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M Scotte

Publications and source records attributed to M Scotte.

At least 19 recordsLinked to original sources
PubMed2001

Gene transcription in hepatocytes during the acute phase of a systemic inflammation: from transcription factors to target genes.

During an acute, systemic inflammation, the liver is triggered by blood-borne pro-inflammatory cytokines such as Tumor Necrosis Factor alpha, Interleukin-1beta and Interleukin-6. The end result is an up- or down-regulated synthesis and/or activation of liver-enriched transcription factors that in turn regulate many target genes coding for resident or secreted acute phase proteins. In this review, various classifications of these acute phase proteins are presented. Major inflammation-driven changes in the synthesis and/or activity of the hepatic transcription factors are illustrated. Some of their up- or down-regulated target genes are used as paradigms of the various transcriptional mechanisms that take place on gene promoters during an acute, systemic inflammation. Finally, further specific features of inflammation-associated gene transcription in liver from acute phase onset to resolution are provided.

Acute-Phase Reaction↗
PubMed2001

Cell proliferation in colorectal adenocarcinomas: comparison between Ki-67 immunostaining and bromodeoxyuridine uptake detected by immunohistochemistry and flow cytometry.

We compared three different means of assaying tumor proliferative activity in 30 human colorectal adenocarcinomas labeled in vivo with bromodeoxyuridine (BrdUrd). The labeling indices (LI) of BrdUrd obtained both by flow cytometry (FCM) and immunohistochemistry (IH) were also compared with the labeling index of Ki-67. These methods were then related to tumor ploidy and pathological features. Flow cytometry was performed in accordance with Begg's method after intravenous infusion of BrdUrd four hours before surgery. Immunohistology was carried out on paraffin-embedded sections with monoclonal antibodies against BrdUrd and Ki-67. A positive correlation was found between BrdUrd LI obtained by both FMC and IH (p<0.0001), a finding that complies with the literature. However, we report on a correlation between Ki-67 LI and BrdUrd LIs in colorectal tumors (p=0.012). The results were valid for all tumors when they were subdivided into diploid and aneuploid groups. The labeling indices were significantly higher in the aneuploid tumor group than in the diploid group (p=0.047). No relationship between proliferation parameters and tumor stage or grade was found. To our knowledge, this is the first report on a positive correlation between tumor proliferation indices in BrdUrd LIs and Ki-67 in colorectal carcinomas. This finding validates the value of Ki-67 immunostaining, which, however, should be confirmed in a larger series under the same technical conditions.

Adenocarcinoma↗
PubMed2000

Viability and drug metabolism capacity of alginate-entrapped hepatocytes after cryopreservation.

In the present study we evaluated viability and detoxifying enzyme capacity of cryopreserved hepatocytes from various species, including man, immobilized in calcium alginate gels. Ethoxyresorufin O-deethylase, phenacetin deethylase, pentoxyresorufin O-dealkylase, tolbutamide hydroxylase, S-mephenytoin hydroxylase, dextromethorphan demethylase, and nifedipine oxidation corresponding to the major cytochromes P450 (CYP) involved in xenobiotic metabolism as well as whole glutathione S-transferase (GST) activity were measured using specific substrates and after exposure or not to prototypical inducers. After deep-freeze storage, viability of immobilized hepatocytes was only slightly reduced and most CYP-related monooxygenase activities were well preserved, being expressed at levels close to those measured in unfrozen hepatocyte monolayers. By contrast, total GST activity was decreased by around 50%. However, as did CYP1A- and 3A-related enzymes, rat GST remained capable of responding to prototypical inducers. The fold increases were comparable in unfrozen and frozen immobilized hepatocytes and in unfrozen hepatocyte monolayers. The duration of storage, even when exceeding one year, did not affect viability and functions. In conclusion, after cryopreservation, alginate-entrapped hepatocytes remain highly viable and capable of expressing most detoxifying enzymes at levels close to those expressed in corresponding unfrozen hepatocyte monolayers and of responding to prototypical inducers.

Alginates↗
PubMed2000

Pre-operative kinetic parameter determination of colorectal adenocarcinomas. Prognostic significance.

BACKGROUND: The aim of this study was to test the prognostic value of pre-operative assessment of tumour kinetics in colorectal adenocarcinoma. METHODS: The study of tumour kinetics was performed using an in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed using flow cytometry. This procedure enables calculation of the in vivo S-phase fraction labelling index (LI), the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). Disease-free survival curves were calculated by a Kaplan-Meier method. The statistical significance between curves was tested by the log rank test. A multivariate analysis was performed using the Cox's proportional hazards model to determine the effect of pathological staging (lymph node involvement), ploidy and kinetic parameters. RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy. In univariate analysis, lymph node involvement, labelling index > 10% and Tpot < 5 days were associated with poor prognosis, with P= 0.0006, 0.049 and 0.029 respectively; no significant differences were found in Ts (P = 0.214), and ploidy (P= 0.095). In multivariate analysis, lymph node involvement, ploidy and Tpot were found to be independent factors of colorectal cancer prognosis (P= 0.028, 0.032 and 0.035 respectively) in all tumours. Tpot was considered a independent prognostic factor in diploid tumours (P= 0.047) but not in aneuploid tumours (P= 0.345). CONCLUSIONS: These results suggest that kinetic parameters determined by pre-operative biopsies of colorectal adenocarcinoma represent a prognosis factor, independent of pathological staging, particularly in diploid tumours.

Adenocarcinoma↗
PubMed1999

Effect of radiation therapy on the potential doubling time of tumours in colorectal cancers.

OBJECTIVE: The aim of the present study was to investigate the effects of standard fractionated radiation therapy on the kinetic parameters of colorectal adenocarcinomas. METHODS: The study of tumour kinetics involved in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed with flow cytometry. This procedure provides a rapid calculation of qualitative parameters such as ploidy and quantitative parameters such as the in vivo S-phase fraction labelling index which indicates the percentage of cells that have entered into the cycle, the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy (group 1) and ten rectal carcinomas were studied following radiation therapy (group 2). In diploid tumours, the labelling index was significantly lower in the post-radiotherapy group than in the pre-radiotherapy group (2.7 +/- 1.1% versus 6.4 +/- 4.2%, respectively; P= 0.01), and the Tpot was significantly longer after radiotherapy (group 2) (22.0 +/- 7.0 days versus 8.6 +/- 6.0 days, P = 0.002). Standard fractionated radiation therapy also appears to result in a longer Tpot in diploid adenocarcinomas of the colon and rectum. This effect was not observed in aneuploid tumours. CONCLUSIONS: The effectiveness of hyperfractionated schedules of radiation therapy for aneuploid rectal tumours with short Tpot warrants further investigation in a larger patient population.

Adenocarcinoma↗
PubMed1997

Comparison between endoscopic and surgical sampling for the measurement of potential doubling time in colorectal cancer.

In colorectal cancer, tumoral kinetic parameters could influence the therapeutic strategy. The aim of this study was to test the validity of a preoperative assessment of tumoral kinetics on biopsies obtained from endoscopic sampling. After infusion of 250 mg of bromodeoxyuridine (BrdUrd), tumor samples were taken. The following kinetic parameters were evaluated by Begg's method: labeling index (LI) of BrdUrd, duration of the S phase (Ts), and potential doubling time (Tpot). We compared the findings in preoperative endoscopic samples (t1), endoscopic samples (t2), and macrobiopsies of the tumor after surgical resection (t3) to test the effect of time, surgical procedures, and sampling mode on results. Eight diploid and 11 aneuploid colorectal cancers were studied. In diploid tumors, no difference in Tpot, Ts, or LI values was found among the three time intervals. In aneuploid tumors, Tpot value at t1 was lower than t3: 2.9 +/- 1.2 versus 4.5 +/- 1.4 days (P = 0.02). This difference seemed to be independent of sampling type but related instead to the time interval between BrdUrd infusion and biopsy and to the changes due to the surgical condition. On the other hand, LI seemed to be the most stable kinetic parameter. With a cutoff value of 4 days for Tpot and of 10% for LI to differentiate slow and fast growing tumors, the positive predictive values of LI were 90% at t1, 80% at t2, and 50% at t3 in aneuploid tumors.

Aneuploidy↗
PubMed1997

Complement classical pathway expression by human skeletal myoblasts in vitro.

Human myoblasts express immunological properties in vitro and we have previously reported that they produce Complement (C) components of the alternative pathway. Myoblasts activate the classical pathway but are fully protected against C attack by the expression of major C regulators. In order to fully understand the relationship between myoblasts and C, we here report the biosynthesis of C components of the classical pathway by skeletal muscle cells. Human myoblasts in vitro produced C1q, C1r, C1s, C2 and C4 constitutively and all syntheses were upregulated after stimulation with IFN-gamma. We suggest that human myoblasts may constitute a local source of C and therefore C could be implicated in inflammatory or physiopathological processes developed in skeletal muscle.

Blotting, Western↗
PubMed1996

Liver preservation below 0 degrees C with UW solution and 2,3-butanediol.

Long-term preservation of the liver is needed to transform liver transplantation from an emergency operation to an elective procedure and therefore to improve the results of liver transplantation. We explored the possibility of extending the cold ischemia time of the rat liver by using a preservation temperature below 0 degrees C together with the addition of a cryoprotective agent (2,3-butanediol) at a low concentration in the preservation solution. Rat livers were preserved for 72 h either with UW solution at +4 degrees C (group 1) or with a UW solution, to which 2,3-butanediol at 8% (at +4 degrees C (group 2) or at -4 degrees C (group 3, experimental group)) was added. Following the preservation process, the viability of the livers was assessed using the isolated perfused liver model. Enzymatic release, bile production, and portal venous flow were not significantly different between group 1 and group 3. In the two groups in which preservation included 2,3-butanediol, the enzymatic release was significantly greater when the preservation temperature was +4 degrees C. We conclude that, using this method, preservation of the rat liver below 0 degrees C seems feasible. However, despite its low concentration, some toxicity of 2, 3-butanediol was suspected. This would counterbalance the benefit resulting from the temperature-related decrease of the enzymatic activities involved in cold ischemia damage. The potential advantages of this method need to be confirmed by assessing liver viability using a liver transplantation model.

Adenosine↗
PubMed1995

Alternative splicing of MLH1 messenger RNA in human normal cells.

The hMLH1 protein, composed of 756 amino acids, is the human homologue of the bacterial DNA mismatch repair protein MutL, and germ line mutations of the hMLH1 gene have been identified in kindreds with hereditary nonpolyposis colorectal cancer. We have detected three alternatively spliced forms of hMLH1 mRNA in normal lymphocytes and tissues. One of the spliced forms lacks the coding region of hMLH1 from codons 227 to 295 and the two other transcripts are predicted to encode two truncated proteins retaining the 264 and 226 N-terminal amino acids of hMLH1, respectively. The biological significance of this alternative splicing remains to be established.

Adaptor Proteins, Signal Transducing↗
PubMed1994

[Laparoscopic drainage of a lymphocele after radical prostatectomy].

A laparoscopic procedure used to achieve transperitoneal drainage of a lymphocele that developed three months after radical prostatectomy for prostate cancer is described. The lymphocele wall was resected through a peritoneal opening. After drainage of the lymphocele, a corner of the omentum was inserted into the cavity. Preoperative aspiration of the lymphocele and computed tomography allowed accurate evaluation of the relationships of the lymphocele with the blood vessels, urinary tract, and digestive tract. These investigations also ruled out an infection and established the diagnosis of lymphocele. Laparoscopic drainage has the same indications as conventional internal drainage and readily allows to perform the same procedures. As a conventional internal drainage and readily allows to perform the same procedures. As a simple procedure associated with low morbidity, laparoscopic drainage could be used as the first-line treatment for large, symptomatic, recurrent lymphoceles developing after pelvic surgery, in particular after extraperitoneal procedures such as radical prostatectomy, provided there is no infection, the lymphocele is readily accessible, and the surgeon is experienced in the use of laparoscopic techniques.

Aged↗
PubMed1994

[Pseudomembranous colitis revealing adult hemolytic-uremic syndrome].

A 33 year old woman presented with abdominal pain and bloody diarrhea. A subtotal colectomy was performed. Following surgery the haemolytic uraemic syndrome unmasked. Such surgical forms of haemolytic uraemic syndrome are rare. They demonstrate that the diagnosis is difficult at the initial abdominal period before renal insufficiency and anemia develop. Review of the literature confirms the severe nature of haemolytic uraemic syndrome associated lesions. Haemolytic uraemic syndrome and pseudomembranous colitis with capillary thrombosis would be two forms of a unique affection, i.e. thrombotic microangiopathy.

Adult↗
PubMed1993

Human inter-alpha-inhibitor family in inflammation: simultaneous synthesis of positive and negative acute-phase proteins.

The inter-alpha-inhibitor (I alpha I) family encompasses four plasma proteins, namely free bikunin as well as I alpha I, pre-alpha-inhibitor (P alpha I) and inter-alpha-like inhibitor (I alpha LI). Each of the last three proteins is a distinct assembly of one bikunin chain with one or more unique heavy (H) chains designated H1, H2 and H3. The three H chains and the bikunin chain are encoded by four distinct mRNAs. These molecules and chains, as well as the corresponding mRNAs, were quantified in sera and liver biopsies from a series of patients with or without mild or severe acute infection. The decrease or increase observed for a given molecule or chain in the serum was in agreement with a similar change in the corresponding liver mRNA. In acute inflammation the H2 and bikunin chains are down-regulated and the relevant molecules (I alpha I, I alpha LI) behave as negative acute-phase proteins, whereas the H3 chain is up-regulated and the corresponding P alpha I molecule is a positive acute-phase protein. Also, P alpha I displays a higher-than-usual M(r); this is probably due to ligand binding. The H1 gene does not seem to be affected by the inflammatory condition. The quantitative changes in RNA levels seen in vivo were confirmed in vitro in the human hepatoma Hep3B cell line prior to or after induction with the acute-phase mediators interleukin-1 and/or -6. These results provide the first example in humans of positive and negative acute-phase proteins that are encoded by evolutionary related genes.

Acute-Phase Proteins↗
PubMed1993

Measuring the rupture stress point of biological sealant-collagen bonding: validation of a technique used after hepatectomy.

The aim of this experimental study was to measure the rupture stress point of a fibrin clot situated on a liver, in realistic surgical conditions. The experimental method was carried out with a machined wooden cylinder bonded on the liver, connected with a wire to a setup and pulled at a constant speed, and a sensor was placed on the wire measuring the applied strength. This method, realized in the dog, made it possible to validate a precise and reproducible method designed for testing the adhesive characteristics of biological sealant-collagen bonding on the liver.

Adhesiveness↗
PubMed1993

[Budd-Chiari's syndrome with caval membranous web treated by liver transplantation].

In this paper, the case of a 30 year-old Asiatic man with a Budd-Chiari syndrome secondary to a caval membranous web, associated with cirrhosis is presented. After unsuccessful percutaneous dilatation, liver transplantation associated with membranotomy treated the venous obstacle and ensured satisfactory recovery. Orthotopic liver transplantation is the most effective treatment in this setting.

Adult↗