In-utero exposed atomic bomb survivors: cancer risk update.
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Cause of Death↗
Biomedical subjects
K Mabuchi
Publications and source records attributed to K Mabuchi.
The effect of additive hyaluronic acid on animal joints with experimentally reduced lubricating ability.
A series of in vitro experiments demonstrated a clear effect of additive hyaluronic acid (HA) on animal joints with experimentally reduced lubricating ability. Eleven canine hip joints were utilized and the experimental conditions tested were: i) intact joints, ii) after washing the joint surfaces, and iii) after adding 1% HA to them. The frictional coefficient of every joint increased after washing and subsequently decreased after adding HA. The mean values were 0.007 (SD 0.004) on the intact joints, 0.020 (SD 0.009) after washing, and 0.013 (SD 0.005) after the addition of HA. The differences between the three values of frictional coefficients were shown to be statistically significant (p < 0.01).
Animals↗
Cancer incidence in Hiroshima and Nagasaki, Japan, 1958-1987.
The Hiroshima and Nagasaki tumour registries, which have been in operation since 1958, are among the few population-based cancer registries in Japan. This analysis evaluated cancer incidence in Hiroshima and Nagasaki between 1958 and 1987. The overall age-adjusted (World Population Standard) cancer incidence has increased from 217 to 301 per 100,000 among males, and from 176 to 197 per 100,000 among females during the first 30 years of cancer registration. The most recent rates are intermediate to rates in other countries. Despite a gradual decrease, gastric cancer remained the most common malignancy among males and females throughout the surveillance period, accounting for 24% of all cancers by the late 1980s. The rate of liver cancer has increased dramatically among males during the past 20 years, with a 2-fold increase in incidence in the past 10 years alone. The populations of Hiroshima and Nagasaki now have among the highest rates of liver cancer in the world. Breast cancer incidence in Hiroshima and Nagasaki, in contrast, is among the lowest in the world, although incidence rates have doubled since the 1960s. Other common malignancies include cancers of the lung, colon and rectum among males and cancers of the colon, cervix and lung among females.
Adolescent↗
Agreement between death certificate and autopsy diagnoses among atomic bomb survivors.
Based on the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation series of over 5,000 autopsies, we examined death certificate accuracy for 12 disease categories and assessed the effect of potential modifying factors on agreement and accuracy. The overall percentage agreement between death certificate and autopsy diagnoses was only 52.5%. Although neoplasms had the highest detection rate, almost 25% of cancers diagnosed at autopsy were nevertheless missed on death certificates. Confirmation and detection rates were above 70% for neoplasms and external causes of death only. Confirmation rates were between 50 and 70% for infectious diseases and heart and other vascular diseases. Detection rates reached a similar level for infectious, cerebrovascular, and digestive diseases. Specificity rates were above 90% for all except the cerebrovascular disease category. Overall agreement decreased with increasing age at death and was worse for deaths occurring outside of hospital. There was some suggestion that agreement improved over time, but no indication that radiation dose, sex, city of residence, or inclusion in a biennial clinical examination program influenced agreement. Since the inaccuracy of death certificate diagnoses can have major implications for health research and planning, it is important to be aware that their accuracy is low and that it can vary widely depending on cause, age and place of death.
Aged↗
Cancer incidence in atomic bomb survivors. Part I: Use of the tumor registries in Hiroshima and Nagasaki for incidence studies.
More than 30 years ago, population-based tumor registries were established in Hiroshima and Nagasaki. This report, the first of a series of papers on cancer incidence, describes methodological aspects of the tumor registries and discusses issues of data quality in the context of the Life Span Study (LSS) cohort, the major atomic bomb survivor population. The tumor registries in Hiroshima and Nagasaki are characterized by active case ascertainment based on abstraction of medical records at area hospitals, augmented by tissue registries operational in the area and a number of clinical and pathological programs undertaken over the years among the atomic bomb survivors. Using conventional measures of quality, the Hiroshima and Nagasaki tumor registries have a death certificate-only (DCO) rate of less than 9%, a mortality/incidence (M/I) ratio of about 50%, and a histological verification (HV) rate in excess of 70%, which place these registries among the best in Japan and comparable to many established registries worldwide. All tumor registry data pertaining to the LSS population were assembled, reviewed and handled with special attention given to the quality and uniformity of data based on standardized procedures. Special studies and monitoring programs were also introduced to evaluate the quality of the tumor incidence data in the LSS. Analyses were performed to examine the quality of incidence data overall and across various substrata used for risk assessment such as age, time and radiation dose groups. No significant associations were found between radiation dose and data quality as measured by various indices. These findings warrant the use of the present tumor registry-based data for studies of cancer incidence in the atomic bomb survivors.
Adolescent↗
Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987.
This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR1Sv) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR1SV = 0.32), colon (ERR1SV = 0.72), lung (ERR1SV = 0.95), breast (ERR1SV = 1.59), ovary (ERR1SV = 0.99), urinary bladder (ERR1SV = 1.02) and thyroid (ERR1SV = 1.15), significant radiation associations were observed. There was some indication of an increase in tumors of the neural tissue (excluding the brain) among persons exposed to the bombs before age 20. For the first time, radiation has been associated with liver (ERR1SV = 0.49) and nonmelanoma skin (ERR1SV = 1.0) cancer incidence in the LSS cohort. The present analysis also strengthened earlier findings, based on a smaller number of cases, of an effect of A-bomb radiation on salivary gland cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Cancer incidence in atomic bomb survivors. Part IV: Comparison of cancer incidence and mortality.
This report compares cancer incidence and mortality among atomic bomb survivors in the Radiation Effects Research Foundation Life Span Study (LSS) cohort. Because the incidence data are derived from the Hiroshima and Nagasaki tumor registries, case ascertainment is limited to the time (1958-1987) and geographic restrictions (Hiroshima and Nagasaki) of the registries, whereas mortality data are available from 1950-1987 anywhere in Japan. With these conditions, there were 9,014 first primary incident cancer cases identified among LSS cohort members compared with 7,308 deaths for which cancer was listed as the underlying cause of death on death certificates. When deaths were limited to those occurring between 1958-1987 in Hiroshima or Nagasaki, there were 3,155 more incident cancer cases overall, and 1,262 more cancers of the digestive system. For cancers of the oral cavity and pharynx, skin, breast, female and male genital organs, urinary system and thyroid, the incidence series was at least twice as large as the comparable mortality series. Although the incidence and mortality data are dissimilar in many ways, the overall conclusions regarding which solid cancers provide evidence of a significant dose response generally confirm the mortality findings. When either incidence or mortality data are evaluated, significant excess risks are observed for all solid cancers, stomach, colon, liver (when it is defined as primary liver cancer or liver cancer not otherwise specified on the death certificate), lung, breast, ovary and urinary bladder. No significant radiation effect is seen for cancers of the pharynx, rectum, gallbladder, pancreas, nose, larynx, uterus, prostate or kidney in either series. There is evidence of a significant excess of nonmelanoma skin cancer in the incidence data, but not in the mortality series. Cancers of the salivary gland and thyroid are also in excess in the incidence series, but they were not evaluated in the earlier mortality analyses. For all solid tumors the estimated excess relative risk at 1 Sv (ERR1Sv) for incidence (ERR1Sv = 0.63) is 40% larger than the excess relative risk (ERR) based on mortality data from 1950-1987 in all Japan (ERR1Sv = 0.45). The corresponding excess absolute risk (EAR) point estimate is 2.7 times greater for incidence than mortality. For some cancer sites, the difference in the magnitude of risk between incidence and mortality is greater. These differences reflect the greater diagnostic accuracy of the incidence data and the lack of full representation of radiosensitive but relatively nonfatal cancers, such as breast and thyroid, in the mortality data. Analyses of both incidence and mortality data are needed since the two end points provide complementary information for risk assessment.
Adolescent↗
Influence of death certificate errors on cancer mortality trends.
BACKGROUND: Evaluation of mortality data is an important tool in assessing both disease time trends and differences in populations. However, the reasons for changes in cancer mortality rates have been controversial. Questions have been raised concerning whether these increases are real or simply the result of changing diagnoses and death certificate reporting. PURPOSE: Our purpose was to determine on the basis of autopsy data if death certificate reporting varies over age, time, and cancer type and to explore the effect of death certificate error on recent cancer mortality trends. METHODS: Data were analyzed from 5886 autopsies collected by the Radiation Effects Research Foundation in Hiroshima, Japan, between 1961 and 1987. Death certificates were linked to autopsy data for analyses. An adjustment factor was calculated as a ratio of the accuracy of these death certificates in identifying cancer (detection rate) and listing cancer (confirmation rate) as the cause of death. This adjustment factor measures bias in mortality rates due to death certification errors and quantifies underestimation and overestimation of cancer mortality rates. RESULTS: Our analyses focused on lymphoma, breast cancer, neoplasms of the brain, multiple myeloma, and melanoma because of reported mortality increases. For these cancers, the adjustment factor decreased significantly (P = .02) over time, implying that death certificate accuracy has improved. This change appears to account for 60% of the observed increase in these cancers during the time period of study. For total cancer, persons 75 years or older have a high adjustment factor but it decreased over time. This decrease suggests an artifactual increase in total cancer mortality rates of about 1% per year for this older group. CONCLUSIONS: The quality of death certificate reporting has generally remained constant for most groups during the period 1961-1987. In the study population, there was a consistent underestimation of total cancer mortality of about 18%. For the five types of cancer studied, there has been less underestimation of cancer mortality since 1976. For some specific cancers and for persons 75 years or older, improvements in death certificate accuracy have occurred over time. These data imply that the total death certificate error rate varies considerably by cancer type, time period, and age at death. IMPLICATIONS: The changes in death certificate reporting for some sites and the elderly appear to have artifactually created increases in cancer mortality rates. These artifacts need to be considered when using mortality data for prevention research and health care planning.
Aged↗
Electron microscopic images suggest both ends of caldesmon interact with actin filaments.
An improved rotary shadowing technique enabled us to visualize chicken gizzard caldesmon (CaD) and its complexes with one or two covalently linked calmodulin (CaM) molecules by electron microscopy. Using a monoclonal antibody against an epitope in the N-terminal region of CaD (anti-N), we can now identify the end of the molecule that is involved in binding to another protein molecule. Thus in the 1:1 complex of CaD and CaM, the CaM molecule was almost always associated with the C-terminus of CaD, indicating preferential CaM-binding to the C-terminal region. We have also studied binding of CaD to filamentous actin (F-actin), using an EM technique that avoids spraying or freeze drying and thereby preserves the structure of F-actin. Only one end of CaD appeared to bind to F-actin, leaving the rest of the molecule projecting away from the filament. While the majority of anti-N bound at the free end of CaD, some antibody molecules were found on F-actin. These findings suggest that either end of CaD can bind to F-actin. Experiments using a monoclonal antibody against the C-terminus of CaD (anti-C) supported this idea. When the native thin filaments that contain endogenous CaD were incubated with anti-N, almost all the bound antibodies were found on the filaments, indicating that the N-terminal regions of CaD interact with actin, and that the binding affinity of the N-terminal region of CaD for actin is higher in vivo than that in vitro, either because the properties of CaD have been altered during purification, or because of the presence of some other component(s) associated with the native filaments.
Actins↗
Characterization of wild type and mutant chicken gizzard alpha calponin expressed in E. coli.
Calponin is a thin filament-associated protein that is implicated in the regulation and maintenance of smooth muscle contraction. Molecular cloning of chicken gizzard calponin indicated the presence of two isoforms, alpha and beta, the expression of the alpha-isoform being uniformly more abundant in various smooth muscle tissues [Takahashi, K. & Nadal-Ginard, B. (1991) J. Biol. Chem. 266, 13284-13288]. For the long-range goal of understanding of the structure and function of calponin, we have started bacterial expression and site-directed mutagenesis of alpha calponin. The amino acid composition and N-terminal sequence of the recombinant alpha calponin were found to be identical to those deduced from its nucleotide sequence. Recombinant alpha calponin is capable of binding to calmodulin, troponin C, tropomyosin, and actin, and of inhibiting skeletal muscle acto-subfragment-1 ATPase activity. A mutant alpha calponin with a replacement in the putative inhibitory region (residues 146-171) has impaired ability to inhibit the acto-subfragment-1 ATPase activity, suggesting that this region of calponin may be involved in the modulation of the actin-myosin interactions.
Actins↗
The use of robotics technology to study human joint kinematics: a new methodology.
Robotics technologies have been modified to control and measure both the force and position of synovial joints for the study of joint kinematics. One such system was developed to perform kinematic testing of a human joint. A 6-axis articulated robotic manipulator with 6 degrees of freedom (DOF) of motion was designed and constructed; a mathematical description for joint force and position was devised; and hardware and software to control forces applied to the joint, as well as position of the joint, were developed. The new methodology was utilized to simulate physiological loading conditions and to perform an anterior-posterior (A-P) translation test on a human cadaveric knee. Testing showed that this new system can stimulate complex loading conditions and also measure the resulting joint kinematics.
Algorithms↗
Modification of acidic residues normalizes sodium dodecyl sulfate-polyacrylamide gel electrophoresis of caldesmon and other proteins that migrate anomalously.
Caldesmon migrates as a 140-kDa protein during polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS), although its true molecular mass is close to 90 kDa. Since caldesmon's high acidic residue content may be responsible for this anomaly, it was reasoned that modification of these residues, with a loss of negative charge, might restore normal electrophoretic migration. Therefore caldesmon was reacted with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide in the presence of excess ethanolamine, which results in negatively charged carboxylates being converted to neutral amides without protein cross-linking. The absence of cross-linking was shown by rotary shadow electron microscopy. In accord with expectations, modified caldesmon migrated as a 94-kDa protein when compared to standards, which were much less affected by modification. The anomalous migration of caldesmon might be due to the repulsion of negatively charged SDS by caldesmon's acidic residues. Low binding of SDS to caldesmon is consistent with the fact that SDS, up to 1%, had little or no effect on the secondary structure of caldesmon, as monitored by circular dichroism. However, other mechanisms can also explain these observations. The abnormal migration of tropomyosin and calsequestrin, both of which have a high percentage of acidic amino acids, was also "normalized" by this treatment. Thus this method might have general application for the electrophoresis of proteins which have a high acidic residue content and migrate anomalously.
Calmodulin-Binding Proteins↗
"Rogue" lymphocytes among Ukrainians not exposed to radioactive fall-out from the Chernobyl accident: the possible role of this phenomenon in oncogenesis, teratogenesis, and mutagenesis.
Cultured lymphocytes exhibiting extreme cytogenetic damage (rogue cells) were observed in preparations from 8 of 24 individuals sampled in Krasilovka, a Ukrainian village receiving little or no increased radiation after the Chernobyl disaster, but were not observed in an additional 24 persons from two Russian towns in the more contaminated area. This observation cements the worldwide occurrence of these cells. The present data plus a review of the literature establish that rogue cells appear in brief bursts simultaneously in certain individuals of discrete populations. We suggest that the pattern is consistent with the action of a viral trigger that acts directly or indirectly--the latter possibly through the activation of latent chromosomal retroposons. If this phenomenon occurs in other tissues, it may have important implications for oncogenesis, teratogenesis, mutagenesis, and evolution.
Accidents↗
Unfolding domains of recombinant fusion alpha alpha-tropomyosin.
The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 degrees C involving the middle of the molecule; (2) a major transition at 46 degrees C involving no more than 36% of the helix from the C-terminus; (3) a major transition at 56 degrees C involving about 46% of the helix from the N-terminus; and (4) a transition from the nonhelical fusion domain at about 70 degrees C. Rabbit skeletal muscle tropomyosin, which lacks the fusion peptide but has the same tropomyosin sequence, does not exhibit the 56 degrees C or 70 degrees C transition. The very stable fusion unfolding domain of fusion-tropomyosin, which appears in electron micrographs as a globular structural domain at one end of the tropomyosin rod, acts as a cross-link to stabilize the adjacent N-terminal domain. The least stable middle of the molecule, when unfolded, acts as a boundary to allow the independent unfolding of the C-terminal domain at 46 degrees C from the stabilized N-terminal unfolding domain at 56 degrees C. Thus, strong localized interchain interactions in coiled-coil molecules can increase the stability of neighboring domains.
Animals↗
Motion of the bipolar hip prosthesis components. Friction studied in cadavers.
It has been postulated that most hip motion occurs at the inner bearing in bipolar hip prosthesis. However, radiography and cineradiography analyses have shown that the inner bearing is not always the primary articulation. We studied the frictional behavior of bipolar prosthesis and Austin-Moore prostheses and the motion of the bipolar prosthesis using a pendulum apparatus. The primary articulation was altered according to the amount of loading. When a load of 10 kg was applied to the joint, motion occurred at both bearings with friction coefficients 0.061 at the inner bearing and 0.026 at the outer bearing. With loads of over 20 kg, the outer bearing was the primary articulation. The inner bearing was the dominant articulation only when the acetabular cartilage had been removed. Our results suggest that the motion of bipolar prostheses occurs mainly at the outer bearing during normal walking, and that this prosthesis cannot be expected to reduce wear of articular cartilage.
Biomechanical Phenomena↗
Development of a flow-transformed pulsatile total artificial heart for total implantation.
To realize a totally implantable total artificial heart (TAH), a new pulsatile TAH, the flow-transformed pulsatile TAH (FTPTAH), was developed. The system was composed of a single centrifugal pump (CFP) and two three-way valves. One port of each three-way valve was connected to the inlet and outlet of a CFP. The other two ports of each valve were connected to the right and left atrium, and the pulmonary artery and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow by switching the two three-way valves. A prototype and the secondary model in which the solenoid valves and a spool valve were included, respectively, were connected to a mock circulatory unit with the results that a pulsatile TAH with physiological flow wave form could be obtained from a single CFP, about 5 L/min of pulsatile output could be obtained alternately on the right and left side by switching the solenoid valves or a spool valve, and flow balance between the right and left could be easily controlled by the switching duration. The system is feasible for a totally implantable TAH because it does not need a compliance chamber and can be miniaturized.
Heart, Artificial↗
Differential effects of platelet-activating factor on superoxide anion production in human eosinophils and neutrophils.
The effect of platelet-activating factor (PAF) on the generation of superoxide anion (O2-) in human eosinophils and neutrophils was examined. The presence of PAF potentiated O2- production in either opsonized zymosan- or formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated cells. The effect of PAF was prominent in opsonized zymosan-stimulated eosinophils and in FMLP-stimulated neutrophils. We also found that eosinophils generate substantial amounts of O2- when treated with PAF alone. The high responsiveness of unstimulated or opsonized zymosan-stimulated eosinophils to PAF to generate O2- may be relevant to the pathological changes at the loci of allergic reactions where eosinophils and PAF are crucially involved.
Eosinophils↗
The effect of diagnostic misclassification on non-cancer and cancer mortality dose response in A-bomb survivors.
We used the EM algorithm in the context of a joint Poisson regression analysis of cancer and non-cancer mortality in the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) to assess whether the observed increased risk of non-cancer death due to radiation exposure (Shimizu et al., RERF Technical Report 02-91, 1991) can be attributed solely to misclassification of cancer as non-cancer on death certificates. We show that greater levels of dose-independent misclassification than are indicated by a series of autopsies conducted on a subset of LSS members would be required to explain the non-cancer dose response, but that a relatively small amount of dose-dependence in the misclassification of cancer would explain the result. The adjustment for misclassification also results in higher risk estimates for cancer mortality. We review applications of similar statistical methods in other contexts and discuss extensions of the methods to more than two causes of death.
Age Factors↗