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Biomedical subjects

C He

Publications and source records attributed to C He.

At least 73 records · Page 4Linked to original sources

[Clinical application of extended resection of Vater's papilla].

OBJECTIVE: To report the surgical technique and clinical application of extended resection of Vater's papilla (ERVP). METHODS: ERVP was performed in 12 selected patients with tumors of ampulla of Vater according to the following criteria: (1) no signs of distant mestastasis before operation; (2) no hepatic and peritoneal mestastasis during exploration, frozen section of peripancreas-duodenal lymph nodes being negative; (3) tumor less than 2 cm in diameter, pathologic examination of tumor being adenocarcinoma or adenoma; (4) pathologic examination of edge of resection being negative. RESULTS: There was no operative death nor complications in 12 cases treated by ERVP. The average time of operation was 2.3 hours, the average amount of blood infused was 433 ml, and the average time of hospitalization was 15.8 days. In 5 of 10 cases of Vater's ampullary adenocarcinoma, the mean survival time was 42 months (36-62 months). The remaining 5 cases are still alive at 20-64 months. Two patients with Vater's ampullary adenoma still survive at 32 and 46 months, respectively. CONCLUSION: ERVP is easy to perform with comparatively less surgical trauma and complication, but redical excision of tumor is not easy. It may be particulary indicated for older and high-risk patients, or patients with cancer less than 2 cm in diameter.

Adenocarcinoma↗

[Pituitary adenylate cyclase activating polypeptide ameliorates the damage and inhibits the increase of intracellular calcium concentration in cultured hippocampal neurons induced by glutamate].

Hippocampal neurons cultured from 7 to 9 d in vitro were used to observe the effect of glutamate. Treatment of glutamate for 24 h greatly decreased neuronal survival and pretreatment with pituitary adenylate cyclase activating polypeptide (PACAP) significantly attenuated hippocampal neuron death induced by glutamate. Moreover, glutamate dose-dependently increased the intracellular calcium concentration in cultured hippocampal neurons, while PACAP inhibited the increase of intracellular calcium concentration induced by glutamate. PACAP 6-38, a specific PACAP type I receptor antagonist, completely inhibited the amelioration of glutamate induced death and the decrease of intracellular calcium concentration induced by PACAP in cultured hippocampal neurons. The data suggest that PACAP has a neuroprotective effect on the hippocampal neuronal damage induced by glutamate, which is related to an inhibition of glutamate-induced increase of intracellular calcium concentration and mediated by PACAP type I receptor.

Animals↗

[Protective effect of exogenous glial cell line derived neurotrophic factor on neurons after sciatic nerve injury in rats].

The aim of the study was to investigate the effect of exogenous glial cell line derived neurotrophic factor (GDNF) on spinal cord neurons after sciatic nerve axotomy. Upon silicone tubulization of transected sciatic nerve in the adult rat, either 0.9% saline or GDNF solution was injected into the silicone chamber. It was observed by Nissl and enzyme histochemistry staining that exogenous GDNF decreased lesion induced motor neuron death in lateral nucleus of spinal anterior horn and the changes in activity of cholinesterase and acid phosphatase in spinal cord and sensory ganglions. These results suggest that exogenous GDNF is capable of protecting motor neurons from death induced by peripheral nerve injury.

Animals↗

[Culture of endotheliocytes derived from guinea-pig common carotid artery and establishment of guinea-pig donor model].

Since endotheliocyte strains of guinea-pig and inbred strains of guinea-pig are not easily obtained, it is impossible to ensure the consistence of antigenicity between endotheliocytes and donor organs when endotheliocytes are used as an inductor in the research of immunological tolerance. So it is necessary to establish the guinea-pig endotheliocyte-donor model. One side of common carotid arteries was removed and reversed. After collagenase digestion, culture of endotheliocytes was performed. And the survival time of guinea-pig was observed. Cultured cells were confirmed as endotheliocytes by the study of morphology, immunohistochemistry and electron microscopy. The two-month-survival of guinea-pigs was 92% (103/112). The establishment of guinea-pig endotheliocyte-donor model can provide the foundation for the research of guinea-pig endotheliocyte and immunological tolerance.

Animals↗

An intragenic deletion of nuclear localization signal-1 of p53 tumor suppressor gene results in loss of apoptosis in murine fibroblasts.

We established mouse lines containing either full-length wild-type p53 or nuclear localization signal-I (NLS-I) deleted p53 to study the role of NLS-I in p53 translocation and function. Induction of apoptosis in response to DNA damage, a primary function of p53, was tested in these cell lines. After exposure to gamma-ionizing radiation or hydrogen peroxide, DNA ladders and labeling of nucelosomal fragments were detected in cells with wild-type p53 gene, but not in p53 null cells or NLS-I deleted cells, suggesting that the NLS-I of p53 protein is necessary for apoptosis. Analysis of p53 protein from subcellular fractions indicated that NLS-I deprived p53 remained in the cytoplasmic fraction, which may explain why NLS-I deleted p53 failed to induce apoptosis.

Animals↗

Determination of polyphenols by high-performance liquid chromatography with inhibited chemiluminescence detection.

A chemiluminescence reaction detector was developed for the detection of polyphenols separated by HPLC based on the inhibition of chemiluminescence from the luminol-potassium hexacyanoferrate(III) reaction by polyphenols. The separation was carried out on a RP-C18 column at 37 degrees C by using stepwise gradient elutions. The detection limits are in the range of 6.8 x 10(-7)-2.0 x 10(-9) g/ml for catechol, protocatechuic acid, chlorogenic acid, rutin, resorcinol, hydroquinone and p-tert.butylpyrocatechol. The method is sensitive, selective, fast and simple. It has been successfully applied to the determination of chlorogenic acid and rutin in real tobacco samples.

Chromatography, High Pressure Liquid↗

Structure and ligand of a histone acetyltransferase bromodomain.

Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.

Acetyltransferases↗

Identification of a potassium channel site that interacts with G protein betagamma subunits to mediate agonist-induced signaling.

Activation of heterotrimeric GTP-binding (G) proteins by their coupled receptors, causes dissociation of the G protein alpha and betagamma subunits. Gbetagamma subunits interact directly with G protein-gated inwardly rectifying K+ (GIRK) channels to stimulate their activity. In addition, free Gbetagamma subunits, resulting from agonist-independent dissociation of G protein subunits, can account for a major component of the basal channel activity. Using a series of chimeric constructs between GIRK4 and a Gbetagamma-insensitive K+ channel, IRK1, we have identified a critical site of interaction of GIRK with Gbetagamma. Mutation of Leu339 to Glu within this site impaired agonist-induced sensitivity and decreased binding to Gbetagamma, without removing the Gbetagamma contribution to basal currents. Mutation of the corresponding residue in GIRK1 (Leu333) resulted in a similar phenotype. Both the GIRK1 and GIRK4 subunits contributed equally to the agonist-induced sensitivity of the heteromultimeric channel. Thus, we have identified a channel site that interacts specifically with Gbetagamma subunits released through receptor stimulation.

Binding Sites↗

Genetic anticipation in a large family with pure autosomal dominant hereditary spastic paraplegia.

We have reinvestigated a large kindred identified over 25 years ago segregating for a form of pure autosomal dominant hereditary spastic paraplegia (HSP). We have examined additional relatives in order to refine the clinical and genetic characteristics of this disorder, and performed an analysis to determine if anticipation is present in this family. Analysis of onset ages in parent-to-child transmissions of HSP is consistent with anticipation. These results provide support for dynamic mutation as the underlying mechanism of this form of HSP, and suggest a trinucleotide repeat instability occurring primarily in the female germ line.

Adolescent↗

Characterization of the advanced glycation end-product receptor complex in human vascular endothelial cells.

Advanced glycation end products (AGEs) have been implicated as causal factors in the vascular complications of diabetes and it is known that these products interact with cells through specific receptors. The AGE-receptor complex, originally described as p60 and p90, has been characterised in hemopoietic cells and the component proteins identified and designated AGE-R1, -R2 and -R3. In the current study we have characterised this receptor in human umbilical vein endothelial cells (HUVECs) and elucidated several important biological properties which may impact on AGE mediated vascular disease. 125I-AGE-BSA binding to HUVEC monolayers was determined with and without various cold competitors. The synthetic AGE, 2-(2-furoyl)-4(5)-furanyl-1H-imidazole (FFI)-BSA, failed to compete with AGE-BSA binding unlike observations already reported in hemopoietic cells. The ability of 125I-AGE-BSA to bind to separated HUVEC plasma membrane (PM) proteins was also examined and the binding at specific bands inhibited by antibodies to each component of the AGE-receptor complex. Western blotting of whole cell and PM fractions, before and after exposure to AGE-BSA, revealed that AGE-R1, -R2 and -R3 are subject to upregulation upon exposure to their ligand, a phenomenon which was also demonstrated by immunofluorescence of non-permeabilised cells. mRNA expression of each AGE-receptor component was apparent in HUVECs, with the AGE-R2 and -R3 gene expression being upregulated upon exposure to AGEs in a time-dependent manner. A phosporylation assay in combination with AGE-R2 immunoprecipitation demonstrated that this component of the receptor complex is phosphorylated by acute exposure to AGE-BSA. These results indicate the presence of a conserved AGE-receptor complex in vascular endothelium which demonstrates subtle differences to other cell-types. In response to AGE-modified molecules, this complex is subject to upregulation, while the AGE-R2 component also displays increased phosphorylation possibly leading to enhanced signal transduction.

Binding Sites↗

Transfer of Neurospora kalilo plasmids among species and strains by introgression.

There are four different variants of the kalilo "family" of linear mitochondrial plasmids. This family is found in several heterothallic species and one pseudohomothallic species of Neurospora, as well as in one homothallic species of Gelasinospora. The mode of dispersal of these plasmids is not known. Horizontal transmission has proved difficult to demonstrate. Another possibility is transfer by introgression, and this is modelled in the present paper. We have used introgression and subsequent heterokaryosis to successfully transfer the LA-kalilo plasmid from a Haitian strain of Neurospora crassa to the standard Oak Ridge N. crassa background, the LA-kalilo plasmid from the pseudohomothallic Neurospora tetrasperma to N. crassa, and the kalilo plasmid from N. crassa to N. tetrasperma. Thus, introgression is shown to be a possible avenue of dispersal between species. The recipient strains were all senescent but the mechanism of this senescence is not known. It could be caused by the plasmids, but if so the mechanism is novel since plasmid/mtDNA junction fragments of the type found in the standard mode of mtDNA insertion could not be detected. However, mtDNA changes were observed in the senescent recipients.

Base Sequence↗

Renal, central nervous system and pancreatic overexpression of recombinant soluble Crry in transgenic mice. A novel means of protection from complement-mediated injury.

Crry is a potent complement regulator that inhibits classical and alternative pathway C3 convertases in rodents. We have produced transgenic animals expressing Crry as a recombinant soluble protein driven by the broadly active metallothionein-I promoter. These animals have high serum and urinary levels of rsCrry leading to inhibition of complement activity. In nephrotoxic serum nephritis (NSN), injected antibodies bind to glomeruli, leading to complement activation and subsequent glomerular injury and albuminuria. We have shown that rsCrry can block such injury and reduce albuminuria by as much as 75%. Corresponding to the reduction in albuminuria was the complete absence of C3 staining in glomeruli by immunofluorescence microscopy in 17/20 transgene positive animals. Support for a local source of protective rsCrry in this model is provided by the demonstration of Crry transgene mRNA in the glomerulus and a very high fractional excretion of rsCrry in the urine. Therefore, rsCrry expression markedly ameliorates an antibody-induced disease model in vivo. In addition, local synthesis of Crry in other organs that are targets of immune injury has been found. For example, Crry transgene mRNA is present throughout the central nervous system and in pancreatic islets. Thus, continuous complement inhibition at the C3 convertase step appears to be feasible and is effective in complement-mediated injury states. A number of disease models affecting these target organs can be tested using these mice.

Animals↗

Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.

Direct interactions of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) with inwardly rectifying potassium channels are stronger with channels rendered constitutively active by binding to PtdIns(4,5)P2, such as IRK1, than with G-protein-gated channels (GIRKs). As a result, PtdIns(4,5)P2 alone can activate IRK1 but not GIRKs, which require extra gating molecules such as the beta gamma subunits of G proteins or sodium ions. Here we identify two conserved residues near the inner-membrane interface of these channels that are critical in interactions with PtdIns(4,5)P2. Between these two arginines, a conservative change of isoleucine residue 229 in GIRK4 to the corresponding leucine found in IRK1 strengthens GIRK4-PtdIns(4,5)P2 interactions, eliminating the need for extra gating molecules. A negatively charged GIRK4 residue, two positions away from the most strongly interacting arginine, mediates stimulation of channel activity by sodium by strengthening channel-PtdIns(4,5)P2 interactions. Our results provide a mechanistic framework for understanding how distinct gating mechanisms of inwardly rectifying potassium channels allow these channels to subserve their physiological roles.

Amino Acid Sequence↗

Transfusion-transmitted virus infection in China: prevalence in blood donors and in patients with liver diseases.

BACKGROUND: Prevalence of transfusion-transmitted virus (TTV) infection among blood donors and in patients with liver diseases in China was studied. METHODS: DNA was extracted from serum and amplified by seminested polymerase chain reaction with reported primer sets from a conserved region of the TTV genome. RESULTS: TT Virus DNA was detected in 55 of 196 blood donors (28%); 31% (40 of 127) in the north and 22% (15 of 69) in the south. TT Virus DNA was also detected in 14 of 31 patients (45%) with non-A-non-G fulminant hepatitis and in eight of 25 patients (32%) with non-A-non-G chronic hepatitis. The rate of TTV viraemia in these patients with liver disease was comparable to that in blood donors. TT Virus DNA sequencing of 12 isolates showed that the prevalence of genotype 2 was significantly higher than that reported in Japan (66.7 vs 2.6%, P < 0.001). Furthermore, genotyping assays based on restriction fragment length polymorphism were carried out on all 88 TTV DNA-positive samples. It was found that 42 isolates (47.7%) belonged to genotype 1 and 40 (45.5%) to genotype 2. It was of particular interest that the prevalence of genotype 1 in patients with non-A-non-G fulminant hepatitis was significantly higher than that in blood donors (10/14 vs 22/55, P < 0.05). CONCLUSIONS: The data indicate that TTV infection is common in China and that the pathogenic potential of TTV toward the liver (if any) may differ between genotypes.

Adult↗

BWMK1, a novel MAP kinase induced by fungal infection and mechanical wounding in rice.

The activation of the mitogen-activated protein (MAP) kinases by different environmental stresses has been previously observed in several dicot plant species. Here, we report the isolation of a novel MAP kinase in rice that is induced during infection by the blast fungus Magnaporthe grisea or upon mechanical wounding. The gene is designated as BWMK1 for blast- and wound-induced MAP kinase. The cDNA of BWMK1 was isolated from rice leaves challenged by the blast pathogen. Transcripts of the corresponding gene accumulated in rice leaves 4 h after blast inoculation and 30 min after mechanical wounding. This gene encodes a 506 amino acid protein that contains a new dual-phosphorylation activation motif TDY and about 150 unique amino acids on its C terminus. In-gel kinase activity and immunoprecipitation assays confirmed that BWMK1 is a functional MAP kinase. These results show that BWMK1 is a new member of the plant MAP kinase family and may mediate both defense and wound signaling in rice.

Amino Acid Sequence↗

Pretransitional behavior above the nematic-isotropic phase transition of an auxetic trimer liquid crystal.

Static light scattering and electric field-induced Kerr measurements were performed above the nematic-isotropic phase transition of a terminal-lateral-lateral-terminal negative Poisson ratio trimer. For both measurements the inverse susceptibility was observed to be nearly linear with temperature, a result inconsistent with our previously reported Kerr data [Phys. Rev. E 58, 2041 (1998)].

Journal Article↗

Dietary glycotoxins: inhibition of reactive products by aminoguanidine facilitates renal clearance and reduces tissue sequestration.

Evidence indicates that the metabolic turnover of food-derived reactive orally absorbed advanced glycation end products (AGEs) or glycotoxins (GTs) is delayed, possibly contributing to the tissue damage induced by endogenous AGEs, especially in patients with diabetes and kidney disease. The aim of this study was to explore whether pharmacologic inhibition of dietary AGE bioreactivity by aminoguanidine (AG) can improve turnover and renal excretion of these substances. Normal Sprague-Dawley rats were fed single-labeled [14C]AGE-ovalbumin, double-labeled [14C-125I]AGE-ovalbumin, or control 125I-labeled ovalbumin diet plus free [14C]glucose, with or without AG (0.2% in water). [14C]AGE- and 125I-labeled peptide-associated radioactivity (RA) were compared with AGE immunoreactivity (by enzyme-linked immunosorbent assay) in tissues, serum, and 72-h urine samples. The effect of AG on dietary AGE bioreactivity was assessed by monitoring the inhibition of covalent complex formation between fibronectin (FN) peptide fragments and serum components, after a meal of labeled dietary AGE with or without AG. The radiolabeled AGE diet produced serum absorption and urinary excretion peaks kinetically distinct from those of free [14C]glucose or [125I]ovalbumin. Some 26% of the orally absorbed AGE-ovalbumin was excreted in the urine, whereas after AG treatment, urinary excre-tion of dietary AGEs increased markedly (to >50% of absorbed). More than 60% of tissue-bound RA was found covalently deposited in kidneys and liver, whereas after treatment with AG, tissue AGE deposits were reduced to <15% of the amount found in untreated AGE-fed controls. Sera enriched for dietary GTs formed covalently linked complexes with FN, a process completely inhibitable by AG cotreatment. Amelioration of dietary GT bioreactivity by AG improves renal elimination and prevents tissue deposition of food GTs. This may afford a novel and potentially protective use of AG against excessive tissue AGE toxicity in diabetic patients with renal disease.

Animals↗