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Biomedical subjects

K George

Publications and source records attributed to K George.

At least 55 records · Page 3Linked to original sources

Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts.

We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

Cells, Cultured↗

Risk estimation based on chromosomal aberrations induced by radiation.

The presence of a causal association between the frequency of chromosomal aberrations in peripheral blood lymphocytes and the risk of cancer has been substantiated recently by epidemiological studies. Cytogenetic analyses of crew members of the Mir Space Station have shown that a significant increase in the frequency of chromosomal aberrations can be detected after flight, and that such an increase is likely to be attributed to the radiation exposure. The risk of cancer can be estimated directly from the yields of chromosomal aberrations, taking into account some aspects of individual susceptibility and other factors unrelated to radiation. However, the use of an appropriate technique for the collection and analysis of chromosomes and the choice of the structural aberrations to be measured are crucial in providing sound results. Based on the fraction of aberrant lymphocytes detected before and after flight, the relative risk after a long-term Mir mission is estimated to be about 1.2-1.3. The new technique of mFISH can provide useful insights into the quantification of risk on an individual basis.

Aerospace Medicine↗

Chromosome aberrations in the blood lymphocytes of astronauts after space flight.

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.

Chromosome Aberrations↗

Allometric analysis of the association between cardiac dimensions and body size variables in 464 junior athletes.

Empirically derived relationships between body size variables and cardiac dimensions have not been published previously for a large sample of male and female athletes. This process would inform scaling practice and facilitate intra- and inter-group comparisons of cardiac data. Therefore we investigated the relationships of body mass (BM), height and body surface area (BS) with a range of cardiac dimensions derived by echocardiography in 464 male and female elite junior athletes (age range 14-18 years; sporting allocation included rowers, cyclists, footballers, tennis players, swimmers and a miscellaneous group). Initial linearity checks suggested that most of the relationships between the body size variables and cardiac dimensions were non-linear, thus precluding the simple ratio standard approach to scaling. Multiple log-log least-squares linear regression confirmed commonality of slopes (between males and females, across the age range and between sporting groups) for all relationships involving BM and BS. Subsequent analyses of the slope exponent (b) for left ventricular dimensions supported previous data and were dimensionally consistent (LVM-BM, b=0.91+/-0.11; LVM-BS, b=1.44+/-0.19; where LVM is left ventricular mass), except for left ventricular internal dimension in diastole (LVIDd) (LVIDd-BM, b=0.25+/-0.04). Data for the left atria internal dimension (LA) were also dimensionally consistent (LA-BM, b=0.29+/-0.09); however, this was not the case for the right ventricular internal dimension in diastole (RVIDd) (RVIDd-BM, b=0.76+/-0.14). It is possible that these results were due to a study-specific limitation in the data range (LVIDd) and the geometric peculiarities of RVIDd compared with LVIDd. The gender/age/sporting groupxbody size interaction factor for virtually all relationships between height and cardiac dimensions was significant (P<0.05), and thus whole-group b exponents could not be generated. Generally these data support previous small-sample research with athletes, and suggest that allometric scaling, as opposed to simple ratio scaling, should be adopted in studies of cardiac dimensions in athletes. This should allow, with minimal mathematical difficulty, the production of body-size-independent cardiac indices to be evaluated in laboratory or clinical work. Further research is required to develop normative 'allometrically derived' cardiac indices, and care should be taken to determine relationships in specific population groups as well as to confirm commonality of slopes in multiple group comparisons. Caution is expressed regarding the use of height as a scaling variable in future research.

Adolescent↗

The effect of space radiation on the induction of chromosome damage.

To obtain information on the cytogenetic damage caused by space radiation, chromosome exchanges in lymphocytes from crewmembers of long-term Mir missions, and a shorter duration shuttle mission, were examined using fluorescence in situ hybridization. A significant increase in chromosomal aberrations was observed after the long duration flights. The ratio of aberrations identified as complex was higher post-flight for some crewmembers, which is thought to be an indication of exposure to high-LET radiation. Ground-based studies have shown that the frequency of aberrations measured post-flight could be influenced by a mitotic delay in cells damaged by high-LET radiation and this effect could lower biological dose estimates. To counteract this effect, prematurely condensed chromosome (PCC) spreads were collected. Frequencies of aberrations in PCC were compared with those in metaphase spreads.

Aerospace Medicine↗

Kinetics of chromatid break repair in G2-human fibroblasts exposed to low- and high-LET radiations.

The purpose of this study is to determine the kinetics of chromatid break rejoining following exposure to radiations of different quality. Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290 MeV/u), silicon (490 MeV/u) and iron (200 MeV/u, 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Prematurely condensed chromosomes were collected after several post-irradiation incubation times, ranging from 5 to 600 minutes, and the number of chromatid breaks and exchanges in G2 cells were scored. The relative biological effectiveness (RBE) for initial chromatid breaks per unit dose showed LET dependency having a peak at 55 keV/micrometers silicon (2.4) or 80 keV/micrometers carbon particles (2.4) and then decreased with increasing LET. The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components. Chromatid breaks decreased rapidly after exposure, and then continued to decrease at a slower rate. The rejoining kinetics was similar for exposure to each type of radiation, although the rate of unrejoined breaks was higher for high-LET radiation. Chromatid exchanges were also formed quickly.

Cell Line↗

Comparison of chromosome aberration frequencies in pre- and post-flight astronaut lymphocytes irradiated in vitro with gamma rays.

If radiosensitivity is altered in a microgravity environment, it will affect the accuracy of assessing astronauts' risk from exposure to space radiation. To investigate the effects of space flight on radiosensitivity, we exposed a crewmember's blood to gamma rays at doses ranging from 0 to 3 Gy and analyzed chromosome aberrations in mitotic lymphocytes. The blood samples were collected 10 days prior to an 8-day Shuttle mission, the day the flight returned, and 14 days after the flight. After exposure, lymphocytes were stimulated to grow in media containing phytohaemagglutinin (PHA) and mitotic cells were harvested for chromosome analysis using a fluorescence in situ hybridization (FISH) with whole chromosome specific probes. The dose response of total exchanges showed no changes in the radiosensitivity after the mission.

Astronauts↗

Treatment of chronic hepatitis C genotype IV with interferon-ribavirin combination in Saudi Arabia: a multicentre study.

Between 1996 and 1997, we conducted a multicentre study to assess the effect of combination therapy of interferon (IFN) + ribavirin on chronic hepatitis C genotype 4. Ninety-seven patients were enrolled. Sixty-eight patients (47 male and 21 female) were non-responders to previous therapy with IFN (Group I). Twenty-nine patients (19 male and 10 female) were new (Group II). Following treatment with IFN, 23% in Group I and 9% in Group II had a sustained biochemical response. Only 12% in Group I and 5% in Group II achieved a sustained virological response. Virus load was found to be the major factor determining response, followed by histology grading and staging. Like HCV genotype 1, HCV genotype 4 seems to have a poor response to therapy.

Adult↗

High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts.

PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

Cell Line↗

Acute fuel selection in response to high-sucrose and high-starch meals in healthy men.

BACKGROUND: Despite considerable controversy over the inclusion of sucrose in the diets of people with diabetes, the acute metabolism of sucrose is not completely understood. OBJECTIVE: Our objective was to investigate the metabolism of the monomeric constituents of sucrose after a high-sucrose meal. DESIGN: Three test meals were consumed in a randomized, crossover design by 7 healthy male volunteers. Two of the meals were high in sucrose; one was supplemented with 200 mg uniformly labeled [13C]fructose and one was supplemented with 200 mg [13C]glucose. The other meal was high in starch, supplemented with 200 mg [13C]glucose. Fifty percent of energy was supplied as sucrose in the high-sucrose meals and as starch in the high-starch meal. Breath (13)CO(2) enrichment was measured at 15-min intervals and indirect calorimetry was performed for five 20-min sessions immediately before and during a 6-h postprandial period. RESULTS: Carbohydrate oxidation rates rose much faster after the high-sucrose meals than after the high-starch meal. Breath (13)CO(2) enrichment rose faster and peaked earlier and at a higher value when [13C]fructose rather than [13C]glucose was given with the high-sucrose test meal. Values for breath (13)CO(2) enrichment from [13C]glucose after the high-starch meal were intermediate. CONCLUSIONS: These results show that fructose is preferentially oxidized compared with glucose after a high-sucrose meal and that glucose is oxidized more slowly after a high-sucrose meal than after a high-starch meal.

Adult↗

Cardiac fatigue following prolonged endurance exercise of differing distances.

PURPOSE: Recent echocardiographic studies have reported cardiac dysfunction following ultra-endurance exercise in trained individuals. The duration of exercise required to elicit cardiac dysfunction and the mechanisms underlying this phenomenon have not been fully elucidated. The aim of the present study was to examine the presence of cardiac dysfunction following a half-Ironman and Ironman triathlon in trained individuals. METHODS: 14 male triathletes (age: 32 +/- 5 yr; height: 180 +/- 8 cm; body mass: 75 +/- 9 kg) completed a half-Ironman triathlon. Following a 4-wk period, 10 of the original 14 triathletes completed an Ironman triathlon. All triathletes were assessed using ECG, echocardiography, and blood analysis pre-, immediately post-, and 48 h postrace for both distances. RESULTS: Echocardiographic results indicated diastolic and systolic left ventricular dysfunction, for both race distances, which were associated with altered relaxation characteristics and a reduced inotropic contractility, respectively. Following 48-h recovery, all echocardiographic measures were similar to resting values. Creatine kinase MB (CKMB) was significantly elevated immediately postrace for both distances; however, it accounted for less than 5% of the total CK value and in the presence of an elevated total CK and CKMM implied that the elevated CKMB was noncardiac in origin. Troponin-T, however, was significantly elevated immediately postrace for both distances and returned to normal following 48-h recovery indicating myocardial damage. CONCLUSIONS: Ironman and half-Ironman competition resulted in reversible abnormalities in resting left ventricular diastolic and systolic function. Results suggest that myocardial damage may be, in part, responsible for cardiac dysfunction, although the mechanisms responsible for this cardiac damage remain to be fully elucidated.

Adult↗

Physiological profile and predictors of cycling performance in ultra-endurance triathletes.

BACKGROUND: To report physiological profiles, and investigate the relationship between selected physiological variables and cycling performance in ultra-endurance triathletes. METHODS PARTICIPANTS: ten male (mean+/-SD, age; 32+/-5 years) ultra-endurance triathletes participated in the study. Physiological profiles were compared with 10 male age-matched control subjects. MEASURES: left ventricular structure (wall thickness [LVPWd], internal diameter [LVIDd], and mass [LVM]) and function (diastolic filling, fractional shortening, and stroke volume [SV]) were assessed using standard M-Mode, 2D, and Doppler echocardiography. Maximal and sub-maximal exercise gas exchange responses were measured on-line during a maximal ramping cycle-ergometer exercise test. RESULTS: Ultra-endurance triathletes demonstrated significantly larger LVPWd, LVIDd, LVM, SV, VO2max anaerobic threshold (AT), and power to body-mass ratio compared with controls. Cycling performance for both Ironman and half Ironman were significantly correlated with LVPWd, LVM, and SV. LVIDd was significantly correlated Ironman cycle time alone. Oxygen consumption (VO2) at AT, percentage of VO2max at AT, and peak power to bodymass ratio were significantly correlated to bike finish time in the half Ironman, but not Ironman. CONCLUSIONS: The correlation between cycling performance, LVM and SV suggests that the more conditioned athletes may be better able to maintain a high cardiac output during prolonged cycling. Sub-maximal gas exchange responses are predictors of cycling performance for the half-Ironman but not the Ironman. These results suggest that other factors including the longer duration swim prior to the cycling component, may impact upon cycle performance.

Adult↗

Absence of human T-lymphotropic virus type I tax sequences in a population of normal blood donors in the Baltimore, MD/Washington, DC, area: results from a multicenter study.

BACKGROUND: It was reported recently that sequences corresponding to the human T-lymphotropic virus type I (HTLV-I) tax gene were detected in peripheral blood mononuclear cells from 8 to 11 percent of healthy blood donors without detectable antibodies to HTLV-I. A multicenter blind study was conducted to determine if these results could be independently confirmed. STUDY DESIGN AND METHODS: Specimens were collected from 100 anti-HTLV-I-negative healthy blood donors and from 11 anti-HTLV-I- or anti-HTLV-II-positive individuals. All samples were coded and distributed to each of four independent testing laboratories for polymerase chain reaction analysis to detect sequences of the HTLV-I or HTLV-II tax gene, using detailed procedures specified by the laboratory reporting the original observation. Each laboratory also tested a dilution panel of a plasmid containing HTLV-I tax to determine the analytical sensitivity of the procedure. RESULTS: The analytical sensitivity of the screening methods permitted detection of as few as 1 to 10 copies of the tax gene. However, HTLV-I tax sequences could not be detected in any of the anti-HTLV-I-negative blood donors at more than one test site. CONCLUSION: HTLV-I tax sequences appear not to be present in this population of 100 blood donors negative for anti-HTLV-I.

Adult↗

Alterations in cardiac morphology and function in elite multi-disciplinary athletes.

Early echocardiographic studies of left ventricular (LV) morphology and function focused on single discipline athletes, primarily endurance and strength trained. To date there are few studies examining multi-disciplinary trained athletes. The present echocardiographic study examined LV morphology and function in 18 elite triathletes (swimming, cycling, and running) and 11 elite modern pentathletes (running, swimming, shooting, fencing, and show-jumping) compared with age- and sex-matched controls. Elite triathletes demonstrated significantly (p < 0.05) increased LV wall thickness and cavity dimensions together with LV mass, both in absolute terms and scaled for body surface area, compared with controls. Elite modern pentathletes demonstrated significantly (p < 0.05) increased LV wall thickness with a non-significant increase in LV internal diameter. Despite significant LV enlargement, the distribution of hypertrophy and diastolic filling indices were normal in both triathletes and modern pentathletes and significantly increased in the triathletes. It is concluded that multi-disciplinary training results in variations in LV morphology. The inciting stimulus resulting in LV enlargement in triathletes is associated with prolonged endurance activity, together with an isometric component accompanying cycling. In contrast, elite modern pentathletes experience a reduced endurance component combined with a high isometric component associated with fencing.

Adult↗

Estimate of the frequency of true incomplete exchanges in human lymphocytes exposed to 1 GeV/u Fe ions in vitro.

PURPOSE: To study the frequency of true incomplete exchanges induced by high-LET radiation. MATERIALS AND METHODS: Human lymphocytes were exposed to 1 GeV/u Fe ions (LET = 140 keV/microm). Chromosome aberrations were analysed by a fluorescence in situ hybridization using a combination of whole-chromosome-specific probes and human telomere probes. Chromosomes 1, 3 and 4 were investigated. RESULTS: The percentage of incomplete exchanges was between 23 and 29% if telomere signals were not considered. The percentage decreased to approximately 10% after ruling out false incomplete exchanges containing telomere signals. The final estimation of true incomplete exchanges was <10%. CONCLUSION: Within a degree of uncertainty, the percentage of true incomplete exchanges in 1 GeV/u Fe ion-irradiated human lymphocytes was similar to that induced by gamma rays.

Chromosome Aberrations↗