MS 066 Guide to the Howard B. Hamilton, MD, papers; 1945-1997

The Howard B. Hamilton, MD, papers, MS 66, includes material from 1945-1997 related to the Atomic Bomb Casualty Commission (ABCC) and the Radiation Effects Research Foundation (RERF). Hamilton was the Chief of Clinical Laboratories for the Atomic Bomb Casualty Commission from 1956 until its dissolution in 1975. He served in the same capacity for the Radiation Effects Research Foundation, which succeeded the ABCC, until 1984. This collection encompasses this period of time in Dr. Hamilton's career, as well as his related scholarly work after his retirement from RERF. Dr. Hamilton donated his collection of letters, reprints, newspaper articles, photographs, memos, and ephemera to the John P. McGovern Historical Collections and Research Center between 1985 and 2002. The collection is in good condition and consists of 3.75 cubic feet (10 boxes).

Modulation of radiation-induced genetic damage by HCMV: A glioma case-control study

Human cytomegalovirus (HCMV) infection occurs early in life and leads to life-long viral persistence. An association between HCMV infection and malignant gliomas has been reported suggesting that HCMV may play a role in glioma pathogenesis. The reported effects of HCMV on cells suggest that it could facilitate accrual of genotoxic damage. We therefore tested the hypothesis that HCMV infection modifies the sensitivity of cells to genetic damage from environmental insults such as γ-irradiation. Peripheral blood lymphocytes from 110 glioma patients and 100 controls were used to measure the level of both chromosome damage and cell death as endpoints for genetic instability. For each study participant, the extent of baseline, HCMV-, γ-radiation- and both – induced genetic instability was evaluated. Radiation induced a significant increase in aberration frequency over baseline in both cases and controls. Similarly, HCMV induced a significant increase in aberration frequency regardless of the disease status. Interestingly, HCMV induced damage was either equal or higher than that induced by radiation. Infected with HCMV prior to challenge with γ-radiation demonstrated a significant increase in the aberration frequency as compared to baseline, radiation- or HCMV-treated cells. With regards to apoptosis, cases showed a lower percentage of induction following in vitro exposure to γ-radiation and/or HCMV infection. The level of apoptosis was inversely related to the amount of chromosome damage in the cases, but not in the controls. These data indicate that, HCMV infection enhances the sensitivity of PBLs to γ-radiation-induced genetic damage.^

Minimizing radiation injury and neoplastic effects during pediatric fluoroscopy: what should we know?

Radiation-induced injuries from fluoroscopic procedures in pediatric patients have occurred, and young patients are at greatest risk of many radiation-induced neoplasms. Some fluoroscopists have been injured from their use of fluoroscopy, and they are known to be at risk of radiation-induced neoplasm when radiation is not well-controlled. This article reviews the circumstances that lead to radiation injury and delineates some procedural methods to avoid injury and limit radiation exposure to both the patient and the fluoroscopist.

The effects of ultraviolet B radiation on immune responses to {\it Borrelia burgdorferi}, the causative agent of Lyme disease

Ultraviolet B (UVB) radiation, in addition to being carcinogenic, is also immunosuppressive. Immunologically, UVB induces suppression locally, at the site of irradiation, or systemically, by inducing the production of a variety of immunosuppressive cytokines. Systemic effects include suppression of delayed-type hypersensitivity (DTH) responses to a variety of antigens (e.g. haptens, proteins, bacterial antigens, or alloantigens). One of the principal mediators of UV-induced immune suppression is the T helper-2 (Th2) cytokine interleukin-10 (IL-10); this suggests that UV irradiation induces suppression by shifting the immune response from a Th1 (cellular) to a Th2 (humoral) response. These "opposing" T helper responses are usually mutually exclusive, and polarized Th1 or Th2 responses may lead to either protection from infection or increased susceptibility to disease, depending on the infectious agent and the route of infection.^ This study examines the effects of UVB irradiation on cellular and humoral responses to Borrelia burgdorferi (Bb), the causative agent of Lyme disease (LD) in both immunization and infectious disease models; in addition, it examines the role of T cells in protection from and pathology of Bb infection. Particular emphasis is placed on the Bb-specific antibody responses following irradiation since UVB effects on humoral immunity are not fully understood. Mice were irradiated with a single dose of UV and then immunized (in complete Freund's adjuvant) or infected with Bb (intradermally at the base of the tail) in order to examine both DTH and antibody responses in both systems. UVB suppressed the Th1-associated antibodies IgG2a and IgG2b in both systems, as well as the DTH response to Bb in a dose dependent manner. Injection of anti-IL-10 antibody into UV-irradiated mice within 24 h after UV exposure restored the DTH response, as well as the Th1 antibody (IgG2a and IgG2b) response. In addition, injecting recombinant IL-10 mimicked some of the effects of UV radiation.^ Bb-specific Th1 T cell lines (BAT2.1-2.3) were generated to examine the role of T cells in Lyme borreliosis. All lines were CD4$\sp+,$ $\alpha\beta\sp+$ and proliferated specifically in response to Bb. The BAT2 cell lines not only conferred a DTH response to naive C3H recipients, but reduced the number of organisms recovered from the blood and tissues of mice infected with Bb. Furthermore, BAT2 cell lines protected mice from Bb-induced periarthritis. ^

Quantitative comparison of late effects following photon versus proton external-beam radiation therapies: Toward an evidence-based approach to selecting a treatment modality

Radiation therapy has been used as an effective treatment for malignancies in pediatric patients. However, in many cases, the side effects of radiation diminish these patients’ quality of life. In order to develop strategies to minimize radiogenic complications, one must first quantitatively estimate pediatric patients’ relative risk for radiogenic late effects, which has not become feasible till recently because of the calculational complexity. The goals of this work were to calculate the dose delivered to tissues and organs in pediatric patients during contemporary photon and proton radiotherapies; to estimate the corresponding risk of radiogenic second cancer and cardiac toxicity based on the calculated doses and on dose-risk models from the literature; to test for the statistical significance of the difference between predicted risks after photon versus proton radiotherapies; and to provide a prototype of an evidence-based approach to selecting treatment modalities for pediatric patients, taking second cancer and cardiac toxicity into account. The results showed that proton therapy confers a lower predicted risk of radiogenic second cancer, and lower risks of radiogenic cardiac toxicities, compared to photon therapy. An uncertainty analysis revealed that the qualitative findings of this study are insensitive to changes in a wide variety of host and treatment related factors.

AN INVESTIGATION OF THE MODIFYING EFFECTS OF VITAMIN A AND HYPOXIC CELL SENSITIZERS IN RADIATION CARCINOGENESIS IN MICE

The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed.^ In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. The circulating level of plasma vitamin A in all four groups of mice was monitored. A difference in circulating vitamin A in the mice maintained on high and low vitamin A diet became evident by 20 weeks and continued for the duration of the experiment. Mice were killed 18, 26, and 40 weeks post irradiation, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet (p < 0.05). Under the conditions of this experiment the development of pulmonary adenomas in irradiated strain A mice appears to relate directly to circulating levels of vitamin A.^ In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2mg/g and 0.6mg/g, were used either alone or in combination with 900 rad of gamma radiation in a fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p < 0.10) in the higher dose group (0.6mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group. Thus, under the experimental exposure conditions used in this investigation, which were very similar to the exposure conditions occurring in clinical treatment, all three hypoxic cell sensitizers did not sensitize the mouse to the carcinogenic effects of gamma radiation.^