By manipulating dietary sugar intake and perfusate glucose concentration, we have identified two independent hepatic immunoregulatory molecules produced by the perfused rat liver. The first is released by injured hepatocytes, appears in perfusates together with hepatocellular glutamic pyruvic transaminase, is quantitatively inhibited by exogenous L-arginine and coelutes with arginase on high-pressure liquid chromatography. Based on these findings, we conclude that this activity is due to the release of cytoplasmic arginase from injured hepatocytes. Since supplementation studies reveal that lymphocyte proliferation is exquisitely arginine-dependent, it is conceivable that arginase released by injured hepatocytes might influence lymphocyte function in vivo by local arginine depletion. The second immunoregulatory molecule is released by noninjured hepatocytes following induction by sugar, particularly glucose, both in vivo or in vitro. This inducible activity is arginase-independent, triglyceride-rich and floats at a density less than 1.006 gm per ml upon ultracentrifugation. Based on these characteristics, we tentatively ascribe this activity to hepatic very low density lipoprotein, the serum counterpart of which is known to express many immunoregulatory properties. These results directly illustrate for the first time the pathophysiological conditions required for the secretion and release of these distinct and independent hepatic immunoregulatory molecules, and they suggest possible routes by which they may influence immunological homeostasis and immunologically mediated liver disease.

Alanine Transaminase↗

PubMedDate not supplied

Detection of high incidence of K-ras oncogenes during human colon tumorigenesis.

RNAse A mismatch cleavage analysis of 66 primary human colon tumors reveals a high incidence of K-ras genes with mutations at position 12. No apparent correlation was found between the presence of mutant oncogenes and the degree of invasiveness of the tumours but evidence for ras mutational activation in premalignant tissue was obtained.

Adenocarcinoma↗

PubMedDate not supplied

Monte Carlo simulation of a cobalt-60 beam.

We have used the Stanford Electron Gamma Shower (EGS) Monte Carlo code to compute photon spectra from an AECL Theratron 780 cobalt-60 unit. Particular attention has been paid to the careful modeling of the geometry and material construction of the cobalt-60 source capsule, source housing, and collimator assembly. From our simulation, we conclude that the observed increase in output of the machine with increasing field size is caused by scattered photons from the primary definer and the adjustable collimator. We have also used the generated photon spectra as input to a pencil beam model to calculate the tissue-air ratios in water and compared it to a model which uses a monochromatic photon energy of 1.25 MeV.

Cobalt Radioisotopes↗

PubMedDate not supplied

The effect of angular spread on the intensity distribution of arbitrarily shaped electron beams.

Knowledge of the relative intensity distribution at the patient's surface is essential for pencil beam calculations of three-dimensional dose distributions for arbitrarily shaped electron beams. To calculate the relative intensity distribution, the spatial spread resulting from angular spread is convolved with a two-dimensional step function whose shape corresponds to the applicator aperture. Two different approaches to obtain angular spread or the equivalent spatial spread are investigated. In the first method, the pencil beam angular spread is assumed to be Gaussian in shape. The angular spread constants (sigma theta) are then obtained from the slopes of measured intensity profiles. In the second method, the angular spread, in the form of an array of numerical values, is obtained by the deconvolution of measured intensity profiles. After obtaining the angular spread, the calculation for convolution is done in a number of parallel planes normal to the central axis at various distances from the electron collimator. Intensity at any arbitrary point in space is computed by interpolating between intensity distributions in adjacent planes on either side of the point. The effects of variations in angular spread as a function of field size for two treatment machines, one with a scanned electron beam and the other with a scattering foil, have been studied. The consequences of assuming angular spread to be of Gaussian shape are also examined. The electron intensity calculation techniques described in this paper apply primarily to methods of dose calculations that employ pencil beams generated using Monte Carlo simulations.

Electrons↗

PubMedDate not supplied

[Specific chemical splitting of proteins].

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Amino Acids↗