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K George

Publications and source records attributed to K George.

At least 37 records · Page 2Linked to original sources
PubMed2004

Complex chromosomal rearrangements induced in vivo by heavy ions.

It has been suggested that the ratio complex/simple exchanges can be used as a biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo, by considering data from several studies that measured complex exchanges in peripheral blood from humans exposed to mixed fields of low- and high-LET radiation. In particular, we studied data from astronauts involved in long-term missions in low-Earth-orbit, and uterus cancer patients treated with accelerated carbon ions. Data from two studies of chromosomal aberrations in astronauts used blood samples obtained before and after space flight, and a third study used blood samples from patients before and after radiotherapy course. Similar methods were used in each study, where lymphocytes were stimulated to grow in vitro, and collected after incubation in either colcemid or calyculin A. Slides were painted with whole-chromosome DNA fluorescent probes (FISH), and complex and simple chromosome exchanges in the painted genome were classified separately. Complex-type exchanges were observed at low frequencies in control subjects, and in our test subjects before the treatment. No statistically significant increase in the yield of complex-type exchanges was induced by the space flight. Radiation therapy induced a high fraction of complex exchanges, but no significant differences could be detected between patients treated with accelerated carbon ions or X-rays. Complex chromosomal rearrangements do not represent a practical biomarker of radiation quality in our test subjects.

Aged↗
PubMed2004

Chromosome aberrations of clonal origin are present in astronauts' blood lymphocytes.

Radiation-induced chromosome translocations remain in peripheral blood cells over many years, and can potentially be used to measure retrospective doses or prolonged low-dose rate exposures. However, several recent studies have indicated that some individuals possess clones of cells with balanced chromosome abnormalities, which can result in an overestimation of damage and, therefore, influence the accuracy of dose calculations. We carefully examined the patterns of chromosome damage found in the blood lymphocytes of twelve astronauts, and also applied statistical methods to screen for the presence of potential clones. Cells with clonal aberrations were identified in three of the twelve individuals. These clonal cells were present in samples collected both before and after space flight, and yields are higher than previously reported for healthy individuals in this age range (40-52 years of age). The frequency of clonal damage appears to be even greater in chromosomes prematurely condensed in interphase, when compared with equivalent analysis in metaphase cells. The individuals with clonal aberrations were followed-up over several months and the yields of all clones decreased during this period. Since clonal aberrations may be associated with increased risk of tumorigenesis, it is important to accurately identify cells containing clonal rearrangements for risk assessment as well as biodosimetry.

Adult↗
PubMed2003

In vivo and in vitro measurements of complex-type chromosomal exchanges induced by heavy ions.

Heavy ions are more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. We measured the induction of complex-type chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to accelerated H-, He-, C-, Ar-, Fe- and Au-ions in the LET range of approximately 0.4-1400 keV/micrometers. Chromosomes were analyzed either at the first post-irradiation mitosis, or in interphase, following premature condensation by phosphatase inhibitors. Selected chromosomes were then visualized after FISH-painting. The dose-response curve for the induction of complex-type exchanges by heavy ions was linear in the dose-range 0.2-1.5 Gy, while gamma-rays did not produce a significant increase in the yield of complex rearrangements in this dose range. The yield of complex aberrations after 1 Gy of heavy ions increased up to an LET around 100 keV/micrometers, and then declined at higher LET values. When mitotic cells were analyzed, the frequency of complex rearrangements after 1 Gy was about 10 times higher for Ar- or Fe- ions (the most effective ions, with LET around 100 keV/micrometers) than for 250 MeV protons, and values were about 35 times higher in prematurely condensed chromosomes. These results suggest that complex rearrangements may be detected in astronauts' blood lymphocytes after long-term space flight, because crews are exposed to HZE particles from galactic cosmic radiation. However, in a cytogenetic study of ten astronauts after long-term missions on the Mir or International Space Station, we found a very low frequency of complex rearrangements, and a significant post-flight increase was detected in only one out of the ten crewmembers. It appears that the use of complex-type exchanges as biomarker of radiation quality in vivo after low-dose chronic exposure in mixed radiation fields is hampered by statistical uncertainties.

Biomarkers↗
PubMed2003

M-FISH analysis of chromosome aberrations in human fibroblasts exposed to energetic iron ions in vitro.

Confluent human fibroblast cells were exposed to 6 Gy gamma-rays or 200 MeV/nucleon Fe ions at 0.7 or 3 Gy. The cells were allowed to repair for 24 hours after exposure and chromosomes were collected using a premature chromosome condensation technique with calyculin-A. Chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results showed that both doses of the Fe ions produced higher ratios of complex to simple exchanges and lower ratio of complete to incomplete exchanges than the 6 Gy gamma-exposure. The ratios of aberration yields were similar for the two doses of Fe ions. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating this is the maximum number of chromosome domains traversed by a single Fe ion track.

Cell Line↗
PubMed2003

Cardiac troponin T in female athletes during a two-day mountain marathon.

BACKGROUND: Equivocal studies exist on the potential of cardiac damage following prolonged endurance exercise. AIMS: The aim of the study was to examine humoral markers of cardiac damage in female athletes during a 2-day mountain endurance race. METHODS: Venous blood samples were drawn from seven female competitors prior to, and immediately following day-1 and day-2 of the event. The serum was analysed for total creatine kinase (CK), creatine kinase isoenzyme MB (CKMB), and cardiac troponin T (cTnT). RESULTS: Elevations in CK and CKMB were apparent following day-1 of the event (mean +/- SD; CK 84.1 +/- 54.6 mg/L vs. 387 +/- 276.7 mg/L, CKMB 2 +/- 1.7 mg/L vs. 5.9 +/- 1.7 mg/L) and subsequently rose further following race completion (CK 743 +/- 500 mg/L, CKMB 11.9 +/- 4.9 mg/L). Elevations in cTnT were noted in three competitors following day-1 cTNT (range 0.013-0.044 mg/L) and remained elevated in two competitors following day-2 (range 0.014-0.017 mg/L). CONCLUSIONS: The elevations in cTnT likely represent release from the cytosolic fraction. The mechanism responsible for such release is yet to be elucidated.

Adult↗
PubMed2002

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding.

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples.

Aluminum↗
PubMed2002

Evidence of exercise-induced cardiac dysfunction and elevated cTnT in separate cohorts competing in an ultra-endurance mountain marathon race.

Cardiac damage has recently been implicated in the aetiology of "exercise induced cardiac dysfunction". The humoral markers of cardiac damage that have been utilised to date are not sufficiently cardio-specific to investigate this hypothesis. The aim of the present study was to examine cardiac function following prolonged exercise, and investigate the contention of cardiac damage utilising a new highly cardio-specific marker. Thirty-seven competitors in the 2-day Lowe Alpine Mountain Marathon 2000 volunteered for the study. Competitors were sub-divided into 2 groups. Group 1 (n = 11) were examined using echocardiography pre and post the event, examining left ventricular diastolic and systolic function. Group 2 (n = 26) had venous blood samples drawn prior to the event and immediately following day-1 and day-2. Blood samples were analysed for total creatine kinase activity (CK), creatine kinase isoenzyme MB(mass) (CK-MB(mass)), and cardiac troponin T. Echocardiographic results indicated left ventricular diastolic and systolic dysfunction following cessation of exercise. CK and CK-MB(mass) were both elevated following day-1, and immediately following race completion. Cardiac troponin T levels were below the 99th percentile (0.01 microg/L) in all subjects prior to the event, following day-1 cTnT was elevated above 0.01 microg/L in 13 subjects, but returned to below 0.01 microg/L following race completion on day-2. However, no individual data reached clinical cut-off levels for acute myocardial infarction (AMI) (0.1 microg/L). Two days arduous exercise over mountainous terrain resulted in cardiac dysfunction, and significant skeletal muscular degradation. The elevation of cTnT above the 99th percentile in the present study is suggestive of minimal myocardial damage. The clinical significance of and exact mechanism responsible for such damage remains to be elucidated.

Adult↗
PubMed2002

Karyotypes of human lymphocytes exposed to high-energy iron ions.

Chromosomal aberrations were analyzed using multicolor fluorescence in situ hybridization (mFISH) in human peripheral blood lymphocytes after in vitro exposure to gamma rays or accelerated (56)Fe ions (1 GeV/nucleon, 145 keV/microm) at Brookhaven National Laboratory (Upton, NY). Doses of 0.3 and 3 Gy were used for both radiation types. Chromosomes were prematurely condensed by a phosphatase inhibitor (calyculin A) to avoid the population selection bias observed at metaphase as a result of the severe cell cycle delays induced by heavy ions. A total of 1053 karyotypes (G(2) and M phases) were analyzed in irradiated lymphocytes. Results revealed different distribution patterns for chromosomal aberrations after low- and high-LET radiation exposures: Heavy ions induced a much higher fraction of cells with multiple aberrations, while the majority of the aberrant cells induced by low doses of gamma rays contained a single aberration. The high fraction of complex-type exchanges after heavy ions leads to an overestimation of simple-type asymmetrical interchanges (dicentrics) from analysis of Giemsa-stained samples. However, even after a dose of 3 Gy iron ions, about 30% of the cells presented no complex-type exchanges. The involvement of individual chromosomes in exchanges was similar for densely and sparsely ionizing radiation, and no statistically significant evidence of a nonrandom involvement of specific chromosomes was detected.

Chromosome Aberrations↗
PubMed2001

Knowledge about vaccine trials and willingness to participate in an HIV/AIDS vaccine study in the Ugandan military.

In preparation for HIV vaccine trials, knowledge about vaccines, willingness to participate in a vaccine study, and motivations for participation must be assessed. The Preparation for AIDS Vaccine Evaluation study assessed knowledge about vaccines and vaccine trials and willingness to participate in a hypothetical trial in 1,182 Ugandan military men (aged 18-30 years). Participants received education about vaccine trials and were interviewed during 24 months of follow-up observation. Its key findings are that: 1) throughout follow-up, most participants expressed willingness to participate in a hypothetical HIV vaccine trial; 2) participants are familiar with vaccines but do not clearly distinguish the use of vaccines for prevention or curing; 3) the most common reason given for being interested in participating in a vaccine trial was to be protected from HIV/AIDS; 4) trials' procedures (e.g., placebos, randomization, and blinding) were unfamiliar; and 5) knowledge about trials' procedures increased incrementally over follow-up, but at different rates for different concepts. These data demonstrate that potential vaccine trials' participants may benefit from vaccine trial education if adequate time is allowed to ensure that participants are able to master the complex information required for trial participation.

AIDS Vaccines↗
PubMed2001

Developing AIDS vaccine trials educational programs in Uganda.

In preparation for HIV vaccine trials, data on a cohort's knowledge about vaccines and vaccine studies are required so as to tailor educational materials to adequately meet local needs. Interviews (n = 1,182) conducted as part of a 3-year prospective study of Ugandan military men aged 18 to 30 years determined what information, in addition to standard trials information, would be required to ensure comprehension of trial procedures. The interviews highlighted four points: (1) the cohort has a lot of knowledge about vaccines but conflates whether vaccines cure or prevent disease; (2) there is a general lack of knowledge about clinical trials procedures; (3) the desire to be protected from HIV/AIDS is a common reason for being willing to participate in a hypothetical vaccine trial; and (4) concern about side effects is a common reason for being unwilling to participate in a trial. These four points guided the focus of the vaccine trials education, which used locally appropriate analogies to introduce complex unfamiliar concepts such as placebos and blinding. This case study highlights the value of incorporating baseline interviews to assess the educational needs of study populations.

AIDS Vaccines↗
PubMed2001

G2-chromosome aberrations induced by high-LET radiations.

We report measurement of initial G2-chromatid breaks in normal human fibroblasts exposed to various types of high-LET particles. Exponentially growing AG 1522 cells were exposed to gamma rays or heavy ions. Chromosomes were prematurely condensed by calyculin A. Chromatid-type breaks and isochromatid-type breaks were scored separately. The dose response curves for the induction of total chromatid breaks (chromatid-type + isochromatid-type) and chromatid-type breaks were linear for each type of radiation. However, dose response curves for the induction of isochromatid-type breaks were linear for high-LET radiations and linear-quadratic for gamma rays. Relative biological effectiveness (RBE), calculated from total breaks, showed a LET dependent tendency with a peak at 55 keV/micrometer silicon (2.7) or 80 keV/micrometer carbon (2.7) and then decreased with LET (1.5 at 440 keV/micrometer). RBE for chromatid-type break peaked at 55 keV/micrometer (2.4) then decreased rapidly with LET. The RBE of 440 keV/micrometer iron particles was 0.7. The RBE calculated from induction of isochromatid-type breaks was much higher for high-LET radiations. It is concluded that the increased production of isochromatid-type breaks, induced by the densely ionizing track structure, is a signature of high-LET radiation exposure.

Cell Line↗
PubMed2001

High serum cobalamin levels in the clinical setting--clinical associations and holo-transcobalamin changes.

Whereas low cobalamin levels have been studied intensively, systematic information about high levels, especially in the clinical setting, is scarce. Therefore, a prospective comparison was done of 60 patients with high cobalamin levels and 75 with normal levels obtained by a hospital laboratory over a 2.5 month period. Associations with clinical disorders and laboratory test results were examined. Transcobalamin (TC) I and II were measured, especially the holoproteins (TC carrying circulating endogenous cobalamin) which were fractionated with microfine silica powder. High cobalamin levels (> 664 pmol/l; > 900 ng/l) occurred in 94 of 670 consecutive clinically requested assays (14%). The only independently significant associations with a high cobalamin level were renal failure among the clinical disorders (P=0.01), elevated serum creatinine (P=0.0001) and diminished albumin (P=0.0002) levels among laboratory tests. Both holo-TC I and holo-TC II levels were increased in renal failure (P=0.0001) but the increase was relatively greater in holo-TC II. The results indicate that high cobalamin levels are more frequent than low ones in clinical practice and appear to be associated often with renal failure. The elevation of both holo-TC II and holo-TC I suggests that several mechanisms are operative. The accumulation of holo-TC II suggests that cellular uptake of cobalamin by the abundant TC II receptors in the kidney may be impaired. The much better known association of high cobalamin levels with leucocytic disorders is rare, and no association was seen with liver disease.

Clinical Chemistry Tests↗
PubMed2001

Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions.

PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.

Azure Stains↗
PubMed2001

High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase.

PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. RESULTS: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

Bisbenzimidazole↗
PubMed2001

Candida colitis in a middle-aged male receiving permanent haemodialysis.

Candida infections of the gastrointestinal tract are not rare, especially in immunocompromised patients. We present a case of candida colitis in a patient receiving permanent haemodialysis. Candida colitis can be a life-threatening condition and should be treated promptly, especially in immunocompromised patients.

Antifungal Agents↗
PubMed2001

Comparison of F ratios generated from interphase and metaphase chromosome damage induced by high doses of low- and high-LET radiation.

Although biophysical models predict a difference in the ratio of interchromosomal to intrachromosomal interarm exchanges (F ratio) for low- and high-LET radiations, few experimental data support this prediction. However, the F ratios in experiments to date have been generated using data on chromosome aberrations in samples collected at the first postirradiation mitosis, which may not be indicative of the aberrations formed in interphase after exposure to high-LET radiations. In the present study, we exposed human lymphocytes in vitro to 2 and 5 Gy of gamma rays and 3 Gy of 1 GeV/nucleon iron ions (LET = 140 keV/micrometer), stimulated the cells to grow with phytohemagglutinin (PHA), and collected the condensed chromosomes after 48 h of incubation using both chemically induced premature chromosome condensation (PCC) and the conventional metaphase techniques. The PCC technique used here condenses chromosomes mostly in the G(2) phase of the cell cycle. The F ratio was calculated using data on asymmetrical chromosome aberrations in both the PCC and metaphase samples. It was found that the F ratios were similar for the samples irradiated with low- and high-LET radiation and collected at metaphase. However, for irradiated samples assayed by PCC, the F ratio was found to be 8.2 +/- 2.0 for 5 Gy gamma rays and 5.2 +/- 0.9 for 3 Gy iron ions. The distribution of the aberrations indicated that, in the PCC samples irradiated with iron ions, most of the centric rings occurred in spreads containing five or more asymmetrical aberrations. These heavily damaged cells, which were either less likely to reach mitosis or may reach mitosis at a later time, were responsible for the difference in the F ratios generated from interphase and metaphase analysis after exposure to iron ions.

Chromosome Aberrations↗