Phenotypic variability in a Spanish family with MNGIE.

Clinical, biochemical, and genetic features of a Spanish family with mitochondrial neurogastrointestinal encephalomyopathy are reported. The proband presented with severe gastrointestinal dysmotility and the affected sister had extraocular muscle weakness. In both affected individuals, biochemical defects of thymidine phosphorylase and a pathogenic G-to-A transition mutation at nucleotide 435 in the thymidine phosphorylase gene were identified. The first thymidine phosphorylase mutation identified in Spain showed phenotypic variability at onset.

The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region.

We applied cDNA selection methods to a genomic clone (YAC 761B5) from chromosome 21 located in the so-called 'Down critical region' in 21q22.3. Starting from human fetal heart and brain mRNAs we obtained and sequenced several cDNA clones. One of these clones (Down region aspartic protease (DRAP), named also BACE2 according to the gene nomenclature) revealed a striking nucleotide and amino acid sequence identity with several motifs present in members of the aspartic protease family. In particular the amino acid sequences comprising the two catalytic sites found in all mammalian aspartic proteases are perfectly conserved. Interestingly, the predicted protein shows a typical membrane spanning region; this is at variance with most other known aspartic proteases, which are soluble molecules. We present preliminary evidence, on the basis of in vitro translation studies and cell transfection, that this gene encodes a glycosylated protein which localizes mainly intracellularly but to some extent also to the plasma membrane. Furthermore DRAP/BACE2 shares a high homology with a newly described beta-secretase enzyme (BACE-1) which is a transmembrane aspartic protease. The implications of this finding for Down syndrome are discussed.

Perioperative prognostic value of dipyridamole echocardiography in vascular surgery: A large-scale multicenter study in 509 patients. EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Patients undergoing major vascular surgery are at a relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for perioperative risk stratification. The aim of the current study was to evaluate the value of dipyridamole echocardiography test (up to 0.84 mg/kg over 10 minutes) in predicting cardiac events in a large-scale, multicenter, prospective, observational study design. METHODS AND RESULTS: Five hundred nine patients (mean age 66+/-10 years) were studied before vascular surgery by dipyridamole stress echocardiography in 11 different centers. All patients underwent preoperative clinical risk assessment according to the American Heart Association guidelines. No major complications occurred during dipyridamole stress echocardiography. Technically adequate images were obtained in all patients; however, in 4 patients only the low dipyridamole dose (0.56 mg/kg over 4 minutes) was given for limiting side effects. Eighty-eight (17.3%) had a positive test. Perioperative events occurred in 31 (6.1%) patients: 6 deaths, 11 myocardial infarctions, and 14 episodes of unstable angina. Sensitivity and specificity of dipyridamole stress echocardiography for predicting spontaneous cardiac events were 81% and 87%, respectively, with a positive predictive value of 28% and negative predictive value of 99%. By multivariate analysis, the difference between wall motion score index at rest and peak stress (Deltawall motion score index), test positivity, and ST-segment depression during dipyridamole infusion were independent predictors of any perioperative cardiac event. CONCLUSIONS: Dipyridamole stress echocardiography is safe and well tolerated in patients undergoing major vascular surgery and provides an effective preoperative screening test for the risk stratification of these patients, mainly because of the extremely high negative predictive value, which is a potent predictor of complication-free procedure.

Human NRD convertase: a highly conserved metalloendopeptidase expressed at specific sites during development and in adult tissues.

We report the cloning of the human homologue of the rat metalloprotease N-arginine dibasic convertase (NRD convertase). This endopeptidase is responsible for the processing, at the Arg-Lys dibasic site on the N-terminal side of the arginine residue, of propeptides and proproteins. Comparisons of the human and rat full-length cDNAs show similarity and identity of 94 and 91%, respectively. In humans NRD convertase is predominantly expressed in heart, skeletal muscle, and testis. We have also studied the expression of this gene in mouse at various developmental stages and found that the neural tissue is the almost exclusive site of expression in early development (between E 10.5 and E 16.5). To gain information about the possibility that defects in this gene are linked to inherited neuromuscular disorders, we determined the chromosomal location of the human NRD convertase gene by FISH analysis, showing that the gene resides at 1p32.2.

Isolation and Metabolic Characterization of a Pseudomonas stutzeri Mutant Able To Grow on the Three Isomers of Xylene.

From an o-xylene-degrading Pseudomonas stutzeri strain (OX1), we previously isolated mutant M1, which had acquired the ability to grow on m-xylene and p-xylene but lost the ability to utilize the ortho isomer. From M1 cultures we have now isolated a revertant strain (R1) which grows on o-xylene and retains the ability to grow with the meta and para isomers regardless of the selective pressure applied. In P. stutzeri R1, o-xylene is degraded through two successive monooxygenations of the aromatic ring, while m-xylene and p-xylene catabolism proceeds through the progressive oxidation of a methyl substituent, although unquantifiable amounts of these two substrates are transformed into the corresponding dimethylphenols, which are not utilized for further growth. The two catabolic pathways are inducible by all three xylene isomers.

Clinical characteristics of anginal pain in man.

The clinical recognition of the cardiac origin of chest pain or discomfort on the basis of the description made by the patient, is often difficult. Nevertheless, considering the importance of the correct diagnosis of such syndrome, much work has been done in this field. In this report we will comment data from the literature and from our own, on the quality, duration, irradiation and on the precipitating or relieving factors that are more frequently associated with anginal pain.