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Biomedical subjects

S B Field

Publications and source records attributed to S B Field.

At least 37 records · Page 2Linked to original sources

The sensitivity to hyperthermia of human granulocyte/macrophage progenitor cells (CFU-GM) derived from blood or marrow of normal subjects and patients with chronic granulocytic leukaemia.

To compare the relative heat sensitivities of human normal and neoplastic cells of the same tissue type, a study was carried out of the relative sensitivities to heat of granulocyte/macrophage progenitor cells (CFU-GM) derived from the peripheral blood and bone marrow of normal subjects and patients with chronic granulocytic leukaemia (CGL). Nucleated haemopoietic cells were incubated at temperatures in the range 41.5 degrees C to 44.0 degrees C for various periods before culture in agar. The results of these experiments showed that CFU-GM from normal blood were consistently less sensitive to damage by heat than normal marrow CFU-GM. There was no comparable difference in the relative heat sensitivities of CFU-GM from blood and marrow of patients with CGL and no significant difference between the heat sensitivities of CFU-GM derived from marrow from normal individuals and patients with CGL. The observed difference in heat sensitivity of CFU-GM from normal blood and marrow accords with other data suggesting that the two progenitor cell compartments are distinct: the blood CFU-GM may represent a more primitive population of committed progenitor cells. In CGL, CFU-GM in the blood may much more closely resemble those in the marrow. The data provide no support for the hypothesis that malignant cells differ intrinsically from their normal counterparts in respect of sensitivity to damage by hyperthermia.

Cell Survival↗

The response of mouse skin to hyperthermia combined with fast neutrons or X-rays.

The effects of hyperthermia combined with fast neutrons (mean energy approximately 7.5 MeV) or X-rays (250 kVp) were studied in the skin of the mouse ear and foot. Hyperthermia was achieved by immersion in water at temperatures of 41.5-43.0 degrees C for 1 hour. The heat treatments used caused no observable tissue injury other than transient erythema but they enhanced the response to both neutrons and X-rays. The enhancement of neutron damage increased as the heating temperature was increased, as is well known for X-rays. When heat was given after irradiation the thermal enhancement ratio (t.e.r.) for neutrons was similar to that for X-rays. When heat was given before irradiation the neutron t.e.r. was less than that for X-rays. Consequently, the relative biological effectiveness of fast neutrons compared with X-rays was not altered by giving heat after irradiation but it was reduced by giving heat before irradiation.

Animals↗

Attachment of fibroblasts following hyperthermia and ultrasound.

The rate of cell attachment to the culture substratum is reduced in mouse L cells by hyperthermia at 44 degrees C. The time for 50 per cent attachment of the cells increases rapidly with increasing time of heating immediately before assay. The rate of attachment after 44 degrees C does not show a linear correlation with clonogenic survival, ruling out the use of attachment as a rapid assay of clonogenic survival. The attachment process is less sensitive to heat in cells made thermally tolerant by a prior heat treatment. In contrast, ultrasound irradiation at 37 degrees C and below the cavitational threshold (1.5 MHz, 2.2 W/cm2, 15 min) did not alter the rate of attachment, but at 44 degrees C, ultrasound decreased both clonogenic survival and the rate of attachment to a much greater extent than 44 degrees C alone. As the temperature increase caused by the ultrasound was less than 0.5 degrees C, the data provide evidence of a non-thermal component of ultrasound damage.

Animals↗

The relationship between heating time and temperature: its relevance to clinical hyperthermia.

It is well known that for a given level of damage to either cells in vitro or tissues in situ the relationship between temperature and time of application undergoes a transition in the range 42-43 degrees C and that above this temperature a change of 1 degree C is equivalent to a change in heating time by a factor of two. The present study has concentrated on establishing the relationship between time and temperature over a wide range. The investigation is in two parts, i.e. a review of the literature and an experimental study in which the endpoint used was necrosis in the tail of the baby rat. The aim is to provide information which might help solve a major clinical problem, namely the lack of a satisfactory means of relating treatments given with different temperatures for different lengths of time. The difficulty arises because there is no satisfactory definition of heat dose, in this context. The results confirm the relationship given above for temperatures above the transition. However, below the transition a change of 1 degree C is equivalent to a change in heating time by a factor of six. It is suggested that these relationships provide a means of monitoring a treatment in which the temperature does not remain constant and may vary within a heated volume. The method may also be used to compare treatments from different centres. An indication of the considerable uncertainties of the procedure is given.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of thermal enhancement ratios for fast neutron and x irradiation of two normal tissues in rodents.

The effects of a hyperthermal treatment of one hour on radiation damage to baby rat cartilage and mouse intestine were compared for 250 kVp X irradiation and cyclotron-produced neutron irradiation (mean energy of about 7.5 MeV). Heat, in the range 41.0 degrees C-43.0 degrees C, caused no observable gross tissue injury when given alone. When heat was given immediately before radiation, the radiation damage was enhanced. There was no qualitative differences between response after fast neutrons and after X rays. Thermal enhancement ratios (TER) were similar for the two tissues and were not affected by the type of radiation used. Thus, the relative biological effectiveness (RBE) of fast neutrons compared with X rays was not markedly altered by combining radiation with hyperthermia.

Animals↗

Thermotolerance: a review of observations and possible mechanisms.

The effects of hyperthermia on the response of cells and tissues to subsequent heating given alone or in combination with X-rays or drugs are considered. Two types of such induced thermotolerance are described: Type I results from continuous heating at temperatures below about 43 degrees C; type II results from a prior heating at a higher temperature, with subsequent incubation at about 37 degrees C. The time courses of the various types of thermotolerance are considered in relation to the magnitude of the priming treatment and whether the test is hyperthermia alone or in combination with X-rays or drugs. Reference is made to in vivo results wherever possible as well as to in vitro data. Factors which influence the development of thermotolerance are discussed, and some tentative hypotheses are made concerning the mechanisms leading to the phenomenon.

Acclimatization↗

The relationship between heating time and temperature for inhibition of growth in baby rat cartilage by combined hyperthermia and X-rays.

The relationship between the Thermal Enhancement Ratio (TER) for X-ray damage and time of heating has been investigated in epiphyseal rat cartilage. The TER at each temperature rises steeply with increasing heating time. Data obtained using various heat treatments with 8 Gy of X-rays have been analysed in terms of stunting "rate' as measured by the slope of the dose-effect curve obtained for each temperature. The "rate' of stunting per unit heating time, induced by thermally enhanced X-ray damage is compared with the "rate' of stunting induced by heat alone. The two are similar each having an activation energy of approximately 550kJ mole-1, as determined using the Arrhenius equation. Halving the heating time requires at 1 degrees C temperature increase to achieve the same degree of thermal enhancement of X-ray damage. Similar results have been reported previously for damage caused by heat alone. Over a range 42 degrees C-45 degrees C, the threshold heating time to cause direct thermal injury falls within the range of times used to enhance X-ray damage. It is suggested that a component of damage due to direct thermal injury, indistinguishable from radiation damage and thermally enhanced radiation damage, will contribute to TER assessments in some experimental systems.

Animals↗

Influence of hyperthermia on the oxygen enhancement ratio for x-rays, measured in vivo.

The skin of mouse tail has been used to study the effect of hyperthermia on the oxygen enhancement ratio (OER). Heating was by immersion of a portion of the tail in hot water. Radiation was given either immediately before or after hyperthermia. The average skin reaction between 15 and 50 days after treatment was taken as the end-point. The OER in the absence of hyperthermia was 1.77, suggesting significant hypoxia of the skin. When hyperthermia was given after irradiation the measured value for the OER was not significantly different, but with prior hyperthermia the OER was increased to an average value of 2.3. This increase in OER is probably due to a transient increase in blood circulation following hyperthermia and causing improved tissue oxygenation during irradiation. As a consequence we would expect a greater thermal enhancement ratio for heat given before irradiation than afterwards, and this has frequently been observed with other normal tissues. There was no evidence that heat reduces OER, as has been reported by some authors on the basis of experiments performed on cells in vitro.

Animals↗

Effects of hyperthermia on the mouse testis and its response to X-rays, as assayed by weight loss.

The effects of both hyperthermia alone and X-rays combined with hyperthermia on mouse testis have been investigated. Testis weight on heating time was observed for temperatures in the range 39.5 to 43.75 degrees C. The relationship between the reaction rate and the reciprocal of absolute temperature indicated that, over the temperature range considered, the activation energy associated with such thermal damage was (646 +/- 45) x 10(3) J mol-1. No evidence was obtained to indicate a change in slope of the Arrhenius plot over this temperature range. Finally, despite the high sensitivity of the testis to heat and X-rays, no thermal enhancement of the weight loss after irradiation was observed when thermal treatments which, if given alone would produce some observable damage, were administered immediately after irradiation.

Animals↗