Quantitative histology of the hypertrophied human heart

Myocardial hypertrophy accompanies systemic hypertension and aortic stenosis, i.e., pressure overload. In man cardiac failure only appears after years of pressure overload, during which time cardiac function had been maintained. The structural correlates of cardiac failure have been a subject of much interest for many years. Several hypotheses relating alterations in muscle fiber alignment, capillary density, or collagen content have been offered. The application of morphometric techniques has provided essential quantitative information on the structural components of the normal and diseased heart. These data indicate that muscle fiber alignment remains normal in the pressure overloaded heart despite the presence of hypertrophy or the appearance of clinical failure. On the other hand, capillary density is decreased and collagen content is increased in hypertrophied hearts. Chemical studies on collagen concentration however have yielded inconsistent results. The relative contribution of the microcirculation and collagenous structure of the myocardium on its respective O2 availability, mechanical behavior, and deterioration in pump function will require further investigation.     

Poly(ADP-ribose) polymerase forms loops with DNA

The interaction between highly purified poly(ADP-ribose) polymerase from calf thymus and different topological forms of pBR322 DNA has been studied by gel retardation electrophoresis and electron microscopy. We show that: (i) in the absence of nicks on DNA the enzyme has a marked affinity for supercoiled (form I) DNA, (ii) in the presence of single stranded breaks poly(ADP-ribose) polymerase preferentially binds to form II, (iii) in all cases enzyme molecules are frequently located at DNA intersections, (iv) a cooperative binding of the enzyme on DNA occurs.     

Results of the study of bird droppings collected in the Lithuanian SSR for the purpose of searching out tularemia epizootics

There are practically no records of cases of tularemia among humans in the Lithuanian SSR. Nevertheless, the mass sero-allergic survey of the population for tularemia, carried out 10-12 years ago, showed that 2.3% of the adult population in the Republic had had contacts with the causative agent of this infection. The work was aimed at the determination of the present activity of the foci of tularemia. During 6 years in 22 rural districts 2582 samples of avian excrements, containing bones and wool of small animals, were collected and studied by means of the antibody neutralization test (ANT). In 132 (5.1 +/- 0.4%) excrement samples collected on the territory of 12 districts Francisella tularensis antigen was detected. The average ANT titer was 45.2, the maximum titer (10 excrement samples) reached 1: 160. The study revealed the existence of the natural foci of tularemia in Lithuania at present, but their activity proved to be low. The most unfavorable situation was found to exist in western districts of the Republic.     

Human endothelin converting enzyme-2 (ECE2): characterization of mRNA species and chromosomal localization.

Generation of the functionally pleiotropic members of the endothelin vasoactive peptide family is critically catalyzed by unique type II metalloproteases, termed endothelin converting enzymes (ECE). Isolation of human ECE-2 (EC 3.4.24.71) cDNAs revealed deduced open reading frames of 787 and 765 amino acids with approximately 60% identity with human ECE-1. Characterization of mRNA variants revealed mRNA structural diversity at the 5'-terminus. Two mRNA species exist containing distinct first and second exons. Furthermore, in one of these species, an in-frame deletion of the intracytoplasmic domain removed 29 amino acids. Because of the previously reported human genetic diseases ascribed to germline mutations of member genes of the endothelin family, ECE2 was localized in human chromosomes with fluorescence in situ hybridization and radiation hybrid mapping to 3q28-q29 and SHGC-20171/D3S1571, respectively.     

Biosynthesis of various types of collagen by human hepatoma cells in vitro

A cloned human hepatoma cell line (HH2-1) produced and formed collagen fibers in vitro. The relative rate of collagen synthesis by the cells was increased with an enhancement of the cell density. An analysis of the components of the collagen using sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the cells synthesized interstitial collagen, types I and III, and other collagenous proteins. Thus, human hepatoma cells may play an important role in the formation of stromal collagen in the tumor.     

Methods for study of mutations and mutagenesis in human lymphocytes

Detailed methods are presented for measurement and study of in vivo mutations and in vitro mutagenesis in human lymphocytes. The methods described include preparation of conditioned medium containing interleukin-2, enumeration of mutant clones, in vitro mutagenesis, and expansion of mutant clones for further study.     

Enhancement of eosinophil effector function by soluble factors released by S. mansoni: role of proteases

Schistosomulum-released products (SRP) have been shown to enhance both expression of rat and human eosinophil Fc receptors and IgG-dependent cytotoxicity. The present work provides additional evidence of the secretion of eosinophil-enhancing factors by schistosomula and other developmental stages of schistosomes, including adult worms. The heat lability, as well as the strong inhibition of the stimulating activity of SRP by the protease inhibitor Trasylol, suggest that thermolabile proteases secreted by the parasite are involved in this mechanism. The purification of the schistosome proteases by preparative isoelectric focusing and gel filtration demonstrated that neutral proteases able to hydrolyze the collagenase substrates Azocoll and Z-Gly-Pro-Leu-Gly-Pro are able to significantly enhance eosinophil effector functions. Purified Clostridium histolyticum collagenase was also able to mimic the enhancing effect of schistosome proteases, suggesting involvement of a collagenase-like activity of the enzymes in the eosinophil stimulation.