[Is there a role for laparoscopic lymphadenectomy in cervical cancers?].
Explore the source record for details and available documents.
Female↗
Biomedical subjects
G Michel
Publications and source records attributed to G Michel.
[Surgical strategy for peritoneal carcinosis of ovarian origin].
Cancer of the ovary is usually discovered in an advanced stage after development of peritoneal carcinosis. Surgery is a fundamental element for diagnosis and treatment. Therapeutic strategy for cancer of the ovary discovered in an advanced stage includes first-line surgery and systematic postoperative chemotherapy. The essential prognostic factor is the quality of the initial surgical resection and the size of the residual tumoral tissue. Hysterectomy with adnexectomy, omentectomy, lumbo-ovarian and pelvic node dissection and extensive excision of visible carcinosis nodules, with if need digestive resection, are required for optimal tumor reduction. This aggressive surgery should be performed by well trained surgical teams.
Adnexa Uteri↗
[Broad-spectrum beta-lactamases: profile and perspectives after 3 years of systematic detection at the Main Hospital of Dakar (1 February 1992 to 1 February 1995)].
After having undertaken an estimation upon infections from bacteria generating extended broad spectrum Beta-lactamase at "Hospital Principal" of Dakar between 1992 to 1993 and after having drawn the attention of authorities of the Hospital to the hazard caused by this sort of infections, authors come back in doing a second estimation during the two following years. The results of this estimation show that measures preciously taken, not with standing an certain impact, are clearly unsufficient and have got a limited effect in the future. They suggest practical solutions in the long run, solutions that have already been taken at "Hospital Principal" of Dakar and deserve to be kept on and encouraged.
Adult↗
A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes.
Psoriasis is a common chronic skin disease mediated by cellular immune mechanisms and characterized by an intense neutrophil cell infiltrate and proliferative activation of epidermal keratinocytes. We have previously described the expression of the inducible nitric oxide synthase (iNOS) in epidermal keratinocytes of psoriatic skin lesions. In this study, the role of iNOS in psoriatic inflammation was explored ex vivo in psoriatic skin biopsies and in vitro in primary cultures of human keratinocytes. Messenger RNA for the iNOS enzyme (iNOS mRNA) was detected by reverse transcriptase polymerase chain reaction in skin biopsies from patients with psoriasis, but not in skin specimens from patients with atopic eczema or from healthy volunteers. As demonstrated by in situ hybridization and immunohistochemistry, expression of iNOS mRNA and its gene product was localized to the epidermal keratinocytes of psoriatic skin lesions. In situ hybridization further revealed a complete colocalization of mRNA expression for iNOS with interleukin (IL) 8 receptor-specific mRNA either in the basal germinative cell layer or at focal sites of ongoing neutrophil inflammation in suprabasal cell layers. Because psoriatic keratinocytes have previously been shown to express mRNA transcripts for IL-8, it seemed reasonable to hypothesize that iNOS expression could be induced in an autocrine loop by IL-8. This hypothesis was substantiated by our in vitro experiments showing that a combination of IL-8 and interferon gamma induces the expression of iNOS-specific mRNA and of the functional enzyme in cultured human keratinocytes. These results suggest an important role for iNOS in concert with IL-8 and its receptor early during the formation of psoriatic lesions.
Biopsy↗
Antioncogene P53 and mitogenic cytokine interleukin-8 aberrantly expressed in psoriatic skin are inversely regulated by the antipsoriatic drug tacrolimus (FK506).
Uncontrolled proliferation of epidermal cells is the most prominent characteristic of psoriasis. This widespread skin disease can be effectively treated with the microbial substance FK506, which acts by modulating gene expression. We, therefore, asked if the drug changes the expression of genes involved in growth regulation (the mitogenic cytokine interleukin-8 (IL-8) and p53, a negative cell cycle regulator) and signal transduction (protooncogenes c-ras, c-raf, and HER-2). Gene expression was monitored by semiquantitative mRNA-PCR and for p53 by immunocytochemistry in cultured primary keratinocytes (KC). In addition, p53 expression was analysed in skin biopsies of psoriatic patients. After 1-3 hr, IL-8 mRNA levels were dose-dependently decreased in tacrolimus (FK506)-treated cells. Protooncogene expression was not significantly altered. Interestingly, p53 transcription was clearly induced by FK506 treatment. This tendency could be verified on the protein level by immunocytochemistry. In contrast, p53 expression was decreased in lesional psoriatic as compared to normal skin, providing evidence that not only posttranslational modification of the p53 protein, but also transcriptional modulation of the p53 gene, are involved in pathological processes and pharmacological drug action in skin. Together with earlier results showing downmodulation for IL-8 receptor type A expression in cultured KC treated with FK506, these results suggest that both the mitogenic IL-8/IL-8R system and the cell cycle inhibitor p53 represent potential targets for the antipsoriatic action of the drug, whereas protooncogenes acting downstream in mitogenic signal transduction cascades are unaffected. The differential modulation of an entire set of genes provides evidence for the specificity of the drug effects and rules out nonspecific toxic effects on KC.
Dose-Response Relationship, Drug↗
Malaria associated pre-eclampsia in Senegal.
Explore the source record for details and available documents.
Adult↗
Desmoplastic small round cell tumors: results of a four-drug chemotherapy regimen in five adult patients.
BACKGROUND: Desmoplastic small round-cell tumor has been identified as a neoplasm with multidirectional immunohistochemical, and molecular features of this tumor sets it apart as a pathologic entity. The optimal treatment remains to be determined. METHODS: Five adult patients were treated according to a uniform first-line chemotherapy program including cisplatin, etoposide, cyclophosphamide, and either doxorubicin or epirubicin. Chemotherapy was delivered after initial surgery in the four patients with intra-abdominal presentation, and at relapse in the fifth patient who had a paratesticular primary tumor. RESULTS: All 4 patients with intra-abdominal disease experienced stability lasting from 4 to 9 months. Only one objective persistent complete response was observed; this was in the patient with a paratesticular primary. No salvage treatment was active in the other four patients who died of progressive disease. CONCLUSIONS: Our experience to a certain degree of chemosensitivity for desmoplastic small round-cell tumors. Despite aggressive treatments, survival rates remain disappointing. Other therapeutic modalities are needed to improve these results.
Adult↗
[Cancer of the cervix uteri. Epidemiology, pathological anatomy, screening, diagnosis, development, prognosis, treatment].
Explore the source record for details and available documents.
Female↗
Characterization of iturin synthetase in the wild-type Bacillus subtilis strain producing iturin and in an iturin deficient mutant.
The multi-enzyme system responsible for the biosynthesis of iturin, an antifungal lipopeptide of Bacillus subtilis, was partially purified by chromatography on different affigels. In the wild-type strain, two subunits of the iturin synthetase (ITs and ITagp) were characterized: ITs activated only L-Ser, one of the iturin amino acid components, and ITagp activated L-Asn, D-Asn, L-Gln and L-Pro, amino acids corresponding to a partial sequence of iturin. In an iturin deficient mutant, the activity of the ITagp subunit was modified.
Anti-Bacterial Agents↗
Exposure of rat hippocampal neurons to amyloid beta peptide (25-35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I/glycogen synthase kinase-3 beta.
Exposure of rat hippocampal neurons to the peptide amyloid beta (A beta) (25-35) as well as A beta (1-40) peptides enhances phosphorylation of tau to a paired helical filament (PHF)-state through activation of tau protein kinase I (TPK I)/glycogen synthase kinase-3 beta (GSK-3 beta) [Busciglio, J., Lorenzo, A., Yeh, J. and Yankner, B.A., Neuron, 14 (1995) 879-888; Takashima, A., Ishiguro, K., Noguchi, K., Michel, G., Hoshi, M., Sato, K., Takahashi, M., Hoshino, T., Uchida, T. and Imahori, K., Neurosci. Meeting Abstr., 671 (1995) 17]. In order to examine the effects of A beta treatment on intracellular signaling mechanism, we have investigated the role of phosphatidyl inositol-3 (PI-3) kinase in the phosphorylation of tau. A beta (25-35) exposure induced an inactivation of PI-3 kinase and an activation of TPK I/GSK-3 beta in rat hippocampal culture. Wortmannin, an inhibitor of PI-3 kinase, also activated TPK I/GSK-3 beta, leading to an enhancement of tau phosphorylation and neuronal death in hippocampal culture. These results suggest that A beta (25-35) inhibition of PI-3 kinase results in the activation of TPK I/GSK-3 beta, the phosphorylation of tau, and resultant neuronal death in rat hippocampal neurons.
Alzheimer Disease↗
Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy.
The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy.
Adolescent↗
Novel and unusual deletion-insertion thalassemic mutation in exon 1 of the beta-globin gene.
Explore the source record for details and available documents.
Exons↗
Induction chemotherapy followed by allogeneic bone marrow transplantation or aggressive consolidation chemotherapy in childhood acute myeloblastic leukemia. A prospective study from the French Society of Pediatric Hematology and Immunology (SHIP).
In the LAME89/91 protocol, children with acute myeloid leukemia (AML) who achieved complete remission (CR) after induction chemotherapy, were treated either with allogeneic bone marrow transplantation (BMT) if they had an HLA-compatible related donor or with chemotherapy including high-dose cytarabine. The objectives of this study were to describe the overall results of this strategy and to compare the two post-remission arms. Two hundred and thirty-one children were enrolled in the protocol. Induction chemotherapy consisted of a combination of cytarabine and mitoxantrone. A CR was achieved in 204 children (88%).
Acute Disease↗
Demonstration of specific detection of anti-HCV IgM core antibodies.
The specificity of IgM isotype response directed against the putative core of hepatitis C virus (HCV core IgM) was demonstrated in HCV IgM EIA reactive samples. No interference was noted when samples with increasing levels of rheumatoid factor (RF) alone, or in combination with graded concentrations of anti-HCV IgG (HCV IgG), were tested. No deterioration in assay specificity was seen in 30 sera from patients wih monoclonal gammapathies (all isotypes). With Protein G affinity chromatography, RF/HCV IgG immune complexes and HCV core IgM antibodies displayed different binding characteristics, HCV core IgM appeared in the buffer eluate while HCV IgG/RF remained bound. With sucrose density gradient centrifugation HCV core IgM sedimented at 17-19S.
Antigens, Viral↗
Lack of monomeric IgM anti-hepatitis C virus (HCV) core antibodies in patients with chronic HCV infection.
Antibodies of the IgM class against the hepatitis C virus core antigen are found in up to 70% of patients with either acute or chronic hepatitis C. The sedimentation rate of such IgM was analyzed by rate-zonal centrifugation of nine sera taken from seven patients, two acutely and five persistently infected with hepatitis C virus. All patients had circulating high-molecular weight (i.e. pentameric) IgM, indicating that the production of low molecular weight IgM, commonly observed in other persistent viral infections, does not apply to hepatitis C virus and cannot be used to distinguish acute from chronic hepatitis C virus infection.
Chronic Disease↗
FK506 in the treatment of inflammatory skin disease: promises and perspectives.
The immunosuppressive macrolide drug FK506 is currently gaining increasing importance in dermatopharmacology. Here, Gunter Michel and colleagues summarize the current state of research into the molecular mechanisms responsible for the functional modulation of cell types other than T cells, particularly epidermal cells, by this drug.
Animals↗
The quantitative humoral immune response to the hepatitis C virus is correlated with disease activity and response to interferon-alpha.
BACKGROUND/AIM: Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated during the clinical course of HCV-infected patients. METHODS: Eighteen selected chronic HCV patients received three doses of 3 or 6 MU interferon-alpha 2a weekly for 6 to 12 months and were followed up for 6 to 60 months. Anti-HCV antibody levels were serially measured either in end-point diluted sera with the Matrix-Assay or with quantitative anti-HC34-IgG and -IgM ELISA. Circulating immune complexes were assessed by flow cytometry and the results were correlated with histology, quantitative HCV-RNA levels and genotypes. RESULTS: Nine complete responders (CR; genotypes 1a n = 4; 1b n = 1; 2a n = 1; 3a n = 3) showing sustained virus elimination and ALT normalisation had low HCV-RNA pretreatment levels (mean 14 x 10(3) copies/ml) compared to six nonresponders and three partial responders (NR/PR; genotypes 1a n = 2; 1b n = 7) who had significantly higher HCV-RNA pretreatment levels (mean 254 x 10(3) copies/ml; p < 0.01). In untreated NR/PR the HC34 core-antigen was most immunogenic, in CR the NS3-derived HC29-antigen. Pre-treatment levels of anti-HC 34-IgG and -IgM antibody levels in NR/PR were higher than in CR (IgM/IgG p = 0.05, n.s.) and these differences became significant during or after therapy (3 months therapy: IgM p < 0.02/IgG p < 0.07; end of therapy: IgM 0.006/IgG p < 0.04; 6 months post-therapy: IgM p < 0.002/IgG p < 0.004). The PR patients showed recurrent anti-HC34 antibody levels that preceded disease reactivation and detectable HCV-RNA in serum. Immune complex formation increased in some patients during treatment but did not correlate with disease activity, quantitative viraemia, antibody levels or therapy outcome. CONCLUSION: Anti-HC34 antibodies, i.e. of the IgM-subtype, correlated quantitatively with viraemia and disease activity. Monitoring the antibody levels may predict the long-term therapy outcome during interferon-alpha treatment.
Adult↗
Serological pattern of hepatitis C virus recurrence after liver transplantation.
BACKGROUND/AIMS: Hepatitis C infection is characterized by a high incidence of liver cirrhosis, frequently requiring liver transplantation. After orthotopic liver transplantation, recurrence of hepatitis C virus infection is common, but often difficult to differentiate from allograft rejection. In this context the role and diagnostic value of hepatitis C virus-associated markers like the anti-GOR response have not yet been determined. In this study we analyzed the time course of hepatitis C virus recurrence in hepatitis C virus-infected patients who underwent liver transplantation because of end-stage cirrhosis or acute liver failure. METHODS: We evaluated the serological pattern and diagnostic significance of anti-HCV, anti-HCV-IgM, anti-HCV-core, anti-HCV-core 5-27, anti-GOR, anti-GOR-IgM and HCV-RNA in serial serum samples during hepatitis C virus recurrence with or without allograft rejection up to 5-64 months after orthotopic liver transplantation. For comparison, we also studied these markers in serial serum samples from previously uninfected patients who acquired hepatitis C virus-infection during or shortly after orthotopic liver transplantation. Hepatitis C virus-infected patients who had undergone orthotopic liver transplantation were identified by screening pre-transplant sera from 235 patients for the presence of anti-HCV (2nd generation ELISA) and serum HCV-RNA (reverse transcription polymerase chain reaction). RESULTS: Of 218 patients transplanted for end-stage liver cirrhosis, 65 (30%) were anti-HCV positive and 33 (15%) were HCV-RNA positive, while only one of 17 patients (6%) transplanted for acute liver failure was found to be anti-HCV positive without detectable HCV-RNA. Fifty-two hepatitis C virus-infected patients were studied serially before and after liver transplantation: 46 patients (89%) showed recurrent anti-HCV antibodies within 3 months and 51 patients (98%) within 42 months after orthotopic liver transplantation. Serum HCV-RNA was detected in 39 patients (75%) within 3 months and in 44 patients (85%) within 42 months after orthotopic liver transplantation. In the patients studied serially during hepatitis C virus-recurrence, anti-GOR antibodies displayed the same serological profile as hepatitis C virus antibodies, i.e. a decrease after orthotopic liver transplantation and slowly rising titers when HCV-RNA became detectable again. De novo infection with hepatitis C virus as studied in four patients produced a significant peak of anti-HCV titers accompanied or followed by an increase in anti-GOR titers, indicating that the immune response to GOR-autoantigen is triggered by the hepatitis C virus. No significant diagnostic difference between anti-GOR and anti-HCV was noted during hepatitis C virus recurrence and allograft rejection.
Amino Acid Sequence↗