Targeting of cytosolic phospholipase A2 to plasma membrane inhibits its activation by G-protein coupled receptors.
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Animals↗
Biomedical subjects
D Wendum
Publications and source records attributed to D Wendum.
Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis.
We tested the potential role of vascular endothelial growth factor (VEGF) and of fibroblast growth factor-2 (FGF-2) in the angiogenesis associated with experimental liver fibrogenesis induced by common bile duct ligation in Sprague-Dawley rats. In normal rats, VEGF and FGF-2 immunoreactivities were restricted to less than 3% of hepatocytes. One week after bile duct ligation, hypoxia was demonstrated by the immunodetection of pimonidazole adducts unevenly distributed throughout the lobule. After 2 weeks, hypoxia and VEGF expression were detected in >95% of hepatocytes and coexisted with an increase in periportal vascular endothelial cell proliferation, as ascertained by Ki67 immunolabeling. Subsequently, at 3 weeks the density of von Willebrand-labeled vascular section in fibrotic areas significantly increased. Semiquantitative reverse transcription polymerase chain reaction showed that VEGF(120) and VEGF(164) transcripts, that correspond to secreted isoforms, increased within 2 weeks, while VEGF(188) transcripts remained unchanged. FGF-2 mainly consisting of a 22-kd isoform, according to Western blot, was identified by immunohistochemistry in 49% and 100% of hepatocytes at 3 and 7 weeks, respectively. Our data provide evidence that in biliary-type liver fibrogenesis, angiogenesis is stimulated primarily by VEGF in response to hepatocellular hypoxia while FGF-2 likely contributes to the maintenance of angiogenesis at later stages.
Animals↗
N-terminal and C-terminal plasma membrane anchoring modulate differently agonist-induced activation of cytosolic phospholipase A2.
The 85 kDa cytosolic phospholipase A2 (cPLA2) plays a key role in liberating arachidonic acid from the sn-2 position of membrane phospholipids. When activated by extracellular stimuli, cPLA2 undergoes calcium-dependent translocation from cytosol to membrane sites which are still a matter of debate. In order to evaluate the effect of plasma membrane association on cPLA2 activation, we constructed chimeras of cPLA2 constitutively targeted to the plasma membrane by the N-terminal targeting sequence of the protein tyrosine kinase Lck (Lck-cPLA2) or the C-terminal targeting signal of K-Ras4B (cPLA2-Ras). Constitutive expression of these chimeras in Chinese hamster ovary cells overproducing the alpha2B adrenergic receptor (CHO-2B cells) did not affect the basal release of [3H]arachidonic acid, indicating that constitutive association of cPLA2 with cellular membranes did not ensure the hydrolysis of membrane phospholipids. However, Lck-cPLA2 increased [3H]arachidonic acid release in response to receptor stimulation and to increased intracellular calcium, whereas cPLA2-Ras inhibited it, compared with parental CHO-2B cells and CHO-2B cells producing comparable amounts of recombinant wild-type cPLA2. The lack of stimulation of cPLA2-Ras was not due to a decreased enzymatic activity as measured using an exogenous substrate, or to a decreased phosphorylation of the protein. These results show that the plasma membrane is a suitable site for cPLA2 activation when orientated correctly.
Amino Acid Sequence↗
Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy.
The association of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is thought to be rare, and its optimal treatment is unknown. Of 130 consecutive patients with a diagnosis of PBC, we identified 12 cases (9.2%) of overlap syndrome (10 females, 2 males; median age, 50 years) strictly defined by the presence of at least two of the three recognized biochemical, serological, and histological criteria of each disease. One patient had initially pure PBC and developed AIH characterized by a flare of alanine transaminase (ALT) (1,330 IU/L; N < 35), elevated immunoglobulin G (IgG) (42 g/L; N < 14.0), and presence of anti-smooth muscle antibodies (ASMA) after 20 months of ursodeoxycholic acid (UDCA) therapy. A complete clinical and biochemical remission was achieved under combination of corticosteroids and UDCA. Eleven patients had features of both diseases at presentation: high serum levels of alkaline phosphatase (AP) (median: 280 IU/L; N < 100), ALT (140 IU/L), and IgG (30.8 g/L), presence of mitochondrial antibodies (n = 9) or ASMA (n = 9), florid bile duct lesions (n = 8), and moderate or severe periportal or periseptal lymphocytic piecemeal necrosis (n = 11). UDCA (13-15 mg/kg/d) given alone in 5 patients induced a significant decrease in biochemical cholestasis but not in ALT levels, and liver fibrosis progressed in 3 patients. Corticosteroids given alone in 6 patients induced a significant decrease in ALT, IgG, and AP levels, but none had a biochemical normalization. The patients with persistently abnormal liver tests under either UDCA or corticosteroids received both UDCA and corticosteroids. A further marked biochemical improvement was observed, and all patients became asymptomatic. We conclude that, in patients with PBC: 1) overlap syndrome with AIH is not rare; 2) flares of AIH may occur either spontaneously or under UDCA; and 3) combination of UDCA and corticosteroids is required in most patients to obtain a complete biochemical response. Overlap syndrome may represent an important and unrecognized cause of resistance to UDCA in patients with PBC.
Adrenal Cortex Hormones↗
Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.
PURPOSE: The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS: Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS: After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION: FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.
Adolescent↗
[Peritoneal tuberculosis. Value of laparoscopy].
We report 6 cases of tuberculous peritonitis, focusing on the contribution of laparoscopic exploration. The initial diagnosis was erroneus in all cases: the polymorphous clinical presentations suggested another infectious disease or cancer disease. Laparoscopy was performed in 5 patients who had ascitis and in 1 with plastic peritonitis. At laparoscopy, the peritoneum showed miliary granulations and inflammatory adherences on the visceral or parietal sheats. Bacteriological analyses of the ascitic fluid were positive in only one case. The diagnosis was confirmed after culture of biopsy specimens and identification of the Kock bacilli or on the basis of objective evidence of an epithelioid giant-cell granuloma with caseous necrosis. Outcome was favorable after appropriate antibiotic therapy.
Adult↗
[Peritoneal tuberculosis].
Peritoneal tuberculosis remains a common problem in impoverished areas of the world. Immigrants and AIDS patients are two population groups at particular risk for abdominal tuberculosis in our country. The most common presenting symptoms of tuberculous peritonitis are abdominal pain, ascites and weight loss in more than 80% of cases. Results of sonographics studies are non specific and high serum CA 125 levels can be found. Pulmonary tuberculosis is concomitantly discovered in 50% of cases. Tuberculous peritonitis is of the exsudative type in 95% of cases and requires multiple studies of peritoneal fluid. Tuberculous peritonitis is suspected when exsudate and lymphocytes are present with no malignant cells, and high interferon gamma and adenosine desaminase activity. AFB is detected in the peritoneal fluid cultured conventionally in 80% of cases. Laparoscopy combined with peritoneal biopsy is effective for the diagnosis of tuberculous peritonitis in 75 to 85% of cases. Peritoneal tuberculosis is treated with antituberculous drugs for a period of nine months.
Antitubercular Agents↗
[Hemorrhagic ascites disclosing massive Fasciola hepatica infection].
Multi-organ infection with Fasciola hepatica is uncommon. We report a case of severe infection with Fasciola hepatica as a cause of liver and peritoneum injuries with hemorrhagic ascites as well as pulmonary, pericardial, splenic and portal system injuries in a 37-year old man who was a native of Green Cape. The patient was in poor general health, had a major inflammatory syndrome, and polyclonal hypergammaglobulinemia (90 g/L). The diagnosis was confirmed by positive distomatosis serology and the presence of eggs of Fasciola hepatica in the histological samples of the liver and peritoneum. After treatment with praziquantel then triclabendazole, the global outcome was favorable.
Adult↗
[Primary leiomyosarcoma of bone: a clinico-pathologic and immunohistochemical study of 3 cases].
Primary leiomyosarcoma of bone is rare. Herein we describe 3 cases with immunohistochemical study. All 3 cases were positive for smooth muscle actin and/or desmin. None was positive for cytokeratin. Differential diagnosis includes metastatic spindle cell carcinoma, other sarcoma (fibrosarcoma, malignant fibrous histiocytoma) and metastatic extra-osseous leiomyosarcoma, mostly from uterus or digestive tract.
Adult↗
[Imaging of primary hepatic pheochromocytoma].
Extra-adrenal pheochromocytoma are extremely uncommon tumors. They demonstrate abdominal (97% of the cases), thoracic, vesical or cervical localizations. We report the case of a hepatic pheochromocytoma in a young patient with a post history of labile arterial hypertension. Ultrasonography, computed tomography and magnetic resonance imaging features were similar to those of adrenal pheochromocytoma. The presence of neuroendocrine cells was supported by immunohistochemical criteria. Histological observation showed a lack of local extension. In addition, four years after surgery, there was no apparent clinical syndrome suggesting tumor recurrence or metastasis occurrence. These observations supports the diagnosis of non malignant, primary hepatic pheochromocytoma. To our knowledge, this is the first radiologic description of this kind of tumor.
Adult↗
[Imaging of peritoneal mesotheliomas].
Peritoneal mesothelioma is a rare, either benign or malignant tumor of the peritoneum. We retrospectively analyzed the imaging features of six malignant and three benign peritoneal mesothelioma. Asbestos exposure was proven in three of the six malignant cases and in none of the three benign cases. Ascites was found in seven patients (78%), peritoneal masses in eight patients (88%), small peritoneal nodules in six patients (66%), parietal peritoneal thickening in six patients (66%), thickened mesentery in five patients (55%) and pleural plaques as well as nodules in one patient. These imaging features support the diagnosis of peritoneal mesothelioma but do not allow differentiation between benign and malignant forms of peritoneal mesothelioma.
Adult↗
Solitary fibrous tumor of the adrenal gland.
Solitary fibrous tumors are rare neoplasms, most commonly involving the pleura, recently described in various other locations. We report a solitary fibrous tumor of the right adrenal gland in a 42-year-old woman, discovered incidentally during abdominopelvic ultrasonographic examination. Pathologic and immunohistologic features of the tumor were identical to those of other solitary fibrous tumors. Three-quarters of this unencapsulated infiltrating tumoral mass presented foci of hemorrhage and were made of small, round, epithelioid-like cells that expressed the CD34 antigen more weakly than do the typical spindle cells usually observed in solitary fibrous tumors. Despite hemorrhage and poor limitation, the tumor behaved in a innocuous manner; the mass remaining unchanged for more than 5 years before the patient agreed to surgical intervention, which was recommended because of a sudden enlargement of the mass.
Adrenal Gland Neoplasms↗
[Imaging of symptomatic giant hemangioma].
A case of symptomatic giant hemangioma of the liver with fever, anemia, and increased erythrocyte sedimentation rate is reported. Spontaneous hyperdense areas at CT, and high signal-intensity areas at T1-weighted MR images were demonstrated within the hemangioma. Marked hemorrhagic zones demonstrated at pathologic examination may explain these uncommon clinical and imaging features.
Adult↗
[A case of polypoid solitary colonic plasmocytoma].
One case of polypoid solitary plasmacytoma in the sigmoid colon of a 60 year-old woman is presented. Plasmacytomas are rarely observed in the gastrointestinal tract and are especially uncommon in the côlon. Eight cases were published since 1972. They show a mean age of 46.3 years, a sex-ratio of 1/1, varying revealing symptoms, and no preferential colonic location. Two differential diagnosis must be discussed: an inflammatory pseudotumor, and a multiple myeloma related tumor. Multiple myeloma must be ruled out by a complete radiographic and biological research. Surgery is the only therapy described and seems to be efficient.
Colonic Polyps↗
Retrorectal developmental cysts in adults: clinical and radiologic-histopathologic review, differential diagnosis, and treatment.
Developmental cysts are the most common retrorectal cystic lesions in adults, occurring mostly in middle-aged women. They are classified as epidermoid cysts, dermoid cysts, enteric cysts (tailgut cysts and cystic rectal duplication), and neurenteric cysts according to their origin and histopathologic features. Although developmental cysts are often asymptomatic, patients may present with symptoms resulting from local mass effect (eg, constipation, rectal fullness, lower abdominal pain, dysuria), with a palpable retrorectal mass at digital rectal examination, or with a complication. Infection with fistulization, bleeding, and malignant degeneration are the major complications of developmental cysts. A well-defined, unilocular or multilocular, thin-walled cystic lesion is the main imaging feature. Uncommonly, a sacral bone defect and calcifications are associated with developmental cysts. The differential diagnosis includes cystic sacrococcygeal teratoma, anterior sacral meningocele, anal duct or gland cyst, necrotic rectal leiomyosarcoma, extraperitoneal adenomucinosis, cystic lymphangioma, pyogenic abscess, neurogenic cyst, and necrotic sacral chordoma. Complete surgical excision is indicated to establish the diagnosis and avoid complications.
Adult↗