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Biomedical subjects

K R Trott

Publications and source records attributed to K R Trott.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1995

The proliferative capacity of mouse fibrosarcoma cells that survived x-irradiation.

Delayed reproductive death, the appearance of colonies with a reduced cell density (impaired colonies) and the number of giant cells per colony were investigated in murine fibrosarcoma cells after irradiation with 3 to 9 Gy of x-rays. Radiation survivors were replated after reaching confluence, which occurred after 13 to 15 doublings; this procedure was repeated three times. The replating efficiency decreased in a dose-dependent manner, the survivors of 9 Gy achieving only 30% of the plating efficiency of unirradiated cells. After the third replating, i.e. after 40 to 45 doublings, the plating efficiency of the survivors approached that of the controls. The median colony size of the survivors showed a similar dose-dependent decrease, which was pronounced after the first replating but still remained significant after the third replating. The fraction of impaired colonies was increased to more than 30% in 9-Gy survivors, and though abating, the increase was still significant even after the third replating. Evidence of residual damage was also provided by the presence of giant cells. For instance, after 6 Gy irradiation and 13 to 15 doublings, the proportion of colonies with giant cells was 60%, decreasing only to 45% after 40 to 45 doublings. The number of giant cells per colony was 1.4 in colonies arising immediately after 6 Gy, decreasing to 0.9 after the third replating. These results suggest that the proliferative capacity of surviving cells is depressed even longer than their clonogenic capacity.

Animals↗
PubMed1995

Epidermal morphology, cell proliferation and repopulation in mouse skin during daily fractionated irradiation.

In mouse, a 2 cm long field of both legs was irradiated daily with 3 Gy, five fractions per week for up to 3 weeks. Epidermal morphology, the circadian variation of the labelling index, and repopulation were determined at the end of each week. After a decrease of epidermal cellularity in the first week, excessive regeneration led to hyperplasia and hypertrophy, which continued throughout the experimental period while the residual tolerance of the epidermis to top-up irradiation decreased progressively. Although the repopulation rate was accelerated five-fold, it was unable to compensate the effects of more than two-thirds of the given dose. The hypertrophic and hyperplastic response is attributed to pronounced acceleration of abortive proliferation of doomed stem cells.

Animals↗
PubMed1995

The effects of local X-irradiation on the distensibility of the rectum in rats.

Proctometry was performed on female Wistar rats following irradiation of the rectum with single doses of 15, 18 and 22 Gy of X-rays. The results indicated a progressive increase in distensibility until week 29 after irradiation which was attributed to degenerative changes in the intestinal wall. A major factor which determines colorectal pressure is the neuromuscular activity, however, neuromuscular transmission was not affected by irradiation.

Animals↗
PubMed1995

[The effect of x-rays on experimental arthritis in the rat].

AIMS: We investigated the therapeutic efficacy of low doses of X-rays on different in-vivo models of monoarticular arthritis which have been developed for the investigation of anti-inflammatory drugs. MATERIAL AND METHODS: Zymosan or heat-inactivated mycobacterium tuberculosis was injected into 1 knee joint of Wistar rats to produce, via different pathogenetic mechanisms, an acute monoarticular arthritis. Five days later, the amount of joint swelling, bone destruction and cartilage catabolism were measured. Immediately after arthritis induction, the knees were irradiated with a single dose of 5 Gy or with 4 daily fractions of 1 Gy. RESULTS: X-irradiation with daily doses of 1 Gy significantly reduced bone loss and cartilage degradation in Zymosan-induced arthritis and joint swelling in mycobacterium tuberculosis induced arthritis. However, a single high radiation dose significantly increased bone loss in mycobacterium tuberculosis induced arthritis. CONCLUSIONS: These data confirm the hypothesis of an anti-inflammatory effect of low radiation doses which so far has been based only on clinical experience. By using an established model of monoarticular arthritis we have now the opportunity to study the mechanism of the anti-inflammatory radiation effect in comparison to that of anti-inflammatory drugs. This way, we hope to provide a scientific basis for the use of radiotherapy in various painful degenerative joint disorders.

Acute Disease↗