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Biomedical subjects

Michael E Ketterer

Publications and source records attributed to Michael E Ketterer.

10 recordsLinked to original sources
PubMed2006

Human lead exposure in a late 19th century mental asylum population.

Lead isotope ratios and lead (Pb) levels were analyzed in 33 individuals from a forgotten cemetery at the Colorado Mental Health Institute at Pueblo, Colorado dating to 1879-1899. Isotopic ratios from healing bone fractures, cortical bone, and tooth dentine provide information about sources of Pb exposures over a range of time that illuminates individual's life histories and migration patterns. Historical records and Pb production data from the 19th century were used to create a database for interpreting Pb exposures for these African, Hispanic and European Americans. The analysis of these individuals suggests that Pb exposure noticeably impacted the mental health of 5-10% of the asylum patients in this frontier population, a high number by standards today, and that differences exist in the three ancestral groups' exposure histories.

Bone and Bones↗
PubMed2004

Chromium is the proximate clastogenic species for lead chromate-induced clastogenicity in human bronchial cells.

Hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen with potentially widespread exposure. Solubility is a key factor in the carcinogenicity of Cr(VI), with the water-insoluble or 'particulate' compounds being the more potent carcinogens. Studies have indicated that the component ions are responsible for their clastogenicity, but it is uncertain whether chromium (Cr), lead (Pb) or some combination of the two is responsible for the clastogenic effects. Accordingly, we compared the clastogenicity of lead chromate (LC) with soluble sodium chromate (SC) and lead glutamate (LG) in WTHBF-6 human lung cells. We found that 1436microM was the maximal intracellular level of Pb after exposure to clastogenic concentrations of LC. However, clastogenesis was not observed after exposure to LG, even when intracellular Pb concentrations reached 13,347microM, indicating that intracellular Pb levels did not reach clastogenic levels in WTHBF-6 cells after LC treatment. By contrast, SC was clastogenic damaging 16 and 44% of metaphase cells at intracellular Cr doses of 312 and 1262microM respectively, which was comparable to the clastogenesis observed after LC treatment. LC damaged 10, 27 and 37% of metaphases at intracellular Cr doses of 288, 926 and 1644microM, respectively. These data indicate that with respect to LC-induced clastogenicity, Cr and not Pb is the proximate clastogenic species in human lung cells.

Bronchi↗
PubMed2004

Rapid dating of recent sediments in Loch Ness: inductively coupled plasma mass spectrometric measurements of global fallout plutonium.

The (239+240)Pu activity profile is determined for a sediment core collected from 170-m depth at Loch Ness, Scotland. These measurements use magnetic sector inductively coupled plasma mass spectrometry for rapid determination of Pu activities and (240)Pu/(239)Pu atom ratios. A (239+240)Pu detection limit of 0.1 Bq/kg is obtained for 2 g of acid-leached sediment; (242)Pu is used as a spike isotope. The Pu activity profile exhibits a maximum of 42.7+/-0.3 Bq/kg (239+240)Pu in the 9-10-cm depth interval. The position of this maximum coincides with peaks in the (241)Am and (137)Cs activity profiles. These peak activities are ascribed to the 1963/1964 peak fallout from atmospheric testing of nuclear weapons. The (240)Pu/(239)Pu atom ratios are in the range 0.15-0.20, in agreement with the expected range of 0.166-0.194 for Northern Hemisphere fallout, and do not suggest the presence of other contributing sources. This study demonstrates that ICPMS has considerable potential for rapid determination of the chronology of post-1950 sediments, and also for validating (210)Pb dates where chronologies over longer time-scales are needed.

Journal Article↗
PubMed2004

Comparison of two particulate hexavalent chromium compounds: Barium chromate is more genotoxic than lead chromate in human lung cells.

Particulate hexavalent chromium [Cr(VI)] compounds are well-established human lung carcinogens. However, their carcinogenic mechanisms are poorly understood as most investigators have used soluble Cr(VI) compounds. Recent work from our laboratory has found that barium chromate (BC) is also cytotoxic and clastogenic. To understand how BC relates to existing data on other particulate Cr(VI) compounds, we compared its cytotoxicity and clastogenicity with lead chromate (LC), which has been used as a prototypical particulate Cr(VI) compound, in WTHBF-6 cells, a near-normal human lung cell line. We found that BC is a more potent cytotoxicant, inducing 67%, 12%, 3%, and 0% relative survival at concentrations of 0.1, 0.5, 1, and 5 microg/cm2, respectively, while LC induced 90%, 71%, 43%, and 15% survival at these same concentrations. We found that BC was also more clastogenic, damaging 22% and 49% of metaphase cells at 0.1 and 0.5 microg/cm2, and causing complete cell cycle arrest at 1 and 5 microg/cm2. By contrast, 0.1, 0.5, and 1.0 microg/cm2 LC damaged 10%, 27%, and 37% of metaphase cells, respectively, and complete cell cycle arrest was not observed until a concentration of 5 microg/cm2 was reached. We found that BC and LC both partially dissolved in complete medium in the presence of cells, producing similar extracellular concentrations. Both compounds were also comparable with respect to particle uptake and the amount of intracellular Cr ions. Considering previous reports showing that lead ions were inactive and that sodium chromate and LC have similar clastogenic potencies, these data suggest that BC genotoxicity may not be solely mediated by Cr ions, but also involve some clastogenic activity of barium ions.

Barium Compounds↗
PubMed2004

Resolving Chernobyl vs. global fallout contributions in soils from Poland using Plutonium atom ratios measured by inductively coupled plasma mass spectrometry.

Plutonium in Polish forest soils and the Bór za Lasem peat bog is resolved between Chernobyl and global fallout contributions via inductively coupled plasma mass spectrometric measurements of 240Pu/230Pu and 241Pu/239Pu atom ratios in previously prepared NdF3 alpha spectrometric sources. Compared to global fallout, Chernobyl Pu exhibits higher abundances of 240Pu and 241Pu. The ratios 240Pu/230Pu and 241Pu/239Pu co-vary and range from 0.186 to 0.348 and 0.0029 to 0.0412, respectively, in forest soils (241Pu/239Pu = 0.2407 x [240Pu/239Pu] - 0.0413; r2 = 0.9924). Two-component mixing models are developed to apportion 239+240Pu and 241Pu activities; various estimates of the percentage of Chernobyl-derived 239+240Pu activity in forest soils range from < 10% to > 90% for the sample set. The 240Pu/230Pu - 241Pu/239Pu atom ratio mixing line extrapolates to estimate 241Pu/239Pu and the 241Pu/239+240Pu activity ratio for the Chernobyl source term (0.123 +/- 0.0007; 83 +/- 5; 1 May 1986). Sample 241Pu activities, calculated using existing alpha spectrometric 239+240Pu activities, and the 240Pu/230Pu and 241Pu/239Pu atom ratios, agree relatively well with previous liquid scintillation spectrometry measurements. Chernobyl Pu is most evident in locations from northeastern Poland. The 241Pu activities and/or the 241Pu/239Pu atom ratios are more sensitive than 240Pu/239Pu or 238Pu/239+240Pu activity ratios at detecting small Chernobyl 239+240Pu inputs, found in southern Poland. The mass spectrometric data show that the 241Pu activity is 40-62% Chernobyl-derived in southern Poland, and 58-96% Chernobyl in northeastern Poland. The Bór za Lasem peat bog (49.42 degrees N, 19.75 degrees E), located in the Orawsko-Nowotarska valley of southern Poland, consists of global fallout Pu.

Environmental Monitoring↗
PubMed2003

Role of ceruloplasmin in macrophage iron efflux during hypoxia.

The reticuloendothelial system has a central role in erythropoiesis and iron homeostasis. An important function of reticuloendothelial macrophages is phagocytosis of senescent red blood cells. The iron liberated from heme is recycled for delivery to erythrocyte precursors for a new round of hemoglobin synthesis. The molecular mechanism by which recycled iron is released from macrophages remains unresolved. We have investigated the mechanism of macrophage iron efflux, focusing on the role of ceruloplasmin (Cp), a copper protein with a potent ferroxidase activity that converts Fe2+ to Fe3+ in the presence of molecular oxygen. As shown by others, Cp markedly increased iron binding to apotransferrin at acidic pH; however, the physiological significance of this finding is uncertain because little stimulation was observed at neutral pH. Introduction of a hypoxic atmosphere resulted in marked Cp-stimulated binding of iron to apotransferrin at physiological pH. The role of Cp in cellular iron release was examined in U937 monocytic cells induced to differentiate to the macrophage lineage. Cp added at its normal plasma concentration increased the rate of 55Fe release from U937 cells by about 250%. The stimulation was absolutely dependent on the presence of apotransferrin and hypoxia. Cp-stimulated iron release was confirmed in mouse peritoneal macrophages. Stimulation of iron release required an intracellular "labile iron pool" that was rapidly depleted in the presence of Cp and apotransferrin. Ferroxidase-mediated loading of iron into apotransferrin was critical for iron release because ferroxidase-deficient Cp was inactive and because holotransferrin could not substitute for apotransferrin. The extracellular iron concentration was critical as shown by inhibition of iron release by exogenous free iron, and marked enhancement of release by an iron chelator. Together these data show that Cp stimulates iron release from macrophages under hypoxic conditions by a ferroxidase-dependent mechanism, possibly involving generation of a negative iron gradient.

Animals↗
PubMed2003

Depth profiling of Pu, 241Am and 137Cs in soils from southern Belarus measured by ICP-MS and alpha and gamma spectrometry.

The depth distribution of plutonium, americium, and 137Cs originating from the 1986 accident at the Chernobyl Nuclear Power Plant (NPP) was investigated in several soil profiles in the vicinity from Belarus. The vertical migration of transuranic elements in soils typical of the 30 km relocation area around Chernobyl NPP was studied using inductively coupled plasma mass spectrometry (ICP-MS), alpha spectrometry, and gamma spectrometry. Transuranic concentrations in upper soil layers ranged from 6 x 10(-12) g g(-1) to 6 x 10(-10) g g(-1) for plutonium and from 1.8 x 10(-13) g g(-1) to 1.6 x 10(-11) g g(-1) for americium. These concentrations correspond to specific activities of (239+240)Pu of 24-2400 Bq kg(-1) and specific activity of 241Am of 23-2000 Bq kg(-1), respectively. Transuranics in turf-podzol soil migrate slowly to the deeper soil layers, thus, 80-95%, of radionuclide inventories were present in the 0-3 cm intervals of turf-podzol soils collected in 1994. In peat-marsh soil migration processes occur more rapidly than in turf-podzol and the maximum concentrations are found beneath the soil surface (down to 3-6 cm). The depth distributions of Pu and Am are essentially identical for a given soil profile. (239+240)Pu/137Cs and 241Am/137Cs activity ratios vary by up to a factor of 5 at some sites while smaller variations in these ratios were observed at a site close to Chernobyl, suggesting that 137Cs is dominantly particle associated close to Chernobyl but volatile species of 137Cs are of relatively greater importance at the distant sites.

Americium↗
PubMed2002

Anticancer activity of sodium stibogluconate in synergy with IFNs.

Cancer cell resistance limits the efficacy of IFNs. In this study, we show that sodium stibogluconate (SSG) and IFN-alpha synergized to overcome IFN-alpha resistance in various human cancer cell lines in culture and eradicated IFN-alpha-refractory WM9 human melanoma tumors in nude mice with no obvious toxicity. SSG enhanced IFN-alpha-induced Stat1 tyrosine phosphorylation, inactivated intracellular SHP-1 and SHP-2 that negatively regulate IFN signaling, and induced cellular protein tyrosine phosphorylation in cancer cell lines. These effects are consistent with inactivation of phosphatases as the basis of SSG anticancer activity. Characterization of SSG by chromatography revealed that only selective compounds in SSG were effective protein tyrosine phosphatase inhibitors. These observations suggest the potential of SSG as a clinically usable protein tyrosine phosphatase inhibitor in cancer treatment and provide insights for developing phosphatase-targeted therapeutics.

Adjuvants, Immunologic↗
PubMed2002

Rapid dating of recent aquatic sediments using Pu activities and 240Pu/239Pu as determined by quadrupole inductively coupled plasma mass spectrometry.

Quadrupole inductively coupled plasma mass spectrometry has been used to rapidly establish the chronology of recent aquatic sediments via measurements of the activities of 239Pu, 240Pu, and the atom ratio 240Pu/239Pu. Following addition of 0.007 Bq of a 242Pu spike isotope, Pu is leached from 3-20 g aliquots of dry-ashed sediments with HNO3. A selective anion exchanger is used to preconcentrate Pu into approximately 2 mL aliquots, which are directly analyzed using a pneumatic nebulizer and double-pass spraychamber operating at 60 microL/min solution uptake rate. The ICPMS data collection is performed for 10 min per sample. The U concentrations were 0.01-0.05 microg/L in the analyzed solutions, and the interference of 238U1H+ upon 239Pu+ was negligible. The method has been applied to determining Pu activities, inventory, and 240Pu/239Pu in a complete sediment core from Old Woman Creek (Huron, OH). The Pu activity profiles, obtained in approximately 6 h of instrumental measurement time, are in agreement with a y spectrometric 137Cs profile. Peak 239+240Pu and 137Cs activities in the core were 1.60 +/- 0.02 and 47.8 +/- 0.8 Bq/kg, respectively; inventories were 108 +/- 2 Bq/m2 239+240Pu and 2710 +/- 40 Bq/m2 137Cs. Detection limits, based upon the analysis of 20 g samples, were 0.004 Bq/kg 239Pu, 0.012 Bq/kg 240Pu, and 0.012 Bq/kg 239+240Pu. 240Pu/239Pu atom ratios of 0.16-0.19 were obtained for all core intervals containing detectable Pu, which indicates that global fallout is the source of these radionuclides.

Environmental Monitoring↗