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Biomedical subjects

H Xin

Publications and source records attributed to H Xin.

At least 37 records · Page 2Linked to original sources

Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines.

Four different human breast cancer cell lines were examined to search for genes associated with tumor growth and metastasis. Each of these cell lines, MDA-MB-453, MCF-7, MDA-MB-231 and MDA-MB-435, displays different phenotypic characteristics ranging from poorly to highly tumorigenic and metastatic. The differences in gene expression profiles of these cell lines generated by differential display technique should allow one to identify candidates as putative oncogenes or tumor/metastasis suppressor genes. A novel cDNA expressed in the highly tumorigenic and metastatic cell line, MDA-MB-435, was identified and isolated by this approach. The function for this gene, designated ALP56 (aspartic-like protease 56 kDa), in tumor progression is suggested by the homology of the encoded protein to aspartic proteases, such as cathepsin D. The amino acid residues in two catalytic domains of this family are highly conserved in those domains of ALP56. Northern hybridization indicated that the expression of ALP56 is associated with growth and metastasis of MDA-MB-435 tumors in immunodeficient mice. In situ hybridization of biopsies from breast cancer and colon cancer patients indicated that ALP56 is upregulated in human primary tumors and liver metastasis. These results suggest that this novel gene correlates with human tumor progression.

Amino Acid Sequence↗

Cytoplasmic localization of the interferon-inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200-gene family.

While interferons (IFNs) (alpha, beta and gamma), a family of cytokines, have the ability to exert the growth-inhibitory effect on target cells, the molecular mechanism(s) by which IFNs inhibit cell growth remains to be identified. Because IFN-inducible 'effector' proteins mediate the biological activities of IFNs, characterization of IFN-inducible proteins is critical to identify their functional role in IFN action. One family (the 200-family) of IFN-inducible proteins is encoded by structurally related murine (Ifi202a, Ifi202b, Ifi203, Ifi204 and D3) and human (IFI16, MNDA and AIM2) genes. The proteins encoded by genes in the family share a unique repeat of 200-amino acids and are primarily nuclear. The AIM2 gene is a newly identified gene that is not expressed in a human melanoma cell line. Here we report that AIM2 is estimated to be a 39 kDa protein and, unlike other proteins in the family, is localized primarily in the cytoplasm. Interestingly, overexpression of AIM2 in transfected cells retards proliferation and, under reduced serum conditions, increases the susceptibility to cell death. Moreover, AIM2 can heterodimerize with p202 in vitro. Together, these observations provide support to the idea that AIM2 may be an important mediator of IFN action.

Amino Acid Sequence↗

Alanine mutagenesis of high-mobility-group-protein-1 box B (HMG1-B).

We have generated a set of alanine-scanning substitutions in high-mobility-group protein 1 box B (HMG1-B; the second domain of the HMG1 nuclear protein from the rat) in order to explore the influence of specific surface side chains on its function and folding. Guanidine hydrochloride and thermal unfolding studies have been carried out to investigate the effect of substituted residues on the folding pathway. Binding to four-way junction and linear-duplex DNA has been assayed to determine which residues play an important role in DNA binding. We have identified several mutants that are more stable or bind more tightly to the junction than the wild-type, including the particular phenylalanine side chain that is thought to intercalate into the DNA. Thus the interaction between HMG1-B and branched DNA substrates should exhibit differences from present models based on the structure of the complexes that have been solved to date.

Alanine↗

Sporadic trichoepithelioma demonstrates deletions at 9q22.3.

BACKGROUND: Trichoepithelioma (TE) is a benign cutaneous tumor that originates from hair follicles and occurs either in multiple or solitary lesions. Multiple TE is transmitted as an autosomal dominant trait, and a region at 9p21 is thought to be involved in the tumorigenesis. Solitary TE occurs more commonly than multiple TE and is not inherited. Histologically, TE tumors contain horn cysts and abortive hair papillae. A basal cell carcinoma appearance in some or all regions of a TE tumor can happen. In sporadic basal cell carcinoma, frequent deletions at 9q22.3 (Drosophila patched gene) have occurred. The objective of this study is to test whether loss of heterozygosity (LOH) on either 9p21 or on chromosome 9q22.3 could be detected in archival sporadic TE. OBSERVATIONS: We studied 29 randomly selected cases of sporadic TE by microdissection and polymerase chain reaction using paraffin-embedded, formalin-fixed tissue specimens on glass slides. Analysis was performed with the polymorphic markers IFNA and D9S171 (9p21) as well as D9S15, D9S303, D9S287, and D9S252 (9q22.3). RESULTS: The LOH at 9q22.3 was identified in 14 (48%) of 29 cases with at least 1 marker, while LOH could not be demonstrated using the markers IFNA and D9S171 (9p21). CONCLUSIONS: The results show that the Drosophila patched gene LOH can be frequently identified in paraffin-embedded sporadic TE after routine processing and indicates a common gatekeeper mechanism for both TE and basal cell carcinoma.

Chromosomes, Human, Pair 9↗

Formation of N-(Nitrosomethyl)urea in stomachs of experimental pigs and human volunteers given fish sauce in vivo.

N-(Nitrosomethyl)urea (NMU) was characterized in carcinogenic nitrosated fish sauce recently (Deng et al. J. Agric. Food Chem. 1998, 46, 202-205; Biomed. Environ. Sci. 1999, 12, 54-61). To study the possibility of intragastric synthesis of NMU, experimental mini-pigs surgically fitted with a flexible stomach cannula and human volunteers were used. Fish sauce samples (20-30 mL) and nitrite were injected into the gastric lumen through the cannula for pigs or taken orally for human volunteers. Gastric juice samples were taken out 30 min later. Concentration of NMU in condensed extracts of these samples was analyzed with HPLC-photohydrolysis-pyrolysis-thermal energy analyzer. Results showed that there was formation of NMU in the gastric lumen of both models in vivo and that the formation of NMU was nitrite- and pH-dependent. NMU was also detectable in the condensed extract of 100 mL of a mixture of pooled fasting human gastric juice samples and fish sauce sample (9:1, v/v) after treatment with 500 micromol/L of nitrite in vitro. In conclusion, there is intragastric formation of NMU, even at natural amounts of nitrite.

Adult↗

Allelic deletion at 9p21-22 in primary cutaneous CD30(+) large cell lymphoma.

The genetic alterations responsible for the development of cutaneous lymphoma are largely unknown. Chromosome region 9p21 contains a gene locus encoding an inhibitor of cyclin-dependent kinase 4, and heterozygous deletions of this tumor suppressor gene (p16) have been shown in a variety of malignant tumors. We studied 11 randomly selected cutaneous CD30-positive large cell lymphomas. Several areas containing 20-50 CD30-positive lymphocytes were microdissected in each case and subjected to single-step DNA extraction. Loss of heterozygosity analysis was performed using polymorphic markers at 9p21 (IFNA, D9S171, D9S169) and 17p13 (TP53). Samples from normal cells apart from CD30-positive lymphocytes, e.g., CD30-negative lymphohistiocytic infiltrates and normal epidermal layer, were also obtained in all cases from the same slide for comparison with the tumor samples. Expression of CD30 and T-lineage antigens (CD3, CD45Ro) was confirmed in all cases. Immunohistochemical staining for p16 and p53 was performed using the monoclonal antibodies sc-1661 and DO-7, respectively. Of the 11 informative cases, seven (64%) exhibited loss of heterozygosity at least for one marker at 9p21 (p16), whereas no allelic deletions were found for the polymorphic marker at 17p13 (p53). On immunohistochemistry loss of the p16 protein was detected in two of 11 cases. Nuclear staining for p53 protein was found in four of 11 cases. Here, we provide the first evidence of the involvement of the tumor suppressor gene p16 in primary cutaneous large cell lymphoma. Whether p16 deletion in these lymphomas is associated with disease progression and whether this method could serve as an early marker to detect lymphomas at an early stage needs to be addressed in future studies. J Invest Dermatol 115:1104-1107 2000

Adult↗

Natrinema versiforme sp. nov., an extremely halophilic archaeon from Aibi salt lake, Xinjiang, China.

A novel extremely halophilic archaeon, strain XF10T, was isolated from a salt lake in China. This organism was neutrophilic, non-motile and pleomorphic, and was rod, coccus or irregularly shaped. It required at least 1.5 M NaCl for growth and grew in a wide range of MgCl2 concentrations (0.005-0.5 M). Lipid extract of whole cells contained two glycolipids with the same chromatographic properties as two unidentified glycolipids found in the two described Natrinema species, Natrinema pellirubrum and Natrinema pallidum. Phylogenetic analysis based on 16S rDNA sequence comparison revealed that strain XF10T clustered with the two described Natrinema species and several other strains (strains T5.7, GSL-11 and Haloterrigena turkmenica JCM 9743) with more than 98.1% sequence similarities, suggesting that strain XF1OT belongs to the genus Natrinema. Comparative analysis of phenotypic properties and DNA-DNA hybridization between strain XF10T and the Natrinema species supported the conclusion that strain XF10T is a novel species within the genus Natrinema. The name Natrinema versiforme sp. nov. is proposed for this strain. The type strain is XF10T (=JCM 10478T=AS 1.2365T=ANMR 0149T).

Base Composition↗

Coherent resonance in a one-way coupled system

We describe the resonancelike behavior of a cooperative phenomenon involving noise, nonlinear systems with intrinsic limit cycle dynamics, and coupling in the absence of an external signal. We show that coupling can significantly sustain the propagation of coherent resonance with considerable enhancement or suppression along a one-way chain. In addition, coherent resonance can occur without tuning for a proper noise level and coupling constant.

Journal Article↗

Image-processing algorithms for behavior analysis of group-housed pigs.

Computational algorithms of image processing were developed and evaluated to select, by motion detection, images of resting artificial pigs and to segment the pigs (mixture of black and white pigs) from their background. Motion detection of the pigs was implemented by detecting interframe differences of postural behavioral images. This algorithm combines the advantages of likelihood ratio method and shading model method and shows a stable performance under noisy and dynamic illumination conditions. Segmentation of the pigs from their background was implemented by employing multilevel thresholding and background reference techniques. The algorithm automatically determines the number of thresholds needed and produces satisfactory segmentation when both black and white pigs with different image intensities are present at the same time (the most complicated situation). The reference background image is updated so that temporal changes in illumination and/or spatial changes of the pen condition have little effect on the performance of image segmentation. The algorithm employs statistical models of the pigs and background and Bayes hypothesis testing to obtain and update the exposed portion of the reference background. Linear filters were used in this process for updating the parameters. These algorithms will serve as essential components for a novel, behavior-based, interactive approach to assess and control thermal comfort of group-housed pigs, which is expected to result in enhanced animal health and well-being.

Algorithms↗

p202 levels are negatively regulated by serum growth factors.

p202 is an IFN-inducible phosphoprotein (Mr 52,000) whose expression in transfected cells retards proliferation. Interestingly, the reduced levels of p202 in fibroblasts (in consequence of the expression of antisense to 202 RNA), under reduced serum conditions, increase the susceptibility of cells to apoptosis. To identify the functional role of p202 in cell growth regulation, we tested whether serum growth factor levels in the culture medium affect p202 levels. Here we report that, under reduced serum conditions, the p202 levels were increased in fibroblasts, and the increase was seen at both the mRNA and protein levels. Moreover, an increase in p202 levels was correlated with cell growth arrest in the G1 phase of the cell cycle. Interestingly, the presence of platelet-derived growth factor AB, basic fibroblast growth factor, or transforming growth factor beta1 in the culture medium abrogated the increase in p202 levels seen under reduced serum conditions. We found that the increase in p202 levels was accompanied by an increase in JunD/activation protein 1(AP-1) levels, and transfection of a JunD-encoding plasmid along with a reporter plasmid in which transcription of the reporter gene (luciferase) was driven by the 5'-regulatory region of the 202 gene resulted in an increase in the activity of luciferase. Additionally, stable overexpression of JunD in cells, under reduced serum conditions, also resulted in an increase in p202 levels. Interestingly, one of the AP-1-like DNA-binding sequences present in the 5'-regulatory region of the 202 gene could selectively bind to the JunD/AP-1 transcription factor. Taken together, our observations reported herein suggest that in fibroblasts, under reduced serum conditions, the increased levels of JunD/AP-1 contribute to the transcriptional up-regulation of p202 levels, which may be important for the regulation of apoptosis.

Animals↗

[The effect of temperature on the structure and properties of polyurethane-urea by FTIR].

The effect of temperature on the structure and properties of polyurethane-urea was investigated by in situ FTIR. Data from FTIR spectra showed that with increasing temperature the nu NHHbonded areas decrease and the nu NHfree band areas increase. The band site of nu NHHbonded shifted to higher wavenumbers and the band site of nu NHfree keeps constant. The band site of Cfree urethane shift from 1,731 cm-1 to 1,736 cm-1. All kinds of carbonly bands sites shifted to high wavenumbers. But the band sites of amide II and the C=C in aromatic ring shifted to low wavenumbers. The properties of PUU polymers was determined by the structure of soft domains.

Polyurethanes↗

The human REV1 gene codes for a DNA template-dependent dCMP transferase.

DNA is frequently damaged by various physical and chemical agents. DNA damage can lead to mutations during replication. In the yeast Saccharomyces cerevisiae, the damage-induced mutagenesis pathway requires the Rev1 protein. We have isolated a human cDNA homologous to the yeast REV1 gene. The human REV1 cDNA consists of 4255 bp and codes for a protein of 1251 amino acid residues with a calculated molecular weight of 138 248 Da. The human REV1 gene is localized between 2q11.1 and 2q11.2. We show that the human REV1 protein is a dCMP transferase that specifically inserts a dCMP residue opposite a DNA template G. In addition, the human REV1 transferase is able to efficiently and specifically insert a dCMP opposite a DNA template apurinic/apyrimidinic (AP) site or a uracil residue. These results suggest that the REV1 transferase may play a critical role during mutagenic translesion DNA synthesis bypassing a template AP site in human cells. Consistent with its role as a fundamental mutagenic protein, the REV1 gene is ubiquitously expressed in various human tissues.

Amino Acid Sequence↗

A novel calmodulin-like protein gene in rice which has an unusual prolonged C-terminal sequence carrying a putative prenylation site.

A rice cDNA encoding a novel calmodulin-like protein was identified. It has 38 additional amino acids at the C-terminus of a complete, typical calmodulin (CaM) sequence of 149 amino acids. The four C-terminal amino acid residues form a CAAL motif which could be a site for protein prenylation and may subsequently cause the protein to become membrane associated. RT-PCR analysis confirmed that such a combined protein gene truly exists in rice. Sequence analysis of its genomic counterpart showed that there is an intron located at junction of the normal CaM sequence and the 38 C-terminal amino acids. This introduces a potential stop codon for normal CaM if an alternative splicing mechanism is involved. Southern blot analysis of rice genomic DNA revealed that there is only one locus for this gene. The northern blot analysis showed that this gene is highly expressed in rice roots, shoots and flowers. The distribution of this protein demonstrates the functional importance of this novel CaM-like protein in rice.

Amino Acid Sequence↗

The sebaceous nevus: a nevus with deletions of the PTCH gene.

Sebaceous nevi (SN) are congenital malformations of the skin with the potential to develop into basal cell carcinoma (BCC). To date, the molecular basis for their carcinogenic potential remains unknown. The genetic defect in BCC is known and involves the human homologue of Drosophila patched (PTCH) on chromosome 9q22.3. The objective of this study was to test whether allelic deletion of the PTCH gene could already be detected in SN. Twenty-one paraffin-embedded SN were investigated in this study. Basaloid cells in conjunction with mature sebaceous glands as well as epidermal layer apart from SN were microdissected and subjected to single-step DNA extraction. We performed the analysis with polymorphic markers at 9q22.3 (D9S15, D9S252, D9S287, and D9S303). Of the 20 informative SN, 8 (40%) exhibited loss of heterozygosity at least at one locus. Here, we provide the first evidence of the involvement of the tumor suppressor gene PTCH in SN. Whether PTCH deletion in SN is associated with progression to BCC and/or other appendageal tumors should be addressed in future studies.

Basal Cell Carcinoma↗

[Cytogenetic aspects of malignant melanoma].

In analogy to colon carcinoma, where a stepwise accumulation of genetic changes have been described during tumor progression, a sequence of genetic events may be responsible for the transformation of melanocytes to dysplastic nevi and melanoma with horizontal and vertical growth phases and finally the formation of distant metastases. The current literature supporting this concept as well as own contributions are presented.

Cell Transformation, Neoplastic↗

Noise-induced oscillation and stochastic resonance in an autonomous chemical reaction system.

An autonomous three-variable chemical reaction model, which has been developed to describe kinetic oscillations in the NO+CO reaction, subjected to external parametric noise, is investigated. Noise-induced coherent oscillations (NICO's) in the absence of deterministic oscillations are observed near supercritical Hopf bifurcation points, and the NICO strength goes through a maximum with increments of noise intensity, characteristic of the occurrence of stochastic resonance. On the other hand, these phenomena do not appear if the limit cycle is created by a saddle-loop bifurcation.

Journal Article↗

Primary choledochorrhaphy after common bile duct exploration.

AIM: To prove further the safety of primary closure of the common bile duct. METHOD: Twenty patients among 99 common bile duct explorations underwent primary closure. Pre- and postoperative liver function test, ultrasound and intraoperative cholangiography data, operation time, postoperative complications and the length of postoperative stay were recorded. RESULTS: Nineteen patients did not suffer any biliary complication. One had bile leakage and bile peritonitis, and another had duodenal leakage. One case was complicated by gastric ulcer perforation. The mean postoperative hospital stay except for the 2 patients with complications was 8.72 +/- 0.75 days. Preoperative abnormal liver function tests recovered within 2-3 weeks after the operation. Postoperative ultrasound scan of the biliary tract within 2 months revealed no stenosis and residual stone. CONCLUSION: Primary common bile duct closure is a safe alternative to routine biliary drainage in selected patients.

Adult↗

Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique.

We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when hydroxypropylmethylcellulose and hydroxypropylmethylcellulose phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8 h. Gastric acidity-controlled rabbits were used to evaluate the variation in absorption after oral administration of the albendazole solid dispersion. For rabbits with low gastric acidity the bioavailability of orally administered albendazole in the granular form prepared by solid dispersion was more than three times that of albendazole in physical mixtures. These results suggest that the bioavailability of albendazole in solid dispersions might be high even if there is a great variation in the gastric pH of patients.

Administration, Oral↗