Biomedical subjects

W Pan

Publications and source records attributed to W Pan.

At least 19 recordsLinked to original sources

PubMed2003

Fractional quantum Hall effect of composite fermions.

In a GaAs/AlGaAs quantum well of density 1 x 10(11) cm(-2) we observed a fractional quantum Hall effect (FQHE) at nu = 4/11 and 5/13, and weaker states at nu = 6/17, 4/13, 5/17, and 7/11. These sequences of fractions do not fit into the standard series of integral quantum Hall effects of composite fermions (CF) at nu = p/(2mp +/- 1). They rather can be regarded as the FQHE of CFs attesting to residual interactions between these composite particles. In tilted magnetic fields the nu = 4/11 state remains unchanged, strongly suggesting it to be spin polarized. The weak nu = 7/11 state vanishes quickly with tilt.

Journal Article↗

PubMed2003

Feeding peptides interact in several ways with the blood-brain barrier.

The blood-brain barrier (BBB) plays a crucial role in the regulation of body weight and feeding by peptides. This review summarizes the components of the BBB as well as the circumventricular organs (CVOs), the methods used for quantification of the passage of feeding peptides across the BBB, and the various ways by which these peptides can interact with the BBB.

Animals↗

PubMed2003

The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

OBJECTIVE: To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region. RESEARCH DESIGN AND METHODS: Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk. RESULTS: In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72-2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38-1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55-1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals. CONCLUSIONS: The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.

Age Distribution↗

PubMed2002

Transition from an electron solid to the sequence of fractional quantum Hall states at very low Landau level filling factor.

At low Landau level filling of a two-dimensional electron system, typically associated with the formation of an electron crystal, we observe local minima in Rxx at filling factors nu = 2/11, 3/17, 3/19, 2/13, 1/7, 2/15, 2/17, and 1/9. Each of these developing fractional quantum Hall (FQHE) states appears only above a filling-factor-specific temperature. This can be interpreted as the melting of an electron crystal and subsequent FQHE liquid formation. The observed sequence of FQHE states follows the series of composite fermion states emanating from nu = 1/6 and nu = 1/8.

Journal Article↗

PubMed2002

Density-induced interchange of anisotropy axes at half-filled high Landau levels.

We observe density-induced 90 degrees rotations of the anisotropy axes in transport measurements at half-filled high Landau levels in the two dimensional electron system, where stripe states are proposed ( nu = 9/2, 11/2, etc.). Using a field effect transistor, we find the transition density to be 2.9x10(11) cm(-2) at nu = 9/2. Hysteresis is observed in the vicinity of the transition. We construct a phase boundary in the filling factor magnetic field plane in the regime 4.4<nu<4.6. An in-plane magnetic field applied along either anisotropy axis always stabilizes the low density orientation of the stripes.

Journal Article↗

PubMed2002

X-ray photoelectron spectroscopy study of disordering in Gd2(Ti1-xZrx)2O7 pyrochlores.

The dramatic increases in ionic conductivity in Gd2(Ti1-xZrx)2O7 solid solution are related to disordering on the cation and anion lattices. Disordering in Gd2(Ti1-xZrx)2O7 was characterized using x-ray photoelectron spectroscopy (XPS). As Zr substitutes for Ti in Gd2Ti2O7 to form Gd2(Ti1-xZrx)2O7 (0.25 < x < or =0.75), the corresponding O 1s XPS spectrum merges into a single symmetric peak. This confirms that the cation antisite disorder occurs simultaneously with anion disorder. Furthermore, the O 1s XPS spectrum of Gd2Zr2O7 experimentally suggests the formation of a split vacancy.

Journal Article↗

PubMed2001

Graphical model checking with correlated response data.

Correlated response data arise often in biomedical studies. The generalized estimation equation (GEE) approach is widely used in regression analysis for such data. However, there are few methods available to check the adequacy of regression models in GEE. In this paper, a graphical method is proposed based on Cook and Weisberg's marginal model plot. A bootstrap method is applied to obtain the reference band to assess statistical uncertainties in comparing two marginal mean functions. We also propose using the generalized additive model (GAM) in a similar fashion. The proposed two methods are easy to implement by taking advantage of existing smoothing and GAM softwares for independent data. The usefulness of the methodology is demonstrated through application to a correlated binary data set drawn from a clinical trial, the Lung Health Study.

Adult↗

PubMed2001

FUP1, a gene associated with hepatocellular carcinoma, stimulates NIH3T3 cell proliferation and tumor formation in nude mice.

Human primary hepatocellular carcinoma (HCC)is one of the highly prevalent malignant diseases worldwide, the identification of HCC-associated genes has been a major approach in elucidating the molecular mechanism of tumorigenesis of HCC. In our previous studies, a function-unknown gene, which displayed marked expression difference between the HCC sample and normal liver control has been detected by cDNA microarray. This gene was named after fup1 (function-unknown protein 1), and was cloned according to the data of GenBank. The cDNA of fup1 has an open-reading frame 1233 base pairs in size. Here, the function analysis of FUP1 related to HCC is being reported. The NIH3T3 cells transiently transfected with FLAG-conjugated FUP1 revealed strong nuclear staining in immunofluorescent assay. Furthermore, cell proliferation enhancing activity of fup1 was shown by MTT assay in stable transfectant NIH3T3 cell line with pcDNA3-derived plasmid having fup1 under the regulation of pCMV, while cell proliferation repressing activity of antisense fup1 was observed in BEL7404 stable transfectant cells. Tumorigenicity of the above stable transfectant cells was analyzed in nude mice compared with appropriate controls. The result was in good agreement with MTT assay. Elevated tumorigenicity of fup1 transfected NIH3T3 cell and repressed tumorigenicity of antisense fup1 transfected BEL7404 cell were clearly demonstrated. The results above suggested that fup1 might be a critical gene related to carcinogenesis of HCC. Detailed molecular function of fup1 remains to be elucidated.

3T3 Cells↗

PubMed2001

Bradykinin antagonist decreases early disruption of the blood-spinal cord barrier after spinal cord injury in mice.

Bradykinin is one of the key molecules involved in the disruption of the blood-brain barrier and blood-spinal cord barrier occurring after spinal cord injury (SCI). Previously we have shown a biphasic opening of the blood-spinal cord barrier as well as increased transport of tumor necrosis factor-alpha (TNFalpha) after SCI by compression of the lumbar spinal cord in mice. To evaluate the role of bradykinin in the two phases of blood-spinal cord barrier disruption, we pretreated mice with a potent bradykinin antagonist, the decapeptide B9430, before SCI. Our results show that B9430 decreased the general blood-spinal cord barrier disruption occurring immediately after SCI but failed to affect the delayed opening of the blood-spinal cord barrier observed 72 h after SCI. By contrast, the entry of TNFalpha after SCI was not affected by B9430 treatment. We conclude that bradykinin is involved in the early phase of blood-spinal cord barrier disruption, with B9430 non-selectively blocking this early disruption without affecting the selective transport system for TNFalpha. This indicates the therapeutic potential of bradykinin antagonists in ameliorating tissue damage induced by SCI.

Animals↗

PubMed2001

[Construction of Cryptococcus neoformans cap70 transformation system].

OBJECTIVE: To construct a transformation system of Cryptococcus neoformans capsule-deficient strain cap70. METHODS: (1)Obtained ura5 mutants by screening the Cryptococcus neoformans cap70 using 5-fluoroorotic acid counter selection method, analyzed the obtaining strain by Southern blot and PCR; (2)Through the plasmid pCXJ18 and pCXJU which contained ura5 gene from Cryptococcus neoformans and ura3 from Kluyveromyces fragilils. as a selective marker, the ura5 strains were transformed by electrotransformation and chemical transformation. RESULTS: Obtained ura5 mutants, they were detected as lack of ura function. The chemical transformation method was first be used in Cryptococcus neoformans transformation. CONCLUSION: A transformation system of Cryptococcus neoformans cap70 has been established, which provides not only the basis for gene cloning from the species for studying gene function and gene expression.

Cryptococcus neoformans↗

PubMed2001

Diurnal variation of leptin entry from blood to brain involving partial saturation of the transport system.

The blood-brain barrier (BBB) regulates the amount of peripherally produced leptin reaching the brain. Knowing that the blood concentration of leptin has a circadian rhythm, we investigated whether the influx of leptin at the BBB followed the same pattern in three main sets of experiments. (a): The entry of 125I-leptin from blood to brain was measured in mice every 4 h, as indicated by the influx rate of 125I-leptin 1-10 min after an iv bolus injection. The blood concentration of endogenous leptin was measured at the same times. Blood leptin concentrations were higher at night and early morning (peak at 0800 h) and lower during the day (nadir at 1600 h). By contrast, the influx of 125I-leptin was fastest at 2000 h and slowest at 0400 h. Addition of unlabeled leptin (1 microg/mouse) significantly decreased the influx rate of 125I-leptin at all time points, indicating saturability of the transport system. The unlabeled leptin also abolished the diurnal variation of the influx of 125I-leptin. (b): The entry of 125I-leptin into spinal cord was faster than that into brain and showed a different diurnal pattern. The greatest influx occurred at 2400 h and the slowest at 0800 h. In spinal cord, unlike brain, unlabeled leptin (1 microg/mouse) neither inhibited the influx of 125I-leptin nor abolished the diurnal rhythm. (c): Higher concentrations of unlabeled leptin (5 microg/mouse) inhibited the uptake of 125I-leptin in spinal cord as well as in brain, but not in muscle. This experiment measured uptake 10 min after iv injection at 0600 h (beginning of the light cycle) and 1800 h (beginning of the dark cycle). Thus, influx of 125I-leptin into the CNS shows diurnal variation, indicating a circadian rhythm in the transport system at the BBB, saturation of the leptin transport system shows differences between the brain and spinal cord, and blood concentrations of leptin suggest that partial saturation of the transport system occurs at physiological concentrations of circulating leptin, contributing to the differing diurnal patterns in brain and spinal cord. Together, the results show that the BBB is actively involved in the neuroendocrine regulation of feeding behavior.

Animals↗

PubMed2001

Changing the chemokine gradient: CINC1 crosses the blood-brain barrier.

Chemokines are a large family of small, inducible, secreted, chemoattractant cytokines that are involved in inflammatory processes. It is well known that systemic and CNS infections cause disruption of the blood-brain barrier (BBB); however, it is not clear how chemokines are involved in this process. We studied the pharmacokinetics of the passage of the chemokine cytokine-induced neutrophil chemoattractant-1 (CINC1) from blood to brain after i.v. bolus injection and its efflux out of the brain after i.c.v. injection. Radiolabeled CINC1 was injected i.v. into mice, and the results were determined by multiple-time regression analysis. Using HPLC, we detected intact CINC1 in brain homogenate and blood after i.v. administration. CINC1 accumulated in the cerebral vasculature but also crossed the BBB completely and rapidly. No saturation of the influx was found, suggesting that either CINC1 crossed the BBB by simple diffusion or the dynamic interactions of binding and internalization precluded the self-inhibition typical of a transport system. Furthermore, there was no efflux system, with CINC1 exiting the brain at the same rate as reabsorption of CSF. The CINC1 injected into blood or CSF did not cause any breakdown of the BBB during the course of the experiments. Thus, the influx of CINC1 may alter the "chemokine gradient" across the BBB and therefore affect inflammatory reactions involving the CNS.

Animals↗

PubMed2001

A cyclin D1/cyclin-dependent kinase 4 binding site within the C domain of the retinoblastoma protein.

Phosphorylation of the retinoblastoma protein (Rb) by the cyclin D1/cyclin-dependent kinase (cdk) 4 complex (cdk4/D1) is a key regulatory step for maintaining the orderly progression of the cell cycle. The B domain of Rb contains a site that recognizes and binds the LXCXE motif found in D-type cyclins. This interaction is important for phosphorylation of Rb by cdk4/D1, although in vitro the Rb C domain alone is efficiently phosphorylated by cdk4/D1. A mutation in the C domain of Rb, L901Q, has been identified that completely abolishes cdk4/D1 phosphorylation of the isolated C domain. By contrast, the L901Q mutation has no effect on phosphorylation by either cyclin E/cdk2 or cyclin B/cdk1, suggesting that the interaction between L901Q and cdk4/D1 is specific. Introduction of the L901Q mutation into Rb containing the A, B, and C domains results in phosphorylation becoming predominantly dependent on the LXCXE binding region. However, when the LXCXE binding region of Rb is mutated, phosphorylation becomes dependent on the L901 site within the C domain. The L901 binding site can supplant the LXCXE binding site for the cdk4/D1-dependent phosphorylation of S780 and S795 but not S807/S811. Despite the limited homology between C domains of Rb, p107, and p130, the L901 site is conserved and introduction of the L925Q mutation into the isolated C domain of p107 also inhibits phosphorylation by cdk4/D1. These data support a model for cdk4/D1 recognizing two independent binding sites in Rb and suggests a conservation of this C domain binding motif for cyclin D1/cdk4 kinase among the Rb family of proteins.

Binding Sites↗

PubMed2001

Intramolecular hydrosilylation and silicon-assisted cross-coupling: an efficient route to trisubstituted homoallylic alcohols.

[figure: see text] Alkylidenesilacyclopentanes (formed by intramolecular hydrosilylation of homopropargyl alcohols) are efficiently coupled with aryl or alkenyl halides in the presence of tetrabutylammonium fluoride and a palladium(0) catalyst. Yields of cross-coupling were generally high, and the reaction is compatible with a wide range of functional groups. The overall transformation achieves the conversion of homopropargyl alcohols to trisubstituted homoallylic alcohols in a highly stereoselective fashion.

Journal Article↗

PubMed2001

Involving AP-2 transcription factor in connexin 26 up-regulation during pregnancy and lactation.

Gap junction connexin 26 (Cx26) is up-regulated in mammary epithelial cells during pregnancy and lactation. To understand the transcriptional regulation of Cx26, we identified a protected DNase I footprint region (-140 to -113) in the rat Cx26 promoter. This rCx26 Promoter Footprinting Region, or CPFR, contains an Sp binding site (CCGCCC) overlapping with an AP-2 binding site (GCCCGCGGC), and is evolutionarily conserved. Nuclear extracts from rat mammary glands and human MCF-10 mammary epithelial cells formed protein-DNA complexes with the labeled CPFR probe in the electrophoretic mobility shift assay (EMSA), and these complexes were markedly enhanced during pregnancy and lactation. Antibody supershift analysis further identified the presence of Sp1, Sp3, and AP-2 in these binding complexes. Human mammary epithelial MCF-10A and MCF-12A cells were transiently transfected with chimeric mutant rCx26 promoter/luciferase reporter constructs, and luciferase activities measured. Mutations along the CPFR fragment drastically reduced the promoter activity, specially at the Sp/AP-2 overlapping site. Cotransfection of AP-2 with rCx26 promoter/reporter constructs into MCF-10 cells markedly induced the reporter activity. These data infer that AP-2, along with previously reported Sp transcription factors, is involved in the up-regulation of Cx26 gene during pregnancy and lactation.

Animals↗

PubMed2001

Increase in TNFalpha transport after SCI is specific for time, region, and type of lesion.

The dynamic changes of the blood-brain barrier and blood-spinal cord barrier (BBB) are an important part of the CNS response to injury. This study addresses the permeability of the BBB in the acute phase of spinal cord injury (SCI) to the thoracic region. SCI by compression or by complete transection was generated in mice. BBB disruption was evaluated by spinal cord uptake of radiolabeled albumin. The BBB of the thoracic spinal cord was disrupted immediately after compression injury, lasting for 2 days. This was followed by a delayed permeability increase in the cervical spinal cord beginning 3 days after injury. After transection, BBB disruption was limited to the thoracic spinal cord and was present only immediately postinjury. The entry of TNFalpha not only was increased at the time of BBB disruption, following the same pattern, but also had secondary changes after the BBB permeability to albumin had returned to normal. The increase of TNFalpha entry, best explained by upregulation of the specific transport system for TNFalpha, was pronounced in the lumbar spinal cord as well as the thoracic region, and followed a different time course after the two types of injury. Integrating our results with those of the literature regarding the roles of inflammatory responses and the effects of TNFalpha in spinal cord regeneration, we conclude that the time-, region-, and lesion-specificity of the upregulation of TNFalpha transport is part of the regulatory changes at the BBB in response to SCI.

Animals↗

PubMed2001

Effects of peptides on animal and human behavior: a review of studies published in the first twenty years of the journal Peptides.

This review catalogs effects of peptides on various aspects of animal and human behavior as published in the journal Peptides in its first twenty years. Topics covered include: activity levels, addiction behavior, ingestive behaviors, learning and memory-based behaviors, nociceptive behaviors, social and sexual behavior, and stereotyped and other behaviors. There are separate tables for these behaviors and a short introduction for each section.

Animals↗

PubMed2001

Validity of multiple-time regression analysis in measurement of tritiated and iodinated leptin crossing the blood-brain barrier: meaningful controls.

Multiple-time regression analysis has been used to study the influx of radiolabeled peptides and polypeptides across the blood-brain barrier (BBB). This study used both tritiated and iodinated leptin to clarify several issues associated with these measurements. Recombinant murine leptin was radiolabeled with 3H by derivatization or with 125I by the iodobead method and each studied separately in mice. Intact 3H-leptin had a higher apparent influx rate from blood to brain than did intact 125I-leptin, correlating with its higher proportion of reversible association with the capillary lumen that would misleadingly appear to reflect entry. Yet the majority of 3H-leptin and 125I-leptin reached brain parenchyma. There was no significant difference in the influx rate between cerebral cortex and the subcortical regions, thus ruling out a predominant contribution of simple diffusion through the circumventricular organs or choroid plexuses outside the BBB. The influx of radiolabeled leptin, especially 125I-leptin, was decreased by excess unlabeled leptin, supporting the presence of a saturable transport system for leptin at the BBB. To identify the specificity of the transport system and determine whether it is shared by 3H-leptin and 125I-leptin, these radioactively labeled leptins were heat-denatured. Denaturation had no effect on the fast influx of 3H-leptin, but abolished the entry of 125I-leptin into brain; excess denatured leptin failed to inhibit the influx of either 3H-leptin or 125I-leptin. This indicates that the conformation of 125I-leptin is similar to that of native unlabeled leptin, so that iodination would be the better choice for investigating the interaction of leptin with the BBB. However, 3H-leptin can use the same transport system, as shown by inhibition of its influx by unlabeled leptin, whereas the derivatization procedure altered its biophysical properties such that its non-saturated influx was greatly enhanced. Finally, the rapid influx of radioactively labeled leptin contrasted greatly with that of the reference compounds 99mTc-albumin and 3H-inulin which had no significant penetration of the BBB. Thus, with additional considerations such as stability and interactions with the vasculature, multiple-time regression analysis is sensitive and selective for study of the penetration of peptides across the BBB.

Animals↗