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Biomedical subjects

Y Xing

Publications and source records attributed to Y Xing.

At least 19 recordsLinked to original sources

Family-based association studies of the TCP1 gene and schizophrenia in the Chinese Han population.

A previous case-control study by Yang et al. indicated that the TCP1 gene in 6q25 was associated with schizophrenia in the Han population. To replicate this result, we selected eight SNPs (rs2273828, rs3818298, rs1547094, rs1547093, rs2295898, rs2295899, rs4832, rs15982) spanning the whole gene and performed a family-based study using 325 trios samples. Our transmission disequilibrium test showed neither allele nor haplotype association with schizophrenia, and suggests that the TCP1 locus is not associated with schizophrenia in the Chinese population. Since 6q25 has consistently been found to be a susceptible region for schizophrenia, we suggest that other genes within this region should be the focus of attention.

Adult↗

Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer.

BACKGROUND: Women with breast cancer are more frequently being treated with preoperative neoadjuvant chemotherapy. The reliability of sentinel lymph node biopsy (SLNB) following chemotherapy has not been determined. This was a meta-analysis of studies that examined the results of SLNB after preoperative chemotherapy. METHODS: Included articles had to meet two criteria. First, patients had to have had operable breast cancer and to have undergone SLNB after preoperative chemotherapy and, second, patients had to have undergone subsequent axillary lymph node dissection. Meta-analyses were performed in which Bayesian hierarchical models were created to estimate the identification rate (IR) and sensitivity of SLNB in this setting. RESULTS: Twenty-one studies were identified that included a total of 1273 patients. The IRs reported ranged from 72 to 100 per cent, with a pooled estimate of 90 per cent. The sensitivity of SLNB ranged from 67 to 100 per cent, with a pooled estimate of 88 (95 per cent confidence interval 85 to 90) per cent. Meta-analyses performed using Bayesian modelling resulted in (posterior) estimates for IR and sensitivity of 91 (95 per cent credible interval 88 to 94) and 88 (95 per cent credible interval 84 to 91) per cent respectively. CONCLUSION: SLNB is a reliable tool for planning treatment after preoperative chemotherapy.

Antineoplastic Agents↗

The relationship among nephrin, podocin, CD2AP, and alpha-actinin might not be a true 'interaction' in podocyte.

The abnormality of a single podocyte molecule, caused by a single gene mutation, such as NPHS1, NPHS2, CD2AP, and ACTN4, can lead to the hereditary/congenital nephrotic syndromes (NS). Further studies suggested that more than one podocyte molecule were together involved in acquired or experimental NS. However, we do not know much on the relationship among these podocyte molecules, and the molecular response induced by the change of each podocyte protein to the remaining ones. We respectively knockdown the nephrin, podocin, CD2AP, or alpha-actinin-4 mRNA by using reconstructed RNA interference vector--psiRNA-hH1GFPzeo in mouse podocyte clone. The molecular behavior or response was revealed by the quantitative expression both at mRNA and protein levels with RT-PCR and Western blot, and by the molecular distribution detected with confocal microscopy. With nephrin knockdown, only CD2AP increased, whereas podocin showed no change. Contrarily, with podocin or CD2AP knockdown, nephrin decreased, while CD2AP or podocin increased. Nephrin, podocin, or CD2AP knockdown did not change the expression of alpha-actinin-4, whereas alpha-actinin-4 knockdown begetted the reduction of nephrin, and the increment of podocin and CD2AP. The redistributions of nephrin, podocin, and CD2AP were revealed around a predominant nuclear staining compared with the membrane surface staining in the control podocytes. Our data imply that the response between the four podocyte molecules is very complicated and evidently different. There is not always an interaction between podocyte molecules. The normal localization of podocyte molecules would depend on their normal expression quantity and the molecular reactions between them.

Actinin↗

Development and aging of N-methyl-D-aspartate receptor expression in the prefrontal/frontal cortex of mice.

The present study was designed to determine whether the changes that occur during aging in the expression of the N-methyl-D-aspartate (NMDA) receptor and two NMDA receptor subunits, zeta1 and epsilon2, are a continuation of developmental processes and whether protein and mRNA expression patterns of the subunits are similar across the lifespan. The prefrontal/frontal cortex of C57BL/6 mice of eight different ages (7-8, 13-15, 30-32, 49-53, and 70-72 days and 4.5, 11, and 25 months of age) were used to examine NMDA-displaceable [(3)H]glutamate binding and mRNA in tissue sections and mRNA and protein from homogenates. The lateral prefrontal/frontal cortex of C57BL/6 mice showed more significant declines in density of agonist binding to NMDA receptors during both development and aging than the medial cortex. Changes in mRNA expression for the epsilon2 subunit across the lifespan appeared to be related to the changes in NMDA receptor binding in the lateral cortex, even though the protein expression of the epsilon2 subunit did not show the same pattern of expression as the mRNA during development. The changes in epsilon2 subunit mRNA expression during adult aging may be a continuation of developmental processes, but there was also evidence that expression levels plateaued during early adulthood. The developmental expression of the zeta1subunit in the prefrontal/frontal cortex was influenced by gender and there was no significant effect of adult aging on either the protein or mRNA expression of this subunit. Determining how the expression of the NMDA receptor and its subunits change throughout the lifespan can help us to better understand the processes affecting the receptor during aging. These results should be useful for designing interventions into the aging process to repair or prevent changes in the NMDA receptor and its associated functions, such as learning and memory.

Aging↗

Genome-wide detection of alternative splicing in expressed sequences using partial order multiple sequence alignment graphs.

We present a method for high-throughput alternative splicing detection in expressed sequence data. This method effectively copes with many of the problems inherent in making inferences about splicing and alternative splicing on the basis of EST sequences, which in addition to being fragmentary and full of sequencing errors, may also be chimeric, misoriented, or contaminated with genomic sequence. Our method, which relies both on the Partial Order Alignment (POA) program for constructing multiple sequence alignments, and its Heaviest Bundling function for generating consensus sequences, accounts for the real complexity of expressed sequence data by building and analyzing a single multiple sequence alignment containing all of the expressed sequences in a particular cluster aligned to genomic sequence. We illustrate application of this method to human UniGene Cluster Hs.1162, which contains expressed sequences from the human HLA-DMB gene. We have used this method to generate databases, published elsewhere, of splices and alternative splicing relationships for the human, mouse and rat genomes. We present statistics from these calculations, as well as the CPU time for running our method on expressed sequence clusters of varying size, to verify that it truly scales to complete genomes.

Alternative Splicing↗

5-Hydroxytryptamine-induced plasma extravasation in the rat knee joint is mediated by multiple prostaglandins.

OBJECTIVE AND DESIGN: This study investigated whether prostaglandins (PGs) are involved in 5-hydroxytryptamine (5-HT)-induced synovial plasma extravasation. MATERIALS AND METHODS: Male Sprague-Dawley rat knee joints were perfused with 5-HT and synovial capillary Evans Blue dye leakage was measured using spectrophotometry. Cyclooxygenase (COX) inhibitors and PG receptor subtype-selective antagonists were tested for the ability to reduce 5-HT-induced synovial plasma extravasation. RESULTS: 5-HT-induced plasma extravasation was inhibited by indomethacin. The COX-1 selective inhibitor SC-560 and the COX-2 selective inhibitor NS-398 were equally effective, indicating that both isoforms are involved. Antagonists selective for EP1, EP2 and DP receptor subtypes significantly attenuated the 5-HT-induced plasma extravasation. However, antagonists selective for FP, IP and TP subtypes failed to reduce 5-HT-induced plasma extravasation. CONCLUSIONS: These results demonstrate that multiple, but selective, subtypes of PGs mediate synovial plasma extravasation produced by 5-HT, and suggest that PGs act downstream of 5-HT in the inflammatory cascade.

Animals↗

Development of studies of TPO gene and its application in nuclear medicine.

Thyroperoxidase (TPO) is a glycosylated protein bound to the apical plasma membrane of thyrocytes. It is the key enzyme in the synthesis of thyroid hormones. Its gene structure and transcriptional regulation have been studied in detail. This article reviews the structure, function and transcriptional regulation of the TPO gene, and the relationship between TPO, thyroid diseases and radioactive iodide therapy.

Amino Acid Sequence↗

Alternatively folded choriogonadotropin analogs. Implications for hormone folding and biological activity.

Most heterodimeric proteins are stabilized by intersubunit contacts or disulfide bonds. In contrast, human chorionic gonadotropin (hCG) and other glycoprotein hormones are secured by a strand of their beta-subunits that is wrapped around alpha-subunit loop 2 "like a seatbelt." During studies of hCG synthesis in COS-7 cells, we found that, when the seatbelt was prevented from forming the disulfide that normally "latches" it to the beta-subunit, its carboxyl-terminal end can "scan" the surface of the heterodimer and become latched by a disulfide to cysteines substituted for residues in the alpha-subunit. Analogs in which the seatbelt was latched to residues 35, 37, 41-43, and 56 of alpha-subunit loop 2 had similar lutropin activities to those of hCG; that in which it was latched to residue 92 at the carboxyl terminus had 10-20% the activity of hCG. Attachment of the seatbelt to alpha-subunit residues 45-51, 86, 88, 90, and 91 reduced lutropin activity substantially. These findings show that the heterodimer can form before the beta-subunit has folded completely and support the notions that the carboxyl-terminal end of the seatbelt, portions of alpha-subunit loop 2, and the end of the alpha-subunit carboxyl terminus do not participate in lutropin receptor interactions. They suggest also that several different architectures could have been sampled without disrupting hormone activity as the glycoprotein hormones diverged from other cysteine knot proteins.

Alanine↗

Germinal center-associated nuclear protein (GANP) has a phosphorylation-dependent DNA-primase activity that is up-regulated in germinal center regions.

Antigen stimulation induces a rapid proliferation of B cells for expansion of specific B cell clones and their further differentiation into antibody-producing cells in germinal centers of T-dependent antigen-immunized mice. Previously, we identified a 210-kDa germinal center-associated nuclear protein (GANP) that is up-regulated selectively in germinal centers and carries an MCM-binding domain in the carboxyl-terminal side. In addition, here, we found a region (from 414 to 550 aa) in GANP molecule that is slightly similar to the known DNA-primase component p49. The recombinant GANP fragment covering this region synthesizes RNA primers for extension by DNA polymerase I with single-stranded DNA templates in vitro. GANP DNA-primase activity is controlled by phosphorylation at Ser(502) that is induced by CD40-mediated signaling in vitro and in the germinal center B cells stimulated with antigen in vivo. Overexpression of ganp cDNA in Daudi B cells caused the increased DNA synthesis more than the levels of the mock-transfectants. These evidences suggested that the novel DNA-primase GANP is involved in regulation of cell proliferation of antigen-driven B cells in germinal centers.

Acetyltransferases↗

The effect of interleukin-6 on the proliferation of prostate cancer cells in vitro and the modulation of this procedure.

The role of interleukin-6 (IL-6) in the growth of an androgen-independent prostate cancer cell line (PC-3 m) was defined and the effect of dexamethasone, which was previously shown to modulate IL-6/IL-6 receptor (IL-6R) on this procedure was investigated. By using a pretty sensitive and specific enzyme immunoassay (ELISA), it was found that PC-3 m produced certain IL-6, but there was no difference in IL-6 secretion between the group with or without dexamethasone treatment. It was also found that PC-3 m cells could not be stimulated to grow by exogenous IL-6 (P > 0.05), while it could be inhibited to grow by anti-IL-6 monoclonal antibody and dexamethasone with a dose-dependent fashion. Our observation indicated that IL-6 acted as an autocrine growth factor for PC-3 m, and dexamethasone could inhibit cell proliferation by a mechanism independent of its effect on IL-6 mRNA expression.

Androgens↗

Transmission of mouse senile amyloidosis.

SUMMARY: In mouse senile amyloidosis, apolipoprotein A-II polymerizes into amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of AApoAII fibrils into young mice induces systemic amyloidosis (Higuchi et al, 1998). We isolated AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2(c) mice and injected them with feeding needles into the stomachs of young R1.P1-Apoa2(c) mice for 5 consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart, and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid deposition was induced in young mice reared in the same cage for 3 months with old mice who had severe amyloidosis. Detection of AApoAII in feces of old mice and induction of amyloidosis by the injection of an amyloid fraction of feces suggested the propagation of amyloidosis by eating feces. Here, we substantiate the transmissibility of AApoAII amyloidosis and present a possible pathogenesis of amyloidosis, ie, oral transmission of amyloid fibril conformation, where we assert that exogenous amyloid fibrils act as templates and change the conformation of endogenous amyloid protein to polymerize into amyloid fibrils.

Amyloid↗

Threading of a glycosylated protein loop through a protein hole: implications for combination of human chorionic gonadotropin subunits.

Chorionic gonadotropin (hCG) is a heterodimeric placental glycoprotein hormone essential for human reproduction. Twenty hCG beta-subunit residues, termed the seatbelt, are wrapped around alpha-subunit loop 2 (alpha 2) and their positions "latched" by a disulfide formed by cysteines at the end of the seatbelt (Cys 110) and in the beta-subunit core (Cys 26). This unique arrangement explains the stability of the heterodimer but raises questions as to how the two subunits combine. The seatbelt is latched in the free beta-subunit. If the seatbelt remained latched during the process of subunit combination, formation of the heterodimer would require alpha 2 and its attached oligosaccharide to be threaded through a small beta-subunit hole. The subunits are known to combine during oxidizing conditions in vitro, and studies described here tested the idea that this requires transient disruption of the latch disulfide, possibly as a consequence of the thioredoxin activity reported in hCG. We observed that alkylating agents did not modify either cysteine in the latch disulfide (Cys 26 or Cys 110) during heterodimer formation in several oxidizing conditions and had minimal influence on these cysteines during combination in the presence of mild reductants (1--3 mM beta-mercaptoethanol). Reducing agents appeared to accelerate subunit combination by disrupting a disulfide (Cys 93--Cys 100) that forms a loop within the seatbelt, thereby increasing the size of the beta-subunit hole. We propose a mechanism for hCG assembly in vitro that depends on movements of alpha 2 and the seatbelt and suggest that the process of glycoprotein hormone subunit combination may be useful for studying the movements of loops during protein folding.

Alkylating Agents↗

Extrahepatic expression of apolipoprotein A-II in mouse tissues: possible contribution to mouse senile amyloidosis.

Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipoprotein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonradioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1-Apoa2C) and amyloid-resistant (SAMR1) mice and revealed that other tissues in addition to the liver synthesize apoA-II. We found a strong hybridization signal in the basal cells of the squamous epithelium and the chief cells of the fundic gland in the stomach, the crypt cells and a small portion of the absorptive epithelial cells in the small intestine, the basal cells of the tongue mucosa, and the basal cells of the epidermis and hair follicles in the skin in both mouse strains. Expression of apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immunolocalization of apoA-II protein also indicated the cellular localization of apoA-II. ApoA-II transcription was not observed in the heart. Amyloid deposition was observed around the cells expressing apoA-II mRNA in the old R1.P1-Apoa2C mice. These results demonstrate that the apoA-II mRNA is transcribed and translated in various extrahepatic tissues and suggest a possible contribution of apoA-II synthesized in these tissues to amyloid deposition.

Aging↗

Lovastatin increases nitric oxide synthesis in IL-1 beta-stimulated smooth muscle cells.

OBJECTIVE: Nitric oxide (NO) production by inducible NO synthase (iNOS) may play an important role in the pathogenesis of atherosclerosis. Although lovastatin has been shown to reduce the progression of atherosclerosis, it is not known whether it regulates NO production. We investigated the effects of lovastatin on NO synthesis and the mechanisms by which lovastatin exerts its effects in rat vascular smooth muscle cells. METHODS: Primary cultures of the vascular smooth muscle cells were obtained from the media of the thoracic aorta of Sprague Dawley rats (200-250 g). Nitrite levels in the culture medium of rat vascular smooth muscle cells were determined colorimetrically. RESULTS: Lovastatin (10(-5) mol/L) significantly increased interleukin-1 beta (IL-1 beta, 10 ng/mL)-induced nitrite accumulation in a time (0-24 hours)-dependent manner. Exogenous mevalonate and geranylgeranyl-pyrophosphate completely reversed the stimulatory effects of lovastatin on nitrite production. Furthermore, inhibition of Rho by C3 exoenzyme mimicked the increase in IL-1 beta-induced nitrite accumulation induced by lovastatin in the vascular smooth muscle cells. CONCLUSION: These results demonstrate that lovastatin up-regulates NO formation in rat vascular smooth muscle cells stimulated by IL-1 beta, and the effect may be associated with the inhibition of Rho activity.

Animals↗

[Role of endogenous cholinergic nerve in esophageal dysmotility with reflux esophagitis].

OBJECTIVE: To study the role of endogenous cholinergic nerve in esophageal dysmotility with reflux esophagitis in a feline model. METHODS: In 16 healthy cats under ketamine anesthesia (20 mg/kg), the abdominal parts of lower esophageal sphincter were cut open to establish the animal model for reflux esophagitis; esophageal motility was measured respectively preoperation and post-esophagitis. The activities of choline acetyltransferase (CHAT) and acetylcholinesterase(ACHE) in medial and distal esophageal body muscle was measured respectively with spectrophotometry, and compared to the normal cats(n = 8). RESULTS: Reflux esophagitis can make distal esophageal peristaltic amplitude decrease, the distal esophageal peristaltic amplitude of cats with reflux esophagitis [above LES 1 cm: (22.65 +/- 16.53) mm Hg; above LES 3 cm:(39.94 +/- 14.78) mm Hg, P < 0.0001] was significantly lower than that of normal cats [above LES 1 cm: (63.71 +/- 21.34) mm Hg; above LES 3 cm: (73.65 +/- 23.42) mm Hg] and the conducting velocity of distal esophagus was slower than that of normal cats [(1.04 +/- 0.36) cm/s vs (1.39 +/- 0.46) cm/s, P < 0.05]. In the esophagus of reflux esophagitis group, CHAT activity was lower in the model, especially in the distal part [(81.01 +/- 22.03) U/g vs (230.13 +/- 30.10) U/g, P < 0.0001] and ACHE activity remains unchanged. CONCLUSION: CHAT activity and pressure level were lower in the distal esophagus with reflux esophagitis compared to the normal cats. This study supported that reflux esophagitis can results in dysmotility of the distal esophagus and the abnormality of endogenous cholinergic innervation is one of the important mechanisms as far as the disorder of esophageal movement in reflux esophagitis.

Acetylcholinesterase↗

[Geostrophic deviation analysis of regional effects of protective forest system in reducing windspeed in north Liaoning plain].

East Asian synoptic charts and ground wind data in April and May of four counties of north Liaoning plain were selected to calculate the regional effects of protective forest system in reducing windspeed by geostrophic deviation method. The results show that the protection effects increased with increasing forestration area. Different protection effects of protective forest appeared at different daytime, with the greatest at 14:00 and smallest at 2:00, and the average windspeed reduced 13.3%. The characteristics of the geostrophic deviation method was also discussed.

China↗