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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 595 records · Page 33Linked to original sources

Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex.

In this study, we tested the hypothesis that chronic administration of phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor antagonist, would cause a long-lasting behavioral sensitization associated with neuronal toxicity. Female Sprague-Dawley rats were administered PCP (20 mg/kg, i.p.) once a day for 5 days, withdrawn for 72 hr, placed in locomotor activity chambers, and challenged with 3.2 mg/kg PCP. Following assessment of locomotor activity, the rats were killed and their brains processed for analysis of apoptosis by either electron microscopy or terminal dUTP nick-end labeling (TUNEL). In study I, PCP challenge produced a much more robust and long-lasting increase in locomotor activity in rats chronically treated with PCP than in those chronically treated with saline. In study II, clozapine pretreatment blunted the degree of sensitization caused by PCP. In study I, a marked increase in TUNEL-positive neurons was found in layer II of the olfactory tubercle and piriform cortex of rats chronically treated with PCP. Many of these neurons had crescent-shaped nuclei consistent with apoptotic condensation and margination of nuclear chromatin under the nuclear membrane. Acute PCP had no effect. Electron microscopy revealed that PCP caused nuclear condensation and neuronal degeneration consistent with apoptosis. Cell counts in layer II of the piriform cortex revealed that chronic PCP treatment resulted in the loss of almost 25% of the cells in this region. However, an increase in glial fibrillary acidic protein (GFAP)-positive cells in the molecular layer suggests that this neurotoxicity also may involve necrosis. In study II, the PCP-induced neuronal degeneration was essentially completely abolished by clozapine pretreatment. This pattern of degeneration was found to coincide with the distribution of the mRNA of the NR1 subunit of the NMDA receptor. The relevance of these data to a PCP model of chronic NMDA receptor hypofunction is discussed.

Animals↗

Bovine serum fetuin is unfolded through a molten globule state.

The reversible heat- and GuHCl-induced unfolding of bovine serum fetuin (BSF) has been studied by differential scanning calorimetry, circular dicroism, tryptophan fluorescence, and size-exclusion chromatography. We show here that thermal unfolding of BSF occurs in two distinct steps corresponding to transitions from the native (N) to an intermediate (I) and from the intermediate to the unfolded state (U). The Nleft and right arrow I transition is highly cooperative and can well be accounted for by a two-state mechanism. The Ileft and right arrow U transition is also cooperative but to a lesser extent than the Nleft and right arrow I transition. CD spectra show that the protein in the I state retains nearly all of the native secondary structure and has a largely disrupted tertiary structure. However, the hydrophobic environment of the single tryptophan residue is not changed, and some compactness is retained in the I state. The structural properties of this intermediate state are apparently characteristic of a molten globule. The GuHCl-induced unfolding is also a two-step process with an I state around 2 M GuHCl. Although the structural features of the denaturant-induced I state are somewhat different from those of the heat-induced I state, the unfolding free energies DeltaG degreesNleft and right arrow I and DeltaG degreesIleft and right arrow U as well as DeltaG degreesNleft and right arrow U obtained from these two methods are comparable. We argue that the observed two-state Nleft and right arrow I transition is due to the melting of the tertiary packing, while leaving quasi-intact the secondary structure and some long-range interactions in the I state. These long-range interactions, together with the secondary structural elements, would be responsible for the observed cooperativity of the Ileft and right arrow U transition.

Animals↗

Kinetics of intragraft cytokine expression, cellular infiltration, and cell death in rejection of renal allografts compared with acceptance of liver allografts in a rat model: early activation and apoptosis is associated with liver graft acceptance.

BACKGROUND: Liver transplants in the rat strain combination PVG-to-Dark Agouti are spontaneously tolerated, whereas kidney transplants in the same strain combination are rejected in 7-9 days. METHODS: To identify organ-specific differences that might yield further information about the mechanism of tolerance induction in this strain combination, liver or kidney grafts, spleen, and draining lymph nodes were harvested at days 1, 3, 5, and 7, and examined by immunohistochemistry, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay, and reverse transcriptase-polymerase chain reaction for interferon-gamma, interleukin (IL)-2, IL-4, and IL-10. RESULTS: Renal allograft rejection was associated with the progressive development of an intense mononuclear cell infiltrate. Markers of lymphocyte activation and cytokine up-regulation appeared from day 3, and many apoptotic parenchymal cells were noted on days 5-7, at the peak of rejection. Conversely, liver allograft tolerance was associated with more rapid infiltration by activated T cells and earlier increases in cytokine expression, but with a more limited degree of cellular infiltration. Concurrent with the early activation, high levels of apoptosis were found in areas of leukocyte infiltrate, paralleling the disappearance of activated T cells from the graft between days 3 and 5. CONCLUSIONS: Apoptosis of infiltrating leukocytes in liver allografts may represent an important process in the induction of spontaneous liver transplant tolerance and may underlie the abortive nature of the effector response observed within tolerated livers. In contrast, activated cells in renal allografts in the same strain combination survive and proliferate, express high levels of cytokines, and are efficient in bringing about graft destruction.

Animals↗

Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis.

The U2 snRNP component SAP 155 contacts pre-mRNA on both sides of the branch site early in spliceosome assembly and is therefore positioned near or at the spliceosome catalytic center. We have isolated a cDNA encoding human SAP 155 and identified its highly related Saccharomyces cerevisiae homolog (50% identity). The carboxy-terminal two-thirds of SAP 155 shows the highest conservation and is remarkably similar to the regulatory subunit A of the phosphatase PP2A. Significantly, SAP 155 is phosphorylated concomitant with or just after catalytic step one, making this the first example of a protein modification tightly regulated with splicing catalysis.

Adaptor Proteins, Signal Transducing↗

Effects of magnets with non-unit magnetic permeability on an elliptically polarizing undulator.

This study employs the three-dimensional magnetostatic code TOSCA to assess numerically the effects of NdFeB magnets with non-unit magnetic permeability on an elliptically polarizing undulator. A reduction of a few percent of the on-axis magnetic field strength is predicted. In addition, a deviation of +/-100 G cm uncompensated dipole steering is predicted in a phase shift of 180 degrees for the elliptically polarizing undulator EPU5.6 (having a period length of 56 mm) at the minimum gap of 18 mm, which is related primarily to the configuration of the device end scheme. Results presented herein demonstrate that implementing an active compensation mechanism is a prerequisite for minimizing the orbit distortion during phase-shift adjustment, particularly for operating such a polarizing undulator in a third-generation machine having a median energy similar to that of the 1.5 GeV storage ring at SRRC.

Journal Article↗

An SRRC elliptically polarizing undulator prototype to examine mechanical design feasibility and magnetic field performance.

In this work, a 1 m long Sasaki-type elliptically polarizing undulator (EPU) prototype with 5.6 cm period length is used to examine the mechanical design feasibility as well as magnetic field performance. The magnetic field characteristics of the EPU5.6 prototype at various phase shifts and gap motion are described. The field errors from mechanical tolerances, magnet block errors, end field effects and phase/gap motion effects are analysed. The procedures related to correcting the field with the block position tuning, iron shimming and the trim blocks at both ends are outlined.

Journal Article↗

Spectral properties of the polarizing devices at SRRC.

User requirements at SRRC for high-brilliance synchrotron light in various polarization states will be fulfilled in the near future by the implementation of two types of polarizing devices in the storage ring: the elliptically polarizing undulator (EPU) and the elliptically polarized bending magnet (EPBM). The EPBM provides a broadband polarized spectrum up to the soft X-ray range with rapid alternation of the left and right helicities. The EPU, which has a magnetic period length of 56 mm, generates a high-brilliance harmonic spectral intensity in the range 80-1400 eV with abundant polarization states, including circular ones. The optimal merit flux is evaluated for the operation of these two polarizing devices in the SRRC 1.5 GeV storage ring. The available polarization states are also surveyed.

Journal Article↗

Central delivery of human tissue kallikrein gene reduces blood pressure in hypertensive rats.

The human tissue kallikrein gene, in the form of naked DNA (CMV-cHK) or an adenoviral vector (Ad.CMV-cHK), was directly delivered by intracerebroventricular injection into spontaneously hypertensive rats. Control rats received the same amount of vector DNA (pcDNA3) or adenoviral vector (Ad.CMV-LacZ) carrying the lacZ gene. A single injection of the human tissue kallikrein gene caused a rapid and prolonged blood pressure-lowering effect that began 1 day post injection and the effect lasted for more than 7 days. The expression of human tissue kallikrein and its mRNA was identified in the cortex, cerebellum, brain stem, hippocampus and hypothalamus. Cellular localization of beta-galactosidase was detected by X-gal staining in the thalamus, hypothalamus and third ventricle in rats injected with Ad.CMV-LacZ. This suggests that the tissue kallikrein-kinin system may function in the central control of blood pressure homeostasis.

Adenoviridae↗

Correlation of thrombosis with increased platelet turnover in thrombocytosis.

There are no readily applicable methods to routinely assess thrombosis risk and treatment response in thrombocytosis. Reticulated platelets (RP) define the most recently released platelets in the circulation, and the RP% has been shown to estimate platelet turnover in thrombocytopenic states. We examined whether increased RP values were associated with thrombotic complications in thrombocytosis. Platelet count, RP%, and absolute RP count were measured at presentation in 83 patients with chronic or transient thrombocytosis, 46 patients with deep vein (DVT) or arterial (ART) thrombosis and normal platelet counts, and 83 healthy controls with normal platelet counts. Chronic thrombocytosis patients presenting with thrombosis (n = 14) had significantly higher RP% (14.7% +/- 10. 1%, mean +/- SD) than asymptomatic chronic thrombocytosis patients (n = 23, RP% = 3.4% +/- 1.8%), healthy controls (3.4% +/- 1.3%), DVT patients (n = 21, 3.8% +/- 2.1%), or ART patients (n = 25, 4.5% +/- 4.1%, P < .05 for all comparisons). Chronic thrombocytosis patients with thrombosis also had significantly higher absolute RP counts than asymptomatic chronic thrombocytosis patients (98 +/- 64 x 10(9)/L [range, 54 to 249 x 10(9)/L] v 30 +/- 13 x 10(9)/L [range, 11 to 51 x 10(9)/L]; P = .0004), whereas healthy controls, DVT, and ART patients had similarly low absolute RP counts (6 +/- 6 x 10(9)/L, 9 +/- 7 x 10(9)/L, and 11 +/- 7 x 10(9)/L, respectively; P > .49). The RP% and absolute RP counts remained significantly higher in chronic thrombocytosis patients with thrombosis when patients were further subdivided into primary myeloproliferative disorders versus secondary thrombocytosis. Similarly elevated RP percentages and absolute counts were also noted in transient thrombocytosis patients with thrombosis (n = 6, 11.5% +/- 4.4% and 90 +/- 46 x 10(9)/L, respectively) when compared with asymptomatic transient thrombocytosis patients (n = 40, 4.5% +/- 2.7% and 35 +/- 16 x 10(9)/L, respectively) and to all control groups (P < .05 for all comparisons). In addition, 7 of 8 thrombocytosis patients who were studied before developing symptoms of thrombosis had elevated absolute RP counts compared with only 1 of 63 thrombocytosis patients who remained asymptomatic. Follow-up studies in seven chronic thrombocytosis patients showed that successful aspirin treatment of symptomatic recurrent thrombosis significantly reduced the RP% from 17.1% +/- 10.9% before therapy to 4.8% +/- 2.0% after therapy; absolute RP counts decreased from 102 +/- 67 x 10(9)/L to 26 +/- 10 x 10(9)/L (P < .01 for both). We conclude that thrombosis in the setting of an elevated platelet count is associated with increased platelet turnover, which is reversed by aspirin therapy. Measurement of reticulated platelets to assess platelet turnover may be useful in evaluating both treatment response and thrombotic risk in thrombocytosis.

Adolescent↗

Molecular cloning and sequencing of the cDNA of cop1 gene from Pisum sativum.

Cop1 protein plays an important role in seedling development of higher plants. The cDNA of cop1 gene from pea (Pisum sativum) was cloned and sequenced. Cop1 protein of pea is predicted to have 672 amino acids and a molecular mass of 76 kDa. Sequence comparison between Cop1 proteins of pea and Arabidopsis thaliana revealed that the two Cop1 proteins were highly homologous in the regions with functional domains and at the C-terminus. Immunoblotting performed with polyclonal antibodies against recombinant Cop1 of pea showed that Cop1 protein was present in seedlings germinated both in light and darkness.

Amino Acid Sequence↗

Conversion of pancreas allograft rejection to acceptance by liver transplantation.

BACKGROUND: Liver allografts of PVG(RT1c)-->DA(RT1a) are spontaneously accepted, whereas pancreas, heart, and kidney allografts are rejected. Our previous studies have shown that simultaneous liver and pancreas transplantation prevents pancreas allograft rejection. The aim of this study was to examine the effect of liver transplantation on subsequent pancreas allografts and on ongoing pancreas rejection. METHODS: Heterotopic, duct-ligated segmental pancreas grafts were transplanted into streptozotocin-induced diabetic recipients (60 mg/kg body weight i.p.) with or without orthotopic liver grafting at different times. Experimental design was as follows. Group 1 received PVG-->PVG pancreas syngrafts (n=6); group 2, PVG-->DA pancreas allografts (n=7); groups 3-5, PVG-->DA pancreas allografts followed by liver transplantation on day 2 (n=6), on day 4 (n=5), and on day 6 (n=5), respectively, group 6, PVG-->DA pancreas allografts after liver transplantation at 4 weeks (n=6). RESULTS: The results showed that pancreas allografts in group 2 were rejected from postoperative day 7 to 13. Liver transplantation prevented subsequent pancreas allograft rejection in group 6. Ongoing pancreas rejection was reversed by liver transplantation with subsequent graft acceptance in groups 3-5. Significant graft-infiltrating lymphocyte apoptosis was demonstrated at 2 weeks in pancreas transplants associated with liver grafting. Graft-versus-host disease was not detected in the pancreas recipients. CONCLUSIONS: We conclude that pancreas allografts in the PVG-->DA combination are rejected rapidly with median survival time of 9 days. Liver transplantation can protect subsequent pancreas grafts from rejection and reverse ongoing pancreas graft rejection with subsequent pancreatic acceptance. Graft-infiltrating lymphocyte apoptosis may be associated with the process of graft acceptance.

Animals↗

Isolation and characterization of a DnaJ-like protein in rats: the C-terminal 10-kDa domain of hsc70 is not essential for stimulating the ATP-hydrolytic activity of hsc70 by a DnaJ-like protein.

A DnaJ-like protein, RDJ1, was isolated from a rat brain cDNA library. The protein is predicted to have 397 amino acid residues and shares 99% identity to that of HDJ2, a human DnaJ-like protein. RDJ1 was also shown to rescue the temperature-sensitive lethality of a strain containing a mutated cytosolic DnaJ in yeast, ydj1-151. Fragments containing the J-domain of RDJ1 either with or without the G/F motif were expressed in Escherichia coli. The purified proteins stimulated the ATPase activity of hsc70 and of the 60-kDa N-terminal fragment of hsc70. These results imply that RDJ1 can interact with the N-terminal 60-kDa fragment of hsc70 to activate ATP hydrolysis by hsc70.

Adenosine Triphosphate↗

Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities.

Sex-typed cognitive abilities were assessed in 33 hypogonadal men receiving testosterone replacement therapy, 10 eugonadal men receiving testosterone in a male contraceptive clinical trial, and 19 eugonadal men not administered testosterone. Prior to and following hormone administration, men completed four tests measuring visuospatial ability, three tests measuring verbal fluency, two tests measuring perceptual speed, and a measure of verbal memory. Group differences in testosterone levels were unrelated to performance on most cognitive measures, including visuospatial ability. Relative to other men, hypogonadal men were impaired in their verbal fluency and showed improved verbal fluency following treatment with testosterone. These data suggest that testosterone may enhance verbal fluency in hypogonadal men and support the general hypothesis that current levels of testosterone may influence some aspects of cognitive function.

Adult↗

Staurosporine-induced apoptosis in cardiomyocytes: A potential role of caspase-3.

Cardiomyocyte apoptosis has been demonstrated in animal models of cardiac injury as well as in patients with congestive heart failure or acute myocardial infarction. Therefore, apoptosis has been proposed as an important process in cardiac remodeling and progression of myocardial dysfunction. However, the mechanisms underlying cardiac apoptosis are poorly understood. The present study was designed to determine whether the family of caspase proteases and stress-activated protein kinase (SAPK/JNK) are involved in cardiac apoptosis. Cultured rat neonatal cardiac myocytes were treated with staurosporine to induce apoptosis as evidenced by the morphological (including ultrastructural) characteristics of cell shrinkage, cytoplasmic and nuclear condensation, and fragmentation. Nucleosomal DNA fragmentation in myocytes was further identified by agarose gel electrophoresis (DNA ladder) as well as in situ nick end-labeling (TUNEL). Staurosporine-induced apoptosis in myocytes was a time- and concentration-(0.25-1 micro M)-dependent process. Staurosporine-induced apoptosis in myocytes was reduced by a cell-permeable, irreversible tripeptide inhibitor of caspases, ZVAD-fmk, but not by the ICE-specific inhibitor, Ac-YVAD-CHO. At 10, 50 and 100 muM of ZVAD-fmk, staurosporine-induced myocyte apoptosis was reduced by 5.8, 39.1 (P<0.01) and 53.8% (P<0.01), respectively. Staurosporine, at 0.25-1 micro M, increased caspase activity in cardiomyocytes by five- to eight-fold, peaking at 4-8 h after stimulation. Based on substrate specificity analysis, the major component of caspases activated in myocytes was consistent with caspase-3 (CPP32). Moreover, the appearance of the 17-kD subunit of active caspase-3 in staurosporine-treated myocytes was demonstrated by immunocytochemical analysis. In contrast, staurosporine induced a rapid and transient inhibition of SAPK/JNK in myocytes. The SAPK activity in myocytes was reduced by 68.3 and 58.3% (P<0.01 v basal) at 10 and 30 min after treatment with 1 micro M of staurosporine, respectively. Our results suggest that staurosporine-induced cardiac myocyte apoptosis involves activation of caspases, mainly caspase-3, but not activation of the SAPK signaling pathway.

Amino Acid Sequence↗

A PAX3 polymorphism (T315K) in a family exhibiting Waardenburg Syndrome type 2.

Waardenburg Syndrome (WS) is an autosomal-dominant disorder phenotypically characterized by sensorineural hearing loss and pigmentary disturbances. Presence of dystopia canthorum is indicative of WS type 1 and results from defects in the PAX3 gene, whereas normally located medial canthi is characteristic of type 2 WS (WS2) and is associated with defects in the microphthalmia-associated transcription factor (MIFT) gene. Here a neutral polymorphism is reported in the PAX3 gene (T315K) in a family with WS2.

Base Sequence↗

Effect of low HDL combined with hypertriglyceridemia in coronary artery disease patients on PGI2 biological activity in relation to lipid regulating treatment.

The purpose of this study was to investigate the effect of low high-density-lipoprotein (HDL) combined with hypertriglyceridemia in coronary artery disease (CAD) patients on prostaglandin I2 (PGI2) biological activity in relation to lipid regulating treatment. The inhibitory rate of PGI2 on ADP-induced platelet aggregation was used as the index for PGI2 biological activity. Twenty health individuals served as normal controls. CAD group consisted of 20 patients with low HDL combined with hypertriglyceridemia. The results showed that, before the treatment, the stabilizing effect on PGI2 activity decreased significantly in CAD group when compared with the control group (P < 0.01). One month after the treatment, HDL level in CAD group increased significantly and TG level significantly decreased (P < 0.001). The different effect on PGI2 activity was no longer found between CAD group and control group (P > 0.05), further confirming the protecting effect of HDL on PGI2 biological activity. Low HDL is considered as an important risk factor of CAD, therefore, impaired PGI2 biological activity and increased platelet aggregation might be responsible mechanisms. Furthermore, raising HDL level by lipid regulating treatment could restore the protective effect of HDL on PGI2 and might be helpful in the prevention of the acute coronary syndrome.

Coronary Disease↗

The effect of neferine on foam cell formation by anti-low density lipoprotein oxidation.

Oxidatively modified low density lipoprtein (LDL) plays an important role in atheroslerosis (AS) development. To investigate the role of neferine (Nef) in anti-LDL oxidation and foam cell formation, the lipoprotein was derived and subjected to three different treatments: N-LDL (normal LDL), Cu2+ + LDL and Cu2+ + Nef + LDL. The LDLs were put at 25 degrees C for 24 h and the thiobarbituric acid reactive substance (TBARS) values were determined. They were 0.57 +/- 0.2, 6.01 +/- 0.22 and 2.26 +/- 0.13 nmol/mg protein, respectively. The difference was very significant (P < 0.01) for each two groups by t test. Mouse peritoneal macrophage (M phi) were exposed to 50 micrograms protein/ml of Cu2+ + LDL and Cu2+ + Nef + LDL at 37 degrees C for 60 h. The tryglyceride (TG) and total cholesterol (TC) content in M phi were assayed. The results showed that Cu2+ + LDL was more efficient than Cu2+ + Nef + LDL in stimulating lipid accumulation in M phi (P < 0.001). The study demonstrated that Nef could inhibit Cu(2+)-mediated LDL oxidation and thereby inhibiting macrophage-derived foam cell formation.

Alkaloids↗

Characterization of two class I genes from the H2-M region: evidence for a new subfamily.

We cloned, sequenced, and mapped two divergent major histocompatibility class Ib genes from BALB/c mice. M9d and M10d both have the potential to encode full-length class I molecules, but transcripts were not readily detectable. M9 is 86% similar to M1 in its nucleotide sequence and maps next to it on YAC clones. M9 is only 64% similar to M10 and 60% to H2-K k. Probes from M10 define a new subfamily of eight class I genes in C3H mice; five cluster directly distal to H2-T1, and three are located between M9-1-7-8 and M6-4-5 in the H2-M region.

Amino Acid Sequence↗