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Biomedical subjects

S Wei

Publications and source records attributed to S Wei.

At least 19 recordsLinked to original sources
PubMed2001

Cloning and characterization of a p53-related protein kinase expressed in interleukin-2-activated cytotoxic T-cells, epithelial tumor cell lines, and the testes.

A human protein kinase, p53-related protein kinase (PRPK), was cloned from an interleukin-2-activated cytotoxic T-cell subtraction library. PRPK appears to be a homologue of a growth-related yeast serine/threonine protein kinase, YGR262c. However, a complementation assay using YGR262c-disrupted yeast indicated that PRPK is not functionally identical to the yeast enzyme. PRPK expression was observed in interleukin-2-activated cytotoxic T-cells, some human epithelial tumor cell lines, and the testes. The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of PRPK to COS-7 cells. PRPK was shown to bind to p53 and to phosphorylate p53 at Ser-15. These results indicate that PRPK may play an important role in the cell cycle and cell apoptosis through phosphorylation of p53.

Amino Acid Sequence↗
PubMed2001

A membrane protein enriched in endoplasmic reticulum exit sites interacts with COPII.

Although all mammalian COPII components have now been cloned, little is known of their interactions with other regulatory proteins involved in exit from the endoplasmic reticulum (ER). We report here that a mammalian protein (Yip1A) that is about 31% identical to S. cerevisiae and which interacts with and modulates COPII-mediated ER-Golgi transport. Yip1A transcripts are ubiquitously expressed. Transcripts of a related mammalian homologue, Yip1B, are found specifically in the heart. Indirect immunofluorescence microscopy revealed that Yip1A is localized to vesicular structures that are concentrated at the perinuclear region. The structures marked by Yip1A co-localized with Sec31A and Sec13, components of the COPII coat protein complex. Immunoelectron microscopy also showed that Yip1A co-localizes with Sec13 at ER exit sites. Overexpression of the hydrophilic N terminus of Yip1A arrests ER-Golgi transport of the vesicular stomatitis G protein and causes fragmentation and dispersion of the Golgi apparatus. A glutathione S-transferase fusion protein with the hydrophilic N terminus of Yip1A (GST-Yip1A) is able to bind to and deplete vital components from rat liver cytosol that is essential for in vitro vesicular stomatitis G transport. Peptide sequence analysis of cytosolic proteins that are specifically bound to GST-Yip1A revealed, among other proteins, mammalian COPII components Sec23 and Sec24. A highly conserved domain at the N terminus of Yip1A is required for Sec23/Sec24 interaction. Our results suggest that Yip1A is involved in the regulation of ER-Golgi traffic at the level of ER exit sites.

Amino Acid Sequence↗
PubMed2001

Cooperative regulation of Mcl-1 by Janus kinase/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils.

Polymorphonuclear neutrophils (PMN) are phagocytic cells constitutively programmed for apoptotic cell death. Exposure to GM-CSF delays apoptosis as measured by annexin-V staining and cell morphological change. We found that STAT5B, STAT1, and STAT3 DNA-binding activity was induced by GM-CSF. We also detected activation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway after GM-CSF treatment which was inhibited by treatment with the PI 3-kinase inhibitors, wortmannin and LY294002. We investigated whether STAT or PI 3-kinase activity was necessary for the pro-survival response of GM-CSF in PMN. Exposure of PMN to GM-CSF in the presence of either AG-490, antisense STAT3 oligonucleotides, or wortmannin resulted in a partial inhibition of GM-CSF-mediated pro-survival activity. GM-CSF induced a time-dependent increase in the mRNA and protein expression of the anti-apoptotic Bcl-2-family protein, Mcl-1. We examined the hypothesis that Janus kinase/STAT and PI 3-kinase regulation of Mcl-1 contributed to GM-CSF-delayed apoptosis. Using either AG-490 or wortmannin alone, we observed a dose-dependent inhibition of GM-CSF-induced Mcl-1 expression. Using suboptimal doses of AG-490 and wortmannin, we found that both drugs together had an additive effect on delayed apoptosis and Mcl-1 expression. These data suggest that cooperative regulation of Mcl-1 by the Janus kinase/STAT and PI 3-kinase pathways contribute to GM-CSF-delayed apoptosis.

Apoptosis↗
PubMed2001

Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster.

An extensive, highly diversified multigene family of novel immune-type receptor (nitr) genes has been defined in Danio rerio (zebrafish). The genes are predicted to encode type I transmembrane glycoproteins consisting of extracellular variable (V) and V-like C2 (V/C2) domains, a transmembrane region and a cytoplasmic tail. All of the genes examined encode immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic tail. Radiation hybrid panel mapping and analysis of a deletion mutant line (b240) indicate that a minimum of approximately 40 nitr genes are contiguous in the genome and span approximately 0.6 Mb near the top of zebrafish linkage group 7. One flanking region of the nitr gene complex shares conserved synteny with a region of mouse chromosome 7, which shares conserved synteny with human 19q13.3-q13.4 that encodes the leukocyte receptor cluster. Antibody-induced crosslinking of Nitrs that have been introduced into a human natural killer cell line inhibits the phosphorylation of mitogen-activated protein kinase that is triggered by natural killer-sensitive tumor target cells. Nitrs likely represent intermediates in the evolution of the leukocyte receptor cluster.

Amino Acid Sequence↗
PubMed2001

Local structure evolution of FexNi77-xCu(1-)Nb2P14B6 soft magnetic materials by mechanical alloying.

Mechanically alloyed Fe(x)Ni77-xCu1Nb2P14B6 soft magnetic materials have been prepared with different atomic compositions. The alloy structures are investigated by X-ray absorption fine structure (XAFS). The results show that mechanical alloying (MA) can drive the Fe(x)Ni77-xCu1Nb2P14B6 powder mixture to produce amorphous alloy while the atomic concentration of Fe element is about and over 40%. On the contrary, the MA Fe(x)Ni77 xCu1Nb2P14B6 is a solid solution with a fcc-like structure in the region of lower Fe atomic concentration (<22%), preserving a medium-range order around Ni and Fe atoms. Moreover, we have found that the local structure geometry of Fe atom is similar to that of Ni atom for all the MA Fe(x)Ni77-xCu1NbP14B6 samples. It indicates that the local structures of Fe and Ni atoms in a Fe(x)Ni77-xCu1Nb2P14B6 sample only depend on the x value of element Ni after ball milling.

Journal Article↗
PubMed2001

U7C beamline and XAFS station of national synchrotron radiation laboratory.

The XAFS station on beamline U7C of National Synchrotron Radiation Laboratory (NSRL) was completely constructed in December 1998. The source for XAFS station is from a 3-pole superconducting wiggler with magnetic field of 6 T inserted in the straight section of the storage ring. Using a Si(111) double crystal monochromator with a fixed slit, the X-ray intensity at the sample position is about 3x10(9) photons/second at the energy of 8980 eV of Cu K-edge. The Keithley 65 17 electrometers are used to record the electron charges that are produced in the ionization chambers. A high ratio of signal to noise has been obtained for the XAFS spectra of Cu, Ni and Fe foils. Furthermore, the XAFS spectrum of Cu foil in NSRL is in good agreement with that obtained in BSRF and KEK.

Journal Article↗
PubMed2001

Annealed crystallization of ultrafine amorphous NiB alloy studied by XAFS.

XAFS has been used to investigate the local structure evolutions of ultrafine amorphous NiB alloy during the annealed crystallization process. A nanocrystalline Ni phase with the local structure of crystalline Ni-like and a crystalline Ni3B, have been produced for ultrafine amorphous NiB alloy under the annealed temperature of 573 K. The results rule out Rojo et al.'s devitrification mechanism of Ni80B20 amorphous alloy in which they considered that an amorphous pure Ni phase is formed in the first exothermic process. However, our results are almost identical with Riveiro et al.'s conclusion in which the intermediate state is interpreted as two metastable crystalline phases of Ni3B and Ni-rich NiB alloy. With the annealed temperature going onto 773 K, the ultrafine NiB sample is further decomposed and crystallized into crystalline Ni with long-range order.

Journal Article↗
PubMed2001

Local structures of mechanically alloyed Fe100-xCux solid solutions studied by X-ray absorption fine structure.

The local structures of the immiscible Fe(100-x)Cu(x) alloys (x= 0, 10, 20, 40, 60, 80 and 100) produced by mechanical alloying have been investigated by XAFS. For the Fe(100-x)Cu(x) (x > or = 40) solid solutions, the local structures around Fe atoms change from bcc structure to fcc one and the Cu atoms maintain the original coordination geometry after milling for 160 hours. On the contrary, the local structures around Cu atoms in both of Fe80Cu20 and Fe90Cu10 alloys appear a transition from fcc to bcc structure. We found that the Debye-waller factor sigma of fcc Fe-Cu phase is larger than that of bcc Fe-Cu phase, and the sigma (0.099 A) around Fe atoms is larger than that (0.089 A) of Cu in the Fe(100-x)Cu(x) (x > or = 40) solid solutions. This suggests that the mechanically alloyed Fe(100-x)Cu(x) supersaturated solid solution is not a homogeneous alloy, and consists of Fe-rich and Cu-rich regions for various compositions. A possible mechanism for bcc-to-fcc and fcc-to-bcc changes in Fe(100-x)Cu(x) solid solutions is discussed in relation to the interdiffusion and transition induced by the ball milling.

Journal Article↗
PubMed2001

Local structures of nanocrystalline GaN studied by XAFS.

X-ray absorption fine structure (XAFS) was used to investigate the local structures around Ga atoms in the hexagonal nanocrystalline and crystalline GaN under 78 and 300 K. For the first nearest neighbor coordination shell of Ga-N. the average bond length R (0.194 nm), coordination number N (4.0), thermal disorder sigma (0.0052 nm) and static disorder sigmaS (0.0007 nm) are neatly independent of the measured temperature and crystalline state. This indicates that the Ga-N covalent bond is much stronger, and the 4 nitrogen atoms in first nearest neighbor around Ga atoms keep the tetrahedral structure (Td). For the second nearest neighbor coordination shell of Ga-Ga, their bond lengths are about 0.318 nm. However, the sigmaS (0.0057 nm) of nanocrystalline GaN is 0.0047 nm larger than that of crystalline GaN (0.001 nm), and the sigmaT of nanocrystalline is 0.0053 nm and 0.0085 nm at the temperature of 78 and 300 K, respectively. The result indicates that the difference of local structure around Ga atoms between nanocrystalline and crystalline GaN occurs mainly at the Ga-Ga second nearest-neighbor coordination shell. The reason is explained as the local lattice distortion and unsaturated surface atoms existing in nanocrystalline GaN.

Journal Article↗
PubMed2001

A modest reduction in c-myc expression has minimal effects on cell growth and apoptosis but dramatically reduces susceptibility to Ras and Raf transformation.

Dergulation of c-myc and mutation of ras genes is commonly found in many human tumors. Several lines of evidence indicate that c-Myc and oncogenic Ras cooperate in causing malignant transformation, but the mechanism of this cooperation is not understood. We set out to investigate the effect on transformation of a modest reduction in endogenous c-Myc expression, which was achieved using a c-myc heterozygous cell line constructed by targeted homologous recombination. In contrast to previous reports where c-Myc expression or activity was ablated using antisense or dominant-defective methods, use of c-myc +/- cells provides a stable and homogeneous cell culture system with a precisely defined c-Myc expression level. In addition, this approach does not suffer from nonspecific artifacts such as antisense oligonucleotide toxicity or interference of dominant-defective proteins with multiple (and often undefined) target proteins. The striking and unexpected finding communicated here is that the relatively modest 50% reduction in c-Myc expression resulted in a greater than 10-fold reduction in susceptibility to transformation by oncogenic Ras or Raf proteins. This very significant defect in transformation potential cannot be explained on the basis of a generalized cell-cycle defect, because c-myc +/- cells exhibit only a minimal (20%) reduction in proliferation. Genetic epistasis analysis indicated that c-Myc and Ras acted by independent pathways that converged to regulate the abundance of the cyclin-dependent kinase inhibitor protein p27Kip1. Anchorage deprivation elicited a strong up-regulation of p27, and a 50% reduction in c-Myc expression significantly compromised the ability of Ras to down-regulate p27. We propose that Ras and c-Myc signals cooperate to regulate the activity of cyclin D-Cdk4/6 complexes: the former by up-regulating the expression of cyclin D1 and the latter by affecting the activity of the complexes. Ectopic expression of cyclin A restored the transformation potential of c-myc +/- cells, implicating it as a downstream genetic component in the pathway. From a therapeutic standpoint, it is of interest that, although transformation appears to be very sensitive to c-Myc expression levels, much larger reductions can be tolerated without causing any significant cell cycle defects.

Animals↗
PubMed2001

Biochemical basis for depressed serum retinol levels in transthyretin-deficient mice.

Transthyretin (TTR) acts physiologically in the transport of retinol in the circulation. We previously reported the generation and partial characterization of TTR-deficient (TTR(-)) mice. TTR(-) mice have very low circulating levels of retinol and its specific transport protein, retinol-binding protein (RBP). We have examined the biochemical basis for the low plasma retinol-RBP levels. Cultured primary hepatocytes isolated from wild type (WT) and TTR(-) mice accumulated RBP in their media to an identical degree, suggesting that RBP was being secreted from the hepatocytes at the same rate. In vivo experiments support this conclusion. For the first 11 h after complete nephrectomy, the levels retinol and RBP rose in the circulations of WT and TTR(-) mice at nearly identical rates. However, human retinol-RBP injected intravenously was more rapidly cleared from the circulation (t(12) = 0.5 h for TTR(-) versus t(12) >6 h for WT) and accumulated faster in the kidneys of TTR(-) compared with WT mice. The rate of infiltration of the retinol-RBP complex from the circulation to tissue interstitial fluids was identical in both strains. Taken together, these data indicate that low circulating retinol-RBP levels in TTR(-) mice arise from increased renal filtration of the retinol-RBP complex.

Animals↗
PubMed2001

Reciprocal regulation of plasmacytoid dendritic cells and monocytes during viral infection.

Reciprocal regulation of opposing functions characterizes biological systems. We now show that adenovirus-infected plasmacytoid dendritic cells (PDC) inhibit monocyte to myeloid dendritic cell (MDC) differentiation and function, and that adenovirus-infected monocytes inhibit PDC type I interferon secretion. Adenovirus-infected PDC secreted IFN-alpha, beta and omega in an 86:2:1 ratio. PDC type I interferons inhibited MDC differentiation and function (reduced IL-12 secretion, IFN-gamma induction, MLR and CD40 expression, and increased CD1a(+)CD14(+) cells). Type I interferon receptor blocking antibody reversed all PDC effects, and recombinant IFN-alpha, beta or omega replicated all effects, except reduced CD40. Adenovirus-infected monocytes suppressed PDC type I interferon secretion, which was reversed with anti-IL-10 neutralizing antibodies. Exogenous IL-10 suppressed PDC type I interferon secretion without reducing PDC viability. Therefore, monocyte IL-10 regulates PDC type I interferon secretion, and PDC type I interferons inhibit MDC differentiation and function. Such reciprocal regulation of potentially opposing influences may help modulate anti-pathogen immunity.

Adenovirus Infections, Human↗
PubMed2001

Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells.

Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid DCs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor DCs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.

Apoptosis↗
PubMed2001

Bending of the distraction site during mandibular distraction osteogenesis in the rabbit: a model for studying segment control and side effects.

PURPOSE: The purpose of this investigation was to develop an animal model for studying and correcting mandibular distraction side effects. MATERIALS AND METHODS: Twenty-nine rabbits underwent bilateral mandibular distraction. Bending of the mandible was accomplished by offsetting a linear distraction by 35 degrees from the occlusal plane (4 screws per distractor), rotating the anterior segment inferiorly (2 screws per distractor), and removing a 3- or 6-mm wedge of the distraction site. The amount of bite opening varied according to the surgical design. Direct measurements, radiographs, and histology samples were compared. RESULTS: Linear distraction produced a 4-mm anterior open bite and a Class III malocclusion after 2 weeks of distraction. Segmental rotation produced an 8-mm anterior open bite without complications. Removal of a wedge initiated rotation of the anterior segment. A large wedge (6 mm) produced fibrous union in the distraction site. The amount of bite opening or closure depended on the number of surgical screws and position of the distractor. Serial histologic sections showed bone formation at the rotated, triangular distraction site. CONCLUSION: Bite opening or closure can occur from loss of segment control or by altering surgical design. This information is needed to counter unwanted side effects or to plan segment rotations.

Analysis of Variance↗
PubMed2001

Audiologic aspects of the search for DFNA20: a gene causing late-onset, progressive, sensorineural hearing loss.

OBJECTIVE: The purpose of this research was to identify the gene responsible for a novel form of nonsyndromic, late-onset, bilateral, progressive, sensorineural hearing loss in a Michigan family of English descent. This report describes the audiologic aspects of the search. DESIGN: Fifty-eight members of the family served as subjects for the study. Family pedigree information was gathered from family interviews, family records, birth and death registration records and census data. Audiologic evaluation was used to describe the hearing loss (phenotype) and classify family members as affected or unaffected based on hearing status. These data then were used in a linkage analysis, a process in which the inheritance of a trait is compared with the inheritance of genetic markers and statistically significant associations are sought. RESULTS: The team mapped the hearing loss to the long arm of chromosome 17 at band 17q25. The pattern of inheritance is autosomal dominant. The search for the gene is continuing using a candidate gene approach. CONCLUSIONS: The hearing loss demonstrated by this mid-Michigan family is a novel form of nonsyndromic, genetic, late-onset, bilateral, progressive, sensorineural hearing loss. The locus of the gene, the 20th for autosomal dominant hearing loss, is at band 17q25 of chromosome 17.

Adolescent↗
PubMed2001

Enhanced renal microvascular reactivity to angiotensin II in hypertension is ameliorated by the sulfonimide analog of 11,12-epoxyeicosatrienoic acid.

OBJECTIVES: Epoxygenase metabolites produced by the kidney affect renal blood flow and tubular transport function and 11,12-epoxyeicosatrienoic acid (11,12-EET) has been putatively identified as an endothelium-derived hyperpolarizing factor. The current studies were performed to determine the influence of 11,12-EET on the regulation of afferent arteriolar diameter in angiotensin II-infused hypertensive rats. MATERIALS AND METHODS: Male Sprague-Dawley rats received angiotensin II (60 ng/min) or vehicle via an osmotic minipump. Angiotensin II-infused hypertensive and vehicle-infused normotensive rats were studied for 2 weeks following implantation of the minipump. Renal microvascular responses to the sulfonimide analog of 11,12-EET (11,12-EET-SI) and angiotensin II were observed utilizing the in-vitro juxtamedullary nephron preparation. Renal cortical epoxygenase enzyme protein levels were quantified by Western blot analysis. Renal microvessels were also isolated and epoxygenase metabolite levels measured by negative ion chemical ionization (NICI)/gas chromatography-mass spectroscopy. RESULTS: Systolic blood pressure averaged 118 +/- 2 mmHg prior to pump implantation and increased to 185 +/- 7 mmHg in rats infused with angiotensin II for 2 weeks. Afferent arteriolar diameters of 2-week normotensive animals averaged 22 +/- 1 microm. Diameters of the afferent arterioles were 17% smaller in hypertensive rats (P< 0.05); however, arterioles from both groups responded to 11,12-EET-SI (100 nmol) with similar 15-17% increases in diameter. As we previously demonstrated, the afferent arteriolar reactivity to angiotensin II was enhanced in angiotensin II-infused animals. Interestingly, elevation of 11,12-EET-SI levels to 100 nmol reversed the enhanced vascular reactivity to angiotensin II associated with angiotensin II hypertension. Renal microvascular EET levels were not different between groups and averaged 81 +/- 9 and 87 +/- 13 pg/mg per 30 min in normotensive and hypertensive animals, respectively. Renal cortical microsomal levels of the epoxygenase CYP2C23 and CYP2C11 proteins were also similar in normotensive and angiotensin II hypertensive rats. CONCLUSIONS: Taken together, these data support the concept that renal microvascular 11,12-EET activity and levels may not properly offset the enhanced angiotensin II renal vasoconstriction during angiotensin II hypertension.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

Differential MAP kinase activation and Na(+)/H(+) exchanger phosphorylation by H(2)O(2) in rat cardiac myocytes.

Bursts in reactive oxygen species production are important mediators of contractile dysfunction during ischemia-reperfusion injury. Cellular mechanisms that mediate reactive oxygen species-induced changes in cardiac myocyte function have not been fully characterized. In the present study, H(2)O(2) (50 microM) decreased contractility of adult rat ventricular myocytes. H(2)O(2) caused a concentration- and time-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein (MAP) kinases in adult rat ventricular myocytes. H(2)O(2) (50 microM) caused transient activation of ERK1/2 and p38 MAP kinase that was detected as early as 5 min, was maximal at 20 min (9.6 +/- 1.2- and 9.0 +/- 1.6-fold, respectively, vs. control), and returned to baseline at 60 min. JNK activation occurred more slowly (1.6 +/- 0.2-fold vs. control at 60 min) but was sustained at 3.5 h. The protein kinase C inhibitor chelerythrine completely blocked JNK activation and reduced ERK1/2 and p38 activation. The tyrosine kinase inhibitors genistein and PP-2 blocked JNK, but not ERK1/2 and p38, activation. H(2)O(2)-induced Na(+)/H(+) exchanger phosphorylation was blocked by the MAP kinase kinase inhibitor U-0126 (5 microM). These results demonstrate that H(2)O(2)-induced activation of MAP kinases may contribute to cardiac myocyte dysfunction during ischemia-reperfusion.

Animals↗