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Biomedical subjects

G M Jones

Publications and source records attributed to G M Jones.

At least 145 records · Page 8Linked to original sources

Morphology and serum dependence of cloned cell lines undergoing spontaneous malignant transformation in culture.

A number of morphological changes were found to correlate with the occurrence of spontaneous neoplastic transformation in sublines of five rigidly isolated clones of mouse embryo fibroblasts. These morphological changes included increased cytoplasmic basophilia, reduced spreading of cells on the substrate, increased nuclear:cytoplasmic ratio, greater heterogeneity in the size and shape of cells and nuclei, and more random orientation of cells. Because these changes were reproducible, occurring in some sublines of all five clones, they have been described and illustrated to serve as a guide for identifying spontaneous transformants among rodent fibroblasts in culture. Neoplastic transformation was determined by the growth of the cells as malignant neoplasms in syngeneic hosts. The spontaneous transformants, as compared with nonneoplastic fibroblasts derived from the same cell, showed similar saturation densities and serum dependence. Some clones had a higher transformation frequency than the parental line, which remained nonneoplastic for years. Thus, the capacity for continuous growth in vitro can be independent of malignant potential. The use of horse serum as supplement to the medium did not accelerate or increase the frequency of neoplastic transformation.

Animals↗

Topography of nonneoplastic and neoplastic cells of common origin.

The possibility that neoplastic transformation may characteristically alter cell surface morphology prompted a comparison by scanning electron microscopy of nonneoplastic and tumorigenic cell lines from a single clone of mouse embryo cells. Among those studied by scanning electron microscopy, six lines of this clone proved nonneoplastic, and nine others underwent neoplastic transformation in culture, as evidenced by tumor production in vivo. Combined cinephotomicrography and scanning electron microscopy allowed the determination of postmitotic time and topography of individual cells without perturbing the cells or detectably altering their surface morphology; no pattern of morphological change as a function of postmitotic time was evident in either nonneoplastic or neoplastic cell populations. Accordingly, these cell populations could be compared under their usual conditions of attached asynchronous growth despite differences in proliferation rates. Cells of the neoplastic lines were characteristically less spread, and some lines displayed greater morphological variability than was evident among cells of nonneoplastic lines. However, most cells in all nine neoplastic lines and all six nonneoplastic lines were smooth surfaced. Thus, the exaggerated incidence of microvilli, ruffles, or blebs reported for established tumor-derived lines and most morphologically transformed lines did not prove a reliable criterion of neoplastic state for these cell lines of common origin grown under the same culture conditions.

Animals↗

Colony morphology and growth in agarose as tests for spontaneous neoplastic transformation in vitro.

Adherent fibroblast-like cells from paired lines, one non-neoplastic and the other "spontaneously" transformed neoplastic, were compared in simultaneous in vivo and in vitro assays. The in vivo assay was the i.m. implantation of 10(6) or 10(7) cells in irradiated syngeneic animals, and the two in vitro assays were the evaluation of colony morphology on plastic and the enumeration of colony growth in semisolid agarose. The percentage of colonies diagnosed from their morphology as neoplastic correlated with tumorigenicity as follows: 100% always indicated a tumorigenic cell population with tumor latent periods from 6 to 230 days and tumor incidence from 40 to 100%; 0% always indicated a nontumorigenic cell population; 1 to 32% indicated either a tumorigenic cell line with long tumor latent period (218 days) with 70% tumor incidence or a nontumorigenic cell line. Growth in agarose, as measured by colony number and size, correlated with tumorigenicity as follows: nontumorigenic cell lines produced no colonies; tumorigenic cell lines produced colonies, but not always larger than 0.1 mm in diameter. The number of size or colonies did not correlate with the tumor latent period or tumor incidence. Therefore, both in vitro tests were reliable qualitative assays of spontaneous neoplastic transformation, but they did not correlate directly with the tumor incidence or mean tumor latent period. The relative success of the agarose assay emphasizes the importance of decreased anchorage dependence for progressive growth of injected cells as a malignant neoplasm in vivo.

Animals↗

Audio-spinal influence in man studied by the H-reflex and its possible role on rhythmic movements synchronized to sound.

An investigation was made of the time course of audio-spinal influences in man using the H-reflex technique and non-startling sounds. It was found that in all subjects the sound potentiated the H-reflex at a central latency of 80 msec, the peak facilitation (185%) being attained at 110--130 msec. The mean duration of this facilitation was 200 msec ranging from 120 to 460 msec. No inhibition was seen to follow the excitatory period. An habituation study showed a significant drop in peak facilitation after exposure to ten conditioning stimuli but a constant increase of the H-reflex above control level even after 60 presentations. The time course of this audiospinal facilitation was superposed over the EMG events during hopping to a simplified musical stimulus. In this situation, landing occurred some 50 msec prior to the ON beat or strong beat of the music. With this mode of synchronization, the timing of the ON and OFF beats of the musical stimulus would be suitable to potentiate the EMG events related respectively to the peak upwards acceleration determining the take-off and to the landing. It is inferred that during synchronized stereotyped movements to repetitive auditory stimuli, the motor events are timed to make best use of a potential audio-spinal facilitation.

Adolescent↗

Short-term adaptive changes in the human vestibulo-ocular reflex arc.

1. Two sets of experiments have examined the vestibulo-ocular response (VOR) to repeated sinusoidal rotation (A) in the dark and (B) after attempting visual tracking of a mirror-reversed image of the visual surround.2. In both A and B a horizontal sinusoidal rotational stimulus of 1/6 Hz and 60 degrees /sec angular velocity amplitude was employed, specifically chosen to lie within the presumed range of natural stimulation of the semicircular canals.3. In A each of seven subjects underwent ten 2-min runs of the standard stimulus in the dark on each of three consecutive days, with 3-min rest periods between runs. Using d.c. electro-oculography (EOG) the VOR gain was measured throughout as eye velocity/head velocity. Mental arousal was maintained by competitive mental arithmetic. Constancy of EOG gain was assured by 50 min dark adaptation before experimentation.4. The results of A showed no consistent change of VOR gain over the three times scales of a run, a day and the 3-day experiment.5. In B the same subjects underwent a similar pattern of vestibular stimulation, but during eight of the 2-min daily runs they attempted the reversed visual tracking task. VOR gain was measured during the 1st, 6th and last runs which were conducted in the dark for this purpose. Constancy of EOG gain was maintained by using red light throughout.6. The results of B showed a substantial (approx. 25%) and highly significant (P << 0.001) reduction of VOR gain attributable solely to the 16 min of reversed visual tracking attempted during the 50 min daily experiment. In addition the pre-test control gain was lower on day 3 than on day 1 (approx. 10% attenuation, P < 0.01) indicating a small cumulative effect from beginning to end of the 3-day experiment.7. It is concluded (A) that the repeated vestibular stimulus did not itself cause significant attenuation of VOR gain, but (B) that superposition of a reversed visual tracking task did induce retained VOR attenuation which was solely due to the antagonistic visual stimulus.8. In conjunction with other experimental evidence it is inferred that this attenuation probably represents an adaptive change in the VOR induced at least in part by retinal image slip.

Journal Article↗

Extreme vestibulo-ocular adaptation induced by prolonged optical reversal of vision.

1. These experiments investigated plastic changes in the vestibulo-ocular reflex (VOR) of human subjects consequent to long-term optical reversal of vision during free head movement. Horizontal vision-reversal was produced by head-mounted dove prisms. Four normal adults were continuously exposed to these conditions during 2, 6, 7 and 27 days respectively.2. A sinusoidal rotational stimulus, previously shown to be nonhabituating (1/6 Hz; 60 degrees /sec amplitude), was used to test the VOR in the dark at frequent intervals both during the period of vision-reversal and an equal period after return to normal vision. D.c. electro-oculography (EOG) was used to record eye movement, taking care to avoid changes of EOG gain due to light/dark adaptation of the retina.3. All subjects showed substantial reduction of VOR gain (eye velocity/head velocity) during the first 2 days of vision-reversal. The 6-, 7- and 27-day subjects showed further reduction of gain which reached a low plateau at about 25% the normal value by the end of one week. At this time the attenuation of some EOG records was so marked as to defy extraction of a meaningful sinusoidal signal.4. After removal of the prisms VOR gain recovered along a time course which approximated that of the original adaptive attenuation.5. In the 27-day experiment large changes of phase developed in the VOR during the second week of vision-reversal. These changes generally progressed in a lagging sense, to reach 130 degrees phase lag relative to normal by the beginning of the third week. Accompanying this was a considerable restoration of gain from 25 to 50% the normal value. These adapted conditions, which approximate functional reversal of the reflex, were then maintained steady, even overnight, until return to normal vision on the 28th day.6. Thereafter, whereas VOR phase returned to near-normal in 2 hr, restoration of gain occupied a further 2-3 weeks.7. There was a highly systematic relation between instantaneous gain and phase, even during periods of widely fluctuating change associated with transition from one steady state to another. During such transition there was a tendency for directional preponderance to occur in the VOR.8. All the observed changes were highly specific to the plane of vision-reversal, no VOR changes being observed in the sagittal plane.9. VOR changes were adaptive, in the sense that they were always goal-directed towards the requirements of retinal image stabilization during head movement. They were plastic to the extent that there was extensive and retained remodelling of the reflex towards this goal.10. It is inferred that all the observed changes in gain and phase are compatible with a simple neural network employing known vestibulo-ocular projections via brainstem and cerebellar pathways, providing that the reversed visual tracking task can produce plastic modulation of efficacy in the cerebellar pathway and that this pathway exhibits a dynamic characteristic producing moderate phase lead in a sinusoidal signal at 1/6 Hz.

Journal Article↗

Utilization of Starea, urea, or soybean meal in complete rations for lactating dairy cows.

Three complete rations containing 15.8% of the dry matter as crude protein were compared to a 14.5% crude protein basal ration (dry matter basis) through eight Holstein cows in a replicated 4 times 4 Latin square design. The high protein rations contained supplemental nitrogen totally from soybean meal, urea, or Starea, the latter two providing 16 and 22% of total ration nitrogen, respectively. Concentrations were mixed with wilted alfalfa-bromegrass silage and complete rations fed ad libitum. Data were collected during the last week of each 28 days. Ration had no effect on milk yield, composition of fat or protein, or apparent digestibility of dry matter, crude protein, or acid detergent fiber. Weight gains and dry matter intake were greatest with the soybean meal ration. Intake of the low protein ration was depressed. There were no significant differences between the high protein rations for efficiency of nitrogen utilization.

Animal Feed↗

Pseudopseudohypoparathyroidism with fibrous dysplasia.

Pseudopseudohypoparathyroidism and pseudohypoparathyroidism have been thought to represent variants of the same disease process, Albright hereditary osteodystrophy. A 31-year-old woman with the characteristic features of pseudopseudohypoparathyroidism, such as shortened metacarpals and metatarsals, round facies, and normal serum calcium values, was studied. Underdeveloped metacarpal and metatarsal heads produced an important diagnostic sign, Albright dimpling sign, which dermatologists can use to make the correct diagnosis. The presence of this sign, together with roentgenographic evidence, will usually exclude other diagnostic possibilities. Our patient had a normal response to parathyroid hormone infusion, including increased urinary adenosine 3',5' cyclic monophosphate excretion. Radiological, light microscopic, and electron microscopic studies of the mandible showed fibrous dysplasia, a disease commonly reported to be present with hyperparathyroidism, but, to our knowledge, never before reported in association with any variant of hypoparathyroidism.

Adult↗

Glucose metabolism in the rat small intestine: the effect of glucose analogues on hexokinase activity.

The effect of intubation of starved rats with solutions of glucose, 3-O-methylglucose, mannose, 2-deoxyglucose and sorbitol on the subcellular location of hexokinase in the mucosa of the small intestine was studied. Glucose, 3-O-methylglucose and mannose caused the soluble hexokinase activity to rise to a value similar to that found in fed animals, whereas sorbitol and 2-deoxyglucose caused smaller increases.

Animals↗