone in the feline oesophageal body. Simultaneous oesophageal barostat and manometry were performed in 20 adult cats under ketamine sedation. Oesophageal tone and peristalsis were assessed in the distal smooth muscle oesophagus. Cholinergic modulation was studied using neostigmine, erythromycin, atropine and vagotomy. Nitrergic regulation was assessed using sildenafil to increase cellular cyclic guanosine monophosphate and the nitric oxide synthase blocker Nomega-nitro-l-arginine (l-NNA). The presence of a tonic contractile activity in the distal oesophageal body was confirmed. Peristaltic contractions proceeded along the oesophageal body over the background tonic contraction. Neostigmine and erythromycin enhanced (20-30%) whereas bilateral vagotomy and atropine strongly decreased oesophageal tone (50-60%). However, l-NNA increased (40%) and sildenafil decreased oesophageal tone (30%). Therefore, tonic contractile activity in the oesophageal body is mainly caused by a continuous cholinergic excitatory input. A nitric oxide inhibitory mechanism may have a complementary role in the regulation of oesophageal tone.

Animals↗

Host plant recognition by the root feeding clover weevil, Sitona lepidus (Coleoptera: Curculionidae).

This study investigated the ability of neonatal larvae of the root-feeding weevil, Sitona lepidus Gyllenhal, to locate white clover Trifolium repens L. (Fabaceae) roots growing in soil and to distinguish them from the roots of other species of clover and a co-occurring grass species. Choice experiments used a combination of invasive techniques and the novel technique of high resolution X-ray microtomography to non-invasively track larval movement in the soil towards plant roots. Burrowing distances towards roots of different plant species were also examined. Newly hatched S. lepidus recognized T. repens roots and moved preferentially towards them when given a choice of roots of subterranean clover, Trifolium subterraneum L. (Fabaceae), strawberry clover Trifolium fragiferum L. (Fabaceae), or perennial ryegrass Lolium perenneL. (Poaceae). Larvae recognized T. repens roots, whether released in groups of five or singly, when released 25 mm (meso-scale recognition) or 60 mm (macro-scale recognition) away from plant roots. There was no statistically significant difference in movement rates of larvae.

Animals↗

Genomic organisation of the chicken ghrelin gene and its single nucleotide polymorphisms detected by denaturing high-performance liquid chromatography.

(1) Ghrelin is a novel endogenous ligand for the growth hormone secretagogue receptor (GHS-R) and is expressed primarily in the stomach and hypothalamus with the probable function of stimulating GH secretion and food intake both in mammals and poultry. The complete sequences of ghrelin gene have been reported in humans and mice; however, that of chickens remains unclear. (2) Here, we report the complete sequence of chicken ghrelin gene (submitted to Genbank; accession number AY303688), which consists of 5 exons and 4 introns. As in mice, the first exon of chicken ghrelin gene does not encode any amino acid. (3) Scanning point mutations with denaturing high-performance liquid chromatography (DHPLC) using WAVE DNA Fragment Analysis Systems and confirmed with direct sequencing for polymerase chain reaction (PCR) products, we analysed the single nucleotide polymorphisms (SNPs) in the entire gene of chicken ghrelin. (4) Results showed that there were 19 SNPs in chicken ghrelin gene, and most of these SNPs were scattered in the 4 introns. In these SNPs, one mutation in exon 5 (A2355G) led to the change of amino acid from glutamine to arginine (Gln 113 Arg): as a result a different ghrelin precursor instead of a mature peptide was produced. In addition, one SNP in 5'UTR (C223G) determined the presence or absence of a potential binding site of transcription factor serum response factor (SRF), which might affect the expression of chicken ghrelin gene. Some of the SNPs detected in the present study could be used in quantitative trait loci (QTL) mapping for growth characters in chickens. (5) Because one SNP is located in a polymorphic site of restriction enzyme PagI of intron 4, it was possible to design a PCR-RFLP procedure and analyse the diversity of 10 chicken populations. Results showed the allelic frequencies of C2100T differ among these breeds, however, no significant difference was observed between imported breeds and Chinese native ones, nor between egg layers and meat type chickens. A chi-square test showed that 4 chicken populations of Beijing Fat, Xinghua, Recessive White and Silky followed the Hardy-Weinberg equilibrium.

Amino Acid Sequence↗

Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta.

BACKGROUND: BM-derived mesenchymal stem cells (MSC) are attractive sources for autotransplantation with no risk of rejection, but the use of these cells bas problems, including the necessity of harvesting BM from donors, the donors' age-dependency, limitation to autologous use and difficulty of use for patients with hereditary diseases. We report a method of isolating placenta-derived mesenchymal progenitor cells (PDMPC) that can be used as an alternative source of MSC. METHODS: We isolated PDMPC from human fetal chorionic villi using the explant culture method, from placentas collected after neonatal delivery (38-40 weeks of gestation). The PDMPC were characterized by morphologic and immunophenotypic analysis. The differentiation ability of mesenchymal and neural lineages was detected using specific culture conditions and determined by morphology, reverse transcription(RT)-PCR, histochemical staining and immunocytostaining. RESULTS: The PDMPC all originated from fetal chorionic villi, as confirmed by fluorescence in situ hybridization analysis. The PDMPC population consisted of spindle-shaped cells and large flat cells. The PDMPCexpressed CD13, CD44, CD73, CD90, CDIO5 and HLA class I as surface epitopes, but not CD31, CD34, CD45 and HLA-DR. These cells differentiated into osteocytes, chondrocytes and adipocytes under specific culture conditions, and were also induced to form neural-like cells. DISCUSSION: Our study shows that PDMPC can differentiate into mesenchymal lineages and be induced to form neural-like cells. Thus, PDMPCisolated from chorionic villi of placenta may provide a novel source for the research of stem and progenitor cells in placenta, cell therapy and regenerative medicine, particularly as a source of allogenic mesenchymal stem and progenitor cells with little ethical conflict and various advantages

Antigens, CD↗

Compound dual radiation action theory for 252Cf brachytherapy.

The existing dosimetry protocol that uses the concept of RBE for 252Cf brachytherapy contains large uncertainties. A new formula has been developed to correlate the biological effect (i.e. cell survival fraction) resulting from a mixed n + gamma radiation field with two physical quantities and two biological quantities. The formula is based on a pathway model evolved from that of the compound-dual-radiation-action (CDRA) theory, previously proposed by Rossi and Zaider. The new model employs the recently published data on radiation-induced DNA lesions. The new formula is capable of predicting quantitatively the synergistic effect caused by the interactions between neutron events and gamma ray events, and it is intended to be included into a new dosimetry protocol for future 252Cf brachytherapy.

Algorithms↗

Characterization and application of two novel monoclonal antibodies against CD40L: epitope and functional studies on cell membrane CD40L and studies on the origin of soluble serum CD40L.

CD40 ligand, a 33-kDa cell membrane molecule, a member of the tumor necrosis factor superfamily, is an important costimulatory molecule during immune response. Here, we report on two functional mouse anti-human CD40L monoclonal antibodies 1B1 and 4F1 characterized by flow cytometry, Western blotting, and competition assay. The antibodies bound to distinct CD40L epitopes and therefore resulted in different bioactivity. Both antibodies could induce CD4+ T-cell alloantigenic hyporesponsiveness ex vivo. The antibodies were matched to develop a two-site enzyme-linked immunosorbent assay (ELISA) for soluble CD40L (sCD40L). Using this ELISA assay, we found major differences between plasma and serum sCD40L levels. Because the count of platelet sharply decreased in aplastic anemia (AA) and idiopathic thrombocytopenic purpura (ITP), we further analyzed the sCD40L concentration in the plasma of AA and ITP patients. The results showed that the sCD40L in serum was much lower than that of healthy subjects. These data demonstrate that platelets seem to be a major contributor to sCD40L, though not the only source of sCD40L in serum.

Animals↗

Characterization and functional study of five novel monoclonal antibodies against human OX40L highlight reverse signalling: enhancement of IgG production of B cells and promotion of maturation of DCs.

OX40 ligand (OX40L), a molecule originally identified as human gp34, is an important co-stimulatory molecule during immune response. In this study, we report on five functional mouse anti-human OX40L monoclonal antibodies named as 9H10, 4C12, 8D10, 4H4 and 1G1, characterized by means of flow cytometry, Western blot and competition assay. These monoclonal antibodies bound to distinct OX40L epitopes on activated B cells and dendritic cells (DCs) and two of them could suppress the proliferation of T lymphocytes co-stimulated by mature DCs. Furthermore, we demonstrated that our monoclonal antibodies, such as 9H10 and 4C12, could trigger OX40L reverse signal that enhanced IgG production of B cells and promoted maturation of DCs as evidenced by the upexpression of CD80, CD86, CD83 and CXCR4 and monoclonal antibody 9H10 could also promote anti-CD40 monoclonal-antibody-stimulated DCs in order to induce T cells to secrete more interleukin-2 and interferon-gamma, which suggested that OX40L signals could strengthen the effect of CD40 signals on promoting Th1 differentiation.

Animals↗