Left Ventricular Stresses in the Intact Human Heart

A set of stress differential equations of equilibrium is presented for a thick prolate spheroid which is the assumed shape for the left ventricle. An analysis for the stresses in the ventricular wall indicates that maximum stresses occur at the inner layers and decrease to a minimum at the epicardial surface, a result that is partially validated by experiment. Simple expressions are available for the evaluation of maximum stresses which occur at the equator and are suitable for small laboratory-oriented digital computers employed in the clinical evaluation of patient status. The surprising result is that Laplace's law yields practical values for mean stresses in thick-walled ventricles.     

The prevalence of proviral bovine leukemia virus in peripheral blood mononuclear cells at two subclinical stages of infection.

The bovine leukemia virus (BLV) is an oncogenic retrovirus that is associated with the development of persistent lymphocytosis (PL) and lymphoma in cattle. While B lymphocytes have been shown to be the primary cellular target of BLV, recent studies suggest that some T lymphocytes and monocytes may be infected by the virus. Because virally altered functions of monocytes and/or T cells could contribute to the development of lymphoproliferative disease, we sought to clarify the distribution of the BLV provirus in subpopulations of peripheral blood mononuclear cells in seropositive cows with and without PL. CD2+ T cells, monocytes, and CD5+ and CD5- B cells were sorted by flow cytometry and tested for the presence of BLV by single-cell PCR. We did not obtain convincing evidence that peripheral blood monocytes or T lymphocytes contain the BLV provirus in seropositive cows with or without PL. In seropositive cows without PL (n=14), BLV-infected CD5+ and CD5- B cells accounted for 9.2% +/- 19% and 0.1% +/- 1.8% of circulating B lymphocytes, respectively. In cows with PL (n=5), BLV-infected CD5+ and CD5- B cells accounted for 66% +/- 4.8% and 13.9% +/- 6.6% of circulating B lymphocytes, respectively. The increase in lymphocyte numbers in cows with PL was entirely attributable to the 45-fold and 99-fold expansions of infected CD5+ and CD5- B-cell populations, respectively. Our results demonstrate that B cells are the only mononuclear cells in peripheral blood that are significantly infected with BLV. On the basis of the absolute numbers of infected cells in seropositive, hematologically normal animals, there appear to be differences in susceptibility to viral spread in vivo that may be under the genetic control of the host.     

Chromium in biological systems, I. Some observations on glucose tolerance factor in yeast

Glucose tolerance factor (GTF) has been isolated from a commercially available yeast extract powder, by a simple procedure under mild conditions. This cationic yellow material enhances considerably CO2 production in several yeast strains, after a lag time which can be eliminated by preincubation with glucose. The enhancement of CO2 production by GTF is not specific for glucose, and its effect on galactose raises the possibility that it influences the transport of the sugar to the cells. The ineffectiveness of GTF on cell free extract and the results of a Michaelis plot for CO2 production support this hypothesis.     

The effect of cholera toxin on myogenesis in rat skeletal muscle cultures

Cholera toxin, when added to rat primary embryonic muscle cultures, stimulates intracellular cyclic AMP and cell fusion. The effect on cell fusion can be mimicked by daily addition of dibutyryl cyclic AMP, but not by choleragenoid, which like cholera toxin binds to the ganglioside G_M1, but does not stimulate adenyl cyclase. The effects on fusion of three other agents known to affect intracellular cyclic AMP levels, indomethacin, isobutylmethyl xanthine, and isoproterenol were also studied. It is concluded that intracellular cyclic AMP levels are important in the control of rat skeletal muscle cell fusion.     

GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.

Recently it has been demonstrated that the growth-associated protein GAP-43 is not confined to neurons but is also expressed by certain central nervous system glial cells in tissue culture and in vivo. This study has extended these observations to the major class of glial cells in the peripheral nervous system, Schwann cells. Using immunohistochemical techniques, we show that GAP-43 immunoreactivity is present in Schwann cell precursors and in mature non-myelin-forming Schwann cells both in vitro and in vivo. This immunoreactivity is shown by Western blotting to be a membrane-associated protein that comigrates with purified central nervous system GAP-43. Furthermore, metabolic labeling experiments demonstrate definitively that Schwann cells in culture can synthesize GAP-43. Mature myelin-forming Schwann cells do not express GAP-43 but when Schwann cells are removed from axonal contact in vivo by nerve transection GAP-43 expression is upregulated in nearly all Schwann cells of the distal stump by 4 wk after denervation. In contrast, in cultured Schwann cells GAP-43 is not rapidly upregulated in cells that have been making myelin in vivo. Thus the regulation of GAP-43 appears to be complex and different from that of other proteins associated with nonmyelin-forming Schwann cells such as N-CAM, glial fibrillary acidic protein, A5E3, and nerve growth factor receptor, which are rapidly upregulated in myelin-forming cells after loss of axonal contact. These observations suggest that GAP-43 may play a more general role in the nervous system than previously supposed.     

Effect of age on passive elastic stiffness of rat heart muscle.

A thick-wall spherical model for the rat left ventricle was used to deduce passive wall stiffness from diastolic pressure-volume data. This was done for rats in three age classes: young (1 mo), adult (17 mo) and old (17 mo). The model was based on finite deformation elasticity theory consistent with the magnitude of observed deformation. A least-squares procedure was used to determine elastic constants in postulated nonlinear stress-stretch relations for the myocardium. It was found that at a given level of stress, wall stiffness for ventricles in the young age class was consistently greater than wall stiffness in the other two classes. In addition, the difference in wall stiffness between rats in the adult and old age classes was found to be approximately 10%.     

History of safe exposure and bioinformatic assessment of phosphomannose-isomerase (PMI) for allergenic risk

Newly expressed proteins in genetically engineered crops are evaluated for potential cross reactivity to known allergens as part of their safety assessment. This assessment uses a weight-of-evidence approach. Two key components of this allergenicity assessment include any history of safe human exposure to the protein and/or the source organism from which it was originally derived, and bioinformatic analysis identifying amino acid sequence relatedness to known allergens. Phosphomannose-isomerase (PMI) has been expressed in commercialized genetically engineered (GE) crops as a selectable marker since 2010 with no known reports of allergy, which supports a history of safe exposure, and GE events expressing the PMI protein have been approved globally based on expert safety analysis. Bioinformatic analyses identified an eight-amino-acid contiguous match between PMI and a frog parvalbumin allergen (CAC83047.1). While short amino acid matches have been shown to be a poor predictor of allergen cross reactivity, most regulatory bodies require such matches be assessed in support of the allergenicity risk assessment. Here, this match is shown to be of negligible risk of conferring cross reactivity with known allergens.