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Biomedical subjects

K O Johnson

Publications and source records attributed to K O Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1979

Validation and characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay system.

The current status of the L5178Y/TK+/- leads to TK-/- mouse-lymphoma mutagenicity assay is described. Dose-survival-mutagenic response data are shown for 43 chemicals. Mutagenicity and cytotoxicity in the presence or absence of non-induced and/or Aroclor-induced rat-liver S-9 are compared for most of these chemicals, 25 of these for which usuable carcinogenicity data exist have been used to construct an approximately linear relationship between oncogenic potency in vivo and mutagenic potency in this system in vitro; linearity between these two endpoints extends over a greater than 100,000-fold range in potencies. Several carcinogens which are negative or difficult to detect in the standard Ames assay are mutagenic in this mammalian cell system. These include natulan, sodium saccharin (lot S-1022), p,p'-DDE (metabolite of DDT), dimethylnitrosamine, diethylnitrosamine and diethylstilbestrol. Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield. Large-colony TK-/- mutants probably represent point or gene mutations affecting the TK locus. In addition, a class of small-colony TK(/- mutants are described and characterized as being heritably growth-deficient; this and other properties suggest that these small-colony TK-/- mutants originate by a heritable and viable chromosomal aberration. Most carcinogens and mutagens tested produce both classes of TK-/- mutants in this system; the relative proportions of small- and large-colony mutants are both mutagen- and dose-dependent. Comparative studies have been done at the rapidly-expressing TK locus and the slowly-expressing HGPRT locus in these cells. Several carcinogens detected at the TK locus are non- or very weakly mutagenic at the HGPRT locus. This findings is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.

Animals↗
PubMed1979

Warm fibers innervating palmar and digital skin of the monkey: responses to thermal stimuli.

1. Three hundred fourteen warm fibers innervating the glabrous skin of the monkey's hand were isolated by dissection in the median and ulnar nerves in two species, Macaca mulatta and M. nemestrina. Fiber samples in the two species were functionally similar and uniform in their properties. Their mean conduction velocity of 1.2 m/s (SD 0.5; n = 50) implies that these warm fibers were all unmyelinated. 2. A parametric study of the responses of warm fibers to near-rectangular warming and cooling pulses applied to glabrous skin was completed using 104 fibers. At a steady base-line skin temperature (T-base) of 34 degrees C all these warm fibers responded to warming pulses in the intensity range 0--8 degrees C with a simple, uniform discharge, which reached a peak rate of 1.5--4.0 s after the onset of stimulation; subsequent decay in this discharge rate had a time constant of 5--12 s and was virtually independent of the intensity of the warm pulse. The intensity function was linear for most fibers when the interstimulus interval was 60 s or longer. At a T-base of 29 degrees C, warm fibers were less responsive, but the temporal profile of the response was similar to that at a T-base of 34 degrees C in the intensity range 4--8 degrees C, and the intensity function was again linear. 3. At a T-base of 39 degrees C the intensity function of each warm fiber was complex. Most fibers responded briskly to warming pulses of 2--4 degrees C: the response to more intense warming pulses, particularly when the skin temperature rose above 45 degrees C, was structured and reproducible, but varied greatly among different fibers. With some the discharge evoked was of very high frequency for a few seconds, and then ceased. More than 80% of the sample of warm fibers did not discharge at all in response to warming pulses, which raised the skin temperature to 50 degrees C or above. 4. The responsiveness of warm fibers to warming pulses was dependent on previous stimulation when the interstimulus interval was less than 60 s. This temporal suppression was precisely structured and was examined quantitatively for trains of warming pulses, each lasting 4.0 s and presented every 10 s. The pattern of suppressive interaction was similar in form to that previously reported for cold fibers innervating palmar skin. 5. A quantitative study of the receptive fields of individual warm fibers demonstrated a spatiotemporal response pattern, which is best described in terms of a focal receptor zone less than 1 mm in diameter surrounded by thermally conducting skin. The skin's thermal conductivity is paramount in determining the warm-fiber's receptive-field characteristics. 6. The responses of warm fibers to cooling pulses and to warming ramps are described.

Animals↗
PubMed1979

Coding of incremental changes in skin temperature by single warm fibers in the monkey.

1. Experiments were designed to answer the question: how well does a single warm fiber innervating the glabrous skin of the monkey's hand resolve incremental changes in the intensity of near-rectangular warming pulses applied to the fiber's receptive field? 2. In these experiments the measure of the warm fiber's capacity to resolve incremental changes in the intensity of successive warming pulses was termed the discriminable stimulus increment (DSI). The DSI is defined as that incremental difference in the intensity of a pair of warming pulses that could be resolved correctly, with a probability of 0.75, by comparing the fiber's responses to these two stimuli. In the specified conditions of the experiment, DSI = 0.67 sigma delta tau/(dR/dI) where sigma delta tau is the standard deviation of the difference in responses of the fiber to pairs of stimuli, and dr/dI is the fiber's sensitivity to incremental stimulus change. (dr/dI) was experimentally determined as the mean rate of change of the fiber's responses to incremental changes in the intensity of the warming pulse. 3. The DSI, as defined above, assumes that the basis for differentiating the stimuli in each pair was that the larger response in the fiber was in each instance generated by the more intense stimulus. A more general form of the DSI was also developed and used to examine the effects on intensity resolution of different discrimination rules that the brain might use. 4. In the experimental analysis the response measure of each warm fiber was the cumulative impulse count over successively longer segments of the stimulus period. With short integration intervals the DSI was high (i.e., intensity resolution was poor), but typically the DSI fell to a plateau level within 2.0--2.5 s of the onset of the warming stimulus. 5. The DSI was measured on 23 warm fibers in Macaca nemestrina for warming pulses with intensities of 0, 2, 4, 6, and 8 degrees C, at T-base levels of 29, 34 (near normal temperature of palmar skin), and 39 degrees C. For most observations the intensity resolution possible from the responses of single warm fibers, measured over this wide variety of stimulus conditions, was less than is achieved by the human observer trained to differentiate comparable warming pulses applied to the skin of the thenar eminence.

Adaptation, Physiological↗