AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jej...AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P < 0.05) in the jejunum,whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.展开更多
This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrat...This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.展开更多
AIM: To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype, we have studied the expression of smoothelin in fibrotic conditions.
The duodenal metastases of a malignant melanoma are rare. We report a case at a 86-year-old, hypertense patient, without tumoral history, who was hospitalized in our department for a change of the general state and an...The duodenal metastases of a malignant melanoma are rare. We report a case at a 86-year-old, hypertense patient, without tumoral history, who was hospitalized in our department for a change of the general state and an anaemia ferriprive without found home (foyer) of display. In the clinical examination, we had found anemia syndrome, nodules under cutaneous about 2 cm in diameter at the level of the thorax, of the belly, the members and of the lower lip partners in a painless left adenopathy axillary about 3 cm in diameter and an absence of méléna in the rectal touch. The gastroscopy had highlighted polypoides ulcéro-bourgeonnantes hurts with a blackish pigmentation by places at the level of the bulb and of the second duodenum. In the histology of biopsie fragments, we noted a fuso-cellular proliferation and epithelioid with deposits of melanin. The positivity of antibodies anti-protein S100 and anti HMB45 in the immunohistochemical study allowed confirming the diagnosis. The gastroduodenal hurts, persons suffering from a liver complaint and lungworts in the scanner testify of a terminal metastatic scattering. The death arose two months later, in a picture of circulatory collapse further to a high digestive bleeding of big abundance.展开更多
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are assoc...Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.展开更多
Introduction. Postransplantlymphoproliferative disorders are well known complications of solid organ transplant, usually associated with Epstein-Barr virus (EBV). Observation. A 25 year old renal transplant patient pr...Introduction. Postransplantlymphoproliferative disorders are well known complications of solid organ transplant, usually associated with Epstein-Barr virus (EBV). Observation. A 25 year old renal transplant patient presented with two subcutaneous nodules on the lower limb that appeared 3 years after a second renal transplantation. Biopsy of one nodule showed an EBV associated plasmocytoma located in the subcutaneous tissue. A complete systemic evaluation showed no evidence of extracutaneous involvement. The patient was treated with anti CD2O therapy (rituximab), and complete remission was achieved. Discussion. Extranodular localisations of postransplant lymphoproliferative disorders are usually reported, but cutaneous localizations are rarely described. Histological presentation are various, but plasmocytoma-type is infrequent. Initial therapy of cutaneous EBV-associated postransplant lymphoproliferative disorders without extracutaneous involvement consists in reduction of the immunosuppression therapy and/or an antiviral treatment and prolonged surveillance. Treatment with monoclonal anti-CD2O antibodies (rituximab) is proposed.展开更多
Objective: The aim of this study was to highlight the outcome of complete hyda tidiform mole (CHM) coexisting with a live co-twin. Methods: We investigated fo ur cases of such pregnancy by ultrasound, pathological, cy...Objective: The aim of this study was to highlight the outcome of complete hyda tidiform mole (CHM) coexisting with a live co-twin. Methods: We investigated fo ur cases of such pregnancy by ultrasound, pathological, cytogenetic, and molecul ar techniques. Information on clinical follow-up and outcome was also available . Results: All four pregnancies were spontaneous: two ended with the delivery of a live-born baby, while the other two were terminated because of signs of seri ous maternal pathology or intrauterine fetal death. The criteria for carrying on with the pregnancy are reviewed. The immediate outcome depends on the maternal criteria of serious pathology and on the likelihood of intrauterine fetal death. The risk of persistent trophoblastic disease (PTD) is the same as in the case o f a singleton complete mole and also seems to be correlated with the zygosity me chanism identified by molecular analysis. Conclusion: Hydatiform mole with a liv e co-twin fetus is a rare obstetric occurrence. In the case of a normal fetal k aryotype, it is justifiable to await developments in the absence of maternal com plications. However, treatment criteria still need improvement and diligent mate rnal follow-up is always warranted in the postpartum period.展开更多
文摘AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P < 0.05) in the jejunum,whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.
基金Supported by Association pour la Recherche sur le Cancer,No.3194
文摘This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.
基金Supported by In part a grant from the French Ministry of Research
文摘AIM: To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype, we have studied the expression of smoothelin in fibrotic conditions.
文摘The duodenal metastases of a malignant melanoma are rare. We report a case at a 86-year-old, hypertense patient, without tumoral history, who was hospitalized in our department for a change of the general state and an anaemia ferriprive without found home (foyer) of display. In the clinical examination, we had found anemia syndrome, nodules under cutaneous about 2 cm in diameter at the level of the thorax, of the belly, the members and of the lower lip partners in a painless left adenopathy axillary about 3 cm in diameter and an absence of méléna in the rectal touch. The gastroscopy had highlighted polypoides ulcéro-bourgeonnantes hurts with a blackish pigmentation by places at the level of the bulb and of the second duodenum. In the histology of biopsie fragments, we noted a fuso-cellular proliferation and epithelioid with deposits of melanin. The positivity of antibodies anti-protein S100 and anti HMB45 in the immunohistochemical study allowed confirming the diagnosis. The gastroduodenal hurts, persons suffering from a liver complaint and lungworts in the scanner testify of a terminal metastatic scattering. The death arose two months later, in a picture of circulatory collapse further to a high digestive bleeding of big abundance.
基金supported by the European Research Council(CoG 2020 grant number 101000948 awarded to GC)the Agence Nationale de la Recherche-Programme d’Investissements d’Avenir(ANR-18-RHUS-005 to GC)+1 种基金the Agence Nationale de la Recherche-Programme de Recherche Collaborative(19-CE14-0030-01 to GC)supported by the CLOVES SYNDROME COMMUNITY(West Kennebunk,USA),Association Syndrome de CLOVES(Nantes,France),Fondation d’entreprise IRCEM(Roubaix,France),Fonds de dotation Emmanuel BOUSSARD(Paris,France),the Fondation DAY SOLVAY(Paris,France),the Fondation TOURRE(Paris,France)to GC,the Fondation BETTENCOURT SCHUELLER(Paris,France)to GC,the Fondation Simone et Cino DEL DUCA(Paris,France),the Fondation Line RENAUD-Loulou GASTE(Paris,France,the Fondation Schlumberger pour l’Education et la Recherche(Paris,France),the Association Robert Debrépour la Recherche.
文摘Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.
文摘Introduction. Postransplantlymphoproliferative disorders are well known complications of solid organ transplant, usually associated with Epstein-Barr virus (EBV). Observation. A 25 year old renal transplant patient presented with two subcutaneous nodules on the lower limb that appeared 3 years after a second renal transplantation. Biopsy of one nodule showed an EBV associated plasmocytoma located in the subcutaneous tissue. A complete systemic evaluation showed no evidence of extracutaneous involvement. The patient was treated with anti CD2O therapy (rituximab), and complete remission was achieved. Discussion. Extranodular localisations of postransplant lymphoproliferative disorders are usually reported, but cutaneous localizations are rarely described. Histological presentation are various, but plasmocytoma-type is infrequent. Initial therapy of cutaneous EBV-associated postransplant lymphoproliferative disorders without extracutaneous involvement consists in reduction of the immunosuppression therapy and/or an antiviral treatment and prolonged surveillance. Treatment with monoclonal anti-CD2O antibodies (rituximab) is proposed.
文摘Objective: The aim of this study was to highlight the outcome of complete hyda tidiform mole (CHM) coexisting with a live co-twin. Methods: We investigated fo ur cases of such pregnancy by ultrasound, pathological, cytogenetic, and molecul ar techniques. Information on clinical follow-up and outcome was also available . Results: All four pregnancies were spontaneous: two ended with the delivery of a live-born baby, while the other two were terminated because of signs of seri ous maternal pathology or intrauterine fetal death. The criteria for carrying on with the pregnancy are reviewed. The immediate outcome depends on the maternal criteria of serious pathology and on the likelihood of intrauterine fetal death. The risk of persistent trophoblastic disease (PTD) is the same as in the case o f a singleton complete mole and also seems to be correlated with the zygosity me chanism identified by molecular analysis. Conclusion: Hydatiform mole with a liv e co-twin fetus is a rare obstetric occurrence. In the case of a normal fetal k aryotype, it is justifiable to await developments in the absence of maternal com plications. However, treatment criteria still need improvement and diligent mate rnal follow-up is always warranted in the postpartum period.