Biomedical subjects

L Wen

Publications and source records attributed to L Wen.

At least 19 recordsLinked to original sources

PubMed2006

Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme.

OBJECTIVE: To investigate the association between muscle-specific creatine kinase (CKMM) gene polymorphism and the effects of endurance training on running economy. METHODS: 102 biologically unrelated male volunteers from northern China performed a 5000-m running programme, with an intensity of 95-105% ventilatory threshold. The protocol was undertaken three times per week and lasted for 18 weeks. Running economy indexes were determined by making the participants run on a treadmill before and after the protocol, and the A/G polymorphism in the 3' untranslated region of CKMM was detected by polymerase chain reaction-restricted fragment length polymorphism (NcoI restriction enzyme). RESULTS: Three expected genotypes for CKMM-NcoI (AA, AG and GG) were observed in the participants. After training, all running economy indexes declined markedly. Change in steady-state consumption of oxygen, change in steady-state consumption of oxygen by mean body weight, change in steady-state consumption of oxygen by mean lean body weight and change in ventilatory volume in AG groups were larger than those in AA and GG groups. CONCLUSIONS: The findings indicate that the CKMM gene polymorphism may contribute to individual running economy responses to endurance training.

Adolescent↗

PubMed2006

Polymorphisms in the HBB gene relate to individual cardiorespiratory adaptation in response to endurance training.

OBJECTIVE: The crucial role of haemoglobin in endurance performance has been well documented. We examined whether polymorphisms in the HBB gene modified aerobic capacity. METHODS: 102 recruits were trained by running 5000 m three times per week for 18 weeks. Exercise intensity progressively increased from an initial heart rate corresponding to 95% of the individual baseline ventilatory threshold during the first 10 weeks to 105% during the last 8 weeks. The phenotypes measured were running economy and VO(2)max. Running economy was determined by measuring submaximal VO(2) for 5 min at a constant running speed of 12 km.h(-1) and VO(2)max was obtained during an incremental test to exhaustion. Genomic DNA was extracted from white cells of peripheral blood and the -551C/T, intron2,+16C/G and +340 A/T genotypes were examined relative to the TAA site variants by PCR-RFLP. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium at three loci. None of the running economy and VO(2)max-related traits were associated with the three polymorphisms or haplotypes at baseline, while the training response of running economy was associated with -551C/T and intron2,+16C/G polymorphisms. Subjects homozygous for intron2,+16C/C or -551C/C had decreased oxygen cost of running compared to the other individuals. DISCUSSION: It was concluded that the -551C/C or intron2,+16C/C genotype might explain part of the individual variation in the cardiorespiratory adaptation to endurance training.

Adaptation, Physiological↗

PubMed2006

Central neurocytoma: clinical, pathological and neuroradiological findings.

AIM: To evaluate the clinical, pathological and neuroradiological features of intraventricular central neurocytoma in six patients. MATERIALS AND METHODS: Six patients were imaged using non-enhanced and contrast-enhanced magnetic resonance imaging (MRI); three of them were also examined using non-enhanced computed tomography (CT). Two radiologists read the images retrospectively. The imaging data were studied with regard to location, size, margin, signal intensity, enhancement characteristics and presence of calcifications. Clinical data (i.e. presenting signs and symptoms, physical findings and medical histories) were collected and histopathological and immunohistochemical studies were performed by two pathologists. RESULTS: All lesions were located in the lateral ventricles. Three tumors were confined to the left side, one to the right side and two cases involved both lateral ventricles. The growth of central neurocytoma was of close spatial relation to the septum pellucidum. On MRI, most of the cases showed a heterogeneous hypointensity on T1-weighted images and hyperintensity on T2-weighted images or FLAIR with a well-defined margin. The presence of cystic components, necroses and calcifications caused these internal heterogeneities. After intravenous administration of gadolinium (Gd-DTPA) all tumours showed a heterogeneous enhancement. CT provided additional information by distinguishing intratumoural calcifications in all three evaluated cases. Immunohistochemical analysis showed positive synaptophysin staining in all cases and positive neuron-specific enolase staining in four cases. In three cases a small proportion of the tumour cells could be labelled with antibodies to glial fibrillary acid protein (GFAP). CONCLUSION: Central neurocytoma should be considered when the following conditions occur: young patients with lesions in the lateral ventricle, which contain calcifications and show some enhancement. This is especially applicable for tumours involving both lateral ventricles with symmetrical growth around the centre of septum pellucidum or for unilateral ventricular tumors with a wide base attachment to the septum pellucidum.

Adolescent↗

PubMed2005

Targeted expression of the anti-apoptotic gene CrmA to NOD pancreatic islets protects from autoimmune diabetes.

The activation of apoptosis is a critical mechanism by which pancreatic beta cells are destroyed in type 1 diabetes (T1DM). Strategies aimed at interfering with the apoptotic pathways could therefore be of potential therapeutic value. To this end, we generated NOD transgenic mice with targeted expression of the anti-apoptotic gene Cytokine response modifier A (CrmA) to pancreatic beta cells using the rat insulin promoter and the reverse tetracycline transactivator to express CrmA in a temporally controlled manner. Two lines of transgenic mice were studied whose expression of CrmA occurred only after feeding doxycycline food. Islet expression of CrmA partially protected pancreatic beta cells from the cytokine-mediated cytotoxicity in vitro and reduced modestly the spontaneous development of diabetes in NOD mice in vivo. In addition, beta cells from NOD CrmA mice were significantly protected from the destruction by diabetogenic T cells after adoptive transfer. More strikingly, NODCrmA mice were significantly resistant to the diabetogenic activity of a potent insulin-specific CD8 T-cell clone. Since these adoptive transfer models mainly represent the effector phase rather than the initiation phase of autoimmune diabetes, our data suggest that the latter is more sensitive to CrmA protection. We conclude that anti-apoptotic genes such as CrmA might be potential candidates to enhance islet graft survival in T1DM.

Adoptive Transfer↗

PubMed2005

Human retinal microglia express candidate receptors for HIV-1 infection.

BACKGROUND/AIMS: Microglia are the primary antigen presenting cells in the central nervous system and the retina, and can harbour viral antigens that may damage neural tissue via the release of neurotoxins. All cells bearing CD4 molecules and co-receptors (members of the chemokine receptor and Fcgamma receptor families) are potential targets for the human immunodeficiency virus (HIV). In this study, retinal microglia (in vitro and in situ) were investigated for the expression of candidate HIV-1 binding receptors. METHODS: Cultured human retinal microglia and frozen sections of human retinas were used. Immunohistochemistry was used to investigate expression of cell surface receptors necessary for HIV-1 infection: CD4, CC chemokine receptor 5 (CCR5), and Fcgamma receptors. RESULTS: Human retinal microglia expressed detectable levels of CD4, CD16, CD64, and CCR5 in vitro and Fcgamma receptor I (CD64) in situ. CONCLUSIONS: Human retinal microglia express several candidate receptors required for viral binding and as such may be a potential reservoir for HIV-1 infection.

Adolescent↗

PubMed2005

How can the innate immune system influence autoimmunity in type 1 diabetes and other autoimmune disorders?

The environment is important in determining the onset of autoimmune diseases such as type 1 diabetes. Genetic susceptibility factors interact with the environment to trigger and modulate a series of immune responses that ultimately lead to destruction of the insulin-producing beta cells of the pancreas. Although T lymphocytes are thought to play a major pathogenic role in the pathogenesis of diabetes, undoubtedly other components of the immune system also contribute to this process. How the environment may alter the course of disease is unknown, although viruses have been implicated in triggering and/or exacerbating the disease process. In this review, we will focus on how infection, particularly with viruses, may influence the onset of type 1 diabetes and other autoimmune diseases. Mechanisms such as molecular mimicry, bystander activation, and uncontrolled polyclonal activation of the immune system may contribute to the immune pathogenesis. We will also explore the interaction of the innate immune system with adaptive immune responses in predisposing individuals to the development of autoimmunity.

Animals↗

PubMed2005

Effect of cordycepin on Hantaan virus 76-118 infection of primary human embryonic pulmonary fibroblasts--characterization of apoptotic effects.

The cDNA microarray technique was used to study gene epression in human embryonic pulmonary fibroblasts (HEPF) infected with Hantaan virus (HTNV) under the influence of cordycepin (Cor), an inhibitor of post-transcriptional pre-mRNA polyadenylation. Four apoptotic genes, the insulin-like growth factor binding protein 1, NFkB inhibitor alpha, caspase-3 and NFkB1 were up-regulated in both infected and uninfected Cor-treated cells and two cell cycle-associated genes, CDC-like kinase and beta-induced transforming growth factor were up-regulated in Cor-untreated cells but down-regulated in Cor-treated cells. Cell morphology examination, quantitative RT-PCR, and immunofluorescence (IF) test suggested that following the Cor treatment the HTNV infection took place, but late viral gene expression was slightly reduced. Three parameters, namely caspase-3 activity, annexin V binding, and cell cycle were used to detect apoptosis. The results suggested that the induction of apoptosis in HEPF by HTNV started at 6 hrs post infection (p.i.). Following the Cor treatment, however, the caspase-3 activity began to increase at 24 hrs p.i. Thus it is suggested that inhibition of de novo late viral protein synthesis by Cor changes the apoptosis pathway and cell cycle by delaying caspase-3 gene expression and by up/down-regulating of expression of other apoptotic and cell cycle-associated genes. This implicates that HTNV can induce apoptosis in HEPF even without de novo viral protein synthesis and with a reduced and slowed viral maturation.

Animals↗

PubMed2004

What can the HLA transgenic mouse tell us about autoimmune diabetes?

Type 1 diabetes mellitus is a polygenic disease strongly associated with the class II molecules DR3, 4 and the linked DQ2, 8 alleles. These molecules play an important role in presentation of peptide antigens after intracellular processing to CD4 T lymphocytes. A number of in vitro approaches have been used to elucidate the molecular basis for the association of particular HLA alleles with susceptibility to or protection from Type 1 diabetes mellitus. These have focused on the structure of the antigen-presenting molecules, together with their peptides. Binding studies, peptide elution, molecular modelling and crystallisation of the peptide MHC complex have between them made it possible to define the peptide-binding regions and to examine the stability of binding of peptides from putative autoantigens. It is difficult to study the role of these molecules in vivo in humans, and HLA transgenic mice have been generated to overcome this problem. Studies of mice expressing the HLA class II alleles associated with diabetes have shown that the presence of HLA molecules alone does not cause disease except in the presence of an islet "insult", even when this "insult" would in itself be insufficient to precipitate disease in the absence of the HLA class II transgene. HLA transgenic mice offer a way to elucidate the in vivo role of these molecules, and could help the development of targeted immunotherapy.

Amino Acid Sequence↗

PubMed2004

Serological characterization of a hantavirus from Hubei, China.

Hantavirus HV114, isolated from urine of a patient during epidemic of hemorrhagic fever with renal syndrome (HFRS) in China, was subjected to a detailed serological characterization using enzyme-linked immunosorbent assay (ELISA), neutralization test and indirect immunofluorescence antibody assay (IFA). It has been found that HV114 is antigenically similar to the hantavirus A9 strain isolated in China and to the Hantaan 76-118 virus (HTNV 76-118), but different from the hantaviruses isolated from Apodemus agrarius in the region endemic for HFRS.

Animals↗

PubMed2003

Critical roles of CD30/CD30L interactions in murine autoimmune diabetes.

CD30/CD30L is a member of tumour necrosis factor (TNF) receptor/TNF superfamily and has been implicated in immune-regulation. A genetic study has also suggested a possible implication of CD30 in spontaneous autoimmune diabetes in NOD mice. In this study, we investigated the involvement of CD30/CD30L in the development of diabetes in NOD mice. Flow cytometric analysis showed that CD30 and CD30L were highly expressed on CD4+ or CD8+ T cells in the spleen and pancreatic lymph node of younger NOD mice. In addition, islet-specific CD4+ or CD8+ T cell lines expressed CD30 and CD30L. Administration of a neutralizing anti-CD30L monoclonal antibody (mAb) from 2 to 10 week of age completely suppressed the development of spontaneous diabetes in NOD mice. In addition, the treatment with anti-CD30L mAb also inhibited the development of diabetes induced by adoptive transfer of spleen cells from diabetic NOD mice or islet-specific CD4+ or CD8+ T cell lines into NOD-SCID mice. Furthermore, anti-CD30L mAb inhibited T cell proliferation in response to islet antigens. These results suggested that CD30/CD30L interaction plays important roles in both induction and effector phases of autoimmune diabetes in NOD mice.

Adoptive Transfer↗

PubMed2002

Performance of steers grazing rhizomatous and nonrhizomatous birdsfoot trefoil in pure stands and in tall fescue mixtures.

This study investigated the performance of steers grazing rhizomatous birdsfoot trefoil (Lotus corniculatus L.) (RBFT) compared to nonrhizomatous birdsfoot trefoil (BFT) in pure stands or when interseeded with endophyte-free tall fescue (Festuca arundinacea Schreb.; TF). Five forage treatments of RBFT, BFT, TF, RBFT+TF, and BFT+TF (four replicate paddocks per treatment) were continuously stocked in spring and fall of 1998 and spring of 1999. Grazing for individual treatments was terminated when pasture mass fell below 900 kg/ha. Average daily gain was greatest (P < 0.10) in pure stands of BFT and RBFT, but total forage production, and thus grazing days, for these treatments was low. Average daily gain for steers grazing BFT+TF and RBFT+TF treatments was not different from (spring and fall 1998) or greater (P < 0.10) (spring 1999) than that for TF. Total forage production of BFT+TF and RBFT+TF was greater (P < 0.10) than that of TF in spring 1998. In fall 1998, BFT+TF produced more (P < 0.10) total forage than either RBFT+TF or TF, and in spring 1999, RBFT+TF had less (P < 0.10) total forage than TF or BFT+TF. Total steer days on mixed pastures were greater (P < 0.10) than that for TF in spring and fall 1998 but not different from those for TF in spring 1999. In all three trials total weight gain/hectare was greater (P < 0.10) for RBFT+TF and BFT+TF than for TF. The RBFT+TF and BFT +TF had greater (P < 0.05) CP than TF in spring and fall 1998 and less (P < 0.05) NDF and ADF in fall 1998. We concluded that either RBFT or BFT could be interseeded with tall fescue to enhance ADG and total steer days.

Animal Feed↗

PubMed2001

[Relationship between basic fibroblast growth factor (bFGF) and cell proliferation, invasion in pituitary adenoma].

Basic fibroblast growth factor (bFGF) and proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry in fifty-one pituitary adenomas. The results showed that the intensity of bFGF expression was strong or intermediate in twenty-nine adenomas, which was positively related to cell proliferation, there was positive relationship between bFGF expressin and tumor invasion in non-functional adenomas. The data suggest that bFGF may play some role in the origin and progression of pituitary adenomas.

Adenoma↗

PubMed2001

Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.

The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1-Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.

Actins↗

PubMed2001

Hemispherical variations in seismic velocity at the top of the Earth's inner core.

Knowledge of the seismic velocity structure at the top of the Earth's inner core is important for deciphering the physical processes responsible for inner-core growth. Previous global seismic studies have focused on structures found 100 km or deeper within the inner core, with results for the uppermost 100 km available for only isolated regions. Here we present constraints on seismic velocity variations just beneath the inner-core boundary, determined from the difference in travel time between waves reflected at the inner-core boundary and those transmitted through the inner core. We found that these travel-time residuals-observed on both global seismograph stations and several regional seismic networks-are systematically larger, by about 0.8 s, for waves that sample the 'eastern hemisphere' of the inner core (40 degrees E to 180 degrees E) compared to those that sample the 'western hemisphere' (180 degrees W to 40 degrees E). These residuals show no correlation with the angle at which the waves traverse the inner core; this indicates that seismic anisotropy is not strong in this region and that the isotropic seismic velocity of the eastern hemisphere is about 0.8% higher than that of the western hemisphere.

Journal Article↗

PubMed2001

The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors.

Migration is a basic feature of many cell types in a wide range of species. Since the 1800s, cell migration has been proposed to occur in the nervous and immune systems, and distinct molecular cues for mammalian neurons and leukocytes have been identified. Here we report that Slit, a secreted protein previously known for its role of repulsion in axon guidance and neuronal migration, can also inhibit leukocyte chemotaxis induced by chemotactic factors. Slit inhibition of the chemokine-induced chemotaxis can be reconstituted by the co-expression of a chemokine receptor containing seven transmembrane domains and Roundabout (Robo), a Slit receptor containing a single transmembrane domain. Thus, there is a functional interaction between single and seven transmembrane receptors. Our results reveal the activity of a neuronal guidance cue in regulating leukocyte migration and indicate that there may be a general conservation of guidance mechanisms underlying metazoan cell migration. In addition, we have uncovered an inhibitor of leukocyte chemotaxis, and propose a new therapeutic approach to treat diseases involving leukocyte migration and chemotactic factors.

Animals↗

PubMed2001

The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons.

The Slit proteins are a new family of secreted guidance cues involved in axon guidance and neuronal migration. Each mammalian Slit protein contains >1400 amino acid residues, with four leucine-rich regions (LRRs), nine epidermal growth factor repeats, a laminin G domain, and a C-terminal cysteine-rich domain. A receptor for Slit is the transmembrane protein Roundabout (Robo), whose extracellular part contains five Ig domains and three fibronectin type III repeats. We report here that the LRRs in Slit are sufficient for binding to the Ig domains of Robo. Mutant forms of Slit containing only the LRRs function as chemorepellents for axons projecting from the olfactory bulb both in vitro and in the telencephalon. The LRRs can repel neurons migrating from the anterior subventricular zone (SVZa) to the olfactory bulb in brain slices isolated from neonatal rodents. However, the LRRs do not show repulsive effects on the SVZa neurons migrating in collagen gels. Our results indicate that the same LRRs are sufficient for guiding both axon projection and neuronal migration and suggest that the other regions in the Slit proteins may be involved in regulating the diffusion and distribution of the Slit proteins. The fact that the same domains are involved in guiding axon projection and neuronal migration further strengthens the idea of a conserved guidance mechanism for these important processes.

Amino Acid Motifs↗

PubMed2001

Identification of a spliced leader RNA binding protein from Trypanosoma cruzi.

Nuclear mRNAs in trypanosomatids are generated by trans-splicing. Although trans-splicing resembles cis-splicing in many ways and most of the U RNA participants have been characterized, relatively few involved proteins have been identified. Herein, we employed a yeast three-hybrid system to identify a protein, XB1, which binds to the Trypanosoma cruzi SL RNA. XB1 is a approximately 45 kDa protein which is homologous to the essential pre-mRNA-splicing factor PRP31p from Saccharomyces cerevisiae. Gel shift assays and UV cross-linking experiments with recombinant XB1 confirmed that this T. cruzi protein binds the SL RNA in vitro. The binding site of XB1 on the SL RNA was mapped to stem-loop II by deletion of the SL RNA 'bait' in the three-hybrid system. Finally, UV cross-linking SL RNA with S100 extract indicated native XB1 protein and SL RNA interaction in T. cruzi extract.

Amino Acid Sequence↗

PubMed2001

Type 1 diabetes-predisposing MHC alleles influence the selection of glutamic acid decarboxylase (GAD) 65-specific T cells in a transgenic model.

The genetic factors that contribute to the etiology of type 1 diabetes are still largely uncharacterized. However, the genes of the MHC (HLA in humans) have been consistently associated with susceptibility to disease. We have used several transgenic mice generated in our laboratory, bearing susceptible or resistant HLA alleles, in the absence of endogenous MHC class II (Abetao), to study immune responses to the autoantigen glutamic acid decarboxylase (GAD) 65 and its relevance in determining the association between autoreactivity and disease pathogenesis. Mice bearing diabetes-susceptible haplotypes, HLA DR3 (DRB1*0301) or DQ8 (DQB1*0302), singly or in combination showed spontaneous T cell reactivity to rat GAD 65, which is highly homologous to the self Ag, mouse GAD 65. The presence of diabetes-resistant or neutral alleles, such as HLA DQ6 (DQB1*0602) and DR2 (DRB1*1502) prevented the generation of any self-reactive responses to rat GAD. In addition, unmanipulated Abetao/DR3, Abetao/DQ8, and Abetao/DR3/DQ8 mice recognized specific peptides, mainly from the N-terminal region of the GAD 65 molecule. Most of these regions are conserved between human, mouse, and rat GAD 65. Further analysis revealed that the reactivity was mediated primarily by CD4(+) T cells. Stimulation of these T cells by rat GAD 65 resulted in the generation of a mixed Th1/Th2 cytokine profile in the Abetao/DR3/DQ8, Abetao/DR3, and Abetao/DQ8 mice. Thus, the presence of diabetes-associated genes determines whether immune tolerance is maintained to islet autoantigens, but autoreactivity in itself is not sufficient to induce diabetes.

Alleles↗