Identification of the gene encoding the human mitochondrial RNA polymerase (h-mtRPOL) by cyberscreening of the Expressed Sequence Tags database

A gene cloning strategy based on the screening of the Expressed Sequence Tags database (dbEST) using sequences of mitochondrial housekeeping proteins of yeast was employed to identify the cDNA encoding the precursor of the human mitochondrial RNA polymerase (h- mtRPOL). The 3831 bp h-mtRPOL cDNA is located on chromosome 19p13.3 and encodes a protein of 1230 amino acid residues. The protein sequence shows significant homologies with sequences corresponding to mitochondrial RNA polymerases from lower eukaryotes, and to RNA polymerases from several bacteriophages. The mitochondrial RNA polymerase carries out the central activity of mitochondrial gene expression and, by providing the RNA primers for replication- initiation, is also implicated in the maintenance and propagation of the mitochondrial genome. Genes involved in the control of mtDNA replication and gene expression are attractive candidates for human disorders due to abnormalities of nucleo-mitochondrial intergenomic signalling. The availability of the h-mtRPOL cDNA will allow us to test its role in mitochondrial pathology. In addition, we propose the 'cyberscreening' of dbEST, based on yeast/human cross-species comparison, as a powerful, simple, rapid and inexpensive method, that may accelerate several-fold the molecular dissection of the human mitochondrial proteome.      

Bullous eosinophilic cellulitis (Wells'' syndrome) associated with Churg–Strauss syndrome

We report a patient with Churg-Strauss syndrome (CSS) with asthma, eosinophilia, nasal polyposis and ANCA-associated multisystem vasculitis, who's skin eruption started with erythematous urticarial-plaques followed by haemorrhagic bullae. Histology of the plaques revealed 'flame figures' in the dermis with no granulomatous or vasculitic process, consistent with the diagnosis of eosinophilic cellulitis or Wells' syndrome. The association of CSS and Wells' syndrome observed in this patient may have a common pathogenesis. CSS may induce Wells' syndrome by an unknown factor.     

Plasma levels of carbamazepine and carbamazepine-10,11-epoxide during treatment of epilepsy

Summary Carbamazepine and its epoxide in plasma were measured by liquid chromatography in 25 patients treated with a mean dose of carbamazepine of 12.5±3.3 mg/kg body weight. The mean concentrations of parent drug and metabolite were 5.4±2.5 µg/ml and 1.10±0.42 µg/ml, respectively. A significant correlation was found between the plasma concentrations of the two compounds (r=0.64; p<0.001), but marked interindividual variation existed in the ratio of carbamazepine to epoxide. Based on simultaneous measurements in plasma and cerebrospinal fluid, the unbound fraction of carbamazepine in plasma was of the order of 20% as compared to 45% for the epoxide. Thirteen ambulant patients suffering from partial epilepsy with complex symptomatology, who were already being treated with phenytoin in optimal doses (plasma level 14–20 µg/ml) were also given carbamazepine. At plasma levels of the latter of about 5 µg/ml there was no further reduction in the frequency of partial or generalized epileptic seizures. In five patients the dose was increased to produce plasma concentrations of 7 – 8 µg/ml. There was still no improvement and side-effects were seen in three patients.