Jose A Centeno

Wright-Patterson Air Force Base, Dayton, Ohio, United States

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Publications (59)126.92 Total impact

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    ABSTRACT: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed. Now more than 20 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As tissue concentrations continue to accrue with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort. Am. J. Ind. Med. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Industrial Medicine 04/2015; 58(6). DOI:10.1002/ajim.22435 · 1.74 Impact Factor
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    ABSTRACT: Mottled-dappled (Mo-dp) is a mouse model of Menkes disease caused by a large, previously uncharacterized deletion in the 5' region of Atp7a, the mouse ortholog of ATP7A. Affected mutants die in utero at embryonic day 17, and show bending and thickening of the ribs and distortion of the pectoral and pelvic girdles and limbs. To characterize this allele, we designed a custom 4x180K microarray on the mouse X chromosome and performed comparative genomic hybridization using extracted DNA from normal and carrier Mo-dp females, and identified an approximately 9 kb deletion. We used PCR to fine-map the breakpoints and amplify a junction fragment of 630 bp. Sequencing of the junction fragment disclosed the exact breakpoint locations and that the Mo-dp deletion is precisely 8,990 bp, including approximately 2 kb in the promoter region of Atp7a. Western blot analysis of Mo-dp heterozygotes brains showed diminished amounts of Atp7a protein, consistent with reduced expression due to the promoter region deletion on one allele. In heterozygous females, brain copper levels tended to be lower compared to wild type whereas neurochemical analyses revealed higher dihydroxyphenylacetic acid: dihydroxyphenylglycol (DOPAC: DHPG) and dopamine: norepinephrine (DA:NE) ratios compared to normal (p = 0.002 and 0.029, respectively), consistent with partial deficiency of dopamine-beta-hydroxylase, a copper-dependent enzyme. Heterozygous females showed no significant differences in body weight compared to wild type females. Our results delineate the molecular details of the Mo-dp mutation for the first time and define novel biochemical findings in heterozygous female carriers of this allele.
    Molecular Genetics and Metabolism 10/2014; 113(4). DOI:10.1016/j.ymgme.2014.10.001 · 2.63 Impact Factor
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    ABSTRACT: The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to embedded fragment wounds containing metal and metal mixtures whose long-term toxicologic and carcinogenic properties are not as yet known. Advances in medical care have greatly increased the survival from these types of injuries. Standard surgical guidelines suggest leaving embedded fragments in place, thus individuals may carry these retained metal fragments for the rest of their lives. Nursing professionals will be at the forefront in caring for these wounded individuals, both immediately after the trauma and during the healing and rehabilitation process. Therefore, an understanding of the potential health effects of embedded metal fragment wounds is essential. This review will explore the history of embedded fragment wounds, current research in the field, and Department of Defense and Department of Veterans Affairs guidelines for the identification and long-term monitoring of individuals with embedded fragments.
    Annual review of nursing research 10/2014; 32(1). DOI:10.1891/0739-6686.32.63
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    ABSTRACT: Background: The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and corrosiveness of the fragments in vivo. Information obtained by chemical analysis of excised fragments can be used to guide clinical decisions regarding the need for fragment removal, to develop therapeutic interventions, and to better anticipate future medical problems from retained fragment related injuries. In response to this need, a new U.S Department of Defense (DoD) directive has been issued requiring characterization of all removed fragments to provide a database of fragment types occurring in combat injuries. Objectives: The objective of this study is to determine the chemical composition of retained embedded fragments removed from injured military personnel, and to relate results to histological findings in tissue adjacent to fragment material. Methods: We describe an approach for the chemical analysis and characterization of retained fragments and adjacent tissues, and include case examples describing fragments containing depleted uranium (DU), tungsten (W), lead (Pb), and non-metal foreign bodies composed of natural and composite materials. Fragments obtained from four patients with penetrating blast wounds to the limbs were studied employing a wide range of chemical and microscopy techniques. Available adjacent tissues from three of the cases were histologically, microscopically, and chemically examined. The physical and compositional properties of the removed foreign material surfaces were examined with energy dispersive x-ray fluorescence spectrometry (EDXRF), scanning electron microscopy (SEM), laser ablation inductively-coupled plasma mass-spectrometry (LA-ICP-MS), and confocal laser Raman microspectroscopy (CLRM). Quantitative chemical analysis of both fragments and available tissues was conducted employing ICP-MS. Results: Over 800 fragments have been characterized and included as part of the Joint Pathology Center Embedded Fragment Registry. Most fragments were obtained from penetrating wounds sustained to the extremities, particularly soft tissue injuries. The majority of the fragments were primarily composed of a single metal such as iron, copper, or aluminum with traces of antimony, titanium, uranium, and lead. One case demonstrated tungsten in both the fragment and the connected tissue, together with lead. Capsular tissue and fragments from a case from the 1991 Kuwait conflict showed evidence of uranium that was further characterized by uranium isotopic ratios analysis to contain depleted uranium. Conclusions: The present study provides a systematic approach for obtaining a full chemical characterization of retained embedded fragments. Given the vast number of combat casualties with retained fragments, it is expected that fragment analysis will have significant implications for the optimal short and long-term care of wounded service members.
    International Journal of Environmental Research and Public Health 02/2014; 11(2):1261-78. DOI:10.3390/ijerph110201261 · 2.06 Impact Factor
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    ABSTRACT: In a population of Gulf War I veterans who sustained inhalational exposure to depleted uranium during friendly fire incidents in 1991, we evaluated whether those with high body burdens of uranium were more likely to have pulmonary health abnormalities than those with low body burdens. We compared self-reported respiratory symptoms, mean pulmonary function values, and prevalence of low-dose chest computed tomography abnormalities between high and low urine uranium groups. We found no significant differences in respiratory symptoms, abnormal pulmonary function values, or prevalence of chest computed tomography abnormalities between high and low urine uranium groups. Overall, the cohort's pulmonary function values fell within the expected clinical range. Our results support previous estimates that the depleted uranium levels inhaled during the 1991 friendly fire incidents likely do not cause long-term adverse pulmonary health effects.
    Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 07/2013; 55(8). DOI:10.1097/JOM.0b013e31829176c7 · 1.63 Impact Factor
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    ABSTRACT: Soil and house dust collected in and around Hg mines and a processing facility in Horlivka, a mid-sized city in the Donets Basin of southeastern Ukraine, have elevated As and Hg levels. Surface soils collected at a former Hg-processing facility had up to 1300 mg kg−1 As and 8800 mg kg−1 Hg; 1MHCl extractions showed 74–93% of the total As, and 1–13% of the total Hg to be solubilized, suggesting differential environmental mobility between these elements. In general, lower extractability of As and Hg was seen in soil samples up to 12 km from the Hg-processing facility, and the extractable (1M HCl, synthetic precipitation, deionized water) fractions of As are greater than those for Hg, indicating that Hg is present in a more resistant form than As. The means (standard deviation) of total As and Hg in grab samples collected from playgrounds and public spaces within 12 km of the industrial facility were 64 (±38) mg kg−1 As and 12 (±9.4) mg kg−1 Hg; all concentrations are elevated compared to regional soils. The mean concentrations of As and Hg in dust from homes in Horlivka were 5–15 times higher than dust from homes in a control city. Estimates of possible exposure to As and Hg through inadvertent soil ingestion are provided.
    Soil and Sediment Contamination 07/2013; 22(5):574-593. DOI:10.1080/15320383.2013.750270 · 1.04 Impact Factor
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    ABSTRACT: Abstract The health consequences of sand particle inhalation are incompletely understood. This project evaluated the respiratory toxicity of sand particles collected at military bases near Fort Irwin USA, in Iraq (Camp Victory, Taji and Talil), and Khost Afghanistan. Our primary focus was on assessing the role of soluble metals in the respiratory toxicity of the sand particles using in vitro and in vivo methods. Replicating rat type II alveolar cell cultures (RLE-6TN) were exposed to sand extracts or vehicle control in serum-free media for ≤24 h. Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and assessment of lactate dehydrogenase leakage. The relative in vitro cytotoxicity of the sand extracts was Taji ≈ Talil > Afghanistan > Camp Victory ≈ Fort Irwin. We also assessed extracts of Camp Victory, Afghanistan, and Taji sand for acute and delayed pulmonary toxicity in rats following intratracheal administration. Assessments included biochemical analysis of bronchoalveolar lavage fluid (BALF) and lung histopathology. The in vitro cytotoxicity assay results were partially predictive of in vivo responses. The more cytotoxic Taji sand extract induced an acute irritant response in rats following intratracheal administration. Rats given the less cytotoxic Camp Victory sand extract had minimal biochemical or cytological BALF changes whereas rats given either the Afghanistan or Taji sand extracts demonstrated BALF changes that were suggestive of mild lung inflammation. Unexpectedly, we observed similar lung pathology in all extract-exposed rats. The results of our study can be used to prioritize future particle inhalation studies or guide epidemiological study design.
    Inhalation Toxicology 06/2013; 25(7):405-416. DOI:10.3109/08958378.2013.797524 · 2.26 Impact Factor
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    ABSTRACT: During the 1991 GulfWar, U.S. service members were exposed to depleted uranium (DU) through friendly-fire incidents involving DU munitions and vehicles protected by DU armor. Routes of exposure to DU involved inhalation of soluble and insoluble DU oxide particles, wound contamination, and retained embedded DU metal fragments that continue to oxidize in situ and release DU to the systemic circulation. A biennial health surveillance program established for this group of Veterans by the U.S. Department of Veterans Affairs has shown continuously elevated urine DU concentrations in the subset of veterans with embedded fragments for over 20 years. While the 2011 assessment was comprehensive, few clinically significant U-related health effects were observed. This report is focused on health outcomes associated with two primary target organs of concern for long term effects of this combat-related exposure to DU. Renal biomarkers showed minimal DU-related effects on proximal tubule function and cytotoxicity, but significant biomarker results were observed when urine concentrations of multiple metals also found in fragments were examined together. Pulmonary tests and questionnaire results indicate that pulmonary function after 20 y remains within the clinical normal range. Imaging of DU embedded fragment-associated tissue for signs of inflammatory or proliferative reactions possibly associated with foreign body transformation or with local alpha emissions from DU was also conducted using PET-CT and ultrasound. These imaging tools may be helpful in guiding decisions regarding removal of fragments.
    Health physics 04/2013; 104(4):347-361. DOI:10.1097/HP.0b013e31827b1740 · 1.27 Impact Factor
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    Robert B. Finkelman · Gary Krieger · Heather Gingerich · Jose A. Centeno ·

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    ABSTRACT: Humans are constantly exposed to hazardous pollutants in the environment—for example, in the air, water, soil, rocks, diet, or workplace. Trace metals are important in environmental pathology because of the wide range of toxic reactions and their potential adverse effects on the physiological function of organ systems. Exposures to toxic trace metals have been the subject of numerous environmental and geochemical investigations, and many studies have been published on the acute and/or chronic effects of high-level exposures to these types of agents; however, much fewer data are available concerning the health effects of low-dose chronic exposure to many trace metals. Chronic low-dose exposures to toxic elements such as cadmium and arsenic have been shown to cause these metals to accumulate in tissues over time, leading to multiple adverse effects in exposed individuals.
    Essentials of Medical Geology, 01/2013: pages 569-596; , ISBN: 978-94-007-4374-8
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    ABSTRACT: Understanding the detrimental effects that geochemical processes and environmental pollutants may have on the health of humans and animals has been the subject of extensive study in medical geology and environmental pathology. For example, information obtained from the chemical analysis of mineral deposits in tissues may provide insight into a particular disease state and assist in the development of new treatments and therapy. In many cases, diseases related to the environment can be directly linked to the presence and distribution of toxic chemical elements in the soil, air, or water, such as chronic exposure to arsenic through contaminated drinking water (Centeno et al. 2002). To demonstrate such links, it is necessary to analyze minerals and geo-environmental toxins to obtain information on the possible origins of such diseases. Because of the ever-growing complexity of geological sources and toxic environmental, biological, and chemical agents, accurate, rapid, and nondestructive techniques for qualitative and quantitative analysis of these materials are essential.
    Essentials of Medical Geology, 01/2013: pages 717-726; , ISBN: 978-94-007-4374-8
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    ABSTRACT: Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.
    Microchemical Journal 11/2012; 105:101-107. DOI:10.1016/j.microc.2012.08.013 · 2.75 Impact Factor
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    ABSTRACT: Isotopic ratios of urinary uranium (U) provide a decisive tool in diagnosing a patient's potential exposure to depleted uranium (DU). This study investigated the measurement of urinary 236U/238U and 235U/238U ratios of ultra trace concentrations using a sector field inductively coupled plasma mass spectrometer (ICP-MS). Uranium was separated from the urinary matrix and pre-concentrated by co-precipitation with calcium and magnesium after addition of ammonium hydroxide. The precipitates were collected, dissolved and analyzed by ICP-MS. 235U/238U and 236U/238U ratios were measured using a desolvating sample introduction system and a sector field ICP-MS. These ratios were accurately measured in samples containing as low as 5 ng L− 1 U. 236U measurement was hindered by abundance sensitivity limitations and uranium hydride (235UH) formation. Measured 235U/238U and 236U/238U ratios were about 7 × 10− 3 and < 5 × 10− 6, respectively, in urine samples from patients not exposed to DU. The 235U/238U ratio was consistently about 2 × 10− 3 in 12 urine samples from patients with embedded fragments of DU, while the corresponding ratio of 236U/238U ranged from 9 × 10− 6 to 33 × 10− 6. This wide range in 236U/238U ratios might suggest different sources of depleted uranium in those DU-urine samples. It is proposed that 235U/238U and 236U/238U ratios are 7 × 10− 3 and < 5 × 10− 6, respectively, in urine samples from individuals not exposed to DU, and 2 × 10− 3 and > 7 × 10− 6, respectively, in urine samples from DU-exposed individuals.
    Microchemical Journal 11/2012; 105:94–100. DOI:10.1016/j.microc.2012.07.004 · 2.75 Impact Factor
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    ABSTRACT: In this study we report uranium analysis for human semen samples. Uranium quantification was performed by inductively coupled plasma mass spectrometry. No additives, such as chymotrypsin or bovine serum albumin, were used for semen liquefaction, as they showed significant uranium content. For method validation we spiked 2g aliquots of pooled control semen at three different levels of uranium: low at 5pg/g, medium at 50pg/g, and high at 1000pg/g. The detection limit was determined to be 0.8pg/g uranium in human semen. The data reproduced within 1.4-7% RSD and spike recoveries were 97-100%. The uranium level of the unspiked, pooled control semen was 2.9pg/g of semen (n=10). In addition six semen samples from a cohort of Veterans exposed to depleted uranium (DU) in the 1991 Gulf War were analyzed with no knowledge of their exposure history. Uranium levels in the Veterans' semen samples ranged from undetectable (<0.8pg/g) to 3350pg/g. This wide concentration range for uranium in semen is consistent with known differences in current DU body burdens in these individuals, some of whom have retained embedded DU fragments.
    Journal of Trace Elements in Medicine and Biology 08/2012; 27(1). DOI:10.1016/j.jtemb.2012.07.004 · 2.37 Impact Factor
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    ABSTRACT: This chapter contains sections titled: SummaryIntroductionBiological MarkersMethodology for Trace Metal Ion Analysis in Clinical, Forensic, and Chemical PathologyCase Studies of Relevance to Research and Diagnosis on Clinical Chemistry, Forensic Toxicology, and Chemical PathologyDisclaimerReferences
    Analytical Techniques for Clinical Chemistry, 06/2012: pages 139-156; , ISBN: 9780470445273
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    ABSTRACT: Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect. In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5weeks gestational age. Copper histidine (900μg per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17μg/dL prior to treatment to 45μg/dL, and ceruloplasmin levels from 39mg/L to 122mg/L. After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5weeks and daily copper histidine therapy (250μg sc b.i.d.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5months of age. The patient's ATP7A mutation (Q724H), which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Western blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances.
    Molecular Genetics and Metabolism 05/2012; 107(1-2):222-8. DOI:10.1016/j.ymgme.2012.05.008 · 2.63 Impact Factor
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    ABSTRACT: To ensure that all veterans with retained embedded fragments are properly monitored for potential health effects of embedded materials. Urine biomonitoring and health surveillance programs were developed to gather information about health risks associated with chemicals released from embedded fragments. Elevated systemic exposure to depleted uranium (DU) that continues to occur in veterans with DU fragments remains a concern, although no clinically significant DU-related health effects have been observed to date. Other metals and local tissue reactions to embedded fragments are also of concern. Knowledge gained from these programs will help to develop guidelines for surgical removal of tissue-embedded fragments.
    Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 04/2012; 54(6):724-32. DOI:10.1097/JOM.0b013e31824fe138 · 1.63 Impact Factor
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    ABSTRACT: Respiratory symptoms are frequently reported in personnel deployed to the Middle East. This project characterized the respiratory toxicity of inhaled Iraqi sand (IS). Adult rats underwent a 6-wk inhalation to air or mainstream cigarette smoke (MSCS) (3 h/d, 5 d/wk) that included exposure to IS or crystalline silica (1 mg/m(3), 19 h/d, 7 d/wk) or air during the last 2 weeks. Assessments included motor activity, whole-body plethysmography, cytological and biochemical analysis of bronchoalveolar lavage fluid, lung metal burden, nasal and lung pathology, and changes in lung protein and gene expression. A number of metals including nickel, manganese, vanadium, and chromium were detected in IS. Elevated lung parenchyma aluminum, silica, barium, manganese, and vanadium concentrations were seen in IS-exposed rats, suggesting that several metals present in IS are bioavailable. Rats exposed to IS only developed mild inflammation in the anterior nose and lung. Silica inhalation was associated with some pulmonary responses that were not seen in IS-exposed rats, such as mild laryngeal and tracheal inflammation, mild tracheal epithelial hyperplasia, and elevated lung silica concentrations. MSCS inhalation with or without co-exposure to either IS or silica resulted in changes consistent with pulmonary inflammation and stress response. Rats exposed to MSCS and silica had more widespread airway lesions when compared with rats exposed to MSCS only. Silica-exposed rats had more robust pulmonary gene expression and proteomic responses than that seen in IS-exposed rat. Our studies show that the respiratory toxicity of IS is qualitatively similar to or less than that seen following short-term silica exposure.
    Inhalation Toxicology 01/2012; 24(2):109-24. DOI:10.3109/08958378.2011.647413 · 2.26 Impact Factor
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    ABSTRACT: Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous copper injections) is not entirely effective in the majority of affected individuals. The mottled-brindled (mo-br) mouse recapitulates the Menkes phenotype, including abnormal copper transport to the brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age. We documented that mo-br mice on C57BL/6 background were not rescued by peripheral copper administration, and used this model to evaluate brain-directed therapies. Neonatal mo-br mice received lateral ventricle injections of either adeno-associated virus serotype 5 (AAV5) harboring a reduced-size human ATP7A (rsATP7A) complementary DNA (cDNA), copper chloride, or both. AAV5-rsATP7A showed selective transduction of choroid plexus epithelia and AAV5-rsATP7A plus copper combination treatment rescued mo-br mice; 86% survived to weaning (21 days), median survival increased to 43 days, 37% lived beyond 100 days, and 22% survived to the study end point (300 days). This synergistic treatment effect correlated with increased brain copper levels, enhanced activity of dopamine-β-hydroxylase, a copper-dependent enzyme, and correction of brain pathology. Our findings provide the first definitive evidence that gene therapy may have clinical utility in the treatment of Menkes disease.
    Molecular Therapy 08/2011; 19(12):2114-23. DOI:10.1038/mt.2011.143 · 6.23 Impact Factor
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    ABSTRACT: There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome. We obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case-control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se. Patients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 µg/g vs. 111 µg/g; P = 0.04) and 21% lower zinc (279 µg/g vs. 346 µg/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 µg/g vs. 0.439 µg/g; 4% higher) and selenium (1.68 µg/g vs. 1.58 µg/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively). There is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated.
    The Prostate 08/2011; 71(11):1231-8. DOI:10.1002/pros.21339 · 3.57 Impact Factor

Publication Stats

987 Citations
126.92 Total Impact Points


  • 2014
    • Wright-Patterson Air Force Base
      Dayton, Ohio, United States
  • 1994-2011
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan
  • 2007
    • University of Texas at Dallas
      Richardson, Texas, United States
    • German Historical Institute, Washington DC
      Washington, Washington, D.C., United States
    • Chang Gung University
      Hsin-chu-hsien, Taiwan, Taiwan
  • 1999
    • Haverford College
      • Department of Chemistry
      Norristown, PA, United States
  • 1990
    • Michigan State University
      • Department of Chemistry
      Ист-Лансинг, Michigan, United States