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Biomedical subjects

G Pan

Publications and source records attributed to G Pan.

At least 19 recordsLinked to original sources
PubMed1998

Identification and functional characterization of DR6, a novel death domain-containing TNF receptor.

Tumor nectosis factor (TNF) receptors are key players in inflammation and immune regulation. A new member of this family, termed death receptor-6 (DR6), has been identified. Like other death receptors, DR6 is a type I transmembrane receptor, possesses four extracellular cysteine-rich motifs and a cytoplasmic death domain. DR6 is expressed in most human tissues and abundant transcript was detected in heart, brain, placenta, pancreas, thymus, lymph node and several non-lymphoid cancer cell lines. DR6 interacts with TRADD, which has previously been shown to associate with TNFR1. Furthermore, ectopic expression of DR6 in mammalian cells induces apoptosis and activation of both NF-kappaB and JNK.

Amino Acid Sequence↗
PubMed1998

Activation of caspases triggered by cytochrome c in vitro.

Previous studies have shown that Apaf-1 and caspase-9 in the presence of cytochrome c and dATP can form an initiating complex for an apoptotic protease cascade. We have developed a cytochrome c-dependent in vitro system in which caspases downstream of this initiation complex are activated. The activation of caspase-9 from zymogen form to active dimeric protease requires intrinsic enzymatic activity. In contrast, caspase-3 and caspase-7 zymogens are proteolytically processed by active caspase-9. Activation of the above caspases is blocked by a dominant negative form of caspase-9. The in vitro system displays surprising specificity in that other caspases, including 1, 2, 4, 8, 10, and 13, are not activated.

Animals↗
PubMed1998

TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signalling.

TRAIL/Apo-2L induces rapid apoptosis of a variety of tumor cell lines. A family of tumor necrosis factor receptor-related molecules have been identified as receptors for TRAIL. Herein, we report the identification of another member of the TRAIL receptor family, TRUNDD (TRAIL receptor with a truncated death domain). The TRUNDD transcript was detected in multiple human tissues. TRUNDD is highly homologous to all known TRAIL receptors and has an extracellular TRAIL-binding domain but lacks a functional intracellular death domain and does not induce apoptosis. Consistent with an inhibitory role, ectopic expression of TRUNDD attenuated TRAIL-induced apoptosis in mammalian cells.

Amino Acid Sequence↗
PubMed1998

Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex.

Genetic analysis of apoptosis in the nematode Caenorhabditis elegans has revealed the cell death machine to be composed of three core interacting components. CED-4 (equivalent to mammalian Apaf-1) is a nucleotide binding molecule that complexes with the zymogen form of the death protease CED-3, leading to its autoactivation and cell death. CED-9 blocks death by complexing with CED-4 and attenuating its ability to promote CED-3 activation. An equivalent ternary complex was found to be present in mammalian cells involving Apaf-1, the mammalian death protease caspase-9, and Bcl-XL, an anti-apoptotic member of the Bcl-2 family. Consistent with a central role for caspase-9, a dominant negative form effectively inhibited cell death initiated by a wide variety of inducers.

Antibodies↗
PubMed1998

Occupational lung diseases and global occupational health on the Net.

Occupational lung disease is a major area of concern in occupational health, exhibiting a diverse panorama across countries. While pneumoconiosis is deemed to be the most common occupational disease in many developing countries, emphasis is shifting towards asbestos-related lung diseases and occupational asthma in industrialized countries. Following the Occupational Health for All strategies set forth by the World Health Organization, we propose that a model system based upon the Global Health Network can serve as an effective vehicle towards the prevention of occupational lung diseases on a global scale. It has the potential to: (1) enhance transmission of data and collaboration with the primary health care system in disease surveillance; (2) strengthen research and information transfer and (3) promote education and training at all levels of prevention, with a possible application to the interpretation of chest radiograms.

Computer Communication Networks↗
PubMed1998

Analytic assessment of the various bioimpedance methods used to estimate body water.

Knowledge of patient fluid distribution would be useful clinically. Both single-frequency (SF) and impedance modeling approaches are proposed. The high intercorrelation between body water compartments makes determining the best approach difficult. This study was conducted to evaluate the merits of an SF approach. Mathematical simulation was performed to determine the effect of tissue change on resistance and reactance. Dilution results were reanalyzed, and resistance and parallel reactance were used to predict the intracellular water for two groups. Results indicated that the amount of intracellular and extracellular water conduction at any SF can vary with tissue change, and reactance at any SF is affected by all tissue parameters. Modeling provided a good prediction of dilution intracellular and extracellular water, but an SF method did not. Intracellular, extracellular, and total body water were equally predicted at all frequencies by SF resistance and parallel reactance. Extracellular and intracellular water are best measured through modeling, because only at the zero and infinite frequencies are the results sensitive only to extracellular and intracellular water. At all other frequencies there are other effects.

Aged↗
PubMed1997

Interaction of elongation factors TFIIS and elongin A with a human RNA polymerase II holoenzyme capable of promoter-specific initiation and responsive to transcriptional activators.

Affinity chromatography on columns containing the immobilized monomeric transcriptional elongation factor TFIIS or the essential large subunit, Elongin A, of the trimeric elongation factor, Elongin, was used to purify a human RNA polymerase II holoenzyme from HeLa whole cell extract. This holoenzyme contained nearstoichiometric amounts of all the general transcription factors, TFIIB, TFIID (TBP + TAFIIs), TFIIE, TFIIF, and TFIIH, required to accurately initiate transcription in vitro at the adenovirus major late promoter. It behaved as a large complex, slightly smaller than 70 S ribosomes, during gel filtration chromatography, and contained nearly half the TFIID that was present in the extract used for the affinity chromatography. It also contained the cyclin-dependent kinase CDK8, a human homologue of the Saccharomyces cerevisiae holoenzyme subunit SRB10, and many other polypeptides. Efficient interaction of holoenzyme with TFIIS or Elongin A required only the amino-terminal region of either protein. These regions are similar in amino acid sequence but dispensable for TFIIS or Elongin to regulate elongation in vitro by highly purified RNA polymerase II. The transcriptional activators GAL4-VP16 and GAL4-Sp1 activated transcription in vitro by purified holoenzyme in the absence of any additional factors.

Amino Acid Sequence↗
PubMed1997

An antagonist decoy receptor and a death domain-containing receptor for TRAIL.

TRAIL, also called Apo2L, is a cytotoxic protein that induces apoptosis of many transformed cell lines but not of normal tissues, even though its death domain-containing receptor, DR4, is expressed on both cell types. An antagonist decoy receptor (designated as TRID for TRAIL receptor without an intracellular domain) that may explain the resistant phenotype of normal tissues was identified. TRID is a distinct gene product with an extracellular TRAIL-binding domain and a transmembrane domain but no intracellular signaling domain. TRID transcripts were detected in many normal human tissues but not in most cancer cell lines examined. Ectopic expression of TRID protected mammalian cells from TRAIL-induced apoptosis, which is consistent with a protective role. Another death domain-containing receptor for TRAIL (designated as death receptor-5), which preferentially engaged a FLICE (caspase-8)-related death protease, was also identified.

Amino Acid Sequence↗
PubMed1997

Test for qualitative interaction of clinical significance.

We generalize the problem of detecting qualitative interaction between treatments and subsets in a two treatment clinical trial to the more practical problem of detecting a qualitative interaction greater than a non-negative value d, corresponding to the minimal treatment difference of clinical significance. We develop a test based on simultaneous confidence intervals for the generalized problem under the assumption of normality. The proposed test is easy to implement, either by hand calculation or through the use of virtually any existing statistical software. We derive explicit power function for the proposed test and give examples to illustrate the procedures.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

The receptor for the cytotoxic ligand TRAIL.

TRAIL (also known as Apo-2L) is a member of the tumor necrosis factor (TNF) ligand family that rapidly induces apoptosis in a variety of transformed cell lines. The human receptor for TRAIL was found to be an undescribed member of the TNF-receptor family (designated death receptor-4, DR4) that contains a cytoplasmic "death domain" capable of engaging the cell suicide apparatus but not the nuclear factor kappa B pathway in the system studied. Unlike Fas, TNFR-1, and DR3, DR4 could not use FADD to transmit the death signal, suggesting the use of distinct proximal signaling machinery. Thus, the DR4-TRAIL axis defines another receptor-ligand pair involved in regulating cell suicide and tissue homeostasis.

Adaptor Proteins, Signal Transducing↗
PubMed1997

The C-terminal domain of RNA polymerase II couples mRNA processing to transcription.

Messenger RNA is produced by RNA polymerase II (pol II) transcription, followed by processing of the primary transcript. Transcription, splicing and cleavage-polyadenylation can occur independently in vitro, but we demonstrate here that these processes are intimately linked in vivo. We show that the carboxy-terminal domain (CTD) of the pol II large subunit is required for efficient RNA processing. Splicing, processing of the 3' end and termination of transcription downstream of the poly(A) site, are all inhibited by truncation of the CTD. We found that the cleavage-polyadenylation factors CPSF and CstF specifically bound to CTD affinity columns and copurified with pol II in a high-molecular-mass complex. Our demonstration of an association between the CTD and 3'-processing factors, considered together with reports of a similar interaction with splicing factors, suggests that an mRNA 'factory' exists which carries out coupled transcription, splicing and cleavage-polyadenylation of mRNA precursors.

Animals↗
PubMed1997

[Potential role of gut peptides in stress-induced colonic motor disorder].

OBJECTIVE: To explore the potential role of gut peptide in stress-induced colonic motor disorder. METHODS: In 9 conscious Wistar rats pre-equipped with strain-gauge transducers on ascending and descending colon, colonic motility was recorded before, during and after stress. And colonic transit was evaluated by instilling Cr into the cecum through chronically implanted cannula in each group of 16 rats with or without stress, and then calculating the geometric center (GC) of radioactivity. The contents of VIP, SP, NT, SST, MOT and Leu-ENK in plasma, colonic mucosa and muscle layer were assessed in 16 stressed and 16 control rats. Exogenous peptides (VIP, SP, SST, NT) were intravenously administered in 9 rats to determine the colonic motor response. Also, the effects of peptides on colonic circular muscle strips were investigated. RESULTS: Motor activity was increased after stress, whereas colonic transit was delayed. In the stressed rats, plasma levels of VIP and Leu-ENK were higher than those in controls. The content of Leu-ENK in muscle tissue decreased. Both in vivo and in vitro studies showed that SP and NT excited, whereas VIP and SST inhibited colonic motor activity. CONCLUSION: Release of certain peptides is altered by stress. Increased release of ENK and VIP may be involved in stress-induced colonic motor disorder and in the regulation of "stress hormone" release.

Animals↗
PubMed1996

Characterization of the interaction between the acidic activation domain of VP16 and the RNA polymerase II initiation factor TFIIB.

Contact between a transcriptional activator and one or more components of the RNA polymerase II transcription initiation machinery is generally believed important for activators to function. Several different molecular targets have been suggested for direct contact by herpes simplex virus virion protein VP16, including the general initiation factor TFIIB. In this report we have used several strategies to critically assess this interaction between VP16 and TFIIB. Affinity columns of VP16 bound TFIIB activity from HeLa cell extracts and the binding was reduced by mutations in the activation domain of VP16. In assays of direct binding, VP16 bound recombinant human TFIIB but not Drosophila or yeast TFIIB. Unlike binding from an extract, however, we found that the interaction between VP16 and recombinant human TFIIB was not affected by mutations in VP16 that reduce transactivation. Point mutations within human TFIIB that reduce transactivation by VP16 have been shown to reduce VP16 binding, but we show here that these same mutations critically affect both the important TBP-TFIIB interaction and the ability of TFIIB to support activator-independent basal transcription in vitro. Taken together our results suggest more evidence is needed to support the notion that TFIIB is a functionally important target for the activator VP16.

Animals↗
PubMed1996

The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition.

BACKGROUND: In the absence of evidence of arteritis or Wegener's granulomatosis, the syndrome of lung hemorrhage and nephritis has been commonly associated with anti-glomerular basement membrane (GBM) antibodies. However, it has been increasingly recognized that many cases are associated with antineutrophil cytoplasmic antibodies (ANCAs). OBJECTIVE: To review available clinical and pathologic findings to determine the diseases accounting for lung hemorrhage and nephritis. METHODS: We studied the records of 750 patients from whom serum samples were sent to our laboratory for anti-GBM antibody assays between 1981 and 1993 and found 88 patients with evidence of lung hemorrhage and nephritis. Serum samples were retested, using current methods, for anti-GBM antibodies (against noncollagenous 1 domain of the alpha 3 chain of type IV collagen) and for antibodies to proteinase 3 and myeloperoxidase--the two types of ANCA of diagnostic value. RESULTS: Of 88 patients with evidence of lung hemorrhage and nephritis, 48 had ANCAs, six had anti-GBM antibodies, and seven had both. In 48 patients with ANCAs, the pathologic findings that accounted for the pulmonary renal syndrome were pauci-immune necrotizing and crescentic glomerulonephritis and pulmonary capillaritis. Only eight had convincing evidence (during life) of Wegener's granulomatosis and only one other had documented arteritis. In 27 patients without ANCAs or anti-GBM antibodies, a variety of unrelated renal and pulmonary diseases were found. CONCLUSIONS: The largest group of patients who present with the syndrome of lung hemorrhage and nephritis have ANCAs and not anti-GMB antibodies. Appropriate tests for antibodies to proteinase 3, antibodies to myeloperoxidase, and anti-GBM antibodies provide reliable guides for making a diagnosis in patients with this pulmonary renal syndrome.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Subset selection with additional order information.

Traditional subset selection procedures were developed without assuming any order information about the response variable. However, in some applications there is additional, even though incomplete, order information about the treatment effects at increasing treatment levels. One important example is the up-then-down umbrella ordering with an unknown peak. This type of additional order information is utilized explicitly in this paper to construct subset selection procedures for several settings studied in the literature where only order restricted tests are known to exist. This paper also proposes a straightforward algorithm to compute the isotonic regression with respect to umbrella orderings, which can be used to carry out the proposed procedures. Examples are given to illustrate the procedures and algorithm.

Algorithms↗
PubMed1996

[Diagnosis of chylous ascites with oral administration of 13C-palmitic acid].

12 cases of chylous ascites in PUMC hospital in the recent 30 years were analysed. The etiology of this disease includes non-traumatic (83.3%) and traumatic (16.7%) causes. All the patients received isotope examination or lymphangiography, but only in 8 patients the site of the lesion was found. As these two kinds of examination can only show the lesions in the right and left lumbar lymph trunks, cisterna chyli and throacic duct but not the intestinal lymph truck, the authors set up a method by administering orally 13C-palmitic acid to detect the lesion of intestinal lymph trunk. Palmitic acid is a long-chain fatty acid, which enters directly into the intestinal lymph trunk after absorption. Palmitic acid labelled with 13C could be detected in the ascitic fluid if there is a leak from intestinal lymph trunk. This new method was used to examine a patients who had negative results with isotope examination and lymphangiography; 13C could be detected in the ascitic fluid 30 minutes after oral administration but not in exhaled air. It can be concluded that cyhle leaked into the peritoneal cavity from the intestinal lymph trunk. This method is also of help to determine the possible site of leakage and the degree of obstruction, so it is quite useful for the diagnosis of chylous ascities.

Administration, Oral↗
PubMed1995

Homology requirements for ligation and strand exchange by the FLP recombinase.

The FLP recombinase of the 2-microns plasmid of Saccharomyces cerevisiae belongs to the integrase family whose members form a covalent bond between a conserved tyrosine of the recombinase and the 3'-phosphoryl group at the site of cleavage. Ligation takes place when the 5'-OH generated during the cleavage step attacks the phosphotyrosine bond and reforms a phosphodiester bond. When the incoming 5'-OH is from the partner duplex, strand exchange occurs. The FLP recognition target (FRT) contains two inverted 13-base pair (bp) FLP binding sequences that surround an 8-bp core region. It has been shown that heterology in the core regions of the recombinase FLP recognition target sites can dramatically impair recombination. Therefore, it was of interest to study the homology requirements of the core sequence for FLP-mediated ligation. Using nicked duplex substrates containing mismatches in the core sequence, we have demonstrated that the FLP ligation reaction can tolerate mismatches at all positions in the 8-bp core except the position immediately adjacent to the cleavage site. Using half-FRT substrates that contain a single-stranded core sequence, we showed that 4 base pairs adjacent to the cleavage site in the core are required for FLP to execute ligation with a single-stranded oligonucleotide. FLP is also able to ligate the protruding single strand on a half-FRT site to the opposite strand to form a hairpin. We have studied the effect of the base composition of the protruding 8-nucleotide single strand upon the efficiency of hairpin ligation. These studies revealed the importance of intrastrand complementarity in the formation of hairpin by FLP. Hence we conclude that the homology in the position adjacent to the cleavage site is most important, and the degree of the homology required is dependent on the nature of the ligation assay.

Base Composition↗