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Biomedical subjects

S Champion

Publications and source records attributed to S Champion.

At least 19 recordsLinked to original sources
PubMed2006

Implantable gastric stimulation to achieve weight loss in patients with a low body mass index: early clinical trial results.

This report describes the authors' early outcomes with implantable gastric stimulation (IGS) used to achieve weight loss in patients with a low body mass index (BMI). After prescreening of potential candidates with a selection algorithm, 24 patients (21 women and 3 men) with a low BMI (30-34.9) underwent IGS implantation at two centers. The patients had a mean age of 43 years (range, 32-60 years), a mean BMI of 33 (range, 30-36), and a mean weight of 92 kg (range, 80-117 kg). At this writing, 6 months postoperatively, there have been no serious adverse events related to the device. The mean percentage of excess weight loss (EWL) was 5.9%, with three patients explanted because of noncompliance. The mean waist circumference decreased 5.8%, which was significant (p = 0.009). A subset of nine patients (37.5%) had an EWL exceeding 10% (mean, 20.1%). A subset of low BMI patients lost a clinically significant amount of weight with IGS within 6 months. Further study is required for better identification of potential candidates for this novel approach.

Adult↗
PubMed2004

Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites.

BACKGROUND AND AIMS: Cytochrome P450 1A1 catalyzes the degradation of endobiotics (estradiol, fatty acids, and so on) and the bioactivation of numerous environmental procarcinogens, such as arylamines and polycyclic aromatic hydrocarbons, that are found in food. Several peroxisome proliferators and arachidonic acid derivatives enhance cytochrome P450 1A1 activity, but the mechanisms involved remain unknown. The aim of this work was to study the role of peroxisome proliferator-activated receptors in cytochrome P450 1A1 gene induction. METHODS: The role of peroxisome proliferator-activated receptor transcription factors in cytochrome P450 1A1 induction was assessed by means of enzymatic activities, quantitative real-time polymerase chain reaction, gene reporter assays, mutagenesis, and electrophoretic mobility shift assay. RESULTS: We show that peroxisome proliferator-activated receptor-alpha agonists (WY-14643, bezafibrate, clofibrate, and phthalate) induce human cytochrome P450 1A1 gene expression, whereas 2,4-thiazolidinedione, a specific peroxisome proliferator-activated receptor-gamma agonist, represses it. The induction of cytochrome P450 1A1 transcripts by WY-14643 was associated with a marked increase of ethoxyresorufin O -deethylase activity (10-fold at 200 mumol/L). Transfection of peroxisome proliferator-activated receptor-alpha complementary DNA enhanced cytochrome P450 1A1 messenger RNA induction by WY-14643, although WY-14643 failed to activate xenobiotic responsive element sequences. Two peroxisome proliferator response element sites were located at positions -931/-919 and -531/-519 of the cytochrome P450 1A1 promoter. Their inactivation by directed mutagenesis suppressed the inductive effect of WY-14643 on cytochrome P450 1A1 promoter activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay experiments showed that the 2 cytochrome P450 1A1 peroxisome proliferator response element sites bind the peroxisome proliferator-activated receptor-alpha/retinoid X receptor-alpha heterodimer. CONCLUSIONS: We describe here a new cytochrome P450 1A1 induction pathway involving peroxisome proliferator-activated receptor-alpha and 2 peroxisome proliferator response element sites, indicating that peroxisome proliferator-activated receptor-alpha ligands, which are common environmental compounds, may be involved in carcinogenesis.

Adenocarcinoma↗
PubMed2003

Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial.

OBJECTIVE: To compare the effect of a Serenoa repens extract with placebo for symptoms of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In a double-blind placebo-controlled randomized trial between January 1999 and March 2000, 100 men with symptoms of BPH, aged < 80 years, with a maximum urinary flow rate of 5-15 mL/s for a voiding volume of 150 mL, were randomly and equally allocated to 320 mg S. repens extract or placebo (paraffin oil). The main outcome measures were the International Prostate Symptom Score (IPSS), peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) questionnaire. RESULTS: There was no significant difference between the treatments over the 12 weeks of the study in the IPSS, peak urinary flow rate or for the IIEF questionnaire. CONCLUSIONS: During the trial all participants had some improvement in their symptoms of BPH but there was no significant beneficial effect of this S. repens extract over placebo in this 12-week trial.

Androgen Antagonists↗
PubMed2001

Rehabilitation of a quadruple amputee subsequent to electrical burns sustained whilst hang gliding.

PURPOSE: The purpose of this article is to describe the management, difficulties encountered and level of independence achieved during the initial stage of a quadruple amputee's rehabilitation. METHOD: This is a case study of the rehabilitation of the first known person losing all four limbs due to electrocution whilst hang gliding. RESULTS: The patient became a successful upper limb prosthetic user and returned to work six hours a day. Full independence in activities of daily living was not achieved nor considered practical. Independent walking was accomplished in physiotherapy. however an electric wheelchair remains the only functional means of mobility. CONCLUSION: The rehabilitation is described in detail to assist those managing such a rare and complex case.

Activities of Daily Living↗
PubMed2001

Involvement of nuclear factor kappaB in c-Myc induction by tubulin polymerization inhibitors.

We showed previously that microtubule disassembly by vinblastine induces the proto-oncogene c-myc in epithelial mammary HBL100 cells. In this study, we demonstrate that vinblastine treatment in these cells, in contrast to what was observed with the colon adenocarcinoma cell line HT29-D4, activated the transcription factor NFkappaB, which has been involved in c-myc regulation. The microtubule disassembly also induced IkappaB degradation. Using transient transfection analysis, we show that the trans-activation of c-myc by vinblastine was decreased when NFkappaB binding sites on c-myc promoter were mutated. Additionally, we demonstrate that microtubule dissolution trans-activated a thymidine kinase-CAT construct containing an NFkappaB binding site at -1180 to -1080 bp relative to the P1 promoter. Thus, vinblastine up-regulates the enhancer activity of the NFkappaB binding site. These results suggest that microtubule disassembly induced by vinblastine can trans-activate the c-myc oncogene through NFkappaB. Taking into consideration the paradoxical roles of both c-myc and NFkappaB in proliferation or apoptosis, this data reveals the complex action mechanism of this microtubule interfering agent.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Role of endoproteolytic processing in the adhesive and signaling functions of alphavbeta5 integrin.

Some integrin alpha subunits undergo a post-translational cleavage in their extracellular domain. However, the role of this cleavage in integrin function is unclear. Enzymes involved in this maturation belong to the subtilisin-like endoprotease family (convertases). To understand the role of the alpha subunit cleavage in integrin function, we have designed stable transfectants (PDX39P cells) expressing alpha(1)-PDX, a convertase inhibitor. Immunoprecipitation of cell surface proteins from PDX39P showed that alpha(3), alpha(6) and alpha(v) integrins lack endoproteolytic cleavage. We have compared adhesion between PDX39P cells and mock-transfected cells on different extracellular matrix proteins. No difference in adhesion could be observed on laminin-1 and type I collagen, while attachment of PDX39P cells to vitronectin (ligand of the alpha(v)beta(5) integrin) was dramatically reduced. The reduced adhesion of PDX39P cells was not due to changes in integrin affinity as determined by solid-phase receptor assay in a cell-free environment. Intracellular signaling pathways activated by alpha(v) integrin ligation were also affected in PDX39P cells. It thus seems that the absence of endoproteolytic cleavage of alpha(v) integrins has important consequences on signal transduction pathways leading to alterations in integrin function such as cell adhesion.

Animals↗
PubMed2000

Ribavirin-induced resistance to heat shock, inhibition of the Ras-Raf-1 pathway and arrest in G(1).

Ribavirin [1-(beta-D-ribofuranosyl)1,2,4-triazole-3-carboxamide (virazole)], a specific inhibitor of inositide 5'-monophosphate dehydrogenase (IMPDH), induces a strong depletion of GTP pools in IGR39 cells. After a 3-day treatment, the cell cycle was reversibly arrested in G(0)/G(1), suggesting the involvement of GTP in the cell cycle process. The reduction of the GTP cell content modified the appearance of the microtubule network, as examined using immunofluorescence. However, the dynamics of repolymerisation were not altered. When arrested in G(0)/G(1), cells displayed a surprising resistance to a 3-h period of heat shock at 45 degrees C. Considering the lack of coimmunoprecipitation of p21ras with Raf-1, the reduction of the level of GTP-associated p21ras and the decrease of the activation of the extracellular signal-regulated protein kinases (ERK), also known as mitogen-activated protein (MAP) kinase, in ribavirin-treated cells, we suggest a possible relationship between the expression of heat-shock proteins and the change, in GTP-depleted cells, of the regulation of Raf kinase by ras protein.

Antimetabolites↗
PubMed1997

Developmental expression analysis of the 1731 retrotransposon reveals an enhancement of Gag-Pol frameshifting in males of Drosophila melanogaster.

Extensive analyses of Drosophila melanogaster retrotransposon transcriptions in cultured cells or during development have been reported, but little is known about their translation during the development of the fly. Analysis of the translational products of the 1731 Drosophila melanogaster retrotransposon in Kc Drosophila cultured cells has been reported, showing the existence of primary products (Gag and Pol) and of processed polypeptides of various sizes. Study of 1731 retrotransposon expression at both levels of transcription and translation during the development of Drosophila melanogaster, is presented. 1731 transcripts were detected by in situ hybridization and 1731 proteins were detected by immunostaining and immunoblotting in embryos and in adult gonads. 1731 transcripts and proteins were detected in the mesoderm and central nervous system during embryonic development, in nurse cells and follicle cells in adult ovaries and in primary spermatocytes in adult testes. Moreover, Western blot analysis of the 1731 proteins with anti-Gag or anti-Pol antibodies in gonads revealed that the 1731 mRNA could be translated differentially according to the expressing tissue: essentially, ovarian translation and/or processing of 1731 products is different from that operating in testes, where the Gag-Pol fusion polyprotein is the most prominent product. Our results indicate that expression of the 1731 mobile element is regulated not only at the transcriptional level but also at the translational level, and that this regulation is different in the two sexes.

Animals↗
PubMed1997

Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif.

Cell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats (LTR) of human immunodeficiency virus. HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins. Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR, we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR. Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB (NF-kappaB) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide. Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha. NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis.

Base Sequence↗
PubMed1997

Induction of transcription from the long terminal repeat of the intracysternal particles type A (IAP) by X-irradiation.

Intracisternal A particles (IAPs) are retrovirus-like entities that are present in many embryonic and transformed cells of Mus musculus. They present long terminal repeats (LTRs) which control the promotion and regulation of their transcription. Using a construction expressing a reporter gene under the control of the entire long terminal repeat (LTR) of IAP in transfected murine fibroblast BALB/c 3T3 cells clone D152, we were able to show that the IAP-LTR is activated by X-irradiation in a time-dependent manner. The relative CAT activity increased with increasing X-irradiation doses, reaching a maximum at 75-150 cGy, followed by a drop in activation. In addition, X-induced D152 mouse cells produced extracellular factor(s), in response to X-irradiation, which activated the IAP-LTR in non-irradiated cells. This factor(s) was detected both when transfected cells were cocultured with inducing cells and when conditioned medium from irradiated cultures was added to the cell cultures. The use of suramin, a strong polyanonic molecule which has been reported to trap growth factors, induces a high reduction of the indirect activation.

3T3 Cells↗
PubMed1996

Activation of the HIV type 1 long terminal repeat by X-irradiation involves two main Re1/NF-kappa B DNA-binding complexes.

Transcription of human immunodeficiency virus type 1 (HIV-1) is regulated by multiple cis-acting regulatory elements located in the viral long terminal repeats (LTRs). HIV-1 LTR enhancer is activated by a variety of heterologous viral, chemical, and physical agents. Studies have demonstrated that irradiation by X-rays induces transcription under the control of the HIV-1 LTR and that ionizing radiations activate DNA binding of the nuclear transcription factor NF-kappa B. Using various constructs expressing a reporter gene under the control of complete or deleted LTRs of HIV-1, we evidenced that a sequence located in the U3 region was involved in X-ray activation of the HIV-1 LTR in the human colonic carcinoma cell line HT29. The cis-acting element conferring X-ray responsiveness is indistinguishable from HIV NF-kappa B tandem repeat binding sites (HIV-1, kappa B). The present work has examined the effects of X-irradiation on the NF-kappa B transcription factor. Furthermore, we characterized the subunit composition of the two major nuclear NF-kappa B complexes that bind HIV-1 kappa B after X-ray irradiation.

Antioxidants↗
PubMed1996

Upregulation of the Drosophila 1731 retrotransposon long-terminal repeat by UV-B irradiation requires a short sequence in the U3 region.

A 1731 is a Drosophila melanogaster retrotransposon, the transcripts of which decrease in Drosophila cells after treatment by the 20-hydroxyecdysone (20-OH), the steroid-molting hormone of insects. In order to analyze the regulation of the long terminal repeat (LTR) directed transcription by UV-B, S2 Drosophila cells were transfected with various chimeric constructs carrying the LTR of 1731 linked to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene and then subjected to UV-B irradiation. The results demonstrated that the 1731 LTR is activated by UV-B irradiation in a dose- and time-dependent manner. Using constructions expressing the reporter gene under the control of either the entire or deleted LTRs of 1731, we established that a sequence located in the U3 region was required for the retrotransposon to respond to UV-B. The cis-acting element is identical to the binding sequence of the dorsal transcription factors. In addition, the S2 Drosophila cell produced extracellular factor(s) in response to UV-B irradiation which activated the 1731 LTR in nonirradiated cells. This factor(s) was detected when responding cells were cocultured with inducing cells and when conditioned medium from irradiated cultures was added to the cell cultures.

Animals↗
PubMed1996

UVB irradiation-induced transcription from the long terminal repeat of intracisternal A particles and UVB-induced secretion of an extracellular factor that induces transcription of the intracisternal A particles in unirradiated cells.

Intracisternal A particles (IAPs) are endogenous defective retroviral-like elements encoded by a family of proviral sequences present as a thousand copies in the mouse genome. In order to analyse the regulation of the long terminal repeat (LTR) directed transcription by UVB, D152 murine cells were transfected with a chimeric construct carrying the LTR of IAP linked to the bacterial chloramphenicol-acetyl-transferase reporter gene and then subjected by UVB irradiation in a dose- and time-dependent manner. Like the human immunodeficiency virus 1 type LTR and in spite of the lack of the nuclear factor kappa B consensus sequence, the IAP LTR could be activated by UVB. In addition, the D152 cells produced an extracellular factor are factors in response to UVB irradiation which activated the IAP LTR in unirradiated cells. This factor was detected both when responding cells were cocultured with inducing cells and when conditioned medium from irradiated cultures was added to the cell cultures.

3T3 Cells↗
PubMed1996

X-irradiation activates the Drosophila 1731 retrotransposon LTR and stimulates secretion of an extracellular factor that induces the 1731-LTR transcription in nonirradiated cells.

Using constructs expressing the reporter gene under the control of the entire or deleted long terminal repeats (LTRs) of 1731, a Drosophila melanogaster retrotransposable element, we show that 1731-LTR is activated by X-irradiation in a dose- and time-dependent manner, and that a sequence located in the U3 region of these LTRs is required. The cis-acting element conferring X-responsiveness shows similarities to kappa B (kappa B)-like binding sequence. In response to X-irradiation, S2 Drosophila cells produced an extracellular factor which activates the 1731-LTR in nonirradiated cells. This factor was detected both when transfected cells were cocultured with inducing cells and when a conditioned medium taken from irradiated cultures was added.

Animals↗