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Biomedical subjects

H Xue

Publications and source records attributed to H Xue.

At least 37 records · Page 2Linked to original sources

A fragment of recombinant GABA(A) receptor alpha1 subunit forming rosette-like homo-oligomers.

The type A gamma-aminobutyric acid (GABA(A)) receptor plays a major role in inhibitory synaptic transmission in the central nervous system. A fragment consisting of residues Cys166 to Leu296 of the alpha1 subunit of the GABA(A) receptor was overexpressed in Escherichia coli and was found to have stable beta-rich structures. Here, results from laser scattering, gel electrophoresis and electron microscopy demonstrated that this recombinant protein formed rosette-like homo-oligomers, mainly pentamers in solution. Therefore, the fragment apparently provides a valuable model system for studying the pentameric holoreceptor assembly. Non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis of the fragment showed that disulfide bonds formed between monomers contributed to the oligomerization of the fragment. The fact that this fragment alone could form pentamers in vitro strongly suggests that amino acid residues located within the Cys166-Leu296 region of the alpha1 subunit may contribute to the oligomerization of GABA(A) receptor in vivo.

Animals↗

Congenital absence of permanent teeth in a six-generation Chinese kindred.

We report on rare, heritable, permanent tooth agenesis in a large Chinese kindred. The congenital absence of permanent teeth except the first and second accessory teeth was observed in 52 individuals through six successive generations in the kindred comprising 328 members. Clinical assessments were carried out, and inheritance mode and spousal influence of the anomaly on their offspring were analyzed. Consequently, the anomaly was transmitted in an autosomal dominant fashion with incomplete penetrance (P = 0.88), and no significant clinical manifestations other than the oligodontia were found. A geographical or environmental effect on the affected individuals was obviously eliminated, because any who are related to the kindred but live under the same conditions are fully healthy. The disorder we describe, therefore, differs from any previously reported oligodontia/anodontia syndromes. The oligodontia ranged from a few teeth to the whole set of teeth, and usually occurred at a period from age 7 or 8 years, the time when primary teeth are normally replaced by permanent teeth, to the forties. Roentgenography of the affected persons indicated that only the first and/or second accessory teeth with tooth buds developed as permanent teeth. In fact, the diphyodontic germination sometimes occurred in the oral cavity of the affected individuals.

China↗

[Weights in Horvitz-Thompson statistic for complex samples].

The problem of using ordinary statistical methods basically for simple random samples in analyzing data from complex surveys for non-simple random samples was discussed. Horvitz-Thompson statistic and the poststratification weights were introduced. Illustrative examples were given to show the validity and superiority of Horvitz-Thompson statistic in comparison with statistic used for simple random samples.

Bias↗

Elevated interleukin-6 expression in keloid fibroblasts.

Keloids are characterized by a net accumulation of collagen. To date, the role of growth factors and various cytokines in the pathogenesis of these lesions has not been fully characterized. Interleukin-6 (IL-6) is an important immunoregulatory cytokine that has been implicated in a number of fibrotic autoimmune diseases such as scleroderma, interstitial nephritis, and pulmonary interstitial fibrosis. However, the role of IL-6 in the development of keloids has yet to be defined. This study demonstrates increased expression of the IL-6 gene in fibroblasts isolated from patients with keloids when compared with control fibroblasts using the ribonuclease protection assay. Subsequent detection of increased levels of IL-6 secretion by keloid fibroblasts is also demonstrated under unstimulated and stimulated conditions using serum and interferon gamma (IFN-gamma) (unstimulated: 0.3694 + 0.2499 pg/cell vs 0.0662 + 0.0786 pg/cell, P = 0.0137; serum: 1.066 + 0.513 pg/cell vs 0.233 + 0.231 pg/cell, P = 0.0027; serum and IFN-gamma: 1.286 + 0.395 pg/cell vs 0.244 + 0.199 pg/cell, P < 0.0001). These results suggest that IL-6 may play a significant role in the pathogenesis of keloids.

Blood Physiological Phenomena↗

Quantification of diffusion distance within the spongy myocardium of hearts from antarctic fishes.

We developed a stereological method for quantifying diffusion distance within spongy myocardium. Using this method we compared the hearts of three species of Antarctic fishes that vary in expression of oxygen-binding proteins. We examined hearts from Gobionotothen gibberifrons, a red-blooded species whose ventricle has myoglobin (Mb), and hearts of two species of icefish that lack hemoglobin (Hb) and vary in expression of cardiac Mb; Chionodraco rastrospinosus expresses Mb, Chaenocephalus aceratus does not. Average diffusion distance within ventricular tissue is greater in red-blooded Antarctic teleosts (9.82 + or - 1.37 microm) compared with icefish (C. rastrospinosus, 6.20 microm + or - 0.86; C. aceratus, 6.23 + or - 0.41 microm). Average diffusion distance to a mitochondrion parallels this trend because mitochondria are uniformly distributed within cardiac muscle. Results show that loss of Hb is correlated with increased trabeculation of heart ventricle. Loss of Mb however, is not correlated with an increase in trabeculation of ventricular tissue, despite significant differences in cellular ultrastructure compared with species that express the protein.

Animals↗

The role of anti-tumor necrosis factor-alpha and interleukin-10 in protecting murine neonates from Escherichia coli sepsis.

BACKGROUND/PURPOSE: The neonate is at much higher risk for septic complications and death than the adult. Although some aspects of the infant's immune response are immature, others are fully functional. Many models of septic death are caused by an overexpression of proinflammatory cytokines. If there were inadequate down regulatory mechanisms, this could lead to an overexpression of proinflammatory cytokines. The authors hypothesized that the high mortality rate of the newborn was caused by overexpression of tumor necrosis factor (TNF-alpha) and that interleukin-10 (IL-10) would attenuate this response. The aim of this study was to determine if TNF-alpha plays an important role in early death from Escherichia coli sepsis in the newborn animal and if blocking TNF improves survival. METHODS: A dose response curve was determined for 1 day old C3H/HEN mice using 10(5) intraperitoneal E coli resulting in a 30% to 50% mortality rate. Litters of newborn (1 day old) C3H/HEN mice received a subcutaneous injection of either 25 or 50 ng of murine IL-10 or 20 microL of anti-TNF-alpha 4 hours before a bacterial challenge. Control animals received nothing. Animals were observed for 5 to 7 days. At least 6 litters (18 pups per group) were used for each regimen. RESULTS: Anti-TNF-alpha resulted in a significant improvement in survival rate compared with controls (100% v 53%, P < .001). In separate experiments, IL-10 at a dose of 25 ng failed to produce any improvement in survival; however, a 50-ng dose resulted in a significant improvement in treated animals compared with controls (95% v 65%, P < .01). CONCLUSIONS: TNF-alpha plays an important role in neonatal sepsis, suggesting that the newborn mouse is capable of mounting a significant proinflammatory response to gram-negative bacteria. Newborn mice may respond to bacterial challenge with an overexpression of proinflammatory cytokines or an underproduction of downregulating cytokines. Future attempts at immunomodulation in human infants must be undertaken with caution until the inflammatory response is better defined.

Animals↗

Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site.

A radioreceptor binding assay was used to guide the isolation of four chemical constituents in the organic solvent extracts of Scutellaria baicalensis Georgi capable of binding to the benzodiazepine site (BZD-S) of the GABAA receptor: wogonin (Ki = 2.03 +/- 0.24 microM), baicalin (Ki = 77.10 +/- 4.79 microM), baicalein (Ki = 5.69 +/- 0.95 microM), and scutellarein (Ki = 12.00 +/- 1.27 microM). All four compounds contain the flavonoid phenylbenzopyrone nucleus. Based on BZD-S binding, the order of affinity among these four compounds was wogonin > baicalein > scutellarein > baicalin.

Benzodiazepines↗

GABAagent: a system for integrating data on GABA receptors.

MOTIVATION: Scientific data pertaining to GABA receptors, which are of medical importance, are widely scattered throughout numerous heterogeneous Internet resources. This situation has made the integrated acquisition of such data difficult and substantially time consuming even for researchers who are Internet aficionados. Thus, there exists a genuine need for the development of Internet applications, such as GABAagent, which provide efficient and timely access to concise and integrated information. RESULTS: We report here the establishment of a novel server (GABAagent) which has been written in Perl script, and which is freely accessible through the Internet. GABAagent is designed to assist researchers in retrieving focused and integrated information related to GABA receptors from various public domain databases. GABAagent relies on server-side flat-file databases that have been created through data mining from Internet sources such as the PubMed, DDBJ, SWISS-PROT and TrEMBL, in addition to the many World Wide Web (Web) sites which are accessible through Excite (E-Web). These warehouse databases are regularly updated and contain among other things, information concerning: (i) GABA receptor publications, (ii) DNA and protein sequences and (iii) the contents of related E-Web sites along with their addresses. Our system also provides hard links to the above-mentioned Web sites and E-Web sites; the feature which adds to it the character of virtual federation type of database. The current version of GABAagent provides two user-friendly services. The first is a search engine possessing intelligent query reformulation support (GABAengine), the second an elaborate email alert service was designed into the system (GABAalert). The GABAengine allows the user to search server-side databases exclusively for GABA receptor-related queries. Whereas, GABAalert allows the user, by means of subscription, to receive immediate and/or monthly updates automatically. AVAILABILITY: GABAagent is freely accessible at the following Web address http://www.ust.hk/gaba.

Databases, Factual↗

An abundant DNA binding protein from the hyperthermophilic archaeon Sulfolobus shibatae affects DNA supercoiling in a temperature-dependent fashion.

The DNA binding protein Ssh10b, a member of the Sac10b family, has been purified from the hyperthermophilic archaeon Sulfolobus shibatae. Ssh10b constitutes about 4% of the cellular protein. Electrophoretic mobility shift assays showed that Ssh10b first bound a double-stranded DNA fragment with an estimated binding size of approximately approximately 12 bp, forming distinct shifts, until the DNA was coated with the protein. Binding of more Ssh10b resulted in the formation of smears of lower mobilities. The migration pattern of the smearing Ssh10b-DNA complexes was affected by temperature, whereas that of complexes associated with the distinct shifts was not. Interestingly, Ssh10b was capable of constraining negative DNA supercoils in a temperature-dependent fashion. While the ability of the protein to constrain supercoils was weak at 25 degrees C, it was enhanced substantially at 45 degrees C or higher temperatures (up to 80 degrees C). Taken together, our data suggest that archaeal proteins of the Sac10b family may affect the topology of chromosomal DNA in thermophilic archaea at their growth temperatures.

Amino Acid Sequence↗

Angiotensin II enhances beta-adrenergic receptor-mediated vasorelaxation in aortas from young but not old rats.

beta-Adrenergic receptor (beta-AR)-mediated (cAMP-dependent) vasorelaxation declines with advancing age. It has been shown that angiotensin II (ANG II), a potent vasoconstrictor, enhances cAMP-mediated vasorelaxation. Therefore, we questioned whether ANG II could reverse age-related, impaired beta-AR-mediated vasorelaxation and cAMP production. Pretreatment of aortic rings from 6-wk-old or 6-mo-old male Fischer 344 rats with ANG II significantly enhanced vasorelaxation induced by isoproterenol (Iso), a beta-AR agonist, and forskolin, a direct activator of adenylyl cyclase, but not dibutyryl-cAMP or isobutylmethylxanthine. The ANG II effect was blocked by losartan but not PD-123319 and was not observed in the aortas from 12- and 24-mo-old animals. Iso-stimulated cAMP production in the aorta was enhanced in the presence of ANG II in the 6-wk-old and 6-mo-old age groups only. Results suggest ANG II cannot reverse the age-related impairment in beta-AR-dependent vasorelaxation. We conclude aging may affect a factor common to both ANG II-receptors and beta-AR signaling pathways or aging may impair cross-talk between these two receptor pathways.

1-Methyl-3-isobutylxanthine↗

Complete genomic sequence of 195 Kb of human DNA containing the gene GABRG2.

GABA (gamma-aminobutyric acid), as the main inhibitory neurotransmitter in the brain, plays an essential role for the overall balance between neuronal excitation and inhibition by acting on GABAA receptors, which are ligand-gated chloride channels. Impaired GABAergic function contributes to certain forms of epilepsy, schizophrenia, Alzheimer's Disease, and other neurological disorders. In order to identify possible genetic features and to further study biological regulation of GABAA receptor genes whose promoter elements and sequence anomalies may contribute to epileptic disorders, as an initial step, we shot-gun sequenced a BAC clone, dj082c10 (195,909-bp in size), encompassing human gamma(2) subunit of GABAA receptor (GABRG2). It is, we believe, the first genomic sequence of the GABA receptor gamma subunit family. Four contigs were assembled from 2950 reads prior to gap in an average redundancy of eight folds over the entire region. The precision of the consensus sequence was predicted to be 99.999% after closing gaps and finishing weak regions. The nine exons of GABRG2 spans an 85-kb region that had 81 SINEs comprising 22.32%, and nine L1 elements comprising 3.40%, respectively. However, the density of L1 in the regions flanking GABRG2 gene (29.45% by 45 elements) is significantly higher than that within the gene. The length of GABRG2 introns varies in the range of 1.5 kb to 38.1 kb.

Amino Acid Sequence↗

[Construction of gene targeting vector for duplicating p35Nck5a gene and its application in the gene targeting of ES cells].

To duplicating the regulatory subunit p35Nck5a gene of mouse neuronal cdc2-like kinase in embryonic stem (ES) cells, about 12.2 kb of pGDTV vector for p35Nck5a gene duplication was constructed. The linearized pGDTV vectors were transfected into ES cells by electroporation. 245 drug-resistant cell clones were obtained in both G418 and GANC medium and the frequency of surviving cells was 6.22 x 10(-5). The ES cell clones were identified to have duplicated the p35Nck5a gene by use of both PCR and genomic Southern blotting, and the frequency of homologous recombination is 5.08 x 10(-7). The use of negative selection gene (HSV-tk) results in 7-fold increase at selection efficiency. This study lays the foundations of preparing mouse models of Alzheimer's disease.

Alzheimer Disease↗

[Effects of space conditions on mutation and inheritance of tomato].

OBJECTIVE: To study the effects of space conditions on mutation and inheritance of tomato. METHOD: Air-dried seeds of tomato were carried by a satellite for 7-15 d. These seeds were planted after returning. The mutagenic effects of space conditions on some of their variations of the botanical characteristics were studied. RESULT: Tomato dry seeds were carried to the outer space by satellite. After returned to the earth it was found that SP1 generation was of their germination percentage lower than the control. This physiological damage returned to normal in SP2 generation. Seeding isoenzyme, plant growth, resistance, and output, showed variation, and profitable variation had been expressed in later generations. The characters were expressed in the progenies. By observation and screen, promising line of tomato TF873, was obtained. CONCLUSION: It was suggested that space conditions induce profitable mutation of crop and it a possible way for plant mutation breeding.

Germination↗

[Portal anticoagulation in preventing thrombosis after porta-azygous devascularization for portal hypertension].

OBJECTIVE: To study the prevention method for thrombosis after porta-azygous devascularization for portal hypertension. METHODS: 71 patients with portal hypertension due to cirrhosis were divided into group A (36 patients) and group B (35 patients). In group A, a anticoagulation tube was inserted via splenic vein branch during shunt and anticoagulation therapy was given after operation. RESULTS: All the patients received color Doppler examination 3 months after operation. No thrombosis occurred in the group A and thrombosis occurred in 13 patients (37.14%) in the group B. CONCLUSION: Portal anticoagulation therapy is the effective in preventing portal thrombosis after porta-azygous devascularization for portal hypertension.

Administration, Oral↗

[Study on clinical and molecular biological characteristics of infant acute leukemia].

OBJECTIVE: To study the clinical and molecular biological characteristics of infant acute leukemia (IAL). METHODS: R and/or G banding technique was used for analysis of karyotype. DNA blotting for HRX gene rearrangement, and polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR) for fusion gene detection. RESULTS: Twenty cases of IAL were detected. HRX gene rearrangement was found in 10 cases, including HRX/AF-4 fusion gene in 5, HRX/AF-9 fusion in 2, and HRX/ENL fusion in 1, HRX self-fusion mediated by alu-repeat homologous recombination and HRX/EEN fusion each in one (HRX/EEN is a novel fusion gene reported for the first time). CONCLUSION: High frequency of HRX gene rearrangement occurred in IAL, which is characterised by a massive leukemia cell burden and 11q23 translocation, forming fusion genes, especially HRX/AF-4 (about 50%). The results are of important significance in guiding clinical treatment and approaching the etiology of IAL.

Acute Disease↗

HemT-3, an alternative transcript of mouse gene HemT specific to male germ cells.

A number of genes are known to be expressed primarily in hematopoietic cells and testis and are thought to function in the control of both blood cell and male germ cell differentiation. We have recently identified a mouse gene, HemT, that encodes two alternatively spliced transcripts specific to hematopoietic cells (HemT-1 and HemT-2) and kidney (HemT-2). We have now isolated a third HemT transcript, HemT-3, that is found only in testis by Northern blot analysis and RT-PCR. HemT-3 is alternatively spliced and may be initiated differently from HemT-1 and HemT-2. RNA in-situ hybridization of testis from wild-type and germ-cell-deficient adult mice, as well as from mice at different developmental stages, indicates that HemT-3 is expressed only in early spermatocytes. HemT-3 cDNA has a major open reading frame related to a human glycosylphosphatidylinositol (GPI)-anchored protein, GML. Using an antibody generated against a peptide derived from the HemT-3 open reading frame, we have detected a testis-specific 22kDa protein by Western blot analysis.

Alternative Splicing↗

A novel mouse gene, HemT, encoding an hematopoietic cell-specific transcript.

We performed differential display to identify hematopoietic cell-specific genes that are expressed differentially before and after mouse erythroleukemia cell (MELC) induction. In this study we report the identification, cloning, and characterization of one such mouse gene, HemT. Using Northern blot, RT-PCR and in situ hybridization, we show that HemT encodes three different transcripts. One of them, HemT-1, is hematopoietic-cell specific and may be erythroid cell-specific. Another, HemT-2, is expressed mainly in hematopoietic cells. HemT-1 and HemT-2 are alternative splicing products. A third type of HemT transcript is expressed only in testis. The erythroid transcript is expressed preferentially in uninduced MELC as compared to induced MELC, and is likely to be expressed in early erythroid cell populations.

Alternative Splicing↗