Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983-2008.

BACKGROUND: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality. METHODS: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors. RESULTS: Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03-0.39) with similar patterns for mortality among technologists born before 1930. CONCLUSIONS: Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

Segmental Maternal UPD6 with Prenatal Growth Restriction.

We report a child with segmental maternal uniparental isodisomy of chromosome 6, involving most of the long arm distal to 6q16, detected by SNP microarray. Clinical features include prenatal growth restriction, global developmental delay, and severe gastro-esophageal reflux disease. Maternal uniparental disomy (UPD) of chromosome 6 has previously been reported to cause intrauterine growth restriction. Paternal UPD of this chromosome is well known to cause transient neonatal diabetes mellitus. We discuss reported cases of maternal UPD of chromosome 6 and consider whether our patient's features may be due to disordered imprinting or unmasking of an autosomal recessive condition.

Increasing parental provision and children's consumption of lunchbox fruit and vegetables in Ireland: the Food Dudes intervention.

BACKGROUND/OBJECTIVES: Previous research in the United Kingdom, where there is a school canteen system, has shown that the Food Dudes intervention substantially increases children's fruit and vegetable consumption. The current study evaluated its effectiveness in Ireland where school meals are not provided and children bring food to school in lunchboxes. SUBJECTS/METHODS: Participants were 4- to 11-year-old children attending two primary schools; the schools were randomly assigned to experimental or control conditions (n=228 and 207, respectively). During the 16-day intervention in the experimental school, children watched video adventures featuring the heroic Food Dudes, and received small rewards for eating fruit and vegetables provided. In both schools, parental provision and children's consumption of fruit and vegetables in the lunchboxes were assessed at baseline and 12-month follow-up (Lunchbox measures). Fruit and vegetables were provided in both schools over an 8-day baseline phase and the 16-day intervention, and children's consumption was measured (school-provided food measures). RESULTS: Relative to baseline, consumption of the school-provided foods increased during the intervention in the experimental school (P<0.001), whereas in the control school it showed a significant decline. At 12-month follow-up, parents in the experimental school provided and their children consumed significantly more lunchbox fruit, vegetables and juice relative to baseline and to the control school (P<0.001 in all instances). CONCLUSIONS: The Food Dudes intervention was effective in changing parental provision and children's consumption of lunchbox fruit and vegetables in Ireland.

Childhood cancer in the offspring born in 1921-1984 to US radiologic technologists.

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Body mass index and all-cause mortality in a nationwide US cohort.

OBJECTIVE: To investigate whether the nature of the relationship between body mass index (BMI (kg/m2)) and all-cause mortality is direct, J- or U-shaped, and whether this relationship changes as people age. DESIGN: Prospective nationwide cohort study of US radiologic technologists (USRT). SUBJECTS: Sixty-four thousand seven hundred and thirty-three female and 19 011 male certified radiation technologists. METHODS: We prospectively followed participants from the USRT study who completed a mail survey in 1983-1989 through 2000. During an average of 14.7 years of follow-up or 1.23 million person-years, 2278 women and 1495 men died. Using Cox's proportional-hazards regression analyses, we analyzed the relationship between BMI and all-cause mortality by gender and by age group (<55 years; > or = 55 years). We also examined risk in never-smokers after the first 5 years of follow-up to limit bias owing to the confounding effects of smoking and illness-related weight loss on BMI and mortality. RESULTS: Risks were generally J-shaped for both genders and age groups. When we excluded smokers and the first 5 year of follow-up, risks were substantially reduced in those with low BMIs. In never-smoking women under the age of 55 years (excluding the initial 5-year follow-up period), risk rose as BMI increased above 21.0 kg/m2, whereas in older women, risk increased beginning at a higher BMI (> or = 25.0 kg/m2). Among younger men who never smoked (excluding the initial 5-year follow-up period), risk began to rise above a BMI of 23.0 kg/m2, whereas in older men, risk did not begin to increase until exceeding a BMI of 30.0 kg/m2. CONCLUSIONS: In younger/middle-aged, but not older, women and men, mortality risks appear directly related to BMI. The more complicated relationship between BMI and mortality in older subjects suggests the importance of assessing whether other markers of body composition better explain mortality risk in older adults.

Incidence of haematopoietic malignancies in US radiologic technologists.

BACKGROUND: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. AIMS: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. METHODS: The investigators followed up 71,894 (77.9% female) US radiologic technologists, first certified during 1926-80, from completion of a baseline questionnaire (1983-89) to return of a second questionnaire (1994-98), diagnosis of a first cancer, death, or 31 August 1998 (731,306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. RESULTS: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases). CONCLUSION: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.

The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins.

This report describes 2 patients with a clinical and hematologic diagnosis of chronic myeloid leukemia (CML) in chronic phase who had an acquired t(8;22)(p11;q11). Analysis by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) indicated that both patients were negative for the BCR-ABL fusion, but suggested that the BCR gene was disrupted. Further FISH indicated a breakpoint within fibroblast growth factor receptor 1 (FGFR1), the receptor tyrosine kinase that is known to be disrupted in a distinctive myeloproliferative disorder, most commonly by fusion to ZNF198. RT-PCR confirmed the presence in both cases of an in-frame messenger RNA fusion between BCR exon 4 and FGFR1 exon 9. Expression of BCR-FGFR1 in the factor-dependent cell line Ba/F3 resulted in interleukin 3-independent clones that grew at a comparable rate to cells transformed with ZNF198-FGFR1. The growth of transformed cells was inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002, the farnesyltransferase inhibitors L744832 and manumycin A, the p38 inhibitors SB202190 and SB203580 but not by the MEK inhibitor PD98059. The growth of BaF3/BCR-FGFR1 and BaF3/ZNF198-FGFR1 was not significantly inhibited by treatment with STI571, but was inhibited by SU5402, a compound with inhibitory activity against FGFR1. Inhibition with this compound was associated with decreased phosphorylation of ERK1/2 and BCR-FGFR1 or ZNF198-FGFR1, and was dose dependent with an inhibitory concentration of 50% of approximately 5 microM. As expected, growth of BaF3/BCR-ABL was inhibited by STI571 but not by SU5402. The study demonstrates that the BCR-FGFR1 fusion may occur in patients with apparently typical CML. Patients with constitutively active FGFR1 fusion genes may be amenable to treatment with specific FGFR1 inhibitors.

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Comparability of national death index plus and standard procedures for determining causes of death in epidemiologic studies.

PURPOSE: To determine whether causes of death obtained through National Death Index (NDI) Plus are comparable to those obtained by requesting death certificates from state vital statistics offices and having deaths coded by contractor nosologists. METHODS: The authors compared underlying cause of death codes obtained from NDI Plus with those assigned by contractor nosologists for a sample of 250 known decedents. RESULTS: The underlying cause of death codes differed for 18 (7%) of 249 successful matches. Independent coding by an expert National Center for Health Statistics (NCHS) nosologist trainer revealed that seven of these had an NDI Plus code that matched the code provided by the NCHS nosologist and a contractor nosologist code that did not match the NCHS nosologist code, seven had a contractor nosologist code that matched the NCHS nosologist code and an NDI Plus code that did not match the NCHS nosologist code, and four had both an NDI Plus and a contractor nosologist code that did not match the NCHS nosologist code. The level of disagreement with the NCHS nosologist and the organ systems involved were similar for NDI Plus and the contractor nosologist. CONCLUSIONS: The authors report that NDI Plus provides comparable information within a substantially shorter time period for most states and, for known decedents, at about half the cost of standard procedures.

Broader range of skills distinguishes successful CFOs.

In recent years, healthcare CFOs have seen their role expand significantly beyond traditional financial duties. A series of trended surveys on CFO roles and responsibilities reveals that today's healthcare CFO requires a broad new range of traits and skills in the areas of leadership, operations, and healthcare strategy. CFOs regard strategic thinking and the ability to communicate clearly as the most important of their essential leadership traits and skills, respectively. Among operational and strategic skills, CFOs most often cite the importance of being able to improve organizational performance and benchmark. Healthcare CFOs can enhance their chances of success by focusing self-improvement efforts on five key areas: implementing the organization's vision; developing tactics that stimulate change; enhancing communication skills; focusing on managing and leading; and strengthening relationships.

Trends in reproductive, smoking, and other chronic disease risk factors by birth cohort in a large occupational study.

PURPOSE: To illustrate the value of using large cohort studies to identify birth cohort trends in several chronic disease risk factors.METHODS: In collaboration with the American Registry of Radiologic Technologists (ARRT) and the University of Minnesota, the National Cancer Institute (NCI) initiated a cohort study of radiologic technologists who were certified by ARRT for at least two years between 1926 and 1982. Over 90,000 technologists (nearly four-fifths female) from all 50 states responded to a mailed questionnaire on reproductive, medical, work, and lifestyle factors. Ten, mostly five-year, birth cohorts, from before 1920 through 1960 and later, were evaluated.RESULTS: In this population, the mean height of both men and women generally rose in each subsequent birth cohort. The proportion of men who smoked before age 18 fell among those born since the late 1920s. In contrast, the proportion of women smoking before age 18 rose among those born since the early 1950s, reaching 14.2% among those born in 1960 and later. The mean age at menarche fell, until leveling off at 12.5, among those born after 1940. Recent birth cohorts (since 1950) show among the highest mean ages at birth of first child (>26 yeras), highest rates of nulliparity at age 25 (>/=63%), and lowest mean parity levels (

Mortality among radiologic technologists in the united states (1926-1997). 2(nd) Follow up.

PURPOSE: To evaluate risk for all-cause and cause-specific mortality in a large, primarily female (73%) cohort of radiologic technologists.METHODS: The study consists of 145,915 radiation technologists, certified in the American Registry of Radiologic Technologists (1926-1982) and followed through 1997. Causes of death were obtained from death certificates or, more recently, through NDI Plus. Standardized Mortality Ratios (SMR) were computed and tests of homogeneity were performed to detect differences in mortality among causes. Poisson models were used to estimate risks using an internal comparison group.RESULTS: Significantly low SMRs were observed for all causes (0.76), all cancers (0.82), and diseases of circulatory system (0.69). Compared to U.S. women, the risk for breast cancer mortality bordered around unity (SMR 1.01, 95% CI 0.94-1.09). However, relative to all other cancers, breast cancer mortality was significantly increased (RSMR 1.24, p < 0.01). Elevated risk for breast cancer was associated with certification before 1940 (SMR 1.55, 95% CI 1.24-1.91), and duration of certification of 20-29 (SMR 1.21, 95% CI 1.06-1.37) and 30+ years (SMR 1.77, 95% CI 1.54-2.02). A 35% increase in leukemia risk was evident for women certified for a duration of 20-29 years and a 36% increase among women certified for 30+ years. Poisson analysis revealed a significant increase in breast cancer risk with increasing number of years certified among women first certified before 1940 (p < 0.001) and during 1940-49 (p = 0.05) compared to women first certified in 1950 or later.CONCLUSIONS: Preliminary findings of this study suggest increased breast cancer risk associated with occupational radiation exposures prior to 1950 and with long-term cumulative exposures. However, potential confounding by reproductive and other risk factors needs to be evaluated.

Breast cancer mortality after diagnostic radiography: findings from the U.S. Scoliosis Cohort Study.

STUDY DESIGN: A retrospective cohort study was conducted in 5573 female patients with scoliosis who were referred for treatment at 14 orthopedic medical centers in the United States. Patients were less than 20 years of age at diagnosis which occurred between 1912 and 1965. OBJECTIVES: To evaluate patterns in breast cancer mortality among women with scoliosis, with special emphasis on risk associated with diagnostic radiograph exposures. SUMMARY OF BACKGROUND DATA: A pilot study of 1030 women with scoliosis revealed a nearly twofold statistically significant increased risk for incident breast cancer. Although based on only 11 cases, findings were consistent with radiation as a causative factor. METHODS: Medical records were reviewed for information on personal characteristics and scoliosis history. Diagnostic radiograph exposures were tabulated based on review of radiographs, radiology reports in the medical records, radiograph jackets, and radiology log books. Radiation doses were estimated for individual examinations. The mortality rate of the cohort through January 1, 1997, was determined by using state and national vital statistics records and was compared with that of women in the general U. S. population. RESULTS: Nearly 138,000 radiographic examinations were recorded. The average number of examinations per patient was 24.7 (range, 0-618); mean estimated cumulative radiation dose to the breast was 10.8 cGy (range, 0-170). After excluding patients with missing information, 5466 patients were included in breast cancer mortality analyses. Their mean age at diagnosis was 10.6 years and average length of follow-up was 40.1 years. There were 77 breast cancer deaths observed compared with the 45.6 deaths expected on the basis of U.S. mortality rates (standardized mortality ratio [SMR] = 1.69; 95% confidence interval [CI] = 1.3-2.1). Risk increased significantly with increasing number of radiograph exposures and with cumulative radiation dose. The unadjusted excess relative risk per Gy was 5.4 (95% CI = 1.2-14.1); when analyses were restricted to patients who had undergone at least one radiographic examination, the risk estimate was 2.7 (95% CI = -0. 2-9.3). CONCLUSIONS: These data suggest that exposure to multiple diagnostic radiographic examinations during childhood and adolescence may increase the risk of breast cancer among women with scoliosis; however, potential confounding between radiation dose and severity of disease and thus with reproductive history may explain some of the increased risk observed.

Mortality among Catholic nuns certified as radiologic technologists.

BACKGROUND: Several studies have shown that Catholic nuns have a different mortality experience than women of similar age in the general population. We had a unique opportunity to evaluate mortality patterns of nuns identified in an occupational study of nearly 145,000 radiologic technologists (73% female). METHODS: A total of 1,103 women were classified as nuns based on their titles of "Sister" or "SR". Their mortality experience was compared to other female radiologic technologists and to U.S. white females. RESULTS: Five hundred eighty-three nuns (53%) were deceased as of January 1, 1995. Compared to other technologists, nuns were at significantly increased risk of dying from all causes (Standardized mortality ratio (SMR)=1.1; 95% Confidence interval (CI)=1.0-1.2, stomach cancer (SMR=2.7; 95% CI=1.2-5.4), diabetes (SMR=2.2; 95% CI=1.0-4.1), ischemic heart disease (SMR=1.2; 95% CI=1.1-1.4), all digestive diseases (SMR=2.0; 95% CI=1.3-3.0), and gastric and duodenal ulcers (SMR=8.3; 95% CI=2.3-21.3). In contrast, we observed a significant deficit in lung cancer (SMR=0.5; 95% CI=0.2-0.9), no deaths from cervical cancer, and a breast cancer risk 10% lower than expected (SMR=0.9; 95% CI=0.6-1.3). When compared to U.S. females, nuns experienced significantly reduced mortality from all causes (SMR=0.8; 95% CI=0.7-0.9), cervical cancer (SMR=0.0; 95% CI=0.0-0.7), all endocrine, metabolic and nutritional diseases (SMR=0.5; 95% CI=0.3-0.9), all circulatory diseases (SMR=0.7; 95% CI=0.7-0.8) including ischemic heart disease and cerebrovascular disease, and all respiratory diseases (SMR=0.5; 95% CI=0.3-0.8), and a nearly significant deficit of diabetes (SMR=0.6; 95% CI=0.3-1.0). In contrast, nuns had an almost 3-fold greater risk of tuberculosis (SMR=2.9; 95% CI=1.4-5.3) and a 20% excess of breast cancer (SMR=1. 2; 95% CI=0.8-1.7). The breast cancer excess was concentrated among nuns first certified before 1940 (SMR=2.0; CI=1.3-3.0), when radiation doses were possibly the highest, but the risk did not increase with increasing length of certification. CONCLUSIONS: Compared with the general population, the mortality experience of nuns was favorable and reflected the "healthy worker effect" commonly seen in occupational studies. Patterns observed for breast and cervical cancer possibly indicate differences in reproductive and sexual activities associated with belonging to a religious order. The possibility of a radiation-related excess for breast cancer among nuns certified before 1940 cannot be completely discounted, although there was no dose-response relationship with a surrogate measure of exposure (number of years certified). When their mortality experience was compared with other radiologic technologists, the influence of lifestyle factors was not apparent. Am. J. Ind. Med. 37:339-348, 2000. Published 2000 Wiley-Liss, Inc. dagger

Effects of ethanol volume percent on fluorescein-labeled spinach apo- and holocalmodulin.

We report the effects of EtOH volume percent (0-70%) on spinach apo- and holocalmodulin that have been site-selectively labeled with fluorescein (F). In these experiments, calmodulin (CaM) has one F reporter group attached to Cys-26, and this site is located immediately adjacent to one of the four primary Ca(2+)-binding sites (EF hands). The optimum analytical CaM-F sensitivity to Ca2+ occurs between approximately 10 and 30% EtOH. Our results also show that added EtOH causes changes in CaM and these changes are surprisingly different for apo- and holo-CaM. Apo-CaM-F appears to lose one of its two waters of hydration at approximately 20% EtOH and retains one water of hydration between approximately 20 and 70% EtOH. In apo-CaM-F, the semiangle that describes the range over which the fluorescein reporter group can precess remains essentially constant (42 +/- 2 degrees) between 0 and 70% EtOH. This shows that the fluorescein reporter group precessional freedom in apo-CaM-F is not affected significantly by EtOH. Holo-CaM-F also appears to lose one water of hydration at approximately 20-30% EtOH but then appears to denature as the EtOH volume percent increases. The fluorescein reporter group semiangle within holo-CaM-F decreases from 43 +/- 1 degrees in neat aqueous buffer to 36 +/- 1 degrees at 70% EtOH. This shows that holo-CaM-F is less nativelike and the EF hand "closes down" about the fluorescein reporter group in holo-CaM-F as the EtOH volume percent increases.

Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group.

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.

Unfolding of acrylodan-labeled human serum albumin probed by steady-state and time-resolved fluorescence methods.

Steady-state and time-resolved fluorescence spectroscopy was used to follow the local and global changes in structure and dynamics during chemical and thermal denaturation of unlabeled human serum albumin (HSA) and HSA with an acrylodan moiety bound to Cys34. Acrylodan fluorescence was monitored to obtain information about unfolding processes in domain I, and the emission of the Trp residue at position 214 was used to examine domain II. In addition, Trp-to-acrylodan resonance energy transfer was examined to probe interdomain spatial relationships during unfolding. Increasing the temperature to less than 50 degrees C or adding less than 1.0 M GdHCl resulted in an initial, reversible separation of domains I and II. Denaturation by heating to 70 degrees C or by adding 2.0 M GdHCl resulted in irreversible unfolding of domain II. Further denaturation of HSA by either method resulted in irreversible unfolding of domain I. These results clearly demonstrate that HSA unfolds by a pathway involving at least three distinct steps. The low detection limits and high information content of dual probe fluorescence should allow this technique to be used to study the unfolding behavior of entrapped or immobilized HSA.

Mortality among United States radiologic technologists, 1926-90.

The possible mortality risk from low level chronic exposures to ionizing radiation was evaluated among 143,517 United States radiologic technologists certified by the American Registry of Radiologic Technologists between 1926-80. This is one of the few occupational studies of primarily women (73 percent) exposed to radiation during their employment. More than 2.8 million person-years of follow-up were accrued through 1990, and 7,345 deaths were identified. A strong healthy-worker effect was observed (standardized mortality ratios [SMR] for all causes and all cancers were 0.69 and 0.79, respectively). Lung cancer (429 deaths) was not increased with available measures of radiation exposure and no significant associations were observed for acute, myelogenous, and monocytic leukemia (74 deaths). Relative to the general population, the standardized mortality ratio (SMR) for female breast cancer was 0.99 (based on 425 deaths); however, breast cancer was significantly elevated relative to all other cancers in a test of homogeneity of SMRs (ratio of SMRs = 1.3, P < 0.0001). Significant risks were correlated with employment before 1940 (SMR = 1.5; 95 percent confidence interval [CI] = 1.2-1.9), when radiation doses were likely highest, and among women certified for more than 30 years (SMR = 1.4, CI = 1.2-1.7) for whom the cumulative exposure was likely greatest. Using an internal referent group, risk increased with duration of certification among the 1,890 women certified before 1940 (P-trend < 0.001). While the findings for breast cancer are consistent with a radiation effect, possible misclassification in exposure (based on number of years certified) and potential confounding associated with reproductive histories preclude a causal conclusion.