Try a new search

Format these results:

Searched for:

person:pollah01

Total Results:

83


STAT3 Gain-of-Function Mutations Underlie Deficiency in Human Nonclassical CD16+ Monocytes and CD141+ Dendritic Cells

Korenfeld, Daniel; Roussak, Kate; Dinkel, Sabrina; Vogel, Tiphanie P; Pollack, Henry; Levy, Joseph; Leiding, Jennifer W; Milner, Joshua; Cooper, Megan; Klechevsky, Eynav
Genetic analysis of human inborn errors of immunity has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. The STAT family of transcription factors orchestrate hematopoietic cell differentiation. Patients with de novo activating mutations of STAT3 present with multiorgan autoimmunity, lymphoproliferation, and recurrent infections. We conducted a detailed characterization of the blood monocyte and dendritic cell (DC) subsets in patients with gain-of-function (GOF) mutations across the gene. We found a selective deficiency in circulating nonclassical CD16+ and intermediate CD16+CD14+ monocytes and a significant increase in the percentage of classical CD14+ monocytes. This suggests a role for STAT3 in the transition of classical CD14+ monocytes into the CD16+ nonclassical subset. Developmentally, ex vivo-isolated STAT3GOF CD14+ monocytes fail to differentiate into CD1a+ monocyte-derived DCs. Moreover, patients with STAT3GOF mutations display reduced circulating CD34+ hematopoietic progenitors and frequency of myeloid DCs. Specifically, we observed a reduction in the CD141+ DC population, with no difference in the frequencies of CD1c+ and plasmacytoid DCs. CD34+ hematopoietic progenitor cells from patients were found to differentiate into CD1c+ DCs, but failed to differentiate into CD141+ DCs indicating an intrinsic role for STAT3 in this process. STAT3GOF-differentiated DCs produced lower amounts of CCL22 than healthy DCs, which could further explain some of the patient pathological phenotypes. Thus, our findings provide evidence that, in humans, STAT3 serves to regulate development and differentiation of nonclassical CD16+ monocytes and a subset of myeloid DCs.
PMCID:8578438
PMID: 34654687
ISSN: 1550-6606
CID: 5063132

Toxocara species environmental contamination of public spaces in New York City

Tyungu, Donna L; McCormick, David; Lau, Carla Lee; Chang, Michael; Murphy, James R; Hotez, Peter J; Mejia, Rojelio; Pollack, Henry
Human toxocariasis has been identified as an under-diagnosed parasitic zoonosis and health disparity of significant public health importance in the United States due to its high seropositivity among socioeconomically disadvantaged groups, and possible links to cognitive and developmental delays. Through microscopy and quantitative PCR, we detected that Toxocara eggs are widespread in New York City public spaces, with evidence of significant levels of contamination in all five boroughs. The Bronx had the highest contamination rate (66.7%), while Manhattan had the lowest contamination rate (29.6%). Moreover, infective eggs were only found in the Bronx playgrounds, with over 70% of eggs recovered in embryonic form and the highest egg burden (p = 0.0365). All other boroughs had eggs in the pre-infectious, unembronyated form. Toxocara cati, the cat roundworm, was the predominant species. These results suggest that feral or untreated cats in New York City represent a significant source of environmental contamination. These findings indicate that human toxocariasis has emerged as an important health disparity in New York City, with ongoing risk of acquiring Toxocara infection in public spaces, especially in poorer neighborhoods. There is a need for reducing environmental Toxocara contamination. Additional rigorous public health interventions should explore further approaches to interrupt transmission to humans.
PMID: 32369482
ISSN: 1935-2735
CID: 4437112

Hepatitis B Screening & Vaccination Behaviors in a Community-based Sample of Chinese & Korean Americans in New York City

Li, Shijian; Sim, Shao-Chee; Lee, Linda; Pollack, Henry J; Wyatt, Laura C; Trinh-Shevrin, Chau; Pong, Perry; Kwon, Simona C
OBJECTIVES: As Asian Americans are dis- proportionately affected by the hepatitis B virus (HBV), we explored predictors of HBV screening and vaccination among Chinese and Korean Americans. METHODS: We used cross-sectional data from a com- munity-based sample of Chinese Americans (N = 502) and Korean Americans (N = 487) residing in the metropolitan New York City area during 2008-2009. Logistic regression models were stratified by Asian-American subgroup and sex to predict HBV screening (for the entire sam- ple) and HBV vaccination (among those not HBV positive). RESULTS: Overall, screening rates were high (71.3% among Chinese and 70.1% among Koreans). The majority of respondents were aware of HBV; however, knowledge about HBV transmission was low. In logistic regression, a physician recommendation was consistently associated with HBV screening and vaccination outcomes across all groups; having heard of HBV was significantly associated with screening and vaccination among Chinese males and screening among Korean males and females. Screening and vaccination barriers were reported among all groups, and included lack of knowledge and feeling well/having no health issues. CONCLUSIONS: Targeted efforts in these at-risk communities are necessary to improve HBV knowledge, address misinformation about HBV, and eliminate provider-, patient-, and resource-related barriers to HBV screening and vaccination.
PMCID:5472990
PMID: 28452698
ISSN: 1945-7359
CID: 2646952

Epidemiology of resistance to metronidazole in clinical isolates of bacteroides fragilis in a New York City Hospital [Meeting Abstract]

Vuppula, S; Lee, C; Pollack, H
Background. Bacteroides fragilis is an important cause of clinical infection. Recently, there have been increasing reports of resistance to metronidazole (MTZ), the antibiotic of choice. We reviewed the microbiologic and clinical epidemiology of B. fragilis to determine trends in resistance to MTZ at our institution. Methods. Retrospective review of B. fragilis isolates from the NYU Langone Medical Center Clinical Microbiology Laboratory from 2010 to 2015. Sensitivity was performed by E-test using the CLSI breakpoints. MIC50, MIC90 and GM were calculated for each year and compared by ANOVA using SPSS 13. Results. There were 574 positive cultures of B. fragilis, of which 402 non-duplicate isolates were analyzed. The majority of cultures were from patients 50 years of age and above. Three hundred eighty-eight (96.5%) isolates were sensitive, 13 (3%) were resistant and 1 showed intermediate sensitivity to MTZ. MTZ-resistant isolates were found in all age groups. The overall distribution of MICs differed significantly by year ( p < 0.000). A trend towards increasing resistance and a gradual increase in MIC and GM over time was seen (table). Isolates recovered from blood were more likely to be resistant to MTZ than those recovered from other sites of infection, 6.4% versus 2%, 42% of the resistant strains were resistant to clindamycin, 92% to penicillin, 8% to amoxicillin-clavulanic acid. All strains were sensitive to carbapenems. Conclusion. Over the last 5 years there has been a gradual increase in MIC to MTZ in B. fragilis isolates and increased frequency of high-level resistance. The rates of resistance at our institution were higher than those previously reported from Europe and North America. Further understanding of the mechanism of B. fragilis MTZ resistance and the factors that are associated with the development of MTZ resistance are critical to reversing this trend and preventing further spread of this problem, as well as providing improved antibiotic stewardship guidance. (Table Presented)
EMBASE:627784490
ISSN: 2328-8957
CID: 3902392

Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures

Oh, Djin-Ye; Dowling, David J; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T; Sauld, John F; Pettengill, Matthew; Kho, Alvin T; Pollack, Henry J; Steen, Hanno; Levy, Ofer
Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which approximately 30 - 40% were common to all treatment conditions and approximately 5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles, paralleling responses to adjuvant-containing vaccines in vivo Age-specific in vitro modeling coupled with proteomics may provide fresh insight into the ontogeny of adjuvant action thereby informing targeted adjuvanted vaccine development for distinct age groups.
PMCID:5083103
PMID: 26933193
ISSN: 1535-9484
CID: 2124482

Sources of Health Information Among Select Asian American Immigrant Groups in New York City

Islam, Nadia S; Patel, Shilpa; Wyatt, Laura C; Sim, Shao-Chee; Mukherjee-Ratnam, Runi; Chun, Kay; Desai, Bhairavi; Tandon, S Darius; Trinh-Shevrin, Chau; Pollack, Henry; Kwon, Simona C
Health information can potentially mitigate adverse health outcomes among ethnic minority populations, but little research has examined how minorities access health information. The aim of this study was to examine variations in the use of health information sources among Asian American (AA) subgroups and to identify differences in characteristics associated with the use of these sources. We analyzed data from a foreign-born community sample of 219 Asian Indians, 216 Bangladeshis, 484 Chinese, and 464 Koreans living in New York City. Results found that use of health information sources varied by AA subgroup. Print media source use, which included newspapers, magazines, and/or journals, was highest among Chinese (84%), Koreans (75%), and Bangladeshis (80%), while radio was most utilized by Chinese (48%) and Koreans (38%). Television utilization was highest among Bangladeshis (74%) and Koreans (64%). Koreans (52%) and Chinese (40%) were most likely to use the Internet to access health information. Radio use was best explained by older age and longer time lived in the United States, while print media were more utilized by older individuals. Results also highlighted differences in native-language versus non-native-language media sources for health information by subgroup. Media sources can be used as a vehicle to disseminate health information among AAs.
PMCID:4628554
PMID: 26266574
ISSN: 1532-7027
CID: 1721762

Chronic Hepatitis B and Liver Cancer Risks among Asian Immigrants in New York City: Results from a Large, Community-Based Screening, Evaluation, and Treatment Program [Editorial]

Pollack, Henry J; Kwon, Simona C; Wang, Su H; Wyatt, Laura C; Trinh-Shevrin, Chau
BACKGROUND: Hepatitis B virus (HBV) infection, the predominant cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects Asian Americans. Limited data exist on the variability and characteristics of infection that determine disease progression risk within U.S. Asian ethnic subgroups. METHODS: Retrospective analyses were conducted on a large, community-based HBV screening and treatment program in New York City (NYC). From 2004 to 2008, the program enrolled 7,272 Asian-born individuals. Determinants of HBV seroprevalence were calculated and risk factors for HCC progression were compared across Asian subgroups. RESULTS: Among newly tested individuals, 13% were HBV positive. Seroprevalence varied significantly with age, gender, education, birthplace, and family history of infection. Chinese-born individuals, particularly from the Fujian province, had the highest seroprevalence (23.2% and 33.1%, respectively). Clinical and virologic characteristics placed HBV-infected individuals at significant risk for HCC. Significant differences in HCC risk existed among Asian subgroups in bivariate analysis, including age, gender, HBV viral load, and HBeAg status. Differences in HBV genotype and family history of HCC may further HCC risk among subgroups. CONCLUSIONS: Asian immigrants in NYC have a high prevalence of HBV infection and are at significant risk of disease progression and HCC. Although heterogeneity in HBV seroprevalence was found by Asian subgroups, HCC risk among infected individuals was primarily explained by age and gender differences. Country and province of birth, age, and gender may further explain seroprevalence differences. IMPACT: Findings provide estimates of HBV burden in Asian ethnic subgroups and identify high-risk groups to target for screening and treatment that can prevent HCC. See all the articles in this CEBP Focus section, "Cancer in Asian and Pacific Islander Populations." Cancer Epidemiol Biomarkers Prev; 23(11); 2229-39. (c)2014 AACR.
PMCID:4373070
PMID: 25368398
ISSN: 1055-9965
CID: 1342002

Identification of a candidate serotonergic receptor in entamoeba invadens [Meeting Abstract]

Ramachandran, V; Pollack, H; Eichinger, D
Entamoeba histolytica, the etiologic agent of amebiasis, is one of the leading causes of parasitic disease, especially in resource limited countries and regions with poor sanitation. The life cycle of Entamoeba alternates between a feeding trophozoite and dormant cyst stage, the latter of which is passed from host to host, therein transmitting infection. The mechanism by which the parasite encysts, or transforms from the trophozoite to cyst form, is not well understood. Previous research has suggested the involvement of classical adrenergic, serotonergic, and histaminergic signaling pathways via G-protein coupled receptors (GPCR) and a cyclic AMP cascade. Agonists of these respective pathways were found to stimulate encystment while antagonists prevented encystment. The object of this study is to verify the presence of a potential serotonergic receptor and understand its role in the process of encystment when bound to serotonin-like agonists. Using the related species E. invadens as a model, the likely genomic sequence coding for the GPCR has been identified based on sequence alignment with known eukaryotic GPCRs. The gene has been PCR amplified and cloned into a pET102/D-TOPO E. coli vector for bacterial expression and in vitro transcription/translation system expression. Expression of the protein in each system has been verified by western blotting. We will now use radiolabeled serotonin-like ligands to confirm the GPCR-ligand relationship, screen libraries of small molecules for novel antagonists, and determine the structure of the ligand binding site for future design of amoeba-specific inhibitors
EMBASE:71312717
ISSN: 0002-9637
CID: 818802

Hepatitis B testing and access to care among racial and ethnic minorities in selected communities across the United States, 2009-2010

Hu, Dale J; Xing, Jian; Tohme, Rania A; Liao, Youlian; Pollack, Henry; Ward, John W; Holmberg, Scott D
Hepatitis B virus (HBV) infection is widely prevalent among racial and ethnic minorities in the United States; however, few data have been available regarding HBV testing and referral to care for these populations. Using survey data collected in 2009-2010 from the Racial and Ethnic Approaches to Community Health (REACH) across the U.S., we assessed rates and determinants of hepatitis B testing and access to care in 28 minority communities in the U.S. Of 53,896 respondents, 21,129 (39.2%) reported having been tested for hepatitis B. Of the 1,235 who reported testing positive, 411 (33.3%) reported currently receiving specialty care. After controlling for demographic and socioeconomic characteristics, the likelihood of having been tested for hepatitis B and receiving care if infected was higher among males, non-English speaking persons, and those having health insurance compared to their counterparts. Compared to college graduates, respondents without a college education were less likely to get tested for hepatitis B. Conclusion: These data indicate that more than half of racial/ethnic minority persons in these communities had not been tested for hepatitis B, and only about one-half of those who tested positive had ever received treatment. More state and federal efforts are needed to screen racial/ethnic minorities, especially foreign-born persons, for HBV and link those with infection to care. (Hepatology 2013;53:856-862).
PMID: 23359276
ISSN: 0270-9139
CID: 550322

Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa-2b plus ribavirin

Kelly, D A; Haber, B; Gonzalez-Peralta, R P; Murray, K F; Jonas, M M; Molleston, J P; Narkewicz, M R; Sinatra, F R; Lang, T; Lachaux, A; Wirth, S; Shelton, M; Te, H S; Pollack, H; Deng, W; Noviello, S; Albrecht, J K
Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.
PMID: 22404724
ISSN: 1352-0504
CID: 165432