Inositol 1,4,5-trisphosphate turnover enzymes--activities and subcellular distribution in hepatocarcinogenesis

The metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5- tetrakisphosphate in homogenates and sub-fractions from normal rat liver and premalignant liver nodules was investigated. The activities of 5-phosphatase, expressed as pmol converted substrate per minute and mg protein, were equal when using the two substrates, and did not differ between normal and nodular homogenates. Subcellular fractions were purified by sequential steps of differential centrifugation and density gradient fractionation procedures. The total phosphatase activity was found to be distributed between cytosol (15%) and membraneous fractions (75%), with most of the enzyme activity residing in the plasma membranes. A doubling of phosphatase specific activity was seen in the nodular low density membrane fraction, containing Golgi apparatus and endosomes, as compared with normal liver. Inositol 1,4,5- trisphosphate 3-kinase activity was found to be exclusively cytosolic. No difference in this enzyme was seen between the two tissue types studied. Vasopressin (0.2 or 2 microM) had no effect either on phosphatase or kinase activity. The compartmentalization of inositol polyphosphate 5-phosphatase activity presents a possible explanation of earlier findings that premalignant liver tissue was able to respond with inositol 1,4,5-trisphosphate, but not inositol 1,3,4,5- tetrakisphosphate formation after agonist stimulation.      

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.     

Visual dysfunction in patients with mitochondrial myopathies

Seventeen patients with biopsy-confirmed mitochondrial progressive external ophthalmoplegia underwent electroretinography and visual evoked potential testing to checkerboard-reversal stimuli to investigate subclinical visual dysfunction. Seven patients (41%) had impaired Snellen visual acuity that was never less than 0.6. Thirteen patients (76%) showed electroretinographic and/or visual evoked potential alterations, whereas six (35%) showed impairment on both tests. Two patients showed delayed VEP P100 latency without fundus, electroretinographic or visual acuity anomalies. Visual dysfunctions were not related to age at onset and course of the disease.Abbreviations PEO progressive external ophthalmoplegia     

Crouzon disease in twins. Clinical and pathological contribution

After a survey of cases in the literature reported, two cases of Crouzon disease, in monovular twins are described. The observation in twins and the opportunity of histologic examination of optic nerve, permitted some considerations in order to help in understanding this syndrome.     

P53 mutations in hepatocellular carcinoma patients in Egypt

The p53 gene plays a major role in hepatocellular carcinoma (HCC). Acquired mutations may provide clues to etiology, as some carcinogenic agents are associated with specific genetic changes in p53. Our aim was to analyze the spectrum of p53 mutations in tumor tissues from subjects with HCC in Egypt, where there is a rising incidence of HCC due to hepatitis C virus (HCV). We collected tumor tissues from 41 subjects with HCC diagnosed at the National Cancer Institute of Cairo University during 2000-2003. Sequence mutations were analyzed by the Affymetrix GeneChip technique. HCV RNA was detected in the sera of 37 subjects (90%). Only one patient had a current HBV infection. A total of 17 of the 41 subjects (41%) had p53 mutations. Thirteen of these were in exon 7, of which 10 were in codon 249, but only 8 of the 10 were the R249S mutation, previously reported to be associated with aflatoxin exposure. The other three exon 7 mutations were found in codons 232, 242 and 248. A total of three mutations were detected in exon 5 codons 133, 144 and 176. One mutation was detected in exon 8 codon 275. Unlike previous studies, this population is characterized by a high prevalence of chronic HCV infection. The presence of the R249S mutation in exon 7 may indicate that these subjects with HCC have been exposed to aflatoxin (AFB1), and further investigation is in progress to measure AFB1-albumin adducts in the sera of these subjects.     

Antioxidants in peripheral arterial disease

Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis that is characterized by obstruction of the arteries in the lower limbs. Experimental and epidemiological studies suggest a key role for oxidative stress in initiation and progression of the atherosclerotic process. The results of these studies provided a good basis for interventional trials with antioxidants, particularly with vitamin E, but the findings were conflicting. In this paper we review the observational and interventional studies with antioxidants, and ask whether vitamin supplementation should be recommended for PAD patients.