In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells.

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Turn public problems to private account.

Many managers face increasing calls to invest corporate resources in charitable causes. How should executives balance a firm's very real economic imperative to maximize profitability with its hypothetical moral imperative to improve society? To provide one answer, the author draws on his experience as president of an economic-development company, IBEC. Viewing profit as "an essential discipline and measure of economic success" but not "the sole corporate goal," the company actively invested in social programs that met four criteria: they served a need of the local population; they required innovative approaches; they made sense on economic grounds; and they respected the social norms of the community. Such civic-minded efforts, the author argues in this prescient 1971 article, not only improve people's lives but also create the foundation for more affluent and dynamic markets--markets that ultimately produce greater profits for business. For example, one of IBEC's earliest ventures was directed toward solving Venezuela's problems in retail food marketing. Many important items were unavailable at the small stores where people shopped. So in 1949, working with local partners, IBEC opened a supermarket. Supermarkets soon changed the food-buying habits of the nation, and the initiative helped alter patterns of food distribution and created the reliable demand needed to establish a host of local suppliers. Return on IBEC's investment, and that of its local partners, was most satisfactory, the author reports. The road to meeting a public need-especially a major one--is rarely easy, the author says. But if management sizes up the need well, there is a good chance its new venture will survive under adversity.

Diagnosis of sclerosing cholangitis with technetium 99m-labeled iminodiacetic acid planar and single photon emission computed tomographic scintigraphy.

The purpose of this study was to determine whether 99mTc-iminodiacetic acid planar biliary scintigraphy combined with single photon emission computed tomography could detect sclerosing cholangitis and provide additional information regarding the extent and severity of disease. Thirteen patients with sclerosing cholangitis and 13 normal control subjects were studied. Scintigraphic results were also compared with previously reported studies of patients with isolated common bile duct obstruction and with primary biliary cirrhosis. The planar scintigraphy in patients with sclerosing cholangitis showed beading or bandlike constrictions of the biliary tract corresponding to lesions seen on cholangiography, and the image pattern was distinctly different from images obtained from patients with isolated common bile duct obstruction or primary biliary cirrhosis. The single photon emission computed tomography images of the liver in patients with sclerosing cholangitis demonstrated multiple focal areas of 99mTc-iminodiacetic acid retention, representing bile stasis in intrahepatic bile ducts. Compared to controls, the mean hepatic clearance half-time of 99mTc-iminodiacetic acid was markedly delayed in patients with sclerosing cholangitis (6-10 times normal). Individual patients with sclerosing cholangitis had wider variation in isotope clearance half-time from three regions of the liver than patients with isolated common bile duct obstruction, consistent with regional difference in disease severity and variable impairment of bile flow. In 4 patients with sclerosing cholangitis with incomplete filling of the right and left hepatic ducts at cholangiography, planar and single photon emission computed tomographic scintigraphy provided evidence of significant intrahepatic sclerosing cholangitis. In conclusion, combined 99mTc-iminodiacetic acid planar and single photon emission computed tomographic scintigraphy is a sensitive noninvasive test for the diagnosis of sclerosing cholangitis and reliably differentiates sclerosing cholangitis from isolated common bile duct obstruction or primary biliary cirrhosis. Measurement of isotope clearance half-time provides quantitative physiologic data that may be useful in the longitudinal follow-up of patients with sclerosing cholangitis.