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Biomedical subjects

X Yan

Publications and source records attributed to X Yan.

At least 19 recordsLinked to original sources

Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.

Excessive glomerular collagen IV and reactive oxygen species (ROS) production are key factors in the development of diabetic nephropathy. Integrin alpha1beta1, the major collagen IV receptor, dowregulates collagen IV and ROS production, suggesting this integrin might determine the severity of diabetic nephropathy. To test this possibility, wild-type and integrin alpha1-null mice were rendered diabetic with streptozotocin (STZ) (100 mg/kg single intraperitoneal injection), after which glomerular filtration rate (GFR), glomerular collagen deposition, and glomerular basement membrane (GBM) thickening were evaluated. In addition, ROS and collagen IV production by mesangial cells as well as their proliferation was measured in vitro. Diabetic alpha1-null mice developed worse renal disease than diabetic wild-type mice. A significant increase in GFR was evident in the alpha1-null mice at 6 weeks after the STZ injection; it started to decrease by week 24 and reached levels of non-diabetic mice by week 36. In contrast, GFR only increased in wild-type mice at week 12 and its elevation persisted throughout the study. Diabetic mutant mice also showed increased glomerular deposition of collagen IV and GBM thickening compared to diabetic wild-type mice. Primary alpha1-null mesangial cells exposed to high glucose produced more ROS than wild-type cells, which led to decreased proliferation and increased collagen IV synthesis, thus mimicking the in vivo finding. In conclusion, this study suggests that lack of integrin alpha1beta1 exacerbates the glomerular injury in a mouse model of diabetes by modulating GFR, ROS production, cell proliferation, and collagen deposition.

Animals↗

Characterization of [125I]ZM 241385 binding to adenosine A2A receptors in the pineal of sheep brain.

Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic actions through activation of A(1), A(2A), A(2B) and A(3) adenosine receptor subtypes. In the central nervous system, adenosine's action in neurons is manifested in its modulation of tonic inhibitory control. Adenosine released in the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action suggested to be mediated by A(2A) receptors in the posteromedial thalamus. In an effort to more accurately define the spatial distribution of adenosine A(2A) receptors in fetal sheep diencephalon, we have used a receptor autoradiographic technique utilizing an iodinated radioligand [(125)I]ZM 241385, which has greater sensitivity and resolution than the tritiated compound. The distribution of ligand binding sites in the fetal sheep diencephalon indicated that the highest levels of binding were in select thalamic nuclei, including those implicated in hypoxic depression of fetal breathing, and the pineal. Given the high density of labeled A(2A) receptors in the pineal, these sites were characterized more fully in homogenate radioligand binding assays. These data indicate that [(125)I]ZM 241385 binding sites display a pharmacological signature consistent with that of adenosine A(2A) receptors and are expressed at similar levels in fetal, lamb and adult ovine brain. The adenosine A(2A) receptor pharmacologic signature of the [(125)I]ZM 241385 binding site in pineal cell membranes generalized to the site characterized in membranes derived from other portions of the lamb thalamus, including the sector involved in hypoxic inhibition of fetal breathing. These results have important implications for the functional roles of adenosine A(2A) receptors in the thalamus and pineal of sheep brain.

Adenosine↗

Nonspherical colloidal crystals fabricated by the thermal pressing of colloidal crystal chips.

Nonspherical colloids and their ordered arrays may be more attractive in applications such as photonic crystals than their spherical counterparts because of their lower symmetries, although such structures are difficult to achieve. In this letter, we describe the fabrication and characterization of colloidal crystals constructed from nonspherical polyhedrons. We fabricated such nonspherical colloidal crystals by pressing spherical polymer colloidal crystal chips at a temperature slightly lower than the glass-transition temperature (T(g)) of these polymer colloids. During this process, the polymer microspheres were distinctively transformed into polyhedrons according to their crystal structures, whereas the long-range order of the 3D lattice was essentially preserved. Because a working temperature lower than T(g) effectively prevented the colloidal crystals from fusing into films, the spherical colloidal crystals were transformed greatly under pressure, which lead to obvious change in the optical properties of colloidal crystals. Besides their special symmetry and optical properties, these nonspherical colloidal crystals can be used as templates for 2D or 3D structures of special symmetry, such as 2D nano-networks. We anticipate that this fabrication technique for nonspherical colloidal crystals can also be extended to nonspherical porous materials.

Journal Article↗

Penis reconstruction using three different operative methods.

To identify the relative success rates, including aesthetic success, of three penis reconstruction techniques, we reviewed 44 cases of penis reconstruction carried out over the past 12 years. The three operative methods we surveyed involved: lower abdominal pedicled fascia flaps; paraumbilical island flaps; and free forearm flaps. Reconstructions survived in only half of the patients receiving lower abdominal pedicled fascia flaps, but 100% success rates were obtained with paraumbilical island flaps and free forearm flaps. The paraumbilical island flap is safe in terms of its blood supply, and the operative procedure is relatively simple in that it does not require microsurgery. Although, the flap is thicker than the forearm skin flap, its shape is satisfactory in slim patients; furthermore, it can be defatted secondarily. The free forearm skin flap provides the best shape, but skilled microsurgery is necessary to carry out the procedure, and damage is likely to the forearm. In conclusion, the best methods to repair defects in the penis in our experience are the paraumbilical island flap and free forearm flap. Lower abdominal pedicled fascia flaps are unsuitable for penile reconstruction and should be used less often.

Abdomen↗

Correlative study of angiogenesis and dynamic contrast-enhanced magnetic resonance imaging features of hepatocellular carcinoma.

PURPOSE: To explore the correlation between contrast-enhancement patterns on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and angiogenesis by analyzing microvessel density (MVD), vascular endothelial growth factor (VEGF), and P53 protein expression in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: MRI was performed with a GE Signa 1.5T MR scanner using SE and FMPSPGR sequences in 30 patients (38 lesions) during the period October 1998 to March 2000. All had histopathologically proven HCC. MR images were reviewed/ analyzed retrospectively. The 30 patients were between 35 and 65 years of age (average age 58; 18 M and 12 F). SE T1WI, PDWI, and T2WI were acquired initially. The FMPSPGR sequence was acquired in the same position. The DCE-MRI was performed in the arterial, portal vein, and delay phase after a bolus injection of Gd-DTPA. The specimens were stained immunohistochemically for CD34, VEGF, and P53. MVD was highlighted by anti-CD34 antibody staining. The enhancement features of HCC lesions were studied correlatively with the tumor MVD, VEGF, and P53 expression at protein level. RESULTS: In the arterial phase, the results showed that MVD of HCC in the high-enhancement group (229.76 +/- 80.96) was higher than that in the equal-enhancement (173.09 +/- 61.38) and low-enhancement groups (153.00 +/- 108.58) (P < 0.01, respectively). VEGF expression of HCC in the high-enhancement group (68.42%) was higher than that in the equal-enhancement (36.36%) and low-enhancement groups (38.89%) (P < 0.05, respectively). In the portal vein phase, MVD of HCC in the enhancement group (259.80 +/- 93.30) was higher than that in the non-enhancement group (178.64 +/- 92.65) (P < 0.05). No significant correlation was found between VEGF expression and the enhancement feature in the portal vein phase. In the delay phase, MVD of HCC in the ring-enhancement group (269.06 +/- 57.89) was significantly higher than that in the non-ring-enhancement group (144.10 +/- 88.90) (P < 0.01). There was a significant difference in VEGF expression between the ring-enhancement group (76.47%) and the non-ring-enhancement group (42.86%) (P < 0.05). No significant correlation was detected between P53 protein expression and the enhancement feature. Relative enhancement (RE) correlated with MVD, but not with VEGF and P53 protein expression. CONCLUSION: The contrast-enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated VEGF expression, and are therefore valuable indicators for accessing tumor angiogenic activity and tumor neovascularization in vivo in HCC patients.

Adult↗

A role for scavenger receptor B-I in selective transfer of rhodamine-PE from liposomes to cells.

We investigated the potential role of scavenger receptor B-I (SR-BI) in the selective removal of liposomal markers from blood by hepatocytes. Liposomes were labeled with [(3)H]cholesteryloleyl-ether ([(3)H]COE), 1,2-di[1-(14)C]palmitoyl-phosphatidylcholine ([(14)C]PC), and N-(lissamine rhodamine-B sulfonyl)-phosphatidylethanolamine (N-Rh-PE). The radiolabels were eliminated at identical rates from plasma, while N-Rh-PE was cleared twice as fast. Involvement of SR-BI in the selective removal of N-Rh-PE from liposomes was studied in transfected Chinese hamster ovary cells over-expressing SR-BI. Uptake of N-Rh-PE from liposomes containing phosphatidylserine was higher than [(3)H]COE, and was further enhanced by apolipoprotein A-I, confirming involvement of SR-BI in the selective uptake of liposomal N-Rh-PE by cells.

Animals↗

The role of beta2-glycoprotein I in liposome-hepatocyte interaction.

Adsorption of serum proteins to the liposomal surface plays a critical role in liposome clearance from the blood. The aim of this study was to investigate the role of liposome-adsorbed serum proteins in the interaction of liposomes with hepatocytes. We analyzed the serum proteins adsorbing to the surface of differently composed small unilamellar liposomes during incubation with human or rat serum, and found that one protein, with a molecular weight of around 55 kDa, adsorbed in a large amount to negatively charged liposomes containing phosphatidylserine (PS) or phosphatidylglycerol (PG). The binding was dependent on the liposomal charge density. The approximately 55-kDa protein was identified as beta2-glycoprotein I (beta2GPI) by Western blotting. Despite the high affinity of beta2GPI for strongly negatively charged liposomes, in vitro uptake and binding experiments with isolated rat hepatocytes, Kupffer cells or liver endothelial cells, and with HepG2 cells showed no enhancing effect of this protein on the association of negatively charged liposomes with any of these cells. On the contrary, an inhibitory effect was observed. We conclude that despite abundant adsorption to negatively charged liposomes, beta2GP1 inhibits, rather than enhances, liposome uptake by liver cells.

Adsorption↗

Steinernema aciari sp. n. (Nematoda: Steinernematidae), a new entomopathogenic nematode from Guangdong, China.

A new species of entomopathogenic nematode, Steinernema aciari sp. n. was described. It was recovered from a soil sample collected from Haimen town, Shantou district in the eastern coast of Guangdong province, the People's Republic of China during a survey for entomopathogenic nematodes. S. aciari sp. n. belongs to the Steinernema glaseri group. It can be separated from all described Steinernema species by the combined morphological and morphometrical characters of various stages of the nematodes. For male, the new species can be recognized by spicule length (86+/-6.3 microm); spicule tip blunt with a hook-like structure; gubernaculum with a short and Y-shaped cuneus and corpus well-separated posteriorly. For infective juvenile, the combination of the following characters: body length (1113+/-68 microm), distance from anterior end to excretory pore (95+/-3.7 microm), tail length (78+/-5.2 microm), and E % (123+/-7) can be used to differentiate the new species from other nematodes. For female, the tail (conoid with a long mamillate terminus and a distinct postanal swelling) and vulva (slightly protruding from body surface with conspicuous double flapped epiptygma) shapes can be used as diagnostic characters for the new species. The new species can also be distinguished from other Steinernema species by DNA sequences of either a partial 28S rDNA or the internal transcribed spacer regions of rDNA, and from the close related species S. glaseri, Steinernema longicaudum CWL05, and Steinernema guangdongense by cross-breeding test.

Animals↗

Optimal cutoff point of glutamate decarboxylase antibody titers in differentiating two subtypes of adult-onset latent autoimmune diabetes.

The optimal cutoff point of glutamate decarboxylase antibody (GAD-Ab) titers for differentiating two latent autoimmune diabetes (LADA) subtypes remains unclear. One hundred and forty-five GAD-Ab-positive patients screened from phenotypic type 2 diabetes were diagnosed as LADA. The clinical features were compared among LADA patients with different GAD-Ab titers. The receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic value of GAD-Ab titers and to define the optimal cutoff point. The heterogeneity of clinical features in LADA could be discriminated by five GAD-Ab titers, with maximal differences at the titer of 175 U/mL. The ROC curve analysis showed that the optimal cutoff point for discriminating two LADA subtypes was at the titer of 175 U/mL, with sensitivity and specificity of 54.5% and 92.1%, respectively. These findings demonstrated that the two clinically distinct subtypes of LADA can be optimally discriminated by the GAD-Ab titers.

Adult↗

The effect of knocking-down nucleostemin gene expression on the in vitro proliferation and in vivo tumorigenesis of HeLa cells.

Previous studies have demonstrated nucleostemin (NS) expressed in undifferentiated cells (e.g. embryonic stem cells and myeloid stem cells) and various cancer cell lines, but didn't express in differentiated adult tissues. In this study, we examined the NS expression in several cancer cell lines and some normal human tissues. Moreover, we used RNAi techniques to knock down the NS gene expression in Hela cells. As a result, we found that all these detected cancer cell lines in our program had high levels of NS expression, which indicated NS played a really important role in the self-renewal of these cancer cells. At the same time, NS expressed in human placenta tissue also at a high level, which may be due to the existence of a mass of placenta stem cells. Only a small quantity of NS expression could be found in normal human muscle tissue due to the existence of myoblasts. And for the first time our findings demonstrated that if NS expression of Hela cells was knocked down, more Hela cells couldn't complete the DNA synthesis to pass through S phase. So the percent of G0/G1 phase increased with the decrease of S phase and cell proliferation rate and in vivo tumorigenic capacity decreased obviously. Our work would help shed light on the self-renewal and malignant growth of cancer cells.

Blotting, Northern↗

Effects of air on the segregation of particles in a shaken granular bed.

Effects of interstitial air on the motions of a large intruder in a shaken granular bed are studied experimentally as a function of ambient air pressure, particle size of the bed, and the density of the intruder. It is found that the intruder always rises from the granular bed in the absence of air. However, the intruder can acquire both positive and negative buoyancy in the presence of air. Negative buoyancy can be observed only when both the density of the intruder and the particle size of the bed are small enough. This negative buoyancy can be explained by the unusual air pressure distribution found in the bed.

Journal Article↗

Localization of nuclear factor-kappa B (NF kappa B) and inhibitory factor-kappa B (I kappa B) in human fetal membranes and decidua at term and preterm delivery.

The human fetal membranes and decidua are thought to be involved in the onset of human parturition. These tissues produce and respond to various cytokines, which may be involved in preterm labour and possibly term labour. They also show increasing production of prostaglandins (PGs) with advancing gestation and labour. The expression of PGHS-2, a rate limiting enzyme in PG synthesis, is increased in the fetal membranes at labour. The gene for PGHS-2 and many of the cytokine genes (e.g. TNFalpha, IL-1, IL-6) are stimulated by the transcription factor NF kappa B. This factor is composed of two subunits, p50 and p65, which are localized in the cytoplasm bound to I kappa B. When activated I kappa B is metabolized, and p50, p65 translocate to the nucleus to activate various genes. The purpose of the present study was to examine the tissue and cellular distribution of p65 and I kappa B in the human fetal membranes and decidua throughout gestation. Term tissues were obtained prior to labour by elective caesarean section (n=10) or following vaginal delivery (n=10) and 10 preterm tissues were obtained following labour prior to 37 weeks gestation. None of the tissues had any evidence of infection. The immunoreactive NF kappa B and I kappa B were localized in the tissues. p65 protein was found in the nucleus and cytoplasm of cells in the amnion, chorion laeve and decidua. In the amnion and chorion laeve, no changes occurred in subcellular localization with advancing gestation or term labour. However, in the decidua, there was a marked increase in the nuclear localization of i.r. p 65 in tissues obtained at term when compared with tissues delivered preterm. In the case of I kappa B, it was localized to the cytoplasm of cells in all tissues and there was an increase i.r. I kappa B in decidua at term compared to preterm but no change occurred in the amnion or chorion. The increase in nuclear localization of p65 in the decidua that occurs with advancing gestation, highlights the potential importance of this factor in the regulation of parturition related genes in this tissue.

Cell Nucleus↗

Transgenic expression of sarcoplasmic reticulum Ca(2+) atpase modifies the transition from hypertrophy to early heart failure.

To examine the contribution of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) to early heart failure, we subjected transgenic (TG) mice expressing SERCA2a gene and wild-type (WT) mice to aortic stenosis (AS) for 7 weeks. At an early stage of hypertrophy (4-week AS), in vivo hemodynamic and echocardiographic indices were similar in TG and WT mice. By 7 weeks of AS, which is the stage of early failure in this model, TG mice with AS had lower mortality than WT mice with AS (6.7% versus 29%). The magnitude of left ventricular (LV) hypertrophy was similar in WT and TG 7-week AS mice. In vivo LV systolic function was higher in TG than in WT 7-week AS mice. In LV myocytes loaded with fluo-3, fractional cell shortening and the amplitude of the [Ca(2+)](i) transients were higher in TG than in WT 7-week AS mice under baseline conditions (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C). The rates of relengthening and decay in [Ca(2+)](i) were faster in TG than in WT 7-week AS myocytes. In myocytes from WT 7-week AS compared with sham-operated WT mice, contractile reserve in response to rapid pacing was depressed with impaired augmentation of both peak-systolic [Ca(2+)](i) and the SR Ca(2+) load. In contrast, contractile reserve and the capacity to augment SR Ca(2+) load were maintained in TG 7-week AS mice. SERCA2a protein levels were depressed in WT 7-week AS mice, but were preserved in TG 7-week AS mice. These data suggest that defective SR Ca(2+) loading contributes to the onset of contractile failure in animals with chronic pressure overload.

Animals↗

The highly recombinogenic bz locus lies in an unusually gene-rich region of the maize genome.

The bronze (bz) locus exhibits the highest rate of recombination of any gene in higher plants. To investigate the possible basis of this high rate of recombination, we have analyzed the physical organization of the region around the bz locus. Two adjacent bacterial artificial chromosome clones, comprising a 240-kb contig centered around the Bz-McC allele, were isolated, and 60 kb of contiguous DNA spanning the two bacterial artificial chromosome clones was sequenced. We find that the bz locus lies in an unusually gene-rich region of the maize genome. Ten genes, at least eight of which are shown to be transcribed, are contained in a 32-kb stretch of DNA that is uninterrupted by retrotransposons. We have isolated nearly full length cDNAs corresponding to the five proximal genes in the cluster. The average intertranscript distance between them is just 1 kb, revealing a surprisingly compact packaging of adjacent genes in this part of the genome. At least 11 small insertions, including several previously described miniature inverted repeat transposable elements, were detected in the introns and 3' untranslated regions of genes and between genes. The gene-rich region is flanked at the proximal and distal ends by retrotransposon blocks. Thus, the maize genome appears to have scattered regions of high gene density similar to those found in other plants. The unusually high rate of intragenic recombination seen in bz may be related to the very high gene density of the region.

Base Sequence↗