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Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 73 records · Page 4Linked to original sources

Orientational ordering of a bent-core mesogen by two-dimensional 13C NMR spectroscopy.

Various two-dimensional (2D) NMR techniques are reported on a bent-core mesogen 4,6-dichloro-1,3-phenylenebis[4'-(9-decenyloxy)-1,1'-biphenyl] carboxylate in its nematic and solid phases in order to unambiguously assign its carbon-13 NMR spectrum. The (13)C chemical shifts from the molecular core were studied as a function of temperature to extract its molecular geometry and orientational order tensor. To this end, the chemical shift anisotropy tensors of some carbon sites were measured in the solid state of this mesogen using a recent method called the separation of undistorted powder patterns by effortless recoupling (SUPER). The average bending angle subtended by the two arms of the bent-core structure is determined to be 148.7 degrees. The C-H dipolar couplings obtained from the separated local field (SLF) experiment for the aromatic rings are used to find the local order parameter tensors.

Journal Article↗

Discovery of LH-regulated genes in the primate corpus luteum.

Circulating LH is essential for the development and function of the primate corpus luteum (CL) during the menstrual cycle. However, the cellular and molecular processes whereby LH controls luteal structure and function are poorly understood. Therefore, studies were initiated to identify gene products that are regulated by gonadotrophin in the monkey CL. Rhesus monkeys either were untreated (controls, CTRL; n = 3) or received the GnRH antagonist Antide (ANT; 3 mg/kg body weight, n = 3) to inhibit pituitary LH secretion on day 6 of the luteal phase in spontaneous menstrual cycles. The CL was removed 24 h later. RNA was extracted and converted to cDNA. The CTRL and ANT cDNA were differentially labelled with fluorescent dyes (Cy3-CTRL and Cy5-ANT) and hybridized onto microarrays containing 11,600 human cDNA. The selected cDNA were analysed further via semi-quantitative RT-PCR (a) to validate the microarray results and (b) to determine if their expression varies in the CL (n = 3/stage) between the mid (day 6-8), late (day 14-16), or very late (day 18-19, menses) luteal phase of the natural cycle. After normalization of the fluorescence data, 206 cDNA (1.8% of the total) exhibited > or = 2-fold change in expression after ANT. Of the 25 cDNA exhibiting a > or = 6-fold change, 6 were up-regulated and 19 were down-regulated. Twenty-two of these 25 cDNA were validated by RT-PCR as differentially expressed in the ANT group, relative to the CTRL group, and 11 of 25 changed (P < 0.05) correspondingly in the late-to-very late luteal phase. Thus, we have identified gene products that are regulated by gonadotrophin in the primate CL that may be important in luteal regression during the menstrual cycle.

Animals↗

Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation.

Porcine small intestinal submucosa (SIS) has been recommended as a cell-free, biocompatible biomaterial for the repair of rotator cuff tendon tear. However, we have observed noninfectious edema and severe pain in patients who have undergone SIS implantation for tendon repair. The aim of this study was to conduct an independent assessment of the safety and efficacy of Restore SIS membrane. The Restore orthobiologic implant was examined by histology and the nested PCR technique using porcine immunoreceptor DAP12 gene to examine if SIS membrane contained porcine cells or DNA, respectively. The material was also implanted into mice and rabbits for the evaluation of biological reaction and inflammatory response. Restore SIS was found to contain multiple layers of porcine cells. Chloroacetate esterase staining showed that some of these cells were mast cells. Nested PCR of the DAP12 gene demonstrated that Restore SIS contained porcine DNA material. Subcutaneous implantation of Restore SIS membrane in mice, and in rabbits for rotator cuff tendon repair, showed that the membrane caused an inflammatory reaction characterized by massive lymphocyte infiltration. In conclusion, Restore SIS is not an acellular collagenous matrix, and contains porcine DNA. Our results contradict the current view that Restore SIS is a cell-free biomaterial, and that no inflammatory response is elicited by its implantation. We suggest that further studies should be conducted to evaluate the clinical safety and efficacy of SIS implant biomaterials.

Adaptor Proteins, Signal Transducing↗

Molecular genetics of mosquito resistance to malaria parasites.

Malaria parasites are transmitted by the bite of an infected mosquito, but even efficient vector species possess multiple mechanisms that together destroy most of the parasites present in an infection. Variation between individual mosquitoes has allowed genetic analysis and mapping of loci controlling several resistance traits, and the underlying mechanisms of mosquito response to infection are being described using genomic tools such as transcriptional and proteomic analysis. Malaria infection imposes fitness costs on the vector, but various forms of resistance inflict their own costs, likely leading to an evolutionary tradeoff between infection and resistance. Plasmodium development can be successfully completed onlyin compatible mosquito-parasite species combinations, and resistance also appears to have parasite specificity. Studies of Drosophila, where genetic variation in immunocompetence is pervasive in wild populations, offer a comparative context for understanding coevolution of the mosquito-malaria relationship. More broadly, plants also possess systems of pathogen resistance with features that are structurally conserved in animal innate immunity, including insects, and genomic datasets now permit useful comparisons of resistance models even between such diverse organisms.

Animals↗

Large dose ketamine inhibits lipopolysaccharide-induced acute lung injury in rats.

BACKGROUND: Sepsis is associated with the highest risk of progression to acute lung injury or the acute respiratory distress syndrome. Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. Our study was designed to investigate the effect of ketamine on the endotoxin-induced acute lung injury in vivo. MATERIALS AND METHODS: Adult male Wistar rats were randomly divided into 6 groups: saline controls; rats challenged with endotoxin (5 mg/kg) and treated with saline; challenged with endotoxin (5 mg/kg) and treated with ketamine (0.5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (50 mg/kg); saline injected and treated with ketamine (50 mg/kg). TNF-alpha, IL-6 and NF-kappa B were investigated in the tissues of the lung after 2 h. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated 6 h later. RESULTS: We demonstrated that intravenous administration of endotoxin could provoke significant lung injury, which was characterized by increase of MPO activity and wet/dry weight ratio, TNF-alpha and IL-6 expression and NF-kappa B activation. Ketamine (5, 50 mg/kg) inhibited endotoxin-induced NF-kappa B activation. Ketamine only at a dose of 50 mg/kg inhibited TNF-alpha and IL-6 production, and decreased MPO activity and wet/dry weight ratio after endotoxin challenge. CONCLUSIONS: Ketamine, only at a supra-anesthetic dosage, could inhibit endotoxin-induced pulmonary inflammation in vivo.

Animals↗

A girl with pervasive developmental disorder and complex chromosome rearrangement involving 8p and 10p.

We report a 4-year-old girl with a de novo, apparently balanced complex chromosome rearrangement. She initially presented for assessment of velopharyngeal insufficiency due to hypernasal speech. She has distinctive facial features (long face, broad nasal bridge, and protuberant ears with simplified helices), bifid uvula, strabismus, and joint laxity. She is developmentally delayed, with language and cognitive skills approximately 2 SD below the mean expected for her age, and meets ADI, ADOS, and DSM-IV criteria for pervasive developmental disorder. She has poor eye contact, atypical communication and social interaction, repetitive behaviours and significant difficulties with processing sensory input. Her karyotype is characterized by the presence of two derivative chromosomes; 46,XX, der(8)(10pter- >10pl2.32::8p12- >8qter), der(l0)(8pter- >8p21.3::10p12.32- >10p11.23::8p21.3- > 8p12::10p11.23- >l0qter). The der(8) is a result of translocation of the segment 10p12.32-pter onto 8p12. The der(l0) has two 8p segments collectively from 8p12-pter in that the segment 8p21.3-pter is translocated onto 10p12.32 and the segment 8p12-p21.3 is inserted at 10p11.23. FISH analysis showed no microdeletion of the major locus at 22q11.2 nor for the minor locus at 10p13p14. This case suggests that aberrations at 8p12, 8p21.3, 10p11.23 and/or 10p12.32 may result in pervasive developmental disorder, associated with mild cognitive delay and specific facial anomalies.

Child Development Disorders, Pervasive↗

Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis.

AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p < 0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r = 0.938, p < 0.001) and histological grade (Spearman rank correlation; r = 0.734, p < 0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r = 0.087, p = 0.410) and MVD (Spearman rank correlation, r = 0.103, p = 0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer.

Adult↗

Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm.

The mu opioid receptor plays an important role in mediating the actions of morphine and morphine-like drugs. Receptor binding and a wide range of pharmacological studies have proposed several mu receptor subtypes, but only one mu opioid receptor (Oprm) gene has been isolated. Like the mouse and rat, the human Oprm gene undergoes alternative splicing. In the present studies, we have identified and characterized six new splice variants from the human Oprm gene using a reverse transcription-polymerase chain reaction strategy, yielding a total of 10 human splice variants of the mu opioid receptor MOR-1. All the variants identified contained exons 1, 2 and 3, but differed from MOR-1 itself and each other by splicing downstream from exon 3, resulting in different amino acid sequences. Northern blot analysis demonstrated expression of the variant mRNAs. Receptor binding assays established that these variants belonged to the mu opioid receptor family with limited differences in mu opioid ligand affinities and selectivity. However, adenylyl cyclase and [35S]GTPgammaS binding assays revealed major differences in both potency and efficacy among these variants. The dissociation between binding affinity, potency and efficacy for the opioids among these variants may provide insights into the wide range of opioid responses among these agents observed clinically and opens new avenues in designing selective drugs based upon their efficacy and potency rather simple binding affinity.

Adenylyl Cyclases↗

Primary care, social inequalities and all-cause, heart disease and cancer mortality in US counties: a comparison between urban and non-urban areas.

OBJECTIVE: The objective of this study was to test whether the association between primary care and income inequality on all-cause, heart disease and cancer mortality at county level differs in urban (Metropolitan Statistical Area-MSA) compared with non-urban (non-MSA) areas. STUDY DESIGN: The study consisted of a cross-sectional analysis of county-level data stratified by MSA and non-MSA areas in 1990. Dependent variables included age and sex-standardized (per 100,000) all-cause, heart disease and cancer mortality. Independent variables included primary care resources, income inequality, education levels, unemployment, racial/ethnic composition and income levels. METHODS: One-way analysis of variance and multivariate ordinary least squares regression were employed for each health outcome. RESULTS: Among non-MSA counties, those in the highest income inequality category experienced 11% higher all-cause mortality, 9% higher heart disease mortality, and 9% higher cancer mortality than counties in the lowest income inequality quartile, while controlling for other health determinants. Non-MSA counties with higher primary care experienced 2% lower all-cause mortality, 4% lower heart disease mortality, and 3% lower cancer mortality than non-MSA counties with lower primary care. MSA counties with median levels of income inequality experienced approximately 6% higher all-cause mortality, 7% higher heart disease mortality, and 7% higher cancer mortality than counties in the lowest income inequality quartile. MSA counties with low primary care (less than 75th percentile) had significantly lower levels of all-cause, heart disease and cancer mortality than those counties with high primary care. CONCLUSIONS: In non-MSA counties, increasing primary physician supply could be one way to address the health needs of rural populations. In MSA counties, the association between primary care and health outcomes appears to be more complex and is likely to require intervention that focuses on multiple fronts.

Analysis of Variance↗

Inhibition of angiogenesis is associated with reduced islet engraftment in diabetic recipient mice.

Rapid reestablishment of a functional microvasculature in transplanted islets is crucial for islet survival and function. To illustrate the importance of angiogenesis in islet engraftment, we took a loss-of-function approach to block angiogenesis in newly transplanted islets and determined the extent of islet engraftment in correlation with islet mass and glycemic control in diabetic recipient mice. Diabetic mice were transplanted with a marginal mass of 200 islets under the renal capsule, followed by once-daily oral administration of saline or 150 mg/kg of C-statin, a potent angiogenic inhibitor, for 14 days. Blood glucose profiles and the amplitude of glucose-stimulated insulin secretion in engrafted islets were determined. At 30 days posttransplant, islet grafts were retrieved for the determination of insulin content and vascular density by immunohistochemistry. When compared to sham-treated controls, diabetic recipient mice receiving a daily oral dose of C-statin exhibited significantly impaired blood glucose profiles and diminished glucose-stimulated insulin secretion in response to glucose challenge, correlating with significantly reduced intragraft insulin content and vascular density. Selective inhibition of angiogenesis was associated with reduced islet mass in diabetic mice. These data extend our view that rapid onset of angiogenesis is crucial for islet survival and engraftment and support the development of therapeutic strategies to stimulate angiogenesis in newly implanted islets for enhancing islet engraftment and improving the outcome of marginal islet transplantation.

Angiogenesis Inhibitors↗

Microencapsulating hepatocytes.

BACKGROUND: Because standardization of the cell microencapsulation procedure has not yet been achieved, we performed hepatocyte microencapsulation using alginate (ALG)-poly-l-lysine (PLL)-ALG (APA) polymer. METHODS: Hepatocytes were microencapsulated using a binozzle air-jet droplet generator. Our study aims were to: (1) clarify how ALG concentration affects the quality of ALG beads; (2) determine how the PLL concentration affects the quality of microcapsules (MCs); (3) ascertain the influence of liquefaction time by sodium citrate (SC) on the quality of the MCs; (4) and clarify how temperature and solution pH, respectively, affect the viability of the hepatocytes inside the MCs. RESULTS: The concentration of ALG must be > or = 3% (w/v) to generate droplets with satisfactory homogeneity in size and roundness (P < .01). The total quantity of PLL molecules is the essential component for MCs (P < .01). As our results show, the numeric ratio of PLL (milligrams) to MCs (milliliters) is roughly 25:1. SC incubation for 8 minutes resulted in the proper thickness of the MC wall; however, the time varied according to the size of the MCs (P < .05). Temperature and pH, although both difficult to control, exerted great influences on cell viability: 4 degrees C and pH 7.2 were found to be optimal by this study (P < .05). CONCLUSIONS: Concentrations of ALG and PLL exerted decisive effects on the quality and strength of MCs. Higher concentrations were suggested. Because temperature and pH greatly affected cell viability, they must be properly monitored.

Alginates↗

Radioprotection by fullerenols of Stylonychia mytilus exposed to gamma-rays.

The aim was to study the protective effects of fullerenols, C60(OH)x, on Stylonychia mytilus cells exposed to 60Co gamma-rays and the probable mechanisms of fullerenols protection. Ciliated protozoans Smytilus, kept in solutions of fullerenols at different concentrations, were irradiated with 60Co gamma-rays to various dose levels. Surviving cells were counted each day over 5 days after irradiation, and the surviving fraction was calculated. The relations of the surviving fraction to radiation dose and to fullerenols concentration were studied. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and lipofusion (LIP) levels in S. mytilus were also measured. The surviving fraction of S. mytilus decreased with increasing gamma-ray doses from 100 to 2000 Gy. Fullerenols enhanced the surviving fraction, except for the highest gamma-ray dose level. The maximum protection by fullernols occurred at a concentration of 0.10 mg ml(-1). However, fullerenols at concentration of 0.25 mg ml(-1) yielded a surviving fraction lower than that for the control sample. Fullerenols at a concentration of 0.10 mg ml(-1) increased the SOD and CAT activities in the gamma-ray plus fullerenols (gamma + F) group compared with the levels in both the gamma-ray (gamma) group (p < 0.01) and the control group (p < 0.01). The MDA and LIP levels in the gamma + F groups (p < 0.01) were significantly lower than that in both the control group (p < 0.05) and the gamma group (p < 0.01). At a concentration of 0.25 mg ml(-1), fullerenols reduced the SOD and CAT activities, but increased the MDA and LIP level compared with the control. There was no significant difference in SOD and CAT activities between the gamma + F group and gamma group. While the MDA and LIP level in the gamma + F and gamma groups were similar at a dose of 500 Gy, the LIP level in the gamma + F group was significantly higher than that in the gamma group (p < 0.01) at a dose of 2000 Gy. Fullerenols are good radiation protectors for the protozoan S. mytilus exposed to gamma-rays. The effectiveness of radioprotection depends on both fullerenols concentration and gamma-ray dose. The protective effect of fullerenols on damage induced by gamma-rays seems to be mediated, at least in part, through their anti-oxidative and radical scavenging activities.

Animals↗

Frequency and distribution of group I intron genotypes of Candida albicans colonising critically ill patients.

A study is performed to examine the distribution and frequency of 25S rRNA intron genotypes of Candida albicans isolated from different anatomical sites of patients in an intensive care unit (ICU) setting. Germ-tube positive Candida isolates (n=65) from 65 patients are included and isolates are characterised by 25S intron genotyping, whereby all can be subdivided into four genotypes (A-D). Results demonstrated that there were no significant differences between the frequency and genotype distribution of the Candida isolates and the anatomical site of colonisation. Furthermore, analysis of the transposable intron region in the 25S rRNA gene demonstrated equal distribution, regardless of age and anatomical site of isolation (groin, throat, etc.). Therefore, there does not appear to be any selective pressure associated with any anatomical site, resulting in an ecological shift in the frequency of genotypes present. This suggests that C. albicans intron genotypes equally colonise those sites of the body examined in this study. Although such an ecological finding as this is interesting, it perpetuates the continued need to find a genotypic typing scheme that helps to identify the source (nosocomial or endogenous) and mode of entry of C. albicans into patients in the ICU setting, resulting in C. albicans bloodstream infection.

Adolescent↗

Quality of life for people with intellectual disabilities in China: a cross-culture perspectives study.

BACKGROUND: The concept of quality of life (QOL) is explained on the basis of traditional Chinese culture and contemporary social and cultural trends. METHOD: The importance of internationally recognized QOL domains and indicators was determined for three respondent groups: consumers, parents of the consumers, and teachers and rehabilitation professionals working with the clients. RESULTS: Principal component analysis confirmed seven factors influencing QOL for people with intellectual disabilities (ID) in China. These seven components are conceptually equivalent to the eight domains found in the international QOL literature. CONCLUSION: The concept of QOL has become one of the most sensitive issues in present Chinese society and peoples' lives, and an important theoretical framework for the education and rehabilitation for people with ID in several ways: curriculum development, service delivery models, education and rehabilitation practices, and employment models.

Adult↗

Evaluation of geranylazide and farnesylazide diphosphate for incorporation of prenylazides into a CAAX box-containing peptide using protein farnesyltransferase.

Protein farnesyltransferase (PFTase) catalyzes the attachment of a geranylazide (C10) or farnesylazide (C15) moiety from the corresponding prenyldiphosphates to a model peptide substrate, N-dansyl-Gly-Cys-Val-Ile-Ala-OH. The rates of incorporation for these two substrate analogs are comparable and approximately twofold lower than that using the natural substrate farnesyl diphosphate (FPP). Reaction of N-dansyl-Gly-Cys(S-farnesylazide)-Val-Ile-Ala-OH with 2-diphenylphosphanylbenzoic acid methyl ester then gives a stable alkoxy-imidate linked product. This result suggests future generations whereby azide groups introduced using this enzymatic approach are functionalized using a broad range of azide-reactive reagents. Thus, chemistry has been developed that could be used to achieve highly specific peptide and protein modification. The farnesylazide analog may be useful in certain biological studies, whereas the geranylazide group may be more useful for general protein modification and immobilization.

Alkyl and Aryl Transferases↗

Sexually dimorphic expression of Usp9x is related to sex chromosome complement in adult mouse brain.

We found the expression of Usp9x, an X-linked gene which encodes a ubiquitin protease implicated in synaptic development, to be significantly higher in the adult female mouse brains than in male brains. The sex difference in expression of Usp9x was localized to specific brain regions such as neocortex. Furthermore, in gonadally intact and gonadectomized mice, XX mice expressed Usp9x mRNA and protein more highly than XY mice irrespective of their gonadal type. No sex difference was found in the neonatal brain or peripheral tissues such as the adult kidney. This finding implies that the difference in sex chromosome complement between XY males and XX females could potentially contribute to sexual differentiation of brain structure and function. The relation of genomic dose and Usp9x expression could help explain the neural and behavioural phenotype of women with XO Turner syndrome.

Animals↗