PubMed Health⌕ Search

Biomedical subjects

J C Marigold

Publications and source records attributed to J C Marigold.

At least 19 recordsLinked to original sources
PubMed1988

Thermotolerance in preirradiated intestine and its influence on time-temperature relationships.

The crypt compartment of mouse jejunum showed a transient increase in thermal susceptibility approximately 10 days after moderate X-ray doses to the abdomen (9-10 Gy). The increase in response was manifest as an increase in slope of the crypt dose-response curve but was limited to temperatures below 43 degrees C. As a result, the 43 degrees C inflexion in the Arrhenius plot (the relationship between treatment time and temperature) for thermal sensitivity of crypts was eliminated in preirradiated tissue, and the curve became monophasic over the range 42.0-44.5 degrees C. At temperatures below 42 degrees C, the curve again deviated. At supranormal temperatures of 42 degrees C and below, the durations of hyperthermia needed for measurable effect were sufficient to allow thermotolerance to be expressed within the heating period. Neither the threshold heating times nor this thermotolerance were affected by prior irradiation. In the temperature range 42-43 degrees C, an earlier development of thermotolerance could be demonstrated in control tissue by challenging with an acute high-temperature heat treatment. This thermotolerance was eliminated in preirradiated tissue, resulting in the apparent increase in sensitivity. The findings support the view that the complex nature of the time-temperature relationship seen in normal tissue in vivo is a manifestation of the ability of the tissue to progressively acquire a thermotolerant state during treatment at temperatures below approximately 43 degrees C, so that the "intrinsic" sensitivity is modulated while being assessed.

Adaptation, Physiological↗
PubMed1988

Development of villous damage in mouse small intestine after local hyperthermia or irradiation.

Damage to mouse small intestine has been assessed in the period up to twenty-four hours after heating a portion of the gut for 20 min at 43 degrees C and also in the period up to nine days after 10 Gy/whole body X-irradiation. The surface changes and the light microscopic appearances after the two types of treatment were described. The damage was evaluated using scores produced by assessing villous collapse as seen with a scanning electron microscope (SEM). Maximum damage was seen two hours after hyperthermia and was more pronounced in antimesenteric portions of the same specimen. Maximum damage was observed three days after X-irradiation. Despite the difference in the time scale and severity of development of surface changes after the two types of treatment, the structure of the damaged and recovering villi looked similar, except for the apical extrusion of the enterocytes immediately following the heat treatment.

Animals↗
PubMed1987

A preliminary study of the role of gastrointestinal endocrine cells in the maintenance of villous structure following X-irradiation.

The mechanism of gastrointestinal villous damage following ionizing irradiation is complex. Various compartments within the gastrointestinal tract have in turn been considered important for the maintenance of normal villous structure. To date, however, evidence for a single overriding regulator of epithelial well-being is lacking. In this study, the role of the gastro-intestinal (enteroendocrine) cells is explored and comparison made between endocrine cell number and villous structure. Experiments were organised using both control and irradiated groups of mice. Two time points (1 and 3 days) and three radiation doses (6, 10 and 18Gy) were employed. A simple method for endocrine cell identification and subsequent quantification is described. Endocrine cell number was then compared with villous surface detail, as seen with a scanning electron microscope (SEM). Results indicated a decrease in the endocrine cell number at all three radiation doses. Whereas at low doses endocrine cell recovery occurred between 1 and 3 days, at medium and high doses further decline was noticed. A similar pattern was seen when considering villous surface structure. It is suggested that both scanning electron microscopy and endocrine cell number provide a more sensitive indicator of gastrointestinal radiation damage than do current crypt counting techniques. In addition, a link between endocrine cell number and villous structure is proposed.

Animals↗
PubMed1986

Thermal enhancement of radiation damage in previously irradiated mouse intestine.

The effects of prior irradiation (8 or 10 Gy of X rays) on the response of mouse jejunum to a test treatment of (a) hyperthermia (42.0 degrees C for 60 min), (b) X rays (8 or 10 Gy) or (c) combined hyperthermia and radiation were investigated at various times up to 7 months after the primary treatment. Tissue injury was quantified by crypt survival 4 days after the test treatment. Although tissue susceptibility to direct thermal injury was increased 10-15 days after irradiation, neither radiation sensitivity nor thermoradiosensitisation were significantly affected at any of the time intervals used. The results support the concept that there are different pathways for the in vivo expression of gross thermal damage and thermoradiosensitisation.

Animals↗
PubMed1985

Time-temperature relationships for hyperthermal radiosensitisation in mouse intestine: influence of thermotolerance.

Thermal enhancement of radiation injury to the crypt compartment of mouse small intestinal mucosa has been measured as a function of heating time for temperatures in the range 41.0-44.0 degrees C. All the hyperthermal treatments used were themselves subthreshold for gross tissue injury. With this limitation, thermoradiosensitisation increased linearly with duration of hyperthermia for temperatures in the range 42.3-44.0 degrees C. Using temperatures below 42.0 degrees C, there was a saturation in effect for treatments longer than approximately 40-90 min, possibly due to the development of thermotolerance. The thermoradiosensitisation isoeffect curve relating heating time with temperature was biphasic with the transition occurring between 41.8 and 42.0 degrees C. For temperatures above the transition, a 1 degree C change was equivalent to a factor of 2.6 in heating time; below the transition, a 1 degree C change was equivalent to a factor of 5.4. Time-temperature relationships for thermoradiosensitisation in other rodent tissues are reviewed and compared with the general relationships for direct thermal injury, previously derived from experimental studies. The results are discussed with relevance to the interpretation of in vivo thermal enhancement of radiation injury.

Animals↗
PubMed1985

Investigation of thermotolerance in mouse testis.

The effect of a two-fraction heat treatment on mouse testis has been assessed by measuring testis weight loss at 1 week after treatment. The rate of repair of 'sublethal' heat damage following the first treatment was dependent on the severity of the treatment. Using a primary treatment of 41.5 degrees C for 30 min, the weight loss following a test treatment of 41.5 degrees C for 30 min returned to that of the test treatment alone within an interval of 16-24 h. Using a milder primary treatment of 40.0 degrees C for 30 min, repair of sublethal heat damage appeared to be complete by 1-2 h. When a single test treatment was used, there was no evidence of heat-induced thermal resistance (thermotolerance) following primary treatments of 40.0 or 41.5 degrees C for 30 min, for periods up to 24 h between treatments. A small degree of thermotolerance could, however, be demonstrated following the most severe primary treatment used if full dose: effect curves were obtained. Thermotolerance, manifest as a decrease in slope, was maximal at approximately 4 h after the primary treatment. The results are discussed with reference to other normal tissue data.

Animals↗
PubMed1985

Changes in surface structure and concanavalin A-binding capacity of urothelium in the mouse bladder after whole-body neutron irradiation.

A broad overview has been compiled of the literature on the effects of radiation on urinary bladder and on selected cell surface markers that may give information on the pathobiological status of the urinary bladder urothelium. Scanning electron microscopy and immunogold labelling have been used in this study which examines the early (6h to 12 day) radiation response of the mouse urinary bladder following whole-body neutron irradiation. Experimentally, after 5 Gy neutron irradiation, changes in the urothelium include surface morphological abnormalities and enhanced concanavalin A surface binding. These changes were most obvious 1 to 5 days post-irradiation, but lessened in their extent from 5 to 12 days after treatment.

Animals↗
PubMed1985

Structural changes in mouse small intestinal villi following lower body hyperthermia.

Heating an exteriorised loop of mouse small intestine resulted in marked changes in the shape of the villi as reported earlier. However, the exteriorisation techniques resulted in non-uniformity in both temperature and effect around circumference of intestine and, in addition, the extent to which handling contributed to the observed damage was not known. The work has therefore been extended using lower-body heating in the temperature range 37.5 degrees - 43.0 degrees C. Heating in the temperature range 37.5 degrees C to 41.0 degrees C produced minimal to moderate structural changes, manifested as scattered, vertically collapsed villi amongst predominantly "normal" villi. No villi showed conical or rudimentary forms of collapse. Such villi were, however, seen after heating at 41.5 degrees C and were greatly increased in number after heating at 42.0 degrees C. The most severe damage was observed after heating at 43.0 degrees C. Although the lower body heating method gave information which was less complicated by technical considerations, the hyperthermic damage observed was qualitatively similar to that previously seen following local administration of hyperthermia to an exteriorised loop of intestine. Direct quantitative comparisons between the two methods of heating are difficult because of differences in equilibration time and temperature. However, using a comparable heating time, less damage was scored following the exteriorisation technique compared with in situ heating.

Animals↗
PubMed1984

The development of thermotolerance in hyperthermal injury to the villus compartment of mouse small intestine.

The development and decay of thermotolerance in the villus compartment of the intestinal mucosa of mouse was investigated by giving a primary treatment of 41.5 degrees C for 1 hour (subthreshold for thermal injury) at various intervals before a second, test treatment of 43.0 degrees C for 30 min. The test treatment was given 65 hours after an intraperitoneal injection of 3H-thymidine (i.e. at a time when the heavily labelled cells could be seen to have moved from the crypts on to the upper halves of the villi) and thermal damage assessed by loss of radioactive label. A transient tolerance to the second treatment was induced by the primary treatment. This 'thermotolerance' was maximal 3-13 hours after the first treatment and had decayed by 24 hours. Both the extent and time course of expression and decay of thermotolerance in this post-mitotic functional compartment were very similar to those previously reported for damage to the proliferative epithelium as assayed by crypt loss. This suggests either that the kinetics of thermotolerance are not dependent on the proliferative status of the tissue or that there is a common limiting factor in thermotolerance development, despite the apparent difference between the two mucosal compartments in their susceptibilities to thermal injury.

Acclimatization↗
PubMed1983

Effect of prolonged heating on the thermal enhancement ratio in X-irradiated murine intestine.

When the jejunum in mice was heated for 20-180 min at temperatures between 40.3 and 42.3 degrees C, followed immediately by X-irradiation, the thermal enhancement ratio (TER) for crypt survival increased and then tended to decline with longer heating times. At the higher temperatures, the TER was higher and the peak value was reached with shorter heating times. The decline in TER with longer heating times may be due to the development of thermotolerance.

Adaptation, Physiological↗
PubMed1983

The effect of local hyperthermia on nonproliferative, compared with proliferative, epithelial cells of the mouse intestinal mucosa.

The effects of local hyperthermia on different components of mouse intestinal mucosa were investigated. The intestine was heated by immersion in Krebs-Ringer solution at various times after intraperitoneal injection of [3H]thymidine, and thermal injury was assessed by measuring loss of label. The interval between labeling and heating was either 14 hr, when the majority of labeled epithelial cells were still in the crypts, or 65-72 hr, when the majority of the label had moved onto the villi. Heating at 42 degrees C for up to 1 hr had no observable effect. When intestine was heated at 43 degrees C 14 hr after labeling, the characteristics of the loss of label were very similar to loss of crypts with regard to both the fraction lost and the time over which the response occurred. The threshold heating time to cause an effect was between 20 and 30 min and the response was complete by 6 hr after treatment. If, however, intestine was heated at 43 degrees C either 65 or 72 hr after injection of [3H]thymidine, the threshold heating time required to cause an effect was reduced to between 10 and 20 min and loss of label was not necessarily accompanied by crypt loss. For example, 40% of radioactivity could be lost from the villi without any corresponding loss of crypts. Both the labeling experiments and histological examination indicated that the nonproliferative cells of the intestinal mucosa that line the lumen are more susceptible to thermal injury than the crypt cells. Thus, although crypt loss may remain a useful endpoint in the assessment of thermal damage, the data would underestimate early mucosal injury and the impairment of functional integrity of small intestine.

Animals↗
PubMed1983

The effect of retinol on the hyperthermal response of normal tissue in vivo.

The effect of prior administration of retinol, a membrane labilizer, on the in vivo hyperthermal response of lysosomes was investigated in the mouse spleen using a quantitative histochemical assay for the lysosomal enzyme acid phosphatase. A dose of retinol which had no effect when given alone enhanced the thermal response of the lysosome, causing an increase in lysosomal membrane permeability. In contrast, the same dose of retinol had no effect on the gross hyperthermal response of mouse intestine; a tissue which is relatively susceptible to hyperthermia. Thermal damage to intestine was assayed directly by crypt loss 1 day after treatment or assessed as thermal enhancement of X-ray damage by counting crypt microcolonies 4 days after a combined heat and X-ray treatment. Thus, although the hyperthermal response of the lysosome could be enhanced by the administration of retinol, thermal damage at a gross tissue level appeared to be unaffected, suggesting that lysosomal membrane injury is unlikely to be a primary event in hyperthermal cell killing.

Acid Phosphatase↗
PubMed1982

Effect of prior hyperthermia on subsequent thermal enhancement of radiation damage in mouse intestine.

Hyperthermia given in conjunction with X-rays results in a greater level of radiation injury than following X-rays alone, giving a thermal enhancement ratio (TER). The effect of prior hyperthermia ('priming') on TER was studied in the small intestine of mouse by giving 42 X 0 degrees C for 1 hour at various times before the combined heat and X-ray treatments. Radiation damage was assessed by measuring crypt survival 4 days after radiation. TER was reduced when 'priming' hyperthermia was given 24-48 hours before the combined treatments. The reduction in effectiveness of the second heat treatment corresponded to a reduction in hyperthermal temperature of approximately 0 X 5 degrees C, a value similar to that previously reported for induced resistance to heat given alone ('thermotolerance') (Hume and Marigold 1980). However, the time courses for development and decay of the TER response were much longer than those for 'thermotolerance', suggesting that different mechanisms are involved in thermal damage following heat alone and thermal enhancement of radiation damage.

Adaptation, Physiological↗
PubMed1982

Increased hyperthermal response of previously irradiated mouse intestine.

The effect of prior irradiation (6-10 Gy of X rays) on the response of mouse jejunum to 43.0 degrees C hyperthermia was investigated. A dose of 6 Gy has no significant effect on the crypt loss measured after hyperthermia. However, intestine which had received 8-10 Gy showed increased susceptibility to subsequent thermal injury. Between approximately one and 2 weeks after 9 Gy, the thermal response of the intestine of CFLP mice increased such that, at maximal effect, heating pre-irradiated intestine at 43.0 degrees C was approximately equivalent to heating untreated intestine at 43.5 degrees C. The effect of prior irradiation was transient and appeared to have been "forgotten" after 2-3 months, a finding of particular relevance to the clinical situation. The results are discussed with reference to any radiation injury to intestine which might influence the expression of hyperthermal damage in situ.

Animals↗
PubMed1982

Scanning and transmission electron microscopy of the damage to small intestinal mucosa following X irradiation or hyperthermia.

Scanning and transmission electron microscopy (S.E.M. and T.E.M.) and resin histology have been used to investigate the effects on mouse small intestinal villi of heating at 43 degrees C for 20 minutes and of irradiation with 10 Gy X-rays. Damage after irradiation included conical villi and giant cells. Damage after heating included the production of conical and rudimentary villi and the stacking of enterocytes. Individual cells showed signs of abnormalities in their cell membranes, nuclei and cytoplasmic components. The differences in the response after irradiation and hyperthermia are linked to the fact that heating has a primary effect on villous structure, whereas irradiation mainly affects the proliferative pool of crypt cells.

Animals↗
PubMed1981

The response of mouse intestine to combined hyperthermia and radiation: the contribution of direct thermal damage in assessment of the thermal enhancement ratio.

The thermal enhancement of X-ray damage to mouse jejunum has been assessed when heating was achieved by immersion of an exteriorized loop of intestine in Krebs-Ringer solution. The results have been compared with those previously obtained following heating in situ. The primary effect of 1 hour of mild hyperthermia was to reduce the should of the crypt survival curve obtained following X-rays given alone. Thermal enhancement ratio (TER) values increased with increasing temperature, up to 42.3 degrees C, and were within the range reported for other normal tissues. However, when hyperthermia itself caused crypt loss and the contribution of hyperthermal killing to the overall tissue response was taken into account, there was little enhancement of radiation damage. There was no evidence of a large increase in TER at high temperatures, as is seen in some tumours and has been reported by Merino, Peters, Mason and Withers (1978) for intestine. It is possible that very high TER values which have previously been reported mainly reflect the heat-alone component of damage. Some of the implications of these results are discussed in relation to the combination of heat and radiation in therapy.

Animals↗