Biomedical subjects

J Cologne

Publications and source records attributed to J Cologne.

5 recordsLinked to original sources

PubMed2004

Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses.

Human fetuses are thought to be highly sensitive to radiation exposure because diagnostic low-dose X rays have been suggested to increase the risk of childhood leukemia. However, animal studies generally have not demonstrated a high radiosensitivity of fetuses, and the underlying causes for the discrepancy remain unidentified. We examined atomic bomb survivors exposed in utero for translocation frequencies in blood lymphocytes at 40 years of age. Contrary to our expectation of a greater radiosensitivity in fetuses than in adults, the frequency did not increase with dose except for a small increase (less than 1%) at doses below 0.1 Sv, which was statistically significant. We interpret the results as indicating that fetal lymphoid precursor cells comprise two subpopulations. One is small in number, sensitive to the induction of both translocations and cell killing, but rapidly diminishing above 50 mSv. The other is the major fraction but is insensitive to registering damage expressed as chromosome aberrations. Our results provide a biological basis for resolving the long-standing controversy that a substantial risk of childhood leukemia is implicated in human fetuses exposed to low-dose X rays whereas animal studies involving mainly high-dose exposures generally do not confirm it.

Chromosome Aberrations↗

PubMed2004

Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.

Quantifying the proliferative capacity of long-term hematopoietic stem cells in humans is important for bone marrow transplantation and gene therapy. Obtaining appropriate data is difficult, however, because the experimental tools are limited. We hypothesized that tracking clonal descendants originating from hematopoietic stem cells would be possible if we used clonal chromosome aberrations as unique tags of individual hematopoietic stem cells in vivo. Using FISH, we screened 500 blood T lymphocytes from each of 513 atomic bomb survivors and detected 96 clones composed of at least three cells with identical aberrations. The number of clones was inversely related to their population size, which we interpreted to mean that the progenitor cells were heterogeneous in the number of progeny that they could produce. The absolute number of progenitor cells contributing to the formation of the observed clones was estimated as about two in an unexposed individual. Further, scrutiny of ten clones revealed that lymphocyte clones could originate roughly equally from hematopoietic stem cells or from mature T lymphocytes, thereby suggesting that the estimated two progenitor cells are shared as one hematopoietic stem cell and one mature T cell. Our model predicts that one out of ten people bears a non- aberrant clone comprising >10% of the total lymphocytes, which indicates that clonal expansions are common and probably are not health-threatening.

Adolescent↗

PubMed2004

Prediction of clonal chromosome aberration frequency in human blood lymphocytes.

We recently conducted a large-scale screening for clonal aberrations among atomic bomb survivors and proposed a model for the gross clonal composition of blood lymphocytes. Here we show an application of the model indicating that the number, m,of clones detectable by cytogenetic methods in an individual is predictable by the equation m= (1.8 + 6.4FG) x FP x n/500, where FG represents the estimated translocation frequency in the 46 chromosome set, FP is the observed translocation frequency with FISH or other methods, and nis the number of cells examined. Application of the equation to the results of seven other reports gave close agreement between the observed and calculated numbers of clones. Since the model assumes that clonal expansion is ubiquitous, and any translocation can be the constituent of a clone detectable by cytogenetic means, the vast majority of observed clonal expansions of these somatic cells are likely the result of random-hit events that are not detrimental to human health. Furthermore, since our model can predict the majority of clonal aberrations among Chernobyl workers who were examined 5-6 years after irradiation, clonal expansion seems to occur primarily within a few years after exposure to radiation, most likely being coupled with the process of recovery from radiation-induced injury in the lymphoid and hematopoietic systems.

Chromosome Aberrations↗

PubMed2000

Prevalence of anti-hepatitis C virus antibody and chronic liver disease among atomic bomb survivors.

To investigate whether exposure to atomic bomb radiation altered the prevalence of hepatitis C virus (HCV) infection or accelerated the progress toward chronic hepatitis after HCV infection, the seropositivity of antibody to hepatitis C virus (anti-HCV) was determined for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. The seropositivity of anti-HCV antibody was 2.5 times higher among those with a history of blood transfusion and 1.2 times higher among those with a family history of liver disease, whereas acupuncture showed no association with anti-HCV. Although the prevalence of anti-HCV was lower for survivors with positive dose estimates than for those with 0 dose (relative prevalence 0.84, P = 0.022), there was no evidence of a smooth dose-response relationship. However, these data suggested that the radiation dose response for chronic liver disease among HCV antibody-positive survivors may be greater than that among HCV antibody-negative survivors (slope ratio 20). In conclusion, no dose-response relationship was found between anti-HCV positivity and radiation dose; a possible increase in the radiation dose response of chronic liver disease among anti-HCV-positive individuals was found. Thus radiation exposure may accelerate the progress of chronic liver disease associated with hepatitis C virus infection.

Aged↗

PubMed1986

Methods of estimation in log odds ratio regression models.

McCullagh's (1984, Journal of the Royal Statistical Society, Series B 46, 250-256) approximation to the conditional maximum likelihood estimator in log odds ratio regression models is shown to have negligible asymptotic bias unless the odds ratios are large and the sample sizes in individual 2 X 2 tables are very small. In application to two sets of case-control data, it yields results virtually indistinguishable from those of the conditional analysis. A generalization of the Mantel-Haenszel estimator proposed by Davis (1985, Biometrics 41, 487-495) does not approximate the conditional results nearly as well.

Biometry↗