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Biomedical subjects

C Sun

Publications and source records attributed to C Sun.

At least 91 records · Page 5Linked to original sources

[Surgical treatment of malignant esophageal tumors in PUMC Hospital].

OBJECTIVE: To study how to prolong the postoperative survival time of the patients with malignant esophageal tumors. METHODS: The clinical data of 1,098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet(FHIT) gene(a tumor suppressor gene) in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT-PCR. RESULTS: The resectability was raised gradually and the operative morbidity and mortality decreased year-by-year, but there was no significant improvement on the postoperative 5-year survival rate. Delayed diagnosis and ir-radical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2% in esophageal cancer and 20% in the resected margin of the cancer. CONCLUSIONS: High atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are essential for the improvement of the postoperative survival time of the patients.

Acid Anhydride Hydrolases↗

Isolation and mapping of rFUS6, a rice orthologue of Arabidopsis thaliana FUS6.

COP9 complex is one of the most important components that act in repressing photomorphogenesis in Arabidopsis thaliana. FUS6 has been identified as one of eight subunits of the COP9 complex in Arabidopsis. Using Arabidopsis Fus6 cDNA as a probe, we screened a rice root cDNA library and a rice genomic library. A 1730-bp cDNA was obtained, which has an open reading frame corresponding to 441-amino-acid. This 441 amino acids putative protein has 67% identity with Arabidopsis COP11/FUS6 (AtFUS6) and 40% identity with human GPS1, an AtFUS6 orthologue. So we designated this novel gene as rFUS6. The 6.2-kb genomic sequence of rFUS6 was also obtained. Sequence comparison showed that the rFUS6 gene had six exons and five introns. Sequence inspection of the 5'-flanking region revealed the presence of some potential light-regulated cis-elements such as a G-box, GT-1 binding sites, and a TGACG motif. Southern hybridization with rice total DNA showed that rFUS6 was perhaps a single copy gene. The rFUS6 locus was mapped by hybridization with a rice BAC library membrane and the results showed that rFUS6 had a locus at 16.3 cM of chromosome 1.

Amino Acid Sequence↗

NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP.

The inhibitor-of-apoptosis (IAP) family of proteins, originally identified in baculoviruses, regulate programmed cell death in a variety of organisms. IAPs inhibit specific enzymes (caspases) in the death cascade and contain one to three modules of a common 70-amino-acid motif called the BIR domain. Here we describe the nuclear magnetic resonance structure of a region encompassing the second BIR domain (BIR2) of a human IAP family member, XIAP (also called hILP or MIHA). The structure of the BIR domain consists of a three-stranded antiparallel beta-sheet and four alpha-helices and resembles a classical zinc finger. Unexpectedly, conserved amino acids within the linker region between the BIR1 and BIR2 domains were found to be critical for inhibiting caspase-3. The absence or presence of these residues may explain the differences in caspase inhibition observed for different truncated and full-length IAPs. Our data further indicate that these residues may bind to the active site and that the BIR domain may interact with an adjacent site on the enzyme.

Amino Acid Sequence↗

The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains.

BACKGROUND: CBFA is the DNA-binding subunit of the transcription factor complex called core binding factor, or CBF. Knockout of the Cbfa2 gene in mice leads to embryonic lethality and a profound block in hematopoietic development. Chromosomal disruptions of the human CBFA gene are associated with a large percentage of human leukemias. RESULTS: Utilizing nuclear magnetic resonance spectroscopy we have determined the three-dimensional fold of the CBFA Runt domain in its DNA-bound state, showing that it is an s-type immunoglobulin (Ig) fold. DNA binding by the Runt domain is shown to be mediated by loop regions located at both ends of the Runt domain Ig fold. A putative site for CBFB binding has been identified; the spatial location of this site provides a rationale for the ability of CBFB to modulate the affinity of the Runt domain for DNA. CONCLUSIONS: Structural comparisons demonstrate that the s-type Ig fold found in the Runt domain is conserved in the Ig folds found in the DNA-binding domains of NF-kappaB, NFAT, p53, STAT-1, and the T-domain. Thus, these proteins form a family of structurally and functionally related DNA-binding domains. Unlike the other members of this family, the Runt domain utilizes loops at both ends of the Ig fold for DNA recognition.

Animals↗

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↗

Assessment of chromosome 8 copy number in cervical cancer by fluorescent in situ hybridization.

Cervical carcinoma is a malignancy which typically occurs at the transformation zone between squamous and glandular epithelium. The vast majority falls into two histologic types, squamous cell and adenocarcinoma. In an effort to identify a subset of cervical cancer characterized by chromosome 8 trisomy, a biomarker extensively explored by this laboratory, we conducted a study of formalin-fixed, paraffin-embedded materials of cervical cancer. A total of 24 cases of cervical cancer were identified from the archives of the Rhode Island Hospital. Fluorescent in situ hybridization (FISH) using a chromosome 8 centromere enumeration probe was conducted to assess the chromosome 8 copy number in these specimens. Hybridization signals were scored among tumor cells in a blinded fashion. Tumors with >/=15% of cells with three signals were scored as trisomic. Of 24 cases studied, 23 were informative. Of the 23 informative cases, 12 (52.2%) were found to be trisomic. Eleven cases (47.8%) were disomic. The frequency of trisomy in a control chromosome 17 probe was 13.0% (3/23). Selected clinicopathologic characteristics of the tumors were also reviewed. The frequency of trisomy 8 among cases of invasive squamous cell carcinoma was 44.4% (8 of 18 tumors) and that of invasive adenocarcinoma was 80% (4 of 5 tumors). The sole tumor which was both trisomic 8 and amplified for the HER-2/neu oncogene was found to be an invasive adenocarcinoma. While the sample size in this pilot study is not large, the data obtained thus far clearly demonstrate that FISH is an appropriate technique for detecting chromosomal trisomies and that a subset of cervical cancer exists that is characterized by chromosome 8 trisomy. Further exploration of this biomarker is warranted.

Adenocarcinoma↗

Inflammatory modulation of calcium-activated potassium channels in canine colonic circular smooth muscle cells.

BACKGROUND & AIMS: The characteristics of colonic circular smooth muscle slow waves are altered during inflammation. The aim of this study was to examine whether inflammation modulates the open-state probability of Ca2+-activated K+ (KCa) channels in these cells to contribute to these alterations. METHODS: The experiments were performed on freshly dissociated single smooth muscle cells from the canine colon using standard patch clamp methods. Inflammation was induced by mucosal exposure to ethanol and acetic acid. RESULTS: Inflammation decreased the open-state probability of large-conductance KCa (BK) channels in the cell-attached and excised inside-out configurations. The voltage sensitivity of the channels was also reduced during inflammation. Inflammation had no significant effect on the large, medium, and small conductances or the unitary current levels of channel openings. However, it decreased the maximum number of simultaneous channel openings. The channels were Ca2+-dependent and were blocked by tetraethylammonium and charybdotoxin in normal and inflamed cells. CONCLUSIONS: Inflammation decreases the open-state probability of BK channels. This may partially reverse the decrease in duration and amplitude of slow waves and depolarization of membrane potential seen in inflammation.

Animals↗

Analyses of isoamylase gene activity in wild-type barley indicate its involvement in starch synthesis.

The notion of debranching enzyme activity as a participant in starch synthesis is gaining acceptance. Inconsistent reports from mutant analyses implicate either isoamylase or pullulanase as a determinant in amylopectin formation and whether wild-type plants utilize one or the other, or both, of these debranching enzymes in starch synthesis is unclear. Recent results on the sul mutant in maize suggest that both forms of debranching enzymes might be involved in amylopectin formation. We wished to find out if isoamylase takes part in starch synthesis by comparing isoamylase gene activity under three conditions: (1) during starch accumulation in developing sink tissues; (2) during starch degradation in germinating seeds; (3) in ectopic expression after applying sucrose, a starch precursor. We isolated the gene for barley isoamylase, isol, and analysed its expression and regulation in germinating seeds, developing endosperm and vegetative tissues, and compared the isoamylase gene expression in sink tissues from three different species. Our results indicate that isoamylase gene activity is involved in starch synthesis in wild-type plants and is modulated by sucrose.

Amino Acid Sequence↗

Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM.

Proximal myotonic myopathy (PROMM) was first described in 1994 as a multisystem disorder with similarity to myotonic dystrophy (DM), but without the abnormal (CTG)n expansion in the DM protein kinase (DMPK) gene. The inheritance is autosomal dominant and the clinical features include myotonia, proximal muscle weakness and cataract. Linkage analysis in nine German PROMM families has indicated the possibility of linkage to DM2 locus on chromosome 3. We report a Norwegian PROMM family in which the proband was clinically diagnosed as DM but without the (CTG)n expansion. Using an intragenic marker we showed that the DMPK gene did not segregate with the disease in this family. All family members are heterozygous for the R894X mutation in CLCN1 gene. Linkage analysis could not be performed, but haplotyping probably excludes the DM2 locus as the disease locus in this family. The present family emphasises that myalgia is a prominent symptom in PROMM and the clinical differences may be explained by genetic heterogeneity. This family will be reinvestigated along with the identification of candidate genes or regions in larger PROMM families.

Adult↗

An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y.

In humans, deletion of any one of three Y-chromosomal regions- AZFa, AZFb or AZFc-disrupts spermatogenesis, causing infertility in otherwise healthy men. Although candidate genes have been identified in all three regions, no case of spermatogenic failure has been traced to a point mutation in a Y-linked gene, or to a deletion of a single Y-linked gene. We sequenced the AZFa region of the Y chromosome and identified two functional genes previously described: USP9Y (also known as DFFRY) and DBY (refs 7,8). Screening of the two genes in 576 infertile and 96 fertile men revealed several sequence variants, most of which appear to be heritable and of little functional consequence. We found one de novo mutation in USP9Y: a 4-bp deletion in a splice-donor site, causing an exon to be skipped and protein truncation. This mutation was present in a man with nonobstructive azoospermia (that is, no sperm was detected in semen), but absent in his fertile brother, suggesting that the USP9Y mutation caused spermatogenic failure. We also identified a single-gene deletion associated with spermatogenic failure, again involving USP9Y, by re-analysing a published study.

Base Sequence↗

Plutonium fecal and urinary excretion functions: derivation from a systemic whole-body retention function.

Liver-bile secretion directly influences the content of plutonium in feces. To assess the reliability of plutonium metabolic models and to improve the accuracy of interpreting plutonium fecal data, we developed a compartmental model that simulates the metabolism of plutonium in humans. With this model, we can describe the transport of plutonium contaminants in the systemic organs and tissues of the body, including fecal and urine excretions, without using elaborate kinetic information. The parameter values of the models, which describe the translocation rates and recycling of plutonium in the body, can be derived from a multi-term exponential systemic function for whole-body retention. The analytical derivations and algorithms for solving translocation parameter values are established for the model and illustrated by applying them to the biokinetics and bioassay of plutonium. This study describes how to (1) design a physiological model for incorporating liver biliary secretion and for obtaining a fecal-excretion function, (2) develop an analytical solution for identifying the translocation-parameter values incorporating the recycling of plutonium in the body, and (3) derive a set of urinary and fecal excretion-functions from a published systemic whole-body retention function, generally acknowledged to be accurate, as a real and practical example.

Algorithms↗

Isolation of cDNAs encoding gibbon and monkey platelet and T cell activation antigen 1 (PTA1).

Human platelet and T cell activation antigen 1 (PTA1) is a 67kDa type I transmembrane glycoprotein mainly expressed on the surface of activated T cells and platelets, and is involved in the development of human cytotoxic T cell (CTL) as well as platelet activation and aggregation. We have cloned and sequenced gibbon PTA1 (gPTA1) and monkey PTA1 (mPTA1) cDNAs by RT-PCR from gibbon leukemic cell line MLA 144 and PHA-induced Rhesus monkey PBMC respectively. The mature proteins of gPTA1, mPTA1 and human PTA1 (hPTA1) share 93-95% amino acid similarity with the highest similarity in domain 1 of extracellular region. All the important features of PTA1 molecule are conserved among these Primates: (1) the ORF encoding 336 amino acid residues including signal sequence (18aa), extracellular region (232aa), transmembrane sequence (25aa) and cytoplasmic region (61aa); (2) two conserved pairs of Cys (Cys19 to Cys90 and Cys134 to Cys204) forming disulfide bonds stabilizing the two immunoglobulin superfamily V-like domains; (3) eight putative N-linked glycosylation sites (except gPTA1 with nine sites) and three O-linked glycosylation sites in extracellular region; and (4) predicated protein kinase C phosphorylation sites (Thr275 and Ser311), casein kinase II sites (Ser295 and The299) and the potential tyrosine phosphorylation site (Tyr304). These data indicate that PTA1 molecule is highly conserved among the Primates and may play important roles in immune response.

Amino Acid Sequence↗

Improved fusion partners transfected with DNA fragment encoding IL-11 on generation of human B lymphocyte hybridomas.

IL-11, a less identified cytokine, possesses some overlapping functions with IL-6 that are able to facilitate the growth and antibody secretion of B lymphocyte hybridomas. In this report, a DNA fragment encoding human IL-11 was transduced into fusion partners (mouse myelomas Ag8.653 and SP2/0, and human lymphoblastoid cell line HF2) mediated by lipofection. The transfected cells selected with G418 secreted IL-11 constitutively over the range of 32.4 +/- 10.5 units/ml to 76.6 +/- 18.4 units/ml, which could be inhibited by an IL-11 neutralizing MAb up to 80%. The fusion frequency of PBMC doubled, while that of LCLs displayed a 2.4- or 3.3-fold increase, when fused with the transfected fusion partners, respectively. The derived hybridomas from IL-11 secreting fusion partner secreted 3 or 4 times as many immunoglobulins as that from its ancestor. Our data indicate that IL-11 gene transfected fusion partners are improved cell lines for generation of human B lymphocyte hybridomas, and IL-11 may contribute to the increased fusion frequency and antibody secretion of B lymphocyte hybridomas.

Animals↗

Use of the Maxwell-Brancheau arthroereisis implant for the correction of posterior tibial tendon dysfunction.

Successful management of the flexible flatfoot deformity relies not only on correcting causal factors, but also on addressing the adaptive changes that have occurred and any coexisting deformities present. The three primary goals of any therapy--relief of pain, biomechanical control of excessive pronation, and prevention of the progression of the deformity--should be considered. With thorough assessment of causal factors and planal dominance of the deforming and compensative forces, one can expect to increase the predictability and success of the surgical management of PTTD in the flexible adult flatfoot deformity.

Adult↗

Purification and properties of genetic expressing product of thermostable protease from Bacillus stearothermophilus HY-69.

The thermostable metal protease gene from Bacillus stearothermophilus HY-69 had been cloned and expressed in Bacillus subtilis MI113. The genetic expressing product of the enzyme was purified by CM-cellulose chromatography. The product shows homogeneity on PAGE. Its molecular weight is 27,000 +/- 1000 by SDS-PAGE and Sephadex G100 filtration, respectively. The alpha-helix content of the protease is estimated to be about 66%, the beta-turn about 28%, the random coil about 6%, but not beta-sheet, calculated from the circular dichroism data. The optimal temperature of the enzyme was 70 degrees C. When the enzyme was denatured in 3 mol/L of Gdn--HCl in phosphate buffer pH6.0 for 20 min, it remained about 40% of original activity. It shows that it is rather resistant to heat and Gdn-HCl denaturation. Its conformational variety coursed by Gdn-HCl was investigated by the far UV circular dichroism and fluorescence spectra. The results show that the enzyme has more compact conformation and internal hydrophobility.

Amino Acids↗

Detection of neuroendocrine feature about salivary adenoid cystic carcinoma.

OBJECTIVE: To study the possibility of neuroendocrine feature of salivary adenoid cystic carcinoma (SACC). METHODS: Immunohistochemical staining was operated in SACC with S-100 protein, neurospecific enolase (NSE), chromogranin A, and synaptophysin, which are specific and correlative with neuroendocrine cells and neoplasias. RESULTS: The positive expression of S-100, NSE, chromogranin, and synaptophysin were 42, 32, 8, and 7, respectively, in 50 cases of SACC. CONCLUSION: Neuroendocrine feature in some SACC cells is possibly indicated.

Adolescent↗