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Biomedical subjects

F Xu

Publications and source records attributed to F Xu.

At least 145 records · Page 8Linked to original sources

Role of the Bötzinger complex in fastigial nucleus-mediated respiratory responses.

We have reported that the phrenic neurogram (PN) is modulated by stimulation of the fastigial nucleus (FN) of the cerebellum. The present study was undertaken to search for brainstem site(s) involved in the FN efferent pathway to modulate phrenic nerve activities. Experiments were performed on 35 anesthetized, paralyzed, and ventilated cats, using the PN as the index of the respiratory motor output. Results showed that bilateral electrolytic lesions of the red nucleus (RN), the paramedian reticular nucleus (PRN), or the pontine respiratory group (PRG) had little effect on the ability of FN stimulation to modulate the respiratory output. However, the modulation was abolished by bilateral electrolytic lesions of the Bötzinger complex (BötC). Further studies showed that bilateral chemical inactivation of BötC neurons produced by topical microinjection of kainic acid or cobalt chloride failed to abolish the modulation. We concluded that fibers of passage, not synapses or cell bodies in the BötC, were involved in the modulatory effect of FN stimulation on the PN. The RN, PRN, and PRG appear not to be important in the neural circuitry responsible for the FN modulation of the phrenic activity.

Animals↗

Infants' ability to use object kind information for object individuation.

The present studies investigate infants reliance on object kind information in solving the problem of object individuation. Two experiments explored whether adults, 10- and 12-month-old infants could use their knowledge of ducks and cars to individuate an ambiguous array consisting of a toy duck perched on a toy car into two objects. A third experiment investigated whether 10-month-old infants could use their knowledge of cups and shoes to individuate an array consisting of a cup perched on a shoe into two objects. Ten-month-old infants failed to use object kind information alone to resolve the ambiguity with both pairs of objects. In contrast, infants this age succeeded in using spatiotemporal information to segment the array into two objects, i.e. they succeeded if shown that the duck moved independently relative to the car, or the cup relative to the shoe. Twelve-month-old infants, as well as adults, succeeded at object individuation on the basis of object kind information alone. These findings shed light on the developmental course of object individuation and provide converging evidence for the Object-first Hypothesis [Xu, F., Carey, S., 1996; Xu, F., 1997b]. Early on, infants may represent only one concept that provides criteria for individuation, namely physical object; kind concepts such as duck, car, cup, and shoe may be acquired later in the first year of life.

Adult↗

"Dip-Pen" nanolithography

A direct-write "dip-pen" nanolithography (DPN) has been developed to deliver collections of molecules in a positive printing mode. An atomic force microscope (AFM) tip is used to write alkanethiols with 30-nanometer linewidth resolution on a gold thin film in a manner analogous to that of a dip pen. Molecules are delivered from the AFM tip to a solid substrate of interest via capillary transport, making DPN a potentially useful tool for creating and functionalizing nanoscale devices.

Journal Article↗

Loss of retrovirus production in JB/RH melanoma cells transfected with H-2Kb and TAP-1 genes.

JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2Kb molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2Kb and cotransfected with the TAP-1 gene, it resulted in the appearance of H-2Kb molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2Kb/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2Kb-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2Kb-positive cells is novel and does not preexist in the parental H-2Kb-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2Kb-positive cells. Our data indicate that stable loss of retroviral production in the H-2Kb/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas.

Using differential display PCR, we have identified a gene [NOEY2, ARHI (designation by the Human Gene Nomenclature Committee)] with high homology to ras and rap that is expressed consistently in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. Reexpression of NOEY2 through transfection suppresses clonogenic growth of breast and ovarian cancer cells. Growth suppression was associated with down-regulation of the cyclin D1 promoter activity and induction of p21(WAF1/CIP1). In an effort to identify mechanisms leading to NOEY2 silencing in cancer, we found that the gene is expressed monoallelically and is imprinted maternally. Loss of heterozygosity of the gene was detected in 41% of ovarian and breast cancers. In most of cancer samples with loss of heterozygosity, the nonimprinted functional allele was deleted. Thus, NOEY2 appears to be a putative imprinted tumor suppressor gene whose function is abrogated in ovarian and breast cancers.

Amino Acid Sequence↗

Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo.

This study reports that recombinant adenovirus-mediated human bone morphogenetic protein-2 gene transfer can induce mesenchymal progenitor cell differentiation and bone formation. The recombinant adenovirus with the human bone morphogenetic protein-2 gene was constructed, and mature human bone morphogenetic protein-2 expression mediated by adenovirus gene transfer was detected by specific antibody. Under adenovirus-mediated bone morphogenetic-protein gene transfer, mesenchymal progenitor cell line C3H/10T 1/2 showed cell proliferation dependent on adenovirus bone morphogenetic-protein dose. The C3H/10T 1/2 cells transduced by adenovirus bone morphogenetic protein also exhibited differentiation to osteoblast phenotype, which indicates alkaline phosphatase activity. Injection of the C3H/10T 1/2 cells into the thigh muscles of nude mice led to ossicle development detectable on radiographs. Histological analysis indicated that the new ossicles that developed in the thigh muscles of the mice had different osseous components including bone trabeculae, bone marrow, and chondrified tissue. The results of this study demonstrate the potential for gene therapy by adenovirus-mediated bone morphogenetic-protein gene transfer.

Adenoviridae↗

Combination of multiple serum markers using an artificial neural network to improve specificity in discriminating malignant from benign pelvic masses.

A panel of four selected tumor markers, CA 125 II, CA 72-4, CA 15-3, and lipid-associated sialic acid, was analyzed collectively using an artificial neural network (ANN) approach to differentiate malignant from benign pelvic masses. A dataset of 429 patients, 192 of whom had malignant histology, was retrospectively used in the study. A prototype ANN classifier was developed using a subset of the data which included 73 patients with malignant conditions and 101 patients with benign conditions. The ANN classifier demonstrated a much improved specificity over that of the assay CA 125 II alone (87.5% vs 68.4%) while maintaining a statistically comparable sensitivity (79.0% vs 82.4%) in discriminating malignant from benign pelvic masses in an independent validation test using data from the remaining 255 patients which had been set aside and kept blind to the developers of the ANN system. A similar improvement in specificity was observed among patients under 50 years of age (82.3% vs 62.0%). The ANN system was further tested using additional serum specimens collected from 196 apparently healthy women. The ANN system had a specificity of 100.0% compared to that of 94.8% with the assay CA 125 II alone.

Antigens, Tumor-Associated, Carbohydrate↗

Object individuation and object identity in infancy: the role of spatiotemporal information, object property information, and language.

Recent work on object individuation and object identity in infancy indicates that at least three sources of information may be used for object individuation and object identity: spatiotemporal information, object property information, and object kind information. Several experiments have shown that a major developmental change occurs between 10 and 12 months of age (Xu & Carey, 1996; Xu, Carey & Welch, in press; Van de Walle, Prevor & Carey, under review; Xu, Carey & Quint, in preparation): Infants at 10 months and younger readily use spatiotemporal information in object individuation and object identity tasks, but not until about 12 months of age are infants able to use object property or object kind information to do so. This paper proposes a two-part conjecture about the mechanism underlying this change. The first part borrows ideas from object-based attention and the distinction between "what" and "where" information in visual processing. The hypothesis is that (1) young infants encode object motion and location information separately from object property information; and (2) toward the end of the first year, infants integrate these two sources of information. The second part of the conjecture posits an important role for language. Infants may take distinct labels as referring to distinct kinds of objects from the onset of word learning, and infants use this information in solving the problem of object individuation and object identity. Evidence from human adults, infants, and non-human primates is reviewed to provide support for the conjecture.

Adult↗

A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice.

BACKGROUND: Olfactorily mediated puberty acceleration in female mice (measured by an increase in uterine weight) has been observed since the 1960s without the active chemosignal being structurally identified. There are many controversies in the literature as to whether this male-originated pheromone is a volatile substance. We investigated the chemical nature of the urinary fractions that are responsible for the characteristic uterine weight increases. RESULTS: The active pheromone was identified as 5,5-dimethyl-2-ethyltetrahydrofuran-2-ol and/or its open-chain tautomer (6-hydroxy-6-methyl-3-heptanone). A series of cyclic vinyl ethers were isolated from chromatographically active fractions of the urine. Because these compounds did not accelerate puberty, we postulated that these ethers were degradation products of a lactol (5,5-dimethyl-2-ethyltetrahydrofuran-2-ol). The lactol was then detected directly in the mouse urine extract using a silylation agent. Synthetic 6-hydroxy-6-methyl-3-heptanone had strong biological activity, whereas its close structural analogs did not. CONCLUSIONS: The male house mouse excretes into its urine a large quantity of a volatile substance that has a unique lactol/hydroxyketone structure. This substance is capable of binding to the less volatile urinary constituents, such as proteins or peptides, and is active in puberty-acceleration bioassays. The controversies regarding the volatility of the puberty-accelerating pheromones can now be explained by considering a complex of volatile lactol/hydroxyketone and urinary proteins.

Animals↗

Randomized clinical trial comparing different iodine interventions in school children.

OBJECTIVE: The purpose of this trial was to compare three different iodine interventions. DESIGN: School children aged 8-10 years were randomized into one of three groups: group A was provided with iodized salt by researchers with an iodine concentration of 25 ppm; group B purchased iodized salt from the market; and group C was similar to group B with the exception that they were given iodized oil capsules containing 400 mg iodine at the beginning of the study. Salt iodine content was measured bimonthly for 18 months and indicators of iodine deficiency were measured at baseline and 6, 9, 12 and 18 months after randomization. RESULTS: The prevalence of abnormal thyroid volumes, based on the World Health Organization (WHO) body surface area reference >97th percentile, was 18% at baseline and declined to less than 5% by 12 months in groups A and C, and to 9% after 18 months in group B. Results for goitre by palpation were similar. The median urinary iodine was 94 microg l(-1) at baseline and increased in all groups to > 200 microg l(-1) at the 6-month follow-up. CONCLUSIONS: In this population of school children with initially a low to moderate level of iodine deficiency, the group receiving salt with 25 ppm (group A) was not iodine deficient on all indicators after 18 months of study. When the iodine content of the salt varied, such as in group B, by 18 months thyroid sizes had not yet achieved normal status.

Child↗

Pseudomonas aeruginosa outer-membrane protein F epitopes are highly immunogenic in mice when expressed on a plant virus.

A synthetic peptide (peptide 10) representing a surface-exposed, linear B cell epitope from outer-membrane (OM) protein F of Pseudomonas aeruginosa was shown previously to afford protection in mice from P. aeruginosa infection. This peptide was expressed in tandem with the protein F peptide 18 on each of the two coat proteins of cowpea mosaic virus (CPMV). The chimaeric virus particles (CVPs) expressing the peptides on the S (small) coat protein (CPMV-PAE4) and L (large) coat protein (CPMV-PAE5) were used to immunize mice. Following subcutaneous immunization in Freund's and QuilA adjuvants, CPMV-PAE4 induced antibodies predominantly against peptide 18, whereas CPMV-PAE5 produced antibodies exclusively against peptide 10, indicating that the site of peptide expression on CPMV influences its immune recognition. The anti-peptide antibodies elicited by CPMV-PAE5 were predominantly of the IgG2a isotype, indicating a highly polarized TH1-type response. The peptide-specific IgG2a strongly recognized the whole F protein, but more importantly, recognized protein F in all seven Fisher-Devlin immunotypes of P. aeruginosa. Furthermore, the peptide-specific IgG2a in CVP/QS-21 adjuvant-immunized mice was shown to bind complement and to augment phagocytosis of P. aeruginosa by human neutrophils in vitro. The ability of CPMV-PAE5 to induce P. aeruginosa-specific opsonic IgG2a gives it potential for further development as a protective vaccine against P. aeruginosa.

Animals↗

Measurement of x-ray attenuation coefficients of aqueous solutions of indocyanine green and glycated chitosan.

We report our experimental results of measurements of x-ray attenuation coefficients of aqueous solutions of a light absorbing dye, indocyanine green, and an immunoadjuvant, glycated chitosan. In the treatment of metastatic tumors in rats using a novel laser immunotherapy these solutions were administered in situ. The x-ray attenuation data of the solutions are essential to development of an x-ray digital imaging system for monitoring the administration of the solution, as well as for the distribution and the diffusion of the solution in tumors and in surrounding tissue. The composition of the solutions, the measurement system configuration, and the technique used to determine the attenuation coefficients are described. The experimental results show that glycated chitosan has a higher attenuation coefficient compared to indocyanine green and water. Our experimental data proved that, even at low concentrations, the x-ray attenuation through these aqueous solutions could be differentiated. Therefore, a digital x-ray imaging technique can be used effectively in monitoring and controlling the intratumor diffusion and distributions of these solutions.

Adjuvants, Immunologic↗

Molecular characterization of laccase genes from the basidiomycete Coprinus cinereus and heterologous expression of the laccase lcc1.

A laccase from Coprinus cinereus is active at alkaline pH, an essential property for some potential applications. We cloned and sequenced three laccase genes (lcc1, lcc2, and lcc3) from the ink cap basidiomycete C. cinereus. The lcc1 gene contained 7 introns, while both lcc2 and lcc3 contained 13 introns. The predicted mature proteins (Lcc1 to Lcc3) are 58 to 80% identical at the amino acid level. The predicted Lcc1 contains a 23-amino-acid C-terminal extension rich in arginine and lysine, suggesting that C-terminal processing may occur during its biosynthesis. We expressed the Lcc1 protein in Aspergillus oryzae and purified it. The Lcc1 protein as expressed in A. oryzae has an apparent molecular mass of 66 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and absorption maxima at 278 and 614 nm. Based on the N-terminal protein sequence of the laccase, a 4-residue propeptide was processed during the maturation of the enzyme. The dioxygen specificity of the laccase showed an apparent K(m) of 21 +/- 2 microM and a catalytic constant of 200 +/- 10 min(-1) for O(2) with 2, 2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) as the reducing substrate at pH 5.5. Lcc1 from A. oryzae may be useful in industrial applications. This is the first report of a basidiomycete laccase whose biosynthesis involves both N-terminal and C-terminal processing.

Amino Acid Sequence↗

Comparison of fungal laccases and redox mediators in oxidation of a nonphenolic lignin model compound.

Several fungal laccases have been compared for the oxidation of a nonphenolic lignin dimer, 1-(3, 4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propan-1,3-diol (I), and a phenolic lignin model compound, phenol red, in the presence of the redox mediators 1-hydroxybenzotriazole (1-HBT) or violuric acid. The oxidation rates of dimer I by the laccases were in the following order: Trametes villosa laccase (TvL) > Pycnoporus cinnabarinus laccase (PcL) > Botrytis cinerea laccase (BcL) > Myceliophthora thermophila laccase (MtL) in the presence of either 1-HBT or violuric acid. The order is the same if the laccases are used at the same molar concentration or added to the same activity (with ABTS [2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)] as a substrate). During the oxidation of dimer I, both 1-HBT and violuric acid were to some extent consumed. Their consumption rates also follow the above order of laccases, i.e., TvL > PcL > BcL > MtL. Violuric acid allowed TvL and PcL to oxidize dimer I much faster than 1-HBT, while BcL and violuric acid oxidized dimer I more slowly than BcL and 1-HBT. The oxidation rate of dimer I is dependent upon both kcat and the stability of the laccase. Both 1-HBT and violuric acid inactivated the laccases, violuric acid to a greater extent than 1-HBT. The presence of dimer I or phenol red in the reaction mixture slowed down this inactivation. The inactivation is mainly due to the reaction of the redox mediator free radical with the laccases. We did not find any relationship between the carbohydrate content of the laccases and their inactivation. When the redox potential of the laccases is in the range of 750 to 800 mV, i.e., above that of the redox mediator, it does not affect kcat and the oxidation rate of dimer I.

Barbiturates↗

New insights into the function of noncoding RNA and its potential role in disease pathogenesis.

All polyadenylated RNAs expressed in mammalian tissues are assumed to be transported to the cytoplasm where they direct the synthesis of a protein product. This mainstream view of the function of polyadenylated transcripts is currently being challenged by the identification of a novel class of genes which, although they encode polyadenylated RNA, do not make a translated protein. Many of these noncoding RNAs are developmentally regulated or show highly restricted patterns of gene expression, and their functions are providing important insight into RNA-based mechanisms of gene expression, genomic imprinting, cell cycle progression, and differentiation. The purpose of this review is to discuss the current understanding of mammalian noncoding RNAs, and to highlight their potential for identifying new pathways of human disease.

Animals↗

Thyroid volumes in US and Bangladeshi schoolchildren: comparison with European schoolchildren.

OBJECTIVE: The World Health Organization (WHO) recently adopted thyroid volume ultrasonography results from European schoolchildren as the international reference for assessing iodine deficiency disorders. Our objective was to describe thyroid volumes measured by ultrasonography in US and Bangladeshi schoolchildren and compare these with European schoolchildren. METHODS: Cross-sectional studies were performed in schoolchildren in the US (n=302) and Bangladesh (n=398). Data were collected on the following: thyroid size by palpation and ultrasonography; urinary iodine; age; sex; weight; and height. RESULTS: Applying the new WHO thyroid volume references to the Bangladeshi children resulted in prevalence estimates of enlarged thyroid of 26% based on body surface area (BSA) and 7% based on age. In contrast, in the US children, the prevalence estimates were less than 1% for each reference. In the US children, the best single predictor of thyroid volume was BSA (R2=0.32), followed by weight (R2=0.31). Using linear regression, upper normal limits (97th percentile) of thyroid volume from US children were calculated for BSA, weight and age, and were found to be lower than the corresponding references based on BSA and age from European schoolchildren. CONCLUSIONS: In areas with malnutrition, such as Bangladesh, the BSA reference should be preferred to the reference based on age. Results from the US children indicated that a thyroid volume reference based on weight alone would perform as well as the one based on BSA. European schoolchildren had larger thyroids than US children, perhaps due to a residual effect of iodine deficiency in the recent past in some areas in Europe.

Age Factors↗

Oxygen uptake kinetics during exercise.

The characteristics of oxygen uptake (VO2) kinetics differ with exercise intensity. When exercise is performed at a given work rate which is below lactate threshold (LT), VO2 increases exponentially to a steady-state level. Neither the slope of the increase in VO2 with respect to work rate nor the time constant of VO2 responses has been found to be a function of work rate within this domain, indicating a linear dynamic relationship between the VO2 and the work rate. However, some factors, such as physical training, age and pathological conditions can alter the VO2 kinetic responses at the onset of exercise. Regarding the control mechanism for exercise VO2 kinetics, 2 opposing hypotheses have been proposed. One of them suggests that the rate of the increase in VO2 at the onset of exercise is limited by the capacity of oxygen delivery to active muscle. The other suggests that the ability of the oxygen utilisation in exercising muscle acts as the rate-limiting step. This issue is still being debated. When exercise is performed at a work rate above LT, the VO2 kinetics become more complex. An additional component is developed after a few minutes of exercise. The slow component either delays the attainment of the steady-state VO2 or drives the VO2 to the maximum level, depending on exercise intensity. The magnitude of this slow component also depends on the duration of the exercise. The possible causes for the slow component of VO2 during heavy exercise include: (i) increases in blood lactate levels; (ii) increases in plasma epinephrine (adrenaline) levels; (iii) increased ventilatory work; (iv) elevation of body temperature; and (v) recruitment of type IIb fibres. Since 86% of the VO2 slow component is attributed to the exercising limbs, the major contributor is likely within the exercising muscle itself. During high intensity exercise an increase in the recruitment of low-efficiency type IIb fibres (the fibres involved in the slow component) can cause an increase in the oxygen cost of exercise. A change in the pattern of motor unit recruitment, and thus less activation of type IIb fibres, may also account for a large part of the reduction in the slow component of VO2 observed after physical training.

Adolescent↗