Ectopic ACTH secretion: a heterogeneous entity

OBJECTIVES: ACTH-secreting non-pituitary tumors are a rare cause of Cushing's disease. We report the clinical course, prognostic aspects and molecular analysis data in three patients for whom the diagnosis was confirmed but who had variable clinical features and laboratory results. CASE REPORTS: Patient n degree 1 had severe hypercorticism which rapidly progressed to death 13 months after diagnosis. In patient n degree 2, signs of hypercorticism severe, leading to death 5 years after discovery of the causal carcinoid tumor. Patient n degree 3 had moderate hypercorticism and has survived for more than 25 years. DISCUSSION: These 3 ectopic tumors are representative examples of a wide range of possible ACTH-secreting ectopic tumors. In highly malignant poorly-differentiated tumors such as small-cell anaplastic carcinomas, ACTH production is aberrant and poorly controlled, and thus not particularly effective. At the other extreme, typical benign bronchial carcinomas have a high degree of neuroendocrine differentiation and secrete ACTH in a well-controlled manner difficult to distinguish from corticotropic adenomas, further exaggerating the diagnostic pitfalls.     

A simple method for the study of cytosolic content of oligonucleotides in cells

BACKGROUND: Nonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement. METHODS AND RESULTS: The attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201Tl study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients. CONCLUSIONS: The results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.     

Plasmid-mediated resistance to antimicrobial agents among listeriae

The resistance to 14 antiseptic-disinfectant and dye compounds of 208 strains of Listeria (132 L. monocytogenes, 63 L. innocua, 8 L. seeligeri, 1 L. ivanovii, 1 L. welshimeri, and 3 Listeria spp.) was tested by the agar-dilution procedure. The Listeria strains were isolated from different varieties of foods, environments of cheese dairies, humans, and wild birds. A total of 14 (6.7%) Listeria strains (12 L. monocytogenes and 2 L. innocua) were resistant to benzalkonium chloride, hexamidine diisethionate, and ethidium bromide. This multiple resistance was observed more frequently from strains of Listeria spp. detected on carcasses of poultry (47%) than strains isolated from human listeriosis cases or carriers (11.5%), red meats (10%), cheeses (5.4%), wild birds (0.9%), and environments of cheese dairies (0%). Among resistant strains, 10 groups of strains (71.5%) were differentiated by serogroup, phage typing, and sensitivity or resistance to cadmium. Extrachromosomal DNA was found in all resistant strains and was transferred at a high frequency among Listeria spp. (8.7 x 10(-6) to 1 x 10(-3) transconjugant CFUs per one donor CFU). These resistances were also transferable between L. monocytogenes and Staphylococcus aureus with similar transfer frequencies (7.8 x 10(-6) to 1 x 10(-4) and between strains of Staphylococcus aureus with similar transfer frequencies from 8 x 10(-7) to 3.3 x 10(-6). These results suggest that emergence of this multiple resistance in Listeria spp. could be due to acquisition of a replicon originating in staphylocci.     

Insight into signal transduction: structural alterations in transmembrane helices probed by multi-1 ns molecular dynamics simulations

The hypothesis of structural alteration in transmembrane helices for signal transduction process is viewed by molecular dynamics simulation techniques. For the c-erbB-2 transmembrane domain involved in oncogenicity, the occurrence of conformational changes has been previously described as transition from the alpha to pi helix. This dynamical feature is thoroughly analyzed for the wild phenotype and oncogenic sequences from a series of 18 simulations carried out on one nanosecond time scale. We show that these structural events do not depend upon the conditions of simulations like force field or starting helix coordinates. We demonstrate that the oncogenic mutations Val659 Glu, Gln and Asp do not prevent the transition. Furthermore, we show that beta branched residues, in conjunction with Gly residues in the c-erbB-2 sequence, act as destabilizers for the alpha helix structure, pi deformations are tightly related to other local structural motifs found in soluble and membrane proteins. These structural alterations are discussed in term of structure-activity relationships for the c-erbB-2 activating mechanism mediated by transmembrane domain dimerization.