What is a 'low dose' of radiation?

Although the expression of radiation-induced biological effects and responses may be at either the cell, organ or organism level, induction of some of these phenomena (e.g. cancer of clastogenic and genetic effects) can have their origin in the interaction of a single charged particle with the target-containing volume (TCV) of the cell, e.g. the cell nucleus. However, the independent variable now used in both organ and cell population studies, the absorbed dose to the organ, provides no information directly on particle-TCV interactions. Even if calculated as a mean to an organized population of cells, the absorbed dose becomes a composite and confounded quantity, (FzN), in which F is the fraction of TCVs 'hit' by a particle during a given exposure, z is the mean value of z1, the energy absorbed in the TCV in a single hit, and N is the mean number of hits per affected TCV. Scientific precepts demand the avoidance of such confounded variables by achieving their isolation. The needed separation can be effected by the use of microdosimetric techniques, which make it possible to hold one component quantity constant while the others are varied. As an example, low-level radiation exposure (LLE) can be used to hold F at a constant value of 0.2 where, on average, there is but one hit per TCV. The probability of a cellular quantal response, as a function of z1 only, can then be determined by use of LLE to radiations covering a wide span of LETs. Conversely, the effect of varying only the fraction of cells hit can be studied by holding z constant. This can be accomplished by working within a narrow band of LET, but only in the LLE range. The effectiveness of preirradiation altering cell sensitivity as a function of the number of hits per TCV can be determined by working within, and somewhat above, the LLE range. In either risk assessment or the application of radiation as a pretreatment, minimal consequences can be assured only if very low-level exposure is employed in order that F will be small, and if the exposure is in a field of radiation of very low LET so that z1 will be as small as possible. That is to say, exposure conditions with low consequences cannot be specified in terms of any single quantity.     

Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins

A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed.     

Construction and expression of synthetic DNA fragments coding for polypeptides with elevated levels of essential amino acids

Summary Polypeptides, with elevated levels of essential amino acids, could be useful as partial protein supplements to food and feeds. To obtain DNA fragments coding for these polymers, oligonucleotides were constructed by random synthesis of a mixture of appropriate codon pairs and inserted into a bacterial plasmid in E. coli. Two of the isolated fragments were subjected to DNA sequence analysis and theoretically code for polypeptides containing up to 23% lysine, 12% tryptophan, 12% methionine, 6% isoleucine, and 6% threonine. These five amino acids make up 60% of the total amino acid content of the peptide, compared with 25% for the same amino acids in lactalbumin, a milk protein considered to be high in essential amino acids. These fragments, when fused to an active bacterial promoter, which directs the synthesis of chloramphenicol acetyl transferase (CAT), cause bacteria, harboring these modified genes, to take up more lysine as compared to control cells and produce commensurately larger CAT polypeptides. This method of gene synthesis may permit production of polypeptides with a specified amino acid composition to supplement specific diets low in the essential amino acids.     

Regulation of product synthesis in cell cultures of Catharanthus roseus (L) G. Don

Cell suspension cultures of the Madagascan Periwinkle Catharanthus roseus (L) G. Don were maintained on Gamborg's B5 medium and their growth monitored by measuring cellular fresh and dry weight, cell number and mitotic activity. Samples of cells of different ages and physiological states were subcultured onto an alkaloid production medium and their rates of growth and alkaloid accumulation measured over a period of 30–45 days. In two experiments the rate of biomass accumulation was directly related to the rate of cellular serpentine accumulation. Possible mechanisms underlying this phenomenon are discussed in relation to the properties of cells comprising the inocula.     

HLA Haplotypes with C4B5; evidence for further allelic heterogeneity

Twenty-three individuals from various disease groups and normal controls were identified by immunofixation with anti-C4, C4-dependent lysis, determination of Rg (Rodgers) and Ch (Chido) phenotypes, and immunoblotting with C4-specific mouse monoclonal antibody. We found that one haplotype predominates with the C4B ^* 5 allele, HLA-A11, B22(55), Cw3, Bf ^* S, C4A ^* 4B ^* 5, which also carries the Ch ^{1,–2, 3} haplotype. The B5 allotype was also found with HLA-1360, HLA-1335 in Caucasoids, and HLA-B18 in non-Caucasoids; these carried the Ch ^{–1, –2, –3} haplotype. Our results are in accord with an earlier report of two B5 subtypes, B5Rg⁺ and B5Rg^– (Roos et al. 1984). The specificity of the mouse monoclonal antibodies IC4 and 21312 had been previously related to C4A and C4B, respectively, but our results suggest that they relate more closely to Rg and Ch determinants.     

Endocytosis and degradation of native, cathepsin D-degraded, and glutathione-inactivated aldolase by perfused rat liver

The uptake and degradation of 125I-labeled (a) native aldolase, (b) cathepsin D-inactivated aldolase, and (c) aldolase inactivated by oxidized glutathione were studied in perfused rat liver. All three forms of aldolase were removed from the perfusion medium and degraded by the liver, but the uptake of the glutathione-inactivated enzyme (half-life in perfusate = 10 min) was much faster than that of the native enzyme (half-life = 30 min) or the cathepsin-inactivated enzyme (half-life = 42 min). The degradation of the enzyme was almost totally inhibited by leupeptin, indicating that thiol proteinases in lysosomes play an important role in the digestion process. Degradation of native and cathepsin D-inactivated aldolase appeared to be slower than that of the glutathione-inactivated enzyme but studies in which liver was preloaded with aldolase by perfusion at 19 degrees C and then warming to 37 degrees C indicated that the rate of degradation of all three forms was similar. It is concluded that the liver is capable of distinguishing between the glutathione-altered aldolase and native or partially degraded aldolase with regard to endocytosis, but that all three forms are degraded at similar rates once within lysosomes.     

An Improved Diluent for Rubella Hemagglutination and Hemagglutination-Inhibition Tests

Rubella hemagglutinating (HA) antigen was prepared in BHK-21 tissue as 5% cell suspensions and from unconcentrated and 20× concentrated infected supernatant fluids. In some instances, unconcentrated fluids were treated with Tween 80 and ether; cell suspensions were treated with ether alone. Preparations were tested for HA activity in dextrose-gelatin-Veronal (DGV) buffer solutions; 0.85% NaCl; Sorenson's phosphate-buffered saline, pH 7.2; and a diluent of 0.9% NaCl, 0.1% CaCl₂ (anhydrous), and 0.1% MgSO₄·7H₂O. HA titers were consistently two- to fourfold higher in the saline with added Ca⁺⁺ and Mg⁺⁺ than in DGV. Hemagglutination-inhibition titers of paired human sera were the same in either diluent. It is suggested that the interaction between rubella HA antigen and the red cells of young (less than 1-day-old) chicks may be at least partially ion dependent and that titers are enhanced by increased quantities of divalent cations.     

Microbiological Contamination of Hospital Air: I. Quantitative Studies

The levels of airborne contamination in various areas of two hospitals were determined during a 15-month sampling period, using Casella and Andersen volumetric samplers. Based on nearly 5,000 samples, the mean count per ft³ ranged from 4.5 in obstetric-gynecology delivery rooms to 72.4 in waste-handling areas. The mean count for the entire hospital environment was on the order of 20 contaminants per ft³; 48% were associated with particles >5 μ diam, 30% with particles between 2 and 6 μ diam, and 22% with particles <2 μ diam. The airborne contamination was influenced by traffic, activity, ventilation considerations, and gross surface contamination, but not markedly by seasonal changes. When suitable control measures were implemented, the level of contamination could be diminished and kept low.