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Biomedical subjects

Min Hu

Publications and source records attributed to Min Hu.

At least 73 records · Page 4Linked to original sources

[Mass size distribution of Beijing particulate matters and its inorganic water-soluble ions in winter and summer].

To understand one of the important characteristics of Beijing particulate matter pollution, the mass size distribution of particulate matters and its water-soluble ions, the particle samples were collected by a MOUDI cascade impactor in Beijing during July 2001, March 2002, July 2002 and January 2003 and every sampling period lasted a week. By analysis, the results indicate that there is "two modes" in the diameter range of the fine particle, one called "condensation mode" and another called "droplet mode", and the reasons of the peak of the accumulation mode appearing in the diameter range of 1 - 1. 8 microm was discussed in this paper. And there was a relatively strong correlation between PM1.8 and PM10 (R2 > 80%), the same to PM(1.8-10) (PM10 minus PM1.8); the ratio of PM1.8s/PM10 varietied between 40% and 60% during the sampling periods; as a result, the mass concentration of PM10 can be decreased by decreasing the concentration of coarse particles; sulfate, nitrate and ammonium are the main component of the inorganic water-soluble ions and the percentage of these three ions in PM1.8 was above 70% when the concentration of fine particle was more than 70 microg x m(-3) and they are the main reason increasing particle concentration.

Air Pollutants↗

[Design and application of internal devices for automatic elasticity distraction osteogenesis].

OBJECTIVE: To improve the design of the devices used for autoatic elasticity distraction osteogenesis, and to preliminarily testify their feasibility for clinical application. METHODS: The internal automatic distraction devices were constructed by three parts, including sinusoid shape memory alloy distractor, reconstructive plate and mini-plate. The animal model of trifocal bone transport reconstruction of canine mandibular mentis was duplicated, in which a 6 cm mandibular mentis segment was removed and the transport disc was created by osteotomy in both ends of the mandibular defect. The plates were used for internal fixation and shape reconstruction of the mandible. They also served as transport distraction guidance for the elasticity distractor. RESULTS: The new devices could complete bone transport as expected. Regenerated bone segments were formed in two months and both sides of the mandibular body were lengthened. Because of the narrow angle and obstruction from the thick soft tissues in the mentis area, the ultimate symphysis mentalis was not reconstructed. CONCLUSION: The design of the internal elasticity distraction devices showed potential feasibility for clinical practice. But further studies are still needed for better control of the strength and balance of distraction forces.

Animals↗

[Segmental mandibular reconstruction by elasticity distraction osteogenesis associated with guided bone regeneration].

OBJECTIVE: To accelerate distraction osteogenesis by utilizing guided bone regeneration technique, and to improve the automatic process of canine segmental mandibular reconstruction by elasticity distraction osteogenesis using shape memory metal alloy distractor. METHODS: Adult hybrid canines were used. Osteotomy was performed to remove a bone segment of 2.5-4.0 cm in one side of the mandible. Mandibular fixation devices and shape memory metal alloy distractor were secured according to the principles of bi-focal distraction technique. A piece of ePTFE membrane was sutured to cover the buccal side of bone defect and osteotomy gap of transport disc, where the periosteum was peeled for exposing mandible in operation. Then the incisions were totally closed. The canines were sacrificed 3 months later to harvest the mandibles for morphological observation and measurement of bone density and intensity. RESULTS: The shape memory metal alloy distractor performed distraction osteogenesis automatically and reconstructed the mandibles with bone defect. A regenerated bone segment of 1.5-2.0 cm was formed in the compression region between transport disc and contralateral mandibular end. The new bone in both of distraction and compression regions had similar height and thickness with normal mandible. Moreover the new bone density and intensity were rather satisfied. CONCLUSIONS: Membrane guided bone regeneration can avoid bone synthesis commonly caused by cicatrization of soft tissue in the bone defect, and accelerate ossification and maturation of new generated bone.

Animals↗

Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin.

Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

Animals↗

Antioxidant activity of a proanthocyanidin-rich extract from grape seed in whey protein isolate stabilized algae oil-in-water emulsions.

Algae oil-in-water emulsions stabilized with 0.2% whey protein isolate (WPI) at pH 3.0 and 7.0 were chosen to evaluate antioxidant activity of a proanthocyanidin-rich extract from grape seed. In this emulsion system, (+)-catechin and ascorbic acid (620 microM) were found to be prooxidative at pH 3.0 and ineffective at pH 7.0. Grape seed extract was not able to effectively inhibit both lipid hydroperoxides and propanal formation when added to the emulsion at 124 microM. However, increasing the concentration of the grape seed extract to 620 microM resulted in inhibition of both lipid hydroperoxide and propanal formation at pH 3.0 and 7.0. None of the antioxidants tested had any effect on the physical stability of the WPI-stabilized emulsion. The superior antioxidant activity of the grape seed extract is likely due to the presence of oligomeric procyanidins which are better antioxidants compared to their monomeric counterparts.

Aldehydes↗

A novel mutation of WT1 exon 9 in a patient with Denys-Drash syndrome and pyloric stenosis.

We report a novel mutation in WT1 exon 9 (1214 A>G) resulting in an amino acid change from H to R at codon 405 in a 46 XY female patient who had congenital hypertrophic pyloric stenosis, pseudohermaphroditism masculinus, renal failure, and Wilms tumor, and died at the age of 22 months. The patient demonstrated the difficulty in diagnosing a patient with intersex before conclusive genetic characterization.

Denys-Drash Syndrome↗

Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion.

Selective depletion of alloreactive T cells from allogeneic stem cell grafts can reduce graft-versus-host disease (GVHD) while preserving beneficial effects of T cells including facilitation of engraftment, protection against opportunistic infection, and reduced relapse risk. Memory T cells (CD62L(-)) represent a population of T cells that have previously encountered pathogens and may contain fewer T cells capable of recognizing neoantigens including recipient allogeneic antigen (aAg). We investigated whether human naive (CD62L(+)) or memory (CD62L(-)) T cells had different capacities to respond to aAg by assessing their ability to proliferate in response to and lyse HLA-mismatched Epstein-Barr virus-transformed B cells. Freshly sorted and in vitro expanded CD62L(-) memory T cells were less responsive to aAg stimulation than were CD62L(+) naive T cells but contained higher levels of cytomegalovirus (CMV)-specific T cells. Analysis of T cell receptor (TCR) repertoire showed restricted TCR diversity in the memory T-cell population possibly due to selection associated with chronic exposure to common pathogens. Memory T cells may represent a donor cell subpopulation suitable for enhancing immune reconstitution without increasing the risk of GVHD.

B-Lymphocytes↗

Sox1 acts through multiple independent pathways to promote neurogenesis.

Although Sox1, Sox2, and Sox3 are all part of the Sox-B1 group of transcriptional regulators, only Sox1 appears to play a direct role in neural cell fate determination and differentiation. We find that overexpression of Sox1 but not Sox2 or Sox3 in cultured neural progenitor cells is sufficient to induce neuronal lineage commitment. Sox1 binds directly to the Hes1 promoter and suppresses Hes1 transcription, thus attenuating Notch signaling. Sox1 also binds to beta-catenin and suppresses beta-catenin-mediated TCF/LEF signaling, thus potentially attenuating the wnt signaling pathway. The C-terminus of Sox1 is required for both of these interactions. Sox1 also promotes exit of cells from cell cycle and up-regulates transcription of the proneural bHLH transcription factor neurogenin 1 (ngn1). These observations suggest that Sox1 works through multiple independent pathways to promote neuronal cell fate determination and differentiation.

Basic Helix-Loop-Helix Proteins↗

The presence of FGF2 signaling determines whether beta-catenin exerts effects on proliferation or neuronal differentiation of neural stem cells.

Neural stem cells proliferate and maintain multipotency when cultured in the presence of FGF2, but subsequent lineage commitment by the cells is nevertheless influenced by the exposure to FGF2. Here we show that FGF2 effects on neural stem cells are mediated, in part, by beta-catenin. Conversely, the effects of beta-catenin in neural stem cells depend in part upon whether there is concurrent fibroblast growth factor (FGF) signaling. FGF2 increases beta-catenin signaling through several different mechanisms including increased expression of beta-catenin mRNA, increased nuclear translocation of beta-catenin, increased phosphorylation of GSK-3beta, and tyrosine phosphorylation of beta-catenin. Overexpression of beta-catenin in the presence of FGF2 helps to maintain neural progenitor cells in a proliferative state. However, overexpression of beta-catenin in the absence of FGF2 enhances neuronal differentiation. Further, chromatin immunoprecipitation (ChIP) assays demonstrate that both beta-catenin and Lef1 bind directly to the neurogenin promoter, and luciferase reporter assays demonstrate that beta-catenin is directly involved in the regulation of neurogenin 1 and possibly other proneural genes when neural stem cells are cultured in the presence of FGF2. We suggest that the balance between the mitogenic effects and the proneural effects of beta-catenin is determined by the presence of FGF signaling.

Animals↗

Nonisotopic single-strand conformation polymorphism analysis of sequence variability in ribosomal DNA expansion segments within the genus Trichinella (Nematoda: Adenophorea).

A nonisotopic single-strand conformation polymorphism (SSCP) approach was employed to 'fingerprint' sequence variability in the expansion segment 5 (ES5) of domain IV and the D3 domain of nuclear ribosomal DNA within and/or among isolates and individual muscle (first-stage) larvae representing all currently recognized species/genotypes of Trichinella. In addition, phylogenetic analyses of the D3 sequence data set, employing three different tree-building algorithms, examined the relationships among all of them. These analyses showed strong support that the encapsulated species T. spiralis and T. nelsoni formed a group to the exclusion of the other encapsulated species T. britovi and its related genotypes Trichinella T8 and T9 and T. murrelli, and T. nativa and Trichinella T6, and strong support that T. nativa and Trichinella T6 grouped together. Also, these eight encapsulated members grouped to the exclusion of the nonencapsulated species T. papuae and T. zimbabwensis and the three representatives of T. pseudospiralis investigated. The findings showed that nonencapsulated species constitute a complex group which is distinct from the encapsulated species and supported the current hypothesis that encapsulated Trichinella group external to the nonencapsulated forms, in accordance with independent biological and biochemical data sets.

Animals↗

Molecular characterization of the tumor microenvironment in breast cancer.

Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.

Biomarkers, Tumor↗

An electrophoretic tool for the genetic characterisation and delineation of lungworms.

In the present study, PCR-based single-strand conformation polymorphism (SSCP) analysis of the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA (rDNA) was applied to the genetic characterisation of Dictyocaulus from red deer from New Zealand and to its differentiation from species of lungworm from cattle and other hosts. Based on SSCP profiles, Dictyocaulus individuals from red deer from different geographical localities in New Zealand could be readily distinguished from those representing other lungworms examined, irrespective of low-level sequence variability in the ITS-2 (0.4-2.6%) detectable among individuals. The ITS-2 of Dictyocaulus from red deer differed in sequence by approximately 7-35% from congeners from other cervid hosts, demonstrating that this parasite is genetically distinct from other species of Dictyocaulus for which ITS-2 sequence data are presently available. The results emphasize the need for a large-scale molecular systematic study of Dictyocaulus specimens from various species of cervid and other ruminant hosts and the usefulness of mutation scanning for taxonomic, epidemiological and population genetic investigations.

Animals↗

Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype.

Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective tissue disease characterized by progressive postnatal heterotopic bone formation. Although the genetic defects of FOP are not known, several lines of evidence have suggested that bone morphogenetic protein-4 (BMP4) may be involved in the pathophysiology. Nevertheless BMP4-transgenic mice have previously failed to develop the disorder and there has been no good animal model of the disease. Here, we report that a unique transgenic mouse line that overexpresses BMP4 under control of the neuron-specific enolase (NSE) promoter develops a FOP-like phenotype. Mating of these animals with transgenic animals that overexpress the BMP inhibitor noggin prevents the disorder, confirming the role of BMP4 in the pathogenesis of the disease. Heterotopic bone formation in these animals appears to follow the classic endochondral ossification pathway. Sex-mismatched cell transplantation experiments indicate that multiple cell sources contribute to the heterotopic ossification. This remarkable animal model provides a unique opportunity to further study the role of the BMP signaling pathway in heterotopic ossification and to improve our understanding of the clinical aspects of FOP.

Animals↗

The mitochondrial genomics of parasitic nematodes of socio-economic importance: recent progress, and implications for population genetics and systematics.

Mitochondria are subcellular organelles in which oxidative phosphorylation and other important biochemical functions take place within the cell. Within these organelles is a genome, called the mitochondrial (mt) genome, which is distinct from, but cooperates closely with the nuclear genome of the cell. Investigating mt genomes has significant implications for various fundamental research areas, including mt biochemistry and physiology, and, importantly, such genomes provide a rich source of markers for population genetic and systematic studies. While approximately 250 complete mt genome sequences have been determined for a range of metazoan organisms from various phyla, few of these represent parasitic helminths. Until 1998, only two mt genome sequences had been determined for parasitic nematodes, in spite of their socio-economic importance and the need for investigations into their population genetics, taxonomy and evolution. However, since that time, there has been some progress. The main focus of the present chapter is to review the state of knowledge of the mt genomics for parasitic nematodes, to describe recent technological improvements to mt genome sequencing, to summarize applications of mt gene markers for studying the systematics and population genetics of parasitic nematodes, and to emphasize prospects and opportunities for future research in these areas.

Animals↗

Prophylactic bilateral nephrectomies in two paediatric patients with missense mutations in the WT1 gene.

BACKGROUND: Denys-Drash syndrome (DDS) is associated with mutations of the Wilms' tumour 1 (WT1) gene, and is characterized by pseudohermaphroditism, a progressive glomerulopathy, and the development of Wilms' tumour. More than 90% of patients with DDS who carry constitutional intragenic WT1 mutations are at high risk (90%) for the development of Wilms' tumour. WT1 is a signalling protein with 90% of WT1 mutations occurring in the WT1 zinc finger region as single nucleotide polymorphisms, the majority of which are missense mutations. METHODS: Constitutional DNA was extracted from peripheral blood. Direct sequencing and restriction enzymes were employed to analyse mutations. RESULTS: Two children, 46XY males who had evidence of pseudohermaphroditism, hypogonadism and renal failure with a glomerulopathy atypical for DDS, but no Wilms' tumour or nephroblastomatosis, on investigation, prior to transplant, were identified with missense mutations in the WT1 gene, in exons 8 and 9, respectively. The decision to do prophylactic nephrectomies was based on the genetic identification of WT1 mutations supporting a diagnosis of incomplete DDS, with the potential for increased risk of malignancy with the development of Wilms' tumour. The nephrectomy specimens demonstrated nephrogenic rests (nephroblastomatosis), which have a potential for malignant transformation. CONCLUSIONS: WT1 missense mutations in exons 8 and 9 can be regarded as having the potential for malignant change supporting prophylactic nephrectomy in apparent incomplete DDS patients with end-stage renal disease.

Child↗