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Biomedical subjects

K R Trott

Publications and source records attributed to K R Trott.

At least 37 records · Page 2Linked to original sources
PubMed1998

Postgraduate studies in radiation biology in Europe.

The present system of radiobiological research in universities and research centres is no longer able to train radiobiologists who have a comprehensive understanding of the entire field of radiation biology including both 'classical' and molecular radiation biology. However, such experts are needed in view of the role radiation protection plays in our societies. No single institution in Europe could now run a 1-year, full-time course which covers all aspects of the radiobiological basis of radiation protection. Therefore, a cooperative action of several universities from different EU member states has been developed and is described herein.

Education, Medical, Graduate↗
PubMed1998

Lack of specificity of chromosome breaks resulting from radiation-induced genomic instability in Chinese hamster cells.

In V79 Chinese hamster cells, radiation-induced genomic instability results in a persistently increased frequency of micronuclei, dicentric chromosomes and apoptosis and in decreased colony-forming ability. These manifestations of radiation-induced genomic instability may be attributed to an increased rate of chromosome breakage events many generations after irradiation. This chromosomal instability does not seem to be a property which has been inflicted on individual chromosomes at the time of irradiation. Rather, it appears to be secondary to an increased level of non-specific clastogenic factors in the progeny of most if not all irradiated cells. This conclusion is drawn from the observations presented here, that all the chromosomes in surviving V79 cells are involved in the formation of dicentric chromosome aberrations 1 or 2 weeks after irradiation with about equal probability if corrections are made for chromosome length.

Animals↗
PubMed1998

The radiosensitivity of recurrent clones of an irradiated murine squamous cell carcinoma in the in vitro megacolony system.

PURPOSE: To measure changes in spontaneous growth rate and radiation response in the progeny of irradiated squamous cell carcinoma cells. MATERIALS AND METHODS: Murine SCC cells of the line AT478 were grown as epithelial megacolonies in vitro, using both the original line and two subsequent passages derived from a clone that had recurred after a high radiation dose. Radiosensitivity was evaluated in terms of local control following single dose irradiation of standard size megacolonies (0.8 cm2). In addition, original megacolonies were given a priming dose of 20 Gy and the recurrent clones arising in situ were retreated at three dose levels for analysis of curability. RESULTS: A marked increase in radiosensitivity was observed in the megacolonies grown from irradiated progeny as compared to original megacolonies, reflected in a shift of the TCD50 from 24.5 to 16.5 Gy. Direct parameter estimation from the cure data suggested that the underlying change was a lowered number of clonogenic 'stem' cells rather than increased cellular sensitivity. A similar decrease in clonogen density was also apparent for the recurrent clones in situ. The change in megacolony curability was paralleled by a substantial growth retardation. CONCLUSION: The data demonstrate persistent changes in the progeny of irradiated SCC tumour cells that affect both growth and radiosensitivity and are compatible with the expression of delayed reproductive death.

Animals↗
PubMed1998

Radiation-induced impairment of bone healing in the rat femur: effects of radiation dose, sequence and interval between surgery and irradiation.

BACKGROUND AND PURPOSE: Impairment of osseous healing in treatment combining surgery and radiotherapy is a frequent complication. Its dependence on sequence and interval was studied in a defined experimental model. MATERIALS AND METHODS: The effect of pre- and postoperative irradiation by single doses of X-rays on osseous closure of a 1.2 mm drill hole in the rat femur was measured 6 or 7 weeks after surgery in histological sections using morphometrical methods. RESULTS: Irradiation delivered between 1 day and 6 months before surgery resulted in a reduction of bone healing following very similar dose response relationships; there was no evidence of any slow repair of latent radiation damage. Radiosensitivity of bone healing during the first 3 days after surgery was not different from preoperative irradiation; however, irradiation 4 days or later after surgery failed to reduce osseous healing even after very high radiation doses. CONCLUSION: Tolerance increases enormously if radiotherapy is given later than 4 days after surgery. This has great implications for combined radiotherapy and surgery schedules involving bone reconstruction, but may be even more important for radiotherapy applied to prevent heterotopic ossification after total hip arthroplasty. Biologically, target cell regeneration alone is insufficient to account for the drastic rise in radiotolerance; it must be accompanied by an increase in cellular resistance due to differentiation.

Animals↗
PubMed1998

Manifestations and mechanisms of radiation-induced genomic instability in V-79 Chinese hamster cells.

PURPOSE: The relationship between different forms of persistent radiation damage in irradiated cells was investigated in order to identify a common underlying mechanism. MATERIAL AND METHODS: V-79 Chinese hamster cells were irradiated with different doses of X-rays, neutrons and alpha-particles. In the progeny of surviving cells, up to 4 weeks after irradiation, delayed reproductive death, delayed micronuclei, delayed appearance of dicentric chromosomes and delayed apoptosis were investigated in parallel. RESULTS: A similar dose-response relationship was found for all endpoints, with a steep rise at low doses to a plateau at doses > 3 Gy. The target for inducing genomic instability by alpha-particles is larger than the nucleus. All chromosomes are equally involved in delayed breakage reunion events. CONCLUSION: The results indicate that non-lethal radiation damage to an extranuclear target leads to a persistent increase in clastogenic activity in the surviving irradiated cells.

Alpha Particles↗
PubMed1998

Mechanisms of the anti-inflammatory activity of low-dose radiation therapy.

PURPOSE: To investigate the hypothesis that modulation of the function of activated macrophages is one of the mechanisms of the clinically observed anti-inflammatory and analgesic efficacy of low-dose radiotherapy in the treatment of a variety of painful joint diseases with total doses between 1 and 6 Gy. MATERIALS AND METHODS: Metabolic activity, cell proliferation, reproductive integrity, nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by unstimulated or [LPS/gamma-IFN-stimulated macrophages in vitro was investigated at different times after radiation doses ranging from 0.3 Gy to 10 Gy. In vivo, chronic granulomatous air pouches were induced in mice and either sham treated or irradiated with 2 Gy on day 2 or day 6, or with five daily doses of 0.5 Gy. On day 7, the iNOS expression was assessed by Western blot and localized by immuno-histochemistry in cryostat sections. RESULTS: In stimulated macrophages, metabolic activity, proliferation and reproductive integrity were not affected by radiation doses up to 10 Gy since they are apparently irreversible post-mitotic cells. However, a dose-dependent modulation of the NO pathway was observed with significant inhibition by the low radiation doses used in anti-inflammatory radiotherapy but with super-stimulation by the high radiation doses used in cancer therapy. CONCLUSIONS: The empirically based anti-inflammatory radiotherapy of benign diseases appears to act through specific modulation of different pathways of inflammatory reactions such as the nitric oxide pathway in stimulated macrophages.

Animals↗
PubMed1997

Differential expression of CD44s and CD44v10 proteins and syndecan in normal and irradiated mouse epidermis.

The role of the CD44s adhesion molecule, its epithelial isoforms and its relationship to epidermal proteoglycans such as syndecan was studied in normal and irradiated mouse skin. In normal mouse skin, only 10% of basal cells are strongly CD44s-immunopositive, with a cytoplasmic expression pattern. Double-label experiments with the basal cell marker keratin 14 confirmed the epithelial nature of the strongly CD44s-positive cell type in the basal layer. Some spinous keratinocytes and the majority of the remaining basal cells exhibited a weak membranous staining pattern. In contrast, the epithelial isoform, CD44v10, was strongly present in all basal and suprabasal epithelial cells of the epidermis, with a membranous staining pattern. Syndecan was found in the granular layer of the normal epidermis only. After 1 week of daily irradiation, the entire basal cell layer of the epidermis expressed CD44s in the membrane, but with a varying degree of staining intensity. This reactivity spread to the upper spinous layer after 3 weeks of treatment. In hyperproliferative epidermis, there was no difference in the staining patterns between CD44s and CD44v10. The expression of syndecan switched from the granular layer to the basal and lower spinous layers after 2 weeks of daily irradiation. Immunoreactivity for syndecan was also strongly enhanced in the dermis of irradiated samples. The results suggest an important role for syndecan and CD44 in proliferative processes during radiation-induced accelerated repopulation.

Animals↗
PubMed1997

An investigation into the prevalence of thyroid disease on Kwajalein Atoll, Marshall Islands.

The prevalence of thyroid nodules and thyroid cancer was studied in the indigenous population residing on Ebeye Island, Kwajalein Atoll, in the Republic of the Marshall Islands. This island, centrally located in the nation, is home to about 25% of the nation's population, many who have migrated there from other atolls. The objective of the study was to obtain thyroid disease rate statistics on as much of the population as possible that was alive during the years of nuclear testing and to test the hypothesis that described a linearly decreasing prevalence of palpable nodules with increasing distance from the Bikini test site. 1,322 Marshallese born before 1965 were given a thyroid examination using neck palpation, fine needle aspiration biopsy, and high resolution ultrasound imaging. Approximately 40% of the total population living on this island who are at risk from exposure to radioactive fallout during the years 1946-1958 were screened. Of that group, 815 were alive at the time of the BRAVO test on 1 March 1954. Two hundred sixty-six people with thyroid nodules were found (32.6%): 132 were palpable nodules (16.2%), and 134 were nodules that could be diagnosed with ultrasound only (15.7%). Prevalence of palpable nodules was particularly high in men and women older than 60 y, in men who were 6 to 15 y of age at the time of the BRAVO test, and in women 1 to 10 y of age at the time of the BRAVO test. In 22 people, the clinical diagnosis was most likely cancer though histopathological evidence was only available from 11 operated cases. Of the 11 operated cases, 10 were cancer. Cancer prevalence was particularly high in those women born between 1944 and 1953 (7/220 = 3.2%), i.e., who were children during the early years of nuclear testing. The Ebeye data showed a marginally significant correlation between palpable nodule prevalence among women and distance to Bikini (r = -0.44, p = 0.06). This report summarizes the clinical findings of the thyroid examinations, the age distributions for nodular disease and cancer, and examines the relationship between prevalence of nodules and present day levels of 137Cs in the environment of each atoll.

Adult↗
PubMed1997

Some reflections on the role of the Scientific Advisory Panel to the Marshall Islands nationwide radiological study.

As a consequence of the U.S. Atomic Weapons Testing Program in the Trust Territory of the Pacific, now the Republic of the Marshall Islands, numerous scientists have advised the Marshallese on matters of radiation and radioactive contamination. Some of the previous advice has appeared to vary or conflict resulting in consequent uncertainty for the people. In a new initiative in 1989, the RMI Government engaged a five member multi-disciplinary Scientific Advisory Panel to oversee the assessment of, and to advise on, the radiological status of the entire nation. The formation of the Panel was accompanied by the establishment of a Resident Scientist position, and ultimately a small scientific team and laboratory on Majuro. The nationwide radiological study was conducted using ground survey methods over the period 1990-1994. Tasks undertaken by the Panel included formulating reasonable objectives for the study and attempting to establish effective communication and understanding of issues with political leaders and RMI Government agencies and people, as well as advising on and monitoring the scientific integrity of the study itself. The attempt was also made to initiate investigations to address matters of concern that emerged. The problem was faced of providing not only technical guidance on radioactivity and radiation measurements, but also explaining the significance of measured values and concepts, such as risk and probability of health effects to a diverse but nontechnical audience, generally across cultural and language barriers. The experience of the Panel in providing advice and guidance to the Republic of the Marshall Islands, while unique in many ways, parallels the difficulties experienced elsewhere in communicating information about risks from radiation exposure.

Humans↗
PubMed1997

Genomic instability in Chinese hamster cells after exposure to X rays or alpha particles of different mean linear energy transfer.

Evidence has accumulated that radiation induces a transmissible persistent destabilization of the genome, which may result in effects arising in the progeny of irradiated but surviving cells. An enhanced death rate among the progeny of cells surviving irradiation persists for many generations in the form of a reduced plating efficiency. Such delayed reproductive death is correlated with an increased occurrence of micronuclei. Since it has been suggested that radiation-induced chromosomal instability might depend on the radiation quality, we investigated the effects of alpha particles of different LET by looking at the frequency of delayed micronuclei in Chinese hamster V79 cells after cytochalasin-induced block of cell division. A dose-dependent increase in the frequency of micronuclei was found in cells assayed 1 week postirradiation or later. Also, there was a persistent increase in the frequency of dicentrics in surviving irradiated cells. Moreover, we found an increased micronucleus frequency in all of the 30 clones isolated from individual cells which had been irradiated with doses equivalent to either one, two or three alpha-particle traversals per cell nucleus. We conclude that the target for genomic instability in Chinese hamster cells must be larger than the cell nucleus.

Alpha Particles↗
PubMed1997

Connexin 43 expression in normal and irradiated mouse skin.

The expression of connexin 43 (Cx43) in normal and irradiated mouse skin was evaluated using immunofluorescence with polyclonal antisera to Cx43 on cryostat sections. One week after the start of daily irradiation with 3 Gy, enhanced immunoreactivity in basal cells and in the lower part of the spinous layer of the epidermis was detected. In hypertrophic and hyperplastic skin, about 3 weeks after irradiation, a further increase in the expression of Cx43 was found in the epidermis as well as in the dermis. Western blot analysis of normal and irradiated skin homogenates confirmed the increased Cx43 protein concentration in the skin. In nuclear extracts of the same preparations, increased AP-1-binding activity was found. These data suggest that the gap-junction protein is expressed in response to irradiation of the skin and may be related to the subsequent hyperproliferative response which is associated with accelerated repopulation.

Animals↗
PubMed1996

Persistent increase in the rates of apoptosis and dicentric chromosomes in surviving V79 cells after X-irradiation.

In parallel to delayed reproductive death and delayed micronuclei in surviving V79 cells that have been reported, the frequency of apoptosis and dicentrics was investigated in the same cell line, 1-2 weeks after X-ray doses between 1 and 12 Gy. Apoptosis was assessed by morphological criteria after staining with Giemsa and using the Apoptag method in parallel. The frequency of apoptosis peaked 48 h after irradiation at about 35% as a function of dose and then decreased to about 10% on day 3. It remained 10 times higher than in unirradiated cells until day 14. The frequency of dicentric chromosomes 24 h after irradiation increased according to a linear-quadratic function, up to about 110% after 12 Gy, decreased 3 days later to about 10% and remained about 5-fold higher than in control cells. The dose-response relationship was similar for all the various end-points of expression of radiation induced genomic instability, showing a steep increase of the frequency with dose up to 3-4 Gy and with no further increase at higher radiation doses.

Animals↗
PubMed1996

Changes in keratinocyte differentiation during accelerated repopulation of the irradiated mouse epidermis.

Epidermal stem cells accelerate their repopulation rate during fractionated irradiation. To study the changes in keratinocyte differentiation associated with radiation-induced repopulation, we investigated the expression of a panel of 14 monoclonal or polyclonal antibodies against keratins, involucrin and others, as well as the expression of 15 lectins in the irradiated mouse leg skin. Tissue samples were collected after 1, 2, and 3 weeks of daily irradiation with 3 Gy per fraction. Abnormal morphological appearance of the irradiated epidermis suggested disturbed terminal differentiation. Keratin 16 (K16) was negative in normal epidermis but intense staining was observed in the irradiated epidermis. Involucrin was expressed in the outmost suprabasal layers only in the normal epidermis but extended to the lower layers in the irradiated epidermis. The lectin binding patterns for agglutinins from Soybean, Dolichos biflorus, and Helix pomatia showed differences between the normal and the irradiated epidermis. From these characteristic changes in staining patterns we concluded that accelerated repopulation of the epidermis during fractionated irradiation is associated with a deficiency in terminal squamous differentiation.

Animals↗
PubMed1996

Increased micronucleus frequency in the progeny of irradiated Chinese hamster cells.

V79 Chinese hamster cells were irradiated with doses of 1-12 Gy 300 kV X-rays. Their colony-forming ability and the frequency of micronuclei in binucleate cells after treatment with cytochalasin B was determined at various times after irradiation. The frequency of micronuclei determined within the first 24 h after irradiation increased with doses up to 4 Gy and decreased as the dose increased further. Up to 4 Gy there was a close correlation between surviving fraction and the fraction of cells without micronuclei although the surviving fraction was 2-3 times lower than the fraction of cells without micronuclei. Six, 10 or 13 days after irradiation with either 9 or 12 Gy the plating efficiency and the frequency of micronuclei after cytokinesis block with cytochalasin B was determined in the irradiated, but surviving, cells. The delayed plating efficiency of irradiated cells was significantly decreased. The proportion of binucleated cells was in the normal range at 6-13 days after irradiation, indicating that the proliferative activity of irradiated but surviving cells was not depressed at that time. The micronucleus frequency, however, was significantly increased at all times after irradiation. There was little heterogeneity of plating efficiency and micronucleus frequency among 12 clones which had been isolated for irradiated cultures, 3 weeks after 12 Gy.

Animals↗
PubMed1996

Exposure to ultraviolet B radiation increases the tolerance of mouse skin to daily X irradiation.

Based on the hypothesis that acceleration of repopulation in skin during fractionated irradiation is triggered by an inflammatory response of the dermis to radiation-induced epidermal hypoplasia, we produced a mild erythema by exposure to UVB radiation before applying different X-irradiation schedules. At different times ranging from 6 h to 14 days after a single exposure to UVB radiation which caused a distinct erythema, a 2-cm skin field on the legs of mice was irradiated with either different single doses or five daily fractions of 3 Gy followed by different single top-up doses of 300 kV X rays. Skin reactions were scored daily for 4 weeks and the occurrence of moist desquamation was taken to construct dose-response curves and to calculate ED50 values. Five days after exposure to UVB radiation and later, radioresistance of epidermis to single and fractionated X irradiation was significantly increased. Results were analyzed using the linear-quadratic formalism to identify possible mechanisms for this UV-radiation-induced radioresistance. The data suggest that exposure to UVB radiation led to a gradual increase in the number of epidermal stem cells and their repopulation rate.

Animals↗
PubMed1996

Radiation-induced changes in neuropeptides in the rat urinary bladder.

PURPOSE: To determine whether there was a change in innervation in the rat urinary bladder following x-ray irradiation. MATERIALS AND METHODS: The urinary bladders were obtained from rats irradiated 6 months previously with single doses of 15 Gy and 25 Gy x-radiation, and from nonirradiated (control) animals. They were examined immunohistochemically to localize neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), met-enkephalin (m-ENK), leu-enkephalin (l-ENK), somatostatin (SOM) and the enzyme, tyrosine-hydroxylase (TH). Computer assisted image analysis was used to assess the density of immunoreactive nerve fibres. RESULTS: The greatest density of nerves observed in the bladder from control animals contained NPY, followed (in decreasing order) by CGRP, VIP, SP and TH. The nerves appeared to run predominantly along the longitudinal axis of the circular and longitudinal muscle fibres. SP-, CGRP-, TH- and occasionally VIP-immunoreactive nerves were observed in the lamina propria, at the base of the urothelium. Perivascular nerves containing neuropeptides and TH were observed throughout the bladder wall. There was an absence of m-ENK-, l-ENK- and SOM-immunoreactive nerves in the control and irradiated rat urinary bladders. In the rat urinary bladder irradiated with 25 Gy x-radiation, there was a significant increase (P < 0.05) in the density of NPY-, TH- and SP- but not CGRP- and VIP-immunoreactive nerves. There were regional differences within the bladder, that is, there was an increase in VIP-, CGRP- and SP-immunoreactive nerves around and within the urothelium. NPY-immunoreactive nerves were seen in the connective tissue and elastic fibres of the lamina propria for the first time. An increase in the density or fluorescence intensity of perivascular TH- but not neuropeptide-containing nerves was observed. CONCLUSIONS: The increase in the density of NPY-, SP- and TH-immunoreactive nerves in the irradiated bladders may be due to axonal sprouting which contributes to the symptoms of radiation injury.

Animals↗