Labeling of human erythrocyte membrane proteins by photoactivatable radioiodinated phosphatidylcholine and phosphatidylserine A search for the aminophospholipid translocase

AbstractWe have synthesized radioiodinated photoactivatable phosphatidylcholine (125-N3-PC) and phosphatidylserine (125I-N3-PS). After incubation with red blood cells in the dark, the labeled PC could be extracted but not the corresponding PS molecule, indicating that the latter was transported by the aminophospholipid translocase, but not the former. When irradiated immediately after incorporation, N3-PS, but not N3-PC, partially blocked subsequent translocation of spin-labeled aminophospholipids. Analysis of probe distribution by SDSpolyacrylamide gel electrophoresis revealed that 125I-N3-PS labeled seven membrane bound components with molecular masses between 140 and 27 kDa: one (or several) of these components should correspond to the aminophospholipid translocase

Association of adenoma and focal nodular hyperplasia: experience of a single French academic center

BACKGROUND: We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was found in five out of 30 cases of "multiple benign hepatocytic nodules" collected in our files of the Department of Pathology of the University Hospital of Bordeaux, during the last 12 years. All five cases were women on oral contraceptives. In all cases, the reason for surgery was the discovery, by imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor, possibly an adenoma. RESULTS: Four cases of FNH were discovered by imaging techniques, prior to surgery. Additional small nodules were diagnosed either during surgery or during the slicing of the specimen in 3 cases. Adenoma and the FNH cases identified by imaging techniques were confirmed as such by light microscopy. Some small nodules could not be categorized with certainty because they contained biliary structures without ductular reaction. In one case, the non-nodular liver was abnormal around the area in which there were multiple nodules: there was approximation of portal tracts with portal and hepatic venous thromboses, and portal tract remnants with arteries surrounded with a rim of fibrosis. In two cases, some large hepatic veins had thickened walls. CONCLUSIONS: The association of FNH and adenoma could be coincidental or secondary to shared causal mechanisms: a) systemic and local angiogenic abnormalities induced by oral contraceptives; b) tumor-induced growth factors; c) thrombosis and local arterio-venous shunting. A better recognition of the association of adenoma and FNH, particularly in the context of multiple nodules, could be useful in clinical practice

Hypervascular nodule in a fibrotic liver overloaded with iron: identification of a premalignant area with preserved liver architecture

BACKGROUND: The presence of a hypervascular nodule in a patient with cirrhosis is highly suggestive of a hepatocellular carcinoma. CASE PRESENTATION: A 55 year old man with idiopathic refractory anaemia was addressed for the cure of a recently appeared 3.3 cm hypervascular liver nodule. The nodule was not visible on the resected fresh specimen, but a paler zone was seen after formalin fixation. The surrounding liver was fibrotic (METAVIR score F3) and overloaded with iron. However, the paler zone, thought to be the nodule, had in fact a normal architecture, was less fibrotic, and contained some "portal tract-like structures" (but with arteries only); moreover, this paler area was devoid of iron, contained less glycogen and was characterized by foci of clear hepatocytes. CONCLUSION: In spite of the absence of architectural distortion, and a normal proliferative index, the possibility of premalignancy or malignancy should be considered in this type of hypervascular and hyposiderotic nodule, occurring in the context of an iron overloaded liver

Hepatocellular adenoma: what is new in 2008

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1α (HNF1α) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1α-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1α germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating β-catenin mutation was found in 10% of HCA. These β-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress β-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express β-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1α-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Sitedirected photochemical coupling of cytochrome b6f-associated chlorophyll. Biochemistry 42

ABSTRACT: Cytochrome b 6 f complexes contain a molecule of chlorophyll a (Chla), which, in Chlamydomonas reinhardtii, can be exchanged for extraneous chlorophyll during protracted incubation of the purified complex in detergent solution. The specificity of the site and its location in the complex have been studied by photochemical coupling and circular dichroism spectroscopy

Unexpected discovery of 2 cases of hepatocyte nuclear factor 1α-mutated infracentimetric adenomatosis

We present 2 cases of hepatocyte nuclear factor 1α (HNF1α)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities