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C Sempoux

Publications and source records attributed to C Sempoux.

At least 37 records · Page 2Linked to original sources
PubMed1999

After portal branch ligation in rat, nuclear factor kappaB, interleukin-6, signal transducers and activators of transcription 3, c-fos, c-myc, and c-jun are similarly induced in the ligated and nonligated lobes.

Several studies have emphasized the involvement of transcription factors, cytokines, and proto-oncogenes in initiating the regenerative process after partial hepatectomy. To assess whether these events do specifically occur in a cellular system undergoing regeneration, we studied the induction of nuclear factor kappaB (NFkappaB), interleukin-6 (IL-6), signal transducers and activators of transcription 3 (Stat3), c-fos, c-myc, c-jun, after portal branch ligation (PBL), which produces atrophy of the deprived lobes (70% of the liver parenchyma), whereas the perfused lobes undergo compensatory regeneration. Nuclear extracts and total RNA were prepared from control livers as well as from atrophying and regenerating lobes at 0.5, 1, 2, 5, and 8 after PBL. NFkappaB and Stat3 induction were studied by electrophoretic mobility shift assays and Western blotting. IL-6 and proto-oncogenes expressions were assessed by reverse transcription polymerase chain reaction and Northern blotting, respectively. Assays were also performed after a sham operation. NFkappaB and Stat3 protein expression and DNA binding were rapidly and similarly induced in nuclear extracts from the atrophying and regenerating lobes. IL-6 was elevated in both lobes from 1 to 8 hours after PBL as well as c-fos, c-myc, and c-jun during the first 2 hours. IL-6 and Stat3 but not NFkappaB were also elevated after a sham operation. These findings suggest that the cellular and molecular changes occurring early in a regenerating liver are nonspecific, possibly stress-induced, cellular responses. They do not indicate the future evolution towards atrophy or regeneration.

Animals↗
PubMed1999

HLA association of amoxicillin-clavulanate--induced hepatitis.

BACKGROUND & AIMS: Drug-induced immunoallergic hepatitis typically affects a minority of patients exposed to a particular drug. Its rarity is believed to be due to metabolic or immunologic idiosyncrasy. The presence of an immunologic idiosyncrasy might imply an HLA association. Previous studies reporting an HLA association of drug-induced hepatitis included only small numbers of patients and used serological HLA typing. METHODS: We studied 35 patients with biopsy-documented amoxicillin-clavulanate-induced hepatitis. HLA-A and -B were typed using alloantisera and compared with those of 300 controls (volunteer bone marrow donors). HLA-DRB and -DWB were typed by polymerase chain reaction-line probe assay, with 60 volunteer bone marrow donors serving as controls. RESULTS: The study group was characterized by a higher frequency of DRB1*1501-DRB5*0101-DQB1*0602 haplotype (57.1% vs. 11.7% in controls, P < 0.000005; after correction for the large number of comparisons, P < 0.0002). Patients with DRB1*1501-DRB5*0101-DQB1*0602 haplotype were more likely than patients without it to have a cholestatic (70% vs. 60%) or mixed (30% vs. 13%) than a hepatocellular pattern of hepatitis (0% vs. 27%) (P < 0.05). CONCLUSIONS: Amoxicillin-clavulanate-induced hepatitis is associated with the DRB1*1501-DRB5*0101-DQB1*0602 haplotype. The data support the view that an immunologic idiosyncrasy, mediated through HLA class II antigens, plays a role in the pathogenesis of drug-induced immunoallergic hepatitis. HLA association has a limited impact on the expression of hepatitis.

Adult↗
PubMed1999

CYP 3A proteins are expressed in human neutrophils and lymphocytes but are not induced by rifampicin.

Cytochrome P-450 3A (CYP 3A) enzymes, the prominent subfamily in the cytochrome system, are expressed in various extrahepatic tissues. Until now, their expression has been demonstrated in human polymorphic neutrophils (PMNs) but not in lymphocytes using immunohistochemistry and immunoblot analysis. Moreover, their potential modulation has not been determined yet. To study such an expression in different peripheral blood cell populations, rifampicin (600 mg/day during 6 days) was given to 8 healthy subjects. PMNs and lymphocytes were isolated by centrifugation of whole white blood cell fractions using Ficoll gradients before drug administration, immediately after, and 3 days after drug withdrawal. PMN and lymphocyte smears and homogenates were subjected to immunostaining and immunoblotting, respectively, with a mouse monoclonal antibody recognizing all CYP 3A proteins. These proteins were quantified by densitometric analysis. Before and after rifampicin administration, a positive cytoplasmic staining was observed in all PMNs and in about 50% of lymphocytes. CYP 3A expression in lymphocytes was further confirmed by positive immunoblots for lymphocyte homogenates. Neither in PMNs nor in lymphocytes, induction of CYP 3A protein expression was observed after rifampicin treatment despite overall induction of CYP 3A activity assessed by the urinary excretion of 6beta-hydroxycortisol. These results demonstrate that CYP 3A proteins are constitutively expressed not only in PMNs but also in lymphocytes. However, in both cell lineages CYP 3A protein expression was not induced by rifampicin.

Adult↗
PubMed1998

Partial or near-total pancreatectomy for persistent neonatal hyperinsulinaemic hypoglycaemia: the pathologist's role.

AIMS: To determine whether the presence of abnormal B-cell nuclei predicts the existence of a focal or of a diffuse form of persistent neonatal and infantile hyperinsulinaemic hypoglycaemia in a series of 20 infants. METHODS AND RESULTS: Intra-operative frozen sections were performed on small specimens from the pancreatic head, isthmus and tail. In 13 cases, abnormal B-cell nuclei were identified, but even a near-total pancreatectomy was insufficient to cure some of these patients, in whom no focal lesion was detected. On the other hand, abnormal insular B-cell nuclei were not found in seven cases; based on the results of selective venous catheterization, a limited resection was performed, sufficient to cure each patient, and a focal adenomatous hyperplasia was found in each resected specimen. CONCLUSIONS: Intra-operative examination of small pancreatic specimens taken from the different parts of the gland allows one to determine the type of lesion (focal or diffuse) in neonatal onset hyperinsulinaemic hypoglycaemia, and to decide on the most appropriate surgical treatment.

Cell Nucleolus↗
PubMed1998

Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis.

The two major forms of infantile persistent hyperinsulinemic hypoglycemia require different treatments, but are difficult to differentiate during surgery. Indeed, one is characterized by focal adenomatous hyperplasia often macroscopically invisible, whereas the other consists of a diffuse, but discreet, beta-cell abnormality. We evaluated, in a large series of persistent hyperinsulinemic hypoglycemia, the reliability of two criteria in differentiating these two forms: the mean beta-cell nuclear radius (MNR) and the beta-cell nuclear crowding, i.e. the number of nuclei per 1000 micron 2 beta-cell (BCNC). The values of the largest MNR and of BCNC in cases bearing a focal lesion (respectively, 3.27 microns +/- 0.25 and 14.62 +/- 1.78) were significantly different from those in the diffuse pathology (4.25 microns +/- 0.43 and 10.00 +/- 1.55). Setting the threshold value of MNR at 3.70 microns and that of BCNC at 12.00 enabled correct classification of 90.9% of the diffuse and 100% of the focal forms. beta-Cell nuclear analysis can thus contribute to a subclassification of the syndrome, not allowed by clinical or biological data. If performed during surgery it could help in determining the extent of pancreatectomy necessary to cure the patient, as the diffuse form, with abnormal nuclei in the whole pancreas, requires subtotal to near-total pancreatectomy, whereas the focal form, devoid of abnormal insular beta-cell nuclei, can be cured by partial pancreatectomy.

Cell Nucleus↗
PubMed1998

Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of infancy: an immunohistochemical study of 18 cases.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by severe hypoglycemia related to inappropriate insulin secretion. Morphologically, a tumoral and a nontumoral form are recognized. The tumoral form can be subdivided into adenomatous hyperplasia (in infants) and adenoma (in children). On the other hand, nesidioblastosis, considered until recently as a persistent B-cell replication, has repeatedly been proposed as the condition responsible for the nontumoral form of PHHI. We studied the proliferation rate of B cells in 18 patients affected by PHHI (7 nontumoral and 11 tumoral cases, including 4 adenomas and 7 adenomatous hyperplasias) and in 18 age-matched controls, using a double immunohistochemical technique detecting Ki-67, a nuclear endogenous antigen only present during cell proliferation, and insulin as pancreatic B-cell markers. Our results clearly show that "nesidioblastosis" is not related to an abnormal B-cell proliferation, because the B-cell labeling index (LI), reported as the mean plus or minus the standard error of the mean, is not statistically different between nontumoral PHHI (29.4 +/- 7.4) and age-matched controls (19.6 +/- 5.3). Furthermore, the Ki-67 positivity was not more prominent in small clusters of B cells in nesidioblastosis than in large islets. In tumoral PHHI, the LI was significantly higher in cases of focal adenomatous hyperplasia (77.6 +/- 10.9) than in either age-matched controls (19.9 +/- 6.9; P < .005) or in adenomas (27.9 +/- 13.7; P < .025); the values of this last group did not differ from those of age-matched controls (18.5 +/- 8.5). These data definitely demonstrate that nesidioblastosis does not correspond to an abnormal B-cell proliferation and that the focal forms of PHHI must be subclassified.

Adenoma↗
PubMed1997

Severe radiation-induced liver disease following localized radiation therapy for biliopancreatic carcinoma: activation of hepatic stellate cells as an early event.

Radiation-induced liver disease is recorded as a form of veno-occlusive disease. Its pathogenesis remains unclear even if the initial injury likely occurs in the endothelial cells of central veins. The aim of our study was to investigate liver morphological features in relation to alpha-isoform of smooth muscle actin expression in hepatic stellate cells in six patients treated by localized radiotherapy on the biliopancreatic area. Within the month after completion of treatment, an activation of hepatic stellate cells strictly confined to irradiated areas and coinciding with congestive changes was observed. At a later stage, collagen deposition gradually increased, replacing the congestive and destroyed areas. This new fibrotic tissue also contained numerous alpha-smooth muscle positive cells. Our data suggest that early hepatic stellate cells activation coinciding with congestive changes plays an important role in radiation liver injury and ensuing fibrosis.

Actins↗
PubMed1997

Acute lobular hepatitis as the first manifestation of recurrent autoimmune hepatitis after orthotopic liver transplantation.

Recurrence of autoimmune hepatitis after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in a 43-year-old man. Diagnosis was based on biological, serological and morphological data, as well as on a complete biological recovery following steroid resumption. Recurrence was observed only 4 months after transplantation, when an abrupt increase in liver function tests was observed in association with a mainly lobular hepatitis in liver biopsy. Such a histological appearance has been previously described in the case of recurrence after immunosuppressive treatment weaning in non-transplanted patients. In contrast, this histological feature has not been reported in the rare transplanted patients in whom such recurrence has been observed. Thereafter, the evolution of the disease in our patient remained slow, likely dampened by the administration of cyclosporine and azathioprine. Morphological features are detailed, and importance of immunosuppressive therapy in patients transplanted for end-stage autoimmune hepatitis is emphasized.

Acute Disease↗
PubMed1997

[Pancreatic adenomatous hyperplasia and sudden infant death].

We report the observation of a sudden infant death in which autopsy revealed a focal pancreatic lesion called adenomatous hyperplasia. Histopathological and immunohistochemical characteristics of this lesion are detailed. Adenomatous hyperplasia and endocrine cell dysplasia are the two pancreatic lesions responsible for hyperinsulinemic hypoglycemia in infants, with a possible fatal evolution. An organic pancreatic lesion is exceptionally reported in observations of sudden infant death. These observations and ours point out the necessity of a meticulous post-mortem examination of the pancreas in sudden infant death.

Adenoma↗
PubMed1996

Hepatic angiomyo(myelo)lipoma: difficulties in radiological diagnosis and interest of fine needle aspiration biopsy.

We report the case of a patient admitted for acute heart failure associated with severe dilated cardiomyopathy in whom a large hepatic tumor of the right lobe of the liver was incidentally discovered. A fine needle biopsy was performed that led to the diagnosis of angiomyo(myelo)-lipoma (AMML). The difficulties in radiological diagnosis of these very rare heterogeneous benign tumors of the liver and the interest of fine needle aspiration biopsy are discussed.

Angiomyolipoma↗
PubMed1995

Nesidioblastosis and persistent neonatal hyperinsulinism.

Neonatal hyperinsulinism is characterized by severe hypoglycaemia which can cause serious neurologic effects. Pancreatic morphological abnormalities involve either focal or diffuse lesions. The former can be cured by resection, whereas the latter, of uncertain pathogenesis, often require subtotal pancreatectomy. We investigated various hypotheses in an effort to explain the origin of this latter form of hyperinsulinism. We determined that nesidioblastosis, long considered to be the basic structural lesion of the diffuse form of hyperinsulinism, is not specific and does not correspond to a continuous proliferation of endocrine cells. We found that an increase in beta-cell mass can be excluded since the volume density of beta cells is not systematically higher in hyperinsulinemic infants than in controls. The hypothesis of a decrease in D cells is attractive but should be considered with due caution since the decrease of the D-cell volume density observed in hypoglycaemic infants is inconstant. Finally, the notion of beta-cell functional abnormality seems the most likely explanation since a higher quantity of proinsulin was detected within the Golgi area by a specific antibody and abnormal nuclei with abundant cytoplasm were observed in some cells. These histological abnormalities can be observed during intraoperative morphological examination. Functional activity might also be evaluated by studying the messenger RNA of proinsulin.

Chronic Disease↗
PubMed1995

[Effect of local medications on intraocular pressure control following trabeculectomy].

Longterm administration of topical antiglaucoma therapies had been indicated to be a serious risk for failure of trabeculectomy through inducing a subclinical inflammation of conjunctival tissues and stimulating secondary fibroblastic proliferation. Our study had 3 main aims: (1) to check if this pejorative effect is present in our population of glaucomatous patients, (2) in order to improve the rate of surgical success in theoretically high risk patients (duration of topical treatment longer than 36 months), to determine the usefulness of the following actions: suppression of beta blocking agents 8 days before surgery, suppression of miotics and eventual topical administration of fluorometholone one month before surgery. (3) to correlate the observed clinical results to the cellular profile of preoperative conjunctival biopsies. We presented in a first step the results of a retrospective analysis including 88 trabeculectomies performed between January '93 and April '95 in 62 GCAO patients older than 40 years and without any previous ocular surgery. The mean age of patients was 66,8 years (41 to 87 years). Patients were classified into "complete success", "qualified success" and "failures" according to the "target" IOP was or was not reached in the last examination. Mean follow up was 5,8 months (1 to 26 months). The second prospective part of our study included 20 trabeculectomies performed in 16 patients we chose according to the nature, the duration of the preoperative topical therapy and the preoperative eventual preparation of the conjunctiva. This study also included a semiquantitative count of the different conjunctival cellular colonies in peroperative biopsies. Mean follow up of this study was 2,3 months (1 to 5 months). 31 "complete success", 52 "qualified success" and 5 "failure" were observed in the retrospective study. The reduction of IOP following trabeculectomy was statistically significant at all examinations (mean IOP in the last examination: 14,9 +/- 4,3 mmHg) but the level of success was not significantly different according to the nature, (mono against polytherapy), the duration of preoperative medical topical treatment, as well as the preoperative actions in order to improve the operative success in high risk patients. Preliminary results of our second prospective study did not yet show any failure and did not exhibit any clear correlation between the counts of the different cellular colonies and the level of operative success on one hand and the different topical therapies in the other hand. The results and limitations of this study were compared to those of the literature.

Adrenergic beta-Antagonists↗
PubMed1994

Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric liver allografts. Efficacy, toxicity, and dose regimen in 23 children.

Twenty-three pediatric liver transplant recipients (median age 3.9 years) were converted from cyclosporine A-based immunosuppression to FK506 for uncontrollable acute rejection (AR; n = 16), chronic rejection (n = 4), or predominantly nonspecific hepatitis (n = 3). Of these, 19 had received poly- or monoclonal anti-T lymphocyte antibodies either for AR prophylaxis or therapy before FK506 conversion. Full clinical and histologic responses to FK506 therapy were observed in 11/16 cases of AR compared with 0/7 cases of non-AR indications (P = 0.006). Acute FK506 toxicity included renal dysfunction in 12/23 children (52%), neurological disorders in 7/23 (30%), and isolated hyperkalemia in 2/23 (9%), with a poor correlation with the corresponding FK506 trough plasma level. Moreover, a significant impairment of glomerular filtration rate was recorded in the 12 children who received FK506 treatment for more than 6 months (P = 0.002). FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n = 4; persistent tremor: n = 1; reason unrelated to FK506: n = 1). Five children developed a lymphoproliferative syndrome (LPS), leading to death in 3 cases despite cessation of the immunosuppressive therapy; in the other 2 patients, LPS was controlled, and the children were successfully retransplanted for chronic rejection under FK506. The occurrence of Epstein-Barr virus primary infection under FK506 therapy was found to constitute a significant risk factor for LPS (P = 0.027). In summary, full response to FK506 conversion was observed in 69% of uncontrollable AR cases; however, 74% and 22% of this probably over-immunosuppressed population experienced major adverse events and LPS under FK506 therapy, respectively.

Adolescent↗