Apoptosis of myocytes and proliferation markers as prognostic factors in end-stage dilated cardiomyopathy.

INTRODUCTION: The aim of the study was to evaluate the role of apoptosis, proliferation markers, volume density of interstitium, and myofibril volume fraction for the prognosis in patients with end-stage dilated cardiomyopathy (DCM). METHODS: Endomyocardial biopsy was performed during open-heart surgery in 56 patients with end-stage DCM. Patients were divided into two groups, one group with shorter survival (24+/-9 months, mean+/-S.D.) and another group with survival of more than 7 years after operation. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of inhibitor of apoptosis (bcl-2) and proliferation markers (PCNA and Ki-67). RESULTS: The increased percentage of apoptotic myocytes, decreased expression of bcl-2, and decreased expression of PCNA and Ki-67 antigen was found in the group with early mortality compared to that with longer survival. Myofibril volume fraction was lower and volume density of interstitium was higher in the group with early mortality compared to that with longer survival. CONCLUSION: Apoptosis, bcl-2 expression, and proliferation activity of myocytes, myofibril volume fraction, and volume density of interstitial tissue might be useful in predicting the prognosis (progressive vs. nonprogressive form) of patients with heart failure due to DCM.     

Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice

Disruption of cell polarity is seen in many cancers; however, it is generally considered a late event in tumor progression. Lethal giant larvae (Lgl) has been implicated in maintenance of cell polarity in Drosophila and cultured mammalian cells. We now show that loss of Lgl1 in mice results in formation of neuroepithelial rosette-like structures, similar to the neuroblastic rosettes in human primitive neuroectodermal tumors. The newborn Lgl1(-/-) pups develop severe hydrocephalus and die neonatally. A large proportion of Lgl1(-/-) neural progenitor cells fail to exit the cell cycle and differentiate, and, instead, continue to proliferate and die by apoptosis. Dividing Lgl1(-/-) cells are unable to asymmetrically localize the Notch inhibitor Numb, and the resulting failure of asymmetric cell divisions may be responsible for the hyperproliferation and the lack of differentiation. These results reveal a critical role for mammalian Lgl1 in regulating of proliferation, differentiation, and tissue organization and demonstrate a potential causative role of disruption of cell polarity in neoplastic transformation of neuroepithelial cells.     

Relating cistrons and functions in bacteriophage PM2

An approach to correlate functions with cistrons in bacteriophage PM2 is presented. Two of the temperature-sensitive mutants obtained differed from the wild type in heat sensitivity and four differed in host range. Comparison of the electrophoretic patterns of DNA from cells infected at the restrictive temperature with those obtained in wildtype infection revealed that viral DNA bands were absent with three additional mutants. Complementation analysis assigned the four host range mutants to cistron I and the three mutants defective in DNA synthesis to cistron IV. Recombination frequencies were used to locate cistrons III and IV on the partial genetic map of PM2.     

Functional insights on the polarized redistribution of leukocyte integrins and their ligands during leukocyte migration and immune interactions

Summary:  Cell–cell and cell–matrix interactions are of critical importance in immunobiology. Leukocytes make extensive use of a specialized repertoire of receptors to mediate such processes. Among these receptors, integrins are known to be of crucial importance. This review deals with the central role of integrins and their counterreceptors during the establishment of leukocyte–endothelium contacts, interstitial migration, and final encounter with antigen-presenting cells to develop an appropriate immune response. Particularly, we have addressed the molecular events occurring during these sequential processes, leading to the dynamic subcellular redistribution of adhesion receptors and the reorganization of the actin cytoskeleton, which is reflected in changes in cytoarchitecture, including leukocyte polarization, endothelial docking structure formation, or immune synapse organization. The roles of signaling and structural actin cytoskeleton-associated proteins and organized membrane microdomains in the regulation of receptor adhesiveness are also discussed.     

Comparison of hepatitis C viral loads in patients with or without coinfection with different genotypes

Hepatitis C virus genotyping was assessed for 257 chronic hepatitis C patients with viral loads above 1,000 IU/ml. Twelve patients were coinfected with more than one genotype. Their median viral loads did not differ significantly from those observed for monoinfected patients, which in turn did not vary significantly among different genotypes.     

Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay

We evaluated a procedure for identifying recent HIV infections, using sequential serum samples from 47 HIV-positive persons for whom the seroconversion date could be accurately estimated. Each serum sample was divided into two aliquots: one diluted with phosphate-buffered saline and the other diluted with 1 M guanidine. We assayed the aliquots with the automated AxSYM HIV1/2gO test (Abbott Diagnostics Division), without modifying the manufacturer's protocol. We then calculated the avidity index (AI): the ratio of the sample/cutoff value for the guanidine aliquot to that of the phosphate-buffered saline aliquot. We analyzed 216 serum samples: 34 samples were collected within 6 months of seroconversion (recent seroconversions), and 182 were collected after 6 months. The mean AIs, by time from seroconversion, were 0.68 +/- 0.16 (within 6 months) and 0.98 +/- 0.10 (after 6 months) (P < 0.0001). AI of <0.90 correctly identified 88.2% of recent infections but misclassified as recent infections 13.2% of serum samples collected afterward. The probability of an infection being classified as recent and having AI of > or = 0.90 would be 0.7% in a population with 5% recent infections. AI can identify with a certain degree of accuracy recent HIV infections, and being a quantitative index, it provides different levels of sensitivity and specificity, depending on the selected cutoff value. The standard assay procedure is not modified. This test is simple and inexpensive and could be used for surveillance, decision-making in treatment, and prevention.