Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
Records 1-10 (of 10 Records) |
Query Trace: Shim YK [original query] |
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Serum microRNA profiles among dioxin exposed veterans with monoclonal gammopathy of undetermined significance
Wang W , Shim YK , Michalek JE , Barber E , Saleh LM , Choi BY , Wang CP , Ketchum N , Costello R , Marti GE , Vogt RF , Landgren O , Calvo KR . J Toxicol Environ Health A 2020 83 (7) 1-10 Previously an increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), was reported among Vietnam veterans exposed to Agent Orange and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dysregulated expression of certain microRNAs (miRNAs) was demonstrated in MGUS and MM. Given the important role of miRNAs in cellular homeostasis, the aim of this study was to determine if there was an association between serum levels of selected miRNAs and TCDD in 47 MGUS cases identified in our previous investigation using serum specimens and exposure data archived by the Air Force Health Study (AFHS). A total of 13 miRNA levels (let-7a, let-7i, miR-16, miR-20a, miR-21, miR-34a, miR-106b, miR-146a, miR-181a, miR-192, miR-205, miR-335, and miR-361) was measured in serum stored during the 2002 AFHS follow-up and the relationship to lipid-adjusted serum TCDD levels in 1987 was determined. miR-34a showed the strongest relationship with TCDD; after age-adjustment, this positive association was more pronounced. In contrast, the other 12 miRNAs displayed absolute values of age adjusted coefficient estimates below 1.16 and non-significant p-values. The observed strong positive association between high body burdens of TCDD and miR-34a, a tumor suppressor regulated by p53, in this MGUS population warrants clarification of the TCDD-miR-34a relationship and its role in the pathogenesis of MGUS and risk for MM. |
9/11 residential exposures: the impact of World Trade Center dust on respiratory outcomes of lower Manhattan residents
Antao VC , Pallos LL , Graham SL , Shim YK , Sapp JH , Lewis B , Bullard S , Alper HE , Cone JE , Farfel MR , Brackbill RM . Int J Environ Res Public Health 2019 16 (5) Thousands of lower Manhattan residents sustained damage to their homes following the collapse of the Twin Towers on 11 September 2001. Respiratory outcomes have been reported in this population. We sought to describe patterns of home damage and cleaning practices in lower Manhattan and their impacts on respiratory outcomes among World Trade Center Health Registry (WTCHR) respondents. Data were derived from WTCHR Wave 1 (W1) (9/2003(-)11/2004) and Wave 2 (W2) (11/2006(-)12/2007) surveys. Outcomes of interest were respiratory symptoms (shortness of breath (SoB), wheezing, persistent chronic cough, upper respiratory symptoms (URS)) first occurring or worsening after 9/11 W1 and still present at W2 and respiratory diseases (asthma and chronic obstructive pulmonary disease (COPD)) first diagnosed after 9/11 W1 and present at W2. We performed descriptive statistics, multivariate logistic regression and geospatial analyses, controlling for demographics and other exposure variables. A total of 6447 residents were included. Mean age on 9/11 was 45.1 years (+/-15.1 years), 42% were male, 45% had ever smoked cigarettes, and 44% reported some or intense dust cloud exposure on 9/11. The presence of debris was associated with chronic cough (adjusted OR (aOR) = 1.56, CI: 1.12(-)2.17), and upper respiratory symptoms (aOR = 1.56, CI: 1.24(-)1.95). A heavy coating of dust was associated with increased shortness of breath (aOR = 1.65, CI: 1.24(-)2.18), wheezing (aOR = 1.43, CI: 1.03(-)1.97), and chronic cough (aOR = 1.59, CI: 1.09(-)2.28). Dusting or sweeping without water was the cleaning behavior associated with the largest number of respiratory outcomes, such as shortness of breath, wheezing, and URS. Lower Manhattan residents who suffered home damage following the 9/11 attacks were more likely to report respiratory symptoms and diseases compared to those who did not report home damage. |
Prevalence and associated demographic characteristics of exposure to multiple metals and their species in human populations: The United States NHANES, 2007-2012
Shim YK , Lewin MD , Ruiz P , Eichner JE , Mumtaz MM . J Toxicol Environ Health A 2017 80 (9) 1-11 Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007-2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011-2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health. |
Agent Orange exposure and monoclonal gammopathy of undetermined significance: an Operation Ranch Hand veteran cohort study
Landgren O , Shim YK , Michalek J , Costello R , Burton D , Ketchum N , Calvo KR , Caporaso N , Raveche E , Middleton D , Marti G , Vogt RF Jr . JAMA Oncol 2015 1 (8) 1061-8 IMPORTANCE: Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans. OBJECTIVE: To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS. EXPOSURES: Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. MAIN OUTCOMES AND MEASURES: Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs. RESULTS: The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P = .007). CONCLUSIONS AND RELEVANCE: Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma. |
Monoclonal B-cell lymphocytosis in healthy blood donors: an unexpectedly common finding.
Shim YK , Rachel JM , Ghia P , Boren J , Abbasi F , Dagklis A , Venable G , Kang J , Degheidy H , Plapp FV , Vogt RF , Menitove JE , Marti GE . Blood 2013 123 (9) 1319-26 Circulating monoclonal B cells may be detected in healthy adults, a condition called monoclonal B-cell lymphocytosis (MBL). MBL has also been identified in donated blood, but no systematic study of blood donors has been reported. Using sensitive and specific laboratory methods, we detected MBL in 149 (7.1%; 95% CI, 6.0%-8.3%) of 2098 unique donors ages 45 years or older in a Midwestern U.S. regional blood center between 2010 and 2011. Most of the 149 donors had low-count MBL, including 99 CLL-like (66.4%), 22 atypical (14.8%), and 19 CD5- (12.8%) immunophenotypes. However, five donors (3.4%) had B-cell clonal counts above 500 cells/microl, including three with 1693-2887 cells/microl; the clone accounted for nearly all their circulating B-cells. Four donors (2.7%) had two distinct MBL clones. Of 51 MBL samples in which IGHV-D-J genotypes could be determined, 71% and 29% used IGHV3- and IGHV4-family genes, respectively. Sequencing revealed 82% with somatic hypermutation, while 18% had greater than 98% germ-line identity, including five with entirely germ-line sequences. In conclusion, MBL prevalence is much higher in blood donors than previously reported and, although uncommon, the presence of high-count MBL warrants further investigations to define the biological fate of the transfused cells in recipients. |
Respiratory protective equipment, mask use, and respiratory outcomes among World Trade Center rescue and recovery workers
Antao VC , Pallos LL , Shim YK , Sapp JH 2nd , Brackbill RM , Cone JE , Stellman SD , Farfel MR . Am J Ind Med 2011 54 (12) 897-905 BACKGROUND: Serious respiratory illnesses have been reported among rescue/recovery workers (RRW) following the World Trade Center (WTC) attacks. METHODS: We studied RRW enrolled in the WTC Health Registry to assess the effects of different respiratory protection equipment (RPE) types on respiratory outcomes, such as recurrent respiratory symptoms and diseases possibly associated with 9/11 exposures. We performed descriptive and multivariate analyses adjusting for demographics and exposure variables. RESULTS: A total of 9,296 RRW met inclusion criteria. The strongest predictors of using adequate RPE were being affiliated with construction, utilities or environmental remediation organizations and having received RPE training. Workers who used respirators were less likely to report adverse respiratory outcomes compared to those who reported no/lower levels of respiratory protection. CONCLUSIONS: Level of respiratory protection was associated with the odds of reporting respiratory symptoms and diseases. Training, selection, fit testing, and consistent use of RPE should be emphasized among emergency responders. Am. J. Ind. Med. (c) 2011 Wiley-Liss, Inc. |
Long-term follow-up of monoclonal B-cell lymphocytosis detected in environmental health studies
Marti GE , Shim YK , Albitar M , Middleton D , Abbasi F , Anderson A , Vogt RF . Cytometry B Clin Cytom 2010 78 Suppl 1 S83-90 BACKGROUND: Four individuals in whom Monoclonal B cell Lymphocytosis (MBL) had been previously detected were evaluated for the fourth time after 15-18 years since initial testing. All four were environmental health study participants without hematologic malignancies who had elevated absolute B cell counts at initial testing. METHODS: The current laboratory evaluation included complete blood counts, lymphocyte immunophenotypes, immunoglobulin heavy-chain variable (IGHV) gene mutation status, and serum tests for monoclonal immunoglobulins and free light chains. Results from this evaluation were compared with those from the three previous evaluations. Clinical status was assessed by reviewing medical records. RESULTS: B-cell clones with phenotypic characteristics of the original MBL clone were detected in three of the four individuals. Since the last evaluation in 2003, one participant who had a clinical diagnosis of Waldenstrom's Macroglobulinemia had developed a diffuse large cell lymphoma and was treated. Another participant continued to show a decline in lymphocyte and B cell counts, reaching clinical lymphocytopenia and B cell lymphopenia. The MBL clone was still detectable. The remaining two participants had stable blood counts and MBL phenotypes. Neither had been diagnosed with a hematologic malignancy. However, molecular analysis revealed clonal changes in both: one showed a marked decline in the percentage of somatically-mutated B cells, and the other showed a clonal transition from IGHV3-13 to IGHV4-34. CONCLUSIONS: A diversity of clonal evolution was observed in these MBL cases. These observations suggest that long-term follow-up studies using standardized MBL subcategories are essential to understanding B-cell pathobiology and optimizing clinical management. |
Commentary: Comparison of current flow cytometry methods for monoclonal B cell lymphocytosis detection
Nieto WG , Almeida J , Teodosio C , Abbasi F , Allgood SD , Connors F , Rachel JM , Ghia P , Lanasa MC , Rawstron AC , Orfao A , Caporaso NE , Hanson CA , Shim YK , Vogt RF , Marti GE . Cytometry B Clin Cytom 2010 78 Suppl 1 S4-9 Monoclonal B cell lymphocytosis (MBL) is now recognized as the B-lymphocyte analogue of a monoclonal gammopathy of unknown significance. MBL can be the precursor of chronic lymphocytic leukemia or associated with non-Hodgkin's lymphoma. It may be associated with an autoimmune abnormality or be related to aging (immunosenescence). The combination of available new fluorochrome-conjugated monoclonal antibody reagents, multilaser instrumentation, and improved software tools have led to a new level of multicolor analysis of MBL. Presently, several centers, including the University of Salamanca (Spain), Duke University (Durham, NC), Mayo Clinic (Rochester, MN), and the National Cancer Institute (Bethesda, MD) in conjunction with the Genetics and Epidemiology of Familial chronic lymphocytic leukemia Consortium, the Food and Drug Administration (Bethesda, MD), and the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (Atlanta, GA) in collaboration with Saint Luke's Hospital (Kansas City, MO), the Universita Vita-Salute San Raffaele in Milan (Italy), and Leeds Teaching Hospital (UK) are all actively conducting studies on MBL. This commentary is an updated summary of the current methods used in these centers. It is important to note the diversity of use in reagents, instruments, and methods of analysis. Despite this diversity, there is a consensus in what constitutes the diagnosis of MBL and its subtypes. There is also an emerging consensus on what the next investigative steps should be. |
Prevalence of monoclonal B-cell lymphocytosis: a systematic review
Shim YK , Middleton DC , Caporaso NE , Rachel JM , Landgren O , Abbasi F , Raveche ES , Rawstron AC , Orfao A , Marti GE , Vogt RF . Cytometry B Clin Cytom 2010 78 Suppl 1 S10-8 BACKGROUND: Individuals with monoclonal B-cell lymphocytosis (MBL) have been identified in clinic outpatients, in unaffected relatives of patients with chronic lymphocytic leukemia (CLL), and in general populations. MBL and its relationship with CLL have been actively investigated over the last decade. This report systematically reviews the prevalence of MBL in the context of the populations studied and the evolution of laboratory methods used to define MBL. METHODS: To identify published studies that have assessed the prevalence of MBL, we systematically searched the MEDLINE databases and consulted with members of the International MBL Study Group. We reviewed the 10 articles that were identified by this process. We abstracted information on study populations, laboratory tests, criteria for designating MBL, and the reported frequencies. RESULTS: Three of the ten studies were published in 2009, three between 2007 and 2008, and four between 2002 and 2004. Reported prevalences varied widely, ranging from 0.12 to 18.2%. This variability was clearly associated with both the laboratory methods and the populations studied. MBL was more common among older individuals and kindred of persons with CLL. The most common MBL subtype was CLL-like MBL. CONCLUSIONS: Large population-based studies of MBL that employ standardized laboratory methods with a consensus case definition are needed to assess prevalence and establish risk factors. These studies should include prospective follow-up of MBL cases to determine the relationship between MBL and CLL. Data from original studies should be reported in sufficient detail to allow future synthesis of information from multiple studies, such as meta-analysis. |
Evolution of a precursor
Caporaso NE , Marti GE , Vogt Jr RF , Shim YK , Middleton D , Landgren O . Cytometry B Clin Cytom 2010 78 (1) 1-3 Many investigators had previously noted collections of CLL-like cells in various clinical settings and reported their observations with colorful descriptors (1) but their precise clinical, population, and phenotypic characteristics were poorly understood. A unifying nomenclature was lacking before 2005 when a group of international investigators forged the terminology and definition of Monoclonal B-Cell Lymphocytosis or “MBL” and consolidated the observations available at that time (2). | As is often the case in science, this permitted rapid progress. Today an increasing number of reports document a steadily expanding understanding. The following are now well-appreciated: | MBL is more common in the elderly and in high-risk B cell malignancy (CLL) kindreds; | MBL precedes virtually all cases of CLL (3); | MBL has strong parallels with MGUS and myeloma as a B-cell precursor (4); | “Low count MBL” with a normal absolute B-cell count has limited potential to progress to CLL (5); |
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