Biomedical subjects
Publications and source records attributed to M Fabre.
Three children with Kawasaki disease had liver biopsies because of evidence of hepatic disease. Cholangitis or bile duct injury and proliferation were found. Similar damage to the hepatic ductular system may explain the hydrops of the gallbladder sometimes seen in this disease.
The effects of ascorbic acid deficiency on mouse incisors, grown in vitro, has been investigated at the histological and cytological levels. In this model, continuously growing mouse incisors are characterized by the existence of different type of predentin-dentin matrix on its lingual (root-analogue) and labial (crown-analogue) surface and the absence of enamel on the lingual surface. Our observations indicated that ascorbate-deficiency affected the behavior of mouse tooth germs in vitro: odontoblast differentiation was disturbed and morphological evidence for odontoblast-mediated collagen resorption were observed. An abnormal amorphous predentin-dentin matrix existed and the basement membrane was prematurely disrupted. The dentin mineralization, as well as functional differentiation of ameloblasts were strongly hampered. Chronic deficiency led to disorganization of the dental tissues.
A two-month-old girl presented with a unilateral benign cystic medulloepithelioma from the ciliary body associated with bilateral retinal non-attachment. The authors discuss the histopathologic findings and the pathogenesis of the congenital retinal non-attachment: are these incidental occurrences or do they arise from a common pathogenetic mechanism?
Mutant p53 has been found in a wide variety of human malignancies including carcinomas of the lung, breast and colon. Because of the controversial mutational rate of the p53 gene in hepatocellular carcinoma, a large series of liver tumors from white patients with different risk factors was examined immunohistochemically for expression of the p53 mutant to assess its prevalence and the relationships between p53 overexpression and clinicopathological data. Nine of 58 specimens were found to have detectable evidence of p53 gene mutation by virtue of the immunohistochemical detection of mutant p53 protein. The p53 mutation was more frequent in patients with serological hepatitis B and C markers than in patients without these markers (p = 0.046). The prevalence of p53-positive tumors was also significantly higher in the group of tumors with invaded portal branches than in the group without (p = 0.02). Our results showed that p53-positive hepatocellular carcinoma is a rare finding in patients exposed to a low dietary aflatoxin intake and that p53 mutation seems to occur at a late stage of the tumoral process and could contribute to an aggressive tumoral phenotype.
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Birbeck granules characterize under the electron microscope epidermal Langerhans cells. These distinctive pentalaminar organelles are indeed not detectable in the possible precursors of human Langerhans cells and tend to disappear in cultured human Langerhans cells. The mechanisms that lead to the appearance of Birbeck granules in epidermal Langerhans cells and to their later disappearance still remain unknown. In the present study we show that the more or less dilated elements of the surface-connected canalicular system of human blood platelets collapse after EDTA treatment. Made up of two parallel limiting membrane and central irregular striated density, these elements show great ultrastructural similarities with the Birbeck granules of human epidermal Langerhans cells. These platelet morphologic changes i) are directly dependent on the EDTA-induced dissociation of the glycoprotein GP IIb-IIIa, the platelet-specific calcium-dependent heterodimer complex, member of the beta 3 integrin subfamily (alpha IIb beta 3) and ii) apparently result from a cross-linking of the dissociated glycoproteins. These findings lead us to propose that in the same manner cells of the Langerhans lineage, on reaching the epidermis, will find themselves in contact with an epidermal specific ligand. Interactions between this epidermal ligand and Langerhans cell receptors could then induce, all along the circuit taken by the ligand-receptor complexes, morphologic modifications, i.e., appearance of structures of Birbeck granule type.
We report two cases of nodular regenerative hyperplasia of the liver associated with primary biliary cirrhosis. Cholestasis and presence of antimitochondrial antibodies were noted in both patients. In one patient, the diagnosis of nodular regenerative hyperplasia was supported by the demonstration of disseminated small hepatic nodules without perinodular fibrosis. Twelve years later, the histopathological picture was one of primary biliary cirrhosis. The other patient presented an histological picture of regenerative hyperplasia of the liver and primary biliary cirrhosis. The association of regenerative hyperplasia of the liver and primary biliary cirrhosis is discussed.
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Cholesterol ester storage disease is a rare disorder characterized by an hereditary deficiency of lysosomal acid lipase that induces an accumulation of cholesterol ester in most tissues of the body, particularly in liver. The diagnosis is usually made during childhood. The aim of this article is to report two new cases diagnosed in adult age. Two patients, 25 and 20 years old, respectively, presented with hepatomegaly, a slight to moderate increase in serum transaminases, and esophageal varices. In both cases, diagnosis was based on the presence of hypercholesterolemia, fatty infiltration of the liver with lipid droplets in hepatic parenchymal cells, foamy macrophages, hepatic storage of cholesterol esters, and low activity of lysosomal acid lipase. Histological abnormalities were associated with portal and periportal fibrosis in one patient and a micronodular cirrhosis in the other; these lesions were probably the cause of portal hypertension. Fibrosis of varied degrees has been previously reported in cholesterol ester storage disease. Its mechanism remains unclear.
A cDNA clone of murine macrophage inflammatory protein 2 (MIP-2) has been isolated from a library prepared from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the nucleotide sequence determined. This cDNA was used to clone cDNAs for human homologues of MIP-2 from a library prepared from phorbol myristate acetate-treated and LPS-stimulated U937 cells. Two homologues were isolated and sequenced. Human MIP-2 alpha and MIP-2 beta are highly homologous to each other and to a previously isolated gene, human gro/melanoma growth-stimulating activity (MGSA). These three human genes, MIP-2 alpha, MIP-2 beta, and gro/MGSA, constitute a sub-family within the cytokine family represented by platelet factor 4 and interleukin 8.
In man, three distinct classes of receptors for the Fc fragments of IgG (FcRI, II, III) have been defined. The FcRI has a Mr of about 72 kDa, binds human IgG-coated E, and is recognized by mAb such as 32. The FcRII has a Mr of 40 kDa, binds murine IgG1-coated E, and reacts with the mAb IV.3 and CIKM5, which recognize CDw32 moieties. Lastly, the FcRIII has a Mr of 50 to 70 kDa and is recognized by anti-CD16 mAb. In the present study we have shown that i) only murine IgG1-coated E form rosettes with 49 +/- 1.5% (mean +/- SEM, n = 9) of CD1a+ epidermal cells (EC) (which represent Langerhans and indeterminate cells) and that ii) the mAb anti-FcRII CIKM5 prevents this rosette formation. Among the mAb reacting with the three different types of FcR, only those recognizing FcRII i) stain about 55 +/- 1.5% (mean +/- SEM, n = 9) of the CD1a+ EC and ii) reveal the presence of dendritic cells in epidermal sheets obtained by suction blister. Under the electron microscope i) apparently all the cells forming rosettes or reacting with the gold-labeled anti-FcRII mAb (CIKM5 or the F(ab) fragment of IV.3) contained Birbeck granules and ii) the gold-labeled mAb were internalized in unfixed Langerhans cells by receptor-mediated endocytosis and accumulated in lysosomes. Labeling by the anti-FcRII mAb of the CD1a+ cells in suspension disappears after 48 h of culture. All these observations strongly suggest that CD1a+ EC express only the FcRII. This conclusion was confirmed by immunoprecipitation experiments, whereas no specific immunoprecipitate was noted with the anti-FcRI or anti-FcRIII mAb, the anti-FcRII mAb immunoprecipitated a protein of Mr 40 kDa.
Three different liver lesions were found in a 20-year-old woman with angioimmunoblastic lymphadenopathy. The lesions included nodular regenerative hyperplasia of the liver, perisinusoidal fibrosis, and peliosis hepatis. It is suggested that the association of angioimmunoblastic lymphadenopathy with this broad spectrum of liver lesions was not fortuitous.
A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood beta-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's urine contained excessive amounts of the C6 to C10 dicarboxylic acids present in almost all defects of fatty acid mitochondrial oxidation. More specifically, gas chromatography-mass spectrometry identified an accumulation of medium- and long-chain (C8 to C14) 3-hydroxy-dicarboxylic acids, suggesting a defect of the mitochondrial enzyme that normally dehydrogenates these 3-hydroxyacyl-CoA esters. Biochemical studies in the patient's cultured fibroblasts confirmed the impairment of medium- and long-chain fatty acid oxidation, and allowed the recognition of the deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase. The activities of long-, medium-, and short-chain acyl-CoA dehydrogenases and 3-ketoacyl-CoA thiolase were normal. These results describe a disorder of fatty acid metabolism that affects the liver, skeletal muscles, and myocardium. It is important to point out that long-chain 3-hydroxyacyl-CoA deficiency shares many clinical similarities with systemic carnitine deficiency, as well as with carnitine-palmityl-CoA transferase and long-chain acyl-CoA dehydrogenase deficiencies. The differential diagnosis of this disease relies on the demonstration of long-chain urinary dicarboxylic acids with a hydroxyl group in 3-position and the study of the enzyme activity in cultured fibroblasts.
A 39-year-old woman presented with polyneuropathy, hepatomegaly, splenomegaly, endocrinopathy, monoclonal protein and skin changes, several of the many clinical features of the recently described POEMS syndrome. In addition, she had a Castleman's disease (angiofollicular lymph node hyperplasia). In this case ascites was a main presenting feature. Thus, the POEMS syndrome must be added to the list of rare causes of ascites. Electron microscopy of the liver showed perisinusoidal fibrosis.
The aim of this study was to determine whether there was any relationship between alcohol consumption, cirrhosis and Helicobacter pylori associated antral gastritis. One hundred and forty-four patients undergoing upper gastrointestinal endoscopy were prospectively included and classified in four groups. The first group of 23 patients had cirrhosis and an alcohol consumption below 80 g per day. The second group of 31 patients had cirrhosis and an alcohol consumption over 80 g per day. The third group of 34 patients had an alcohol consumption over 80 g per day without cirrhosis. The fourth group of 56 patients had an alcohol consumption below 80 g per day without any preexisting liver disease and underwent upper gastrointestinal endoscopy for non specific digestive symptoms. The diagnosis of Helicobacter pylori was made at histological examination using the hematoxylin and eosin stain and the Whartin-Starry stain in each case. Histopathological results were confirmed by a bacteriological study in 15 cases. One hundred and twelve of 144 patients (78 percent) had gastritis. Gastritis was more frequent (p less than 0.01) when Helicobacter pylori was present than when it was not (90 percent vs 68 percent). Gastritis was more frequent when alcohol consumption was high (86 percent vs 72 percent). Helicobacter pylori was found in 26 percent of the first group, 48 percent of the second group, 65 percent of the third group and 45 percent of the fourth group. These differences were significantly different (p less than 0.05). A statistically significant relationship between high alcohol consumption and the presence of Helicobacter pylori was noted, even in the presence of cirrhosis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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We report on a brother and sister with hyperinsulinism and nesidioblastosis of the pancreas. In addition, one brother and one sister who died in the neonatal period were probably affected. The parents of these children were healthy and consanguineous. We think that this is strongly suggestive of autosomal recessive inheritance. Seven other reports of presumed autosomal recessive hyperinsulinism are reviewed. To our knowledge, we report the first case in sibs whose parents were consanguineous. We think that early recognition of the condition is of obvious importance not only for therapy, but also for purposes of genetic counseling.
In an attempt to determine the importance of perivenular fibrosis (PVF) in alcoholic liver disease, we studied 71 liver biopsies using histological grading and a morphometric method. The histological grading used 7 variables which allowed us to classify the patients into 7 groups: controls, patients without alcoholic hepatitis but with steatosis, steato-fibrosis, portal fibrosis and patients with mild, moderate, or severe alcoholic hepatitis. The quantitative analysis examined 3 parameters: (1) The inner diameter of the terminal hepatic veins (THV). (2) The thickness of the THV rims, related to perivenular fibrosis (PVF). (3) Centrolobular fibrosis (CLF) which represented the association of perivenular and perisinusoidal centrolobular fibrosis. No changes in the inner diameter of the terminal hepatic veins was observed for the different groups except in the case of severe alcoholic hepatitis. This fact indicated the absence of veno-occlusive lesions in early stages of mild and moderate alcoholic disease. In severe alcoholic hepatitis, THV were destroyed by centrolobular scars and most of them were indistinguishable and unmeasurable. Of the 26 cases with steatosis (with or without portal fibrosis) only two cases with steatofibrosis showed perivenular fibrosis. In contrast, a significant increase in PVF and in CLF appeared in patients with alcoholic hepatitis. CLF is easier to quantify and more significative than PVF. Thus, it seems to us that CLF is a better indicator of the intensity of sclerosis and of the risk of developing cirrhosis than PVF alone.