Steven H Hinrichs

The Nebraska Medical Center, Omaha, Nebraska, United States

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Publications (170)857.87 Total impact

  • American Journal of Clinical Pathology 01/2015; 143(1):4-5. · 2.88 Impact Factor
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    ABSTRACT: Tularemia in the United States was examined by reviewing 106 Francisella tularensis isolates, mostly from Nebraska, collected during 1998-2012: 48% of Nebraska cases were cat-associated; 7/8 human cases were caused by subtype A.I. A vaccine is needed to reduce feline-associated tularemia, and cat owners should protect against bites/scratches and limit their pet's outdoor access.
    Emerging infectious diseases. 12/2014; 20(12).
  • Marilynn A Larson, Oksana Lockridge, Steven H Hinrichs
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    ABSTRACT: Human butyrylcholinesterase (BChE) protects against the toxicity of organophosphorus nerve agents and pesticides. BChE purified from human plasma is limited and pathogen carry-over is a concern. Unlike the native BChE tetrameric complex with a residence time of days, recombinant BChE (rBChE) is produced predominantly as dimers and monomers that are cleared from the circulation within minutes. Assembly into tetramers requires incorporation of proline-rich peptides, a process that was thought to occur intracellularly. Our goal was to determine whether polyproline added to rBChE under cell-free conditions would promote tetramerization. Secreted rBChE was purified by procainamide affinity chromatography, and synthetic polyprolines (8-mer to 300-mer) were tested to determine their effect on tetramer assembly. These studies demonstrated that 90-98% of purified rBChE (65 µM) could be assembled into tetramers when incubated with synthetic 17-mer or 50-mer polyproline peptides (100 µM) for 1.5 h at 25˚C. However, rBChE tetramerization was inefficient with smaller 8-mer polyproline peptides and larger 300-mer polyproline proteins. Collectively, these studies demonstrated that the eukaryotic cellular machinery is not required for assembly of active BChE into tetramers and that this process can occur in vitro with purified rBChE in the presence of peptides containing 15 to 50 consecutive proline residues.
    The Biochemical journal. 06/2014;
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    ABSTRACT: This research investigated the use of SNOMED CT to represent diagnostic tissue morphologies and notable tissue architectures typically found within a pathologist's microscopic examination report to identify gaps in expressivity of SNOMED CT for use in anatomic pathology. 24 breast biopsy cases were reviewed by two board certified surgical pathologists who independently described the diagnostically important tissue architectures and diagnostic morphologies observed by microscopic examination. In addition, diagnostic comments and details were extracted from the original diagnostic pathology report. 95 unique clinical statements were extracted from 13 malignant and 11 benign breast needle biopsy cases. 75% of the inventoried diagnostic terms and statements could be represented by valid SNOMED CT expressions. The expressions included one pre-coordinated expression and 73 post-coordinated expressions. No valid SNOMED CT expressions could be identified or developed to unambiguously assert the meaning of 21 statements (ie, 25% of inventoried clinical statements). Evaluation of the findings indicated that SNOMED CT lacked sufficient definitional expressions or the SNOMED CT concept model prohibited use of certain defined concepts needed to describe the numerous, diagnostically important tissue architectures and morphologic changes found within a surgical pathology microscopic examination. Because information gathered during microscopic histopathology examination provides the basis of pathology diagnoses, additional concept definitions for tissue morphometries and modifications to the SNOMED CT concept model are needed and suggested to represent detailed histopathologic findings in computable fashion for purposes of patient information exchange and research. UNMC Institutional Review Board ID# 342-11-EP.
    Journal of the American Medical Informatics Association 05/2014; · 3.57 Impact Factor
  • Laboratory medicine. 01/2014; 45(4):e146-51.
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    ABSTRACT: This study investigated the diagnostic accuracy of whole slide imaging (WSI) in breast needle biopsy diagnosis in comparison with standard light microscopy (LM). The study examined the effects of image capture magnification and computer monitor quality on diagnostic concordance of WSI and LM. Four pathologists rendered diagnoses using WSI to examine 85 breast biopsies (92 parts; 786 slides) consisting of benign and malignant cases. Each WSI case was evaluated using images captured at either 20x or 40x magnifications and viewed using a DICOM grade, color-calibrated monitor or a standard, desktop LCD monitor. For each combination, the WSI result was compared to the original, LM diagnosis. The overall concordance rate observed between WSI and LM was 97.1% (95% CI:94.3%-98.5%). After a washout period, all cases were reviewed a second time by each pathologist after using LM, and the second LM diagnosis was compared to the WSI diagnosis rendered by the same pathologist. Intraobserver concordance between WSI and LM was 95.4% (95% CI:92.2%- 97.4%). The second LM diagnoses were also compared to the original LM diagnoses, and the observed interobserver LM concordance rate was 97.3% (95% CI:93.1% -99.0%). The study data demonstrated that breast needle biopsy diagnoses rendered by WSI were equivalent to diagnoses rendered by LM. No diagnostic differences were detected between the underlying viewing system parameters of monitor quality and image capture resolution. The results of this study demonstrated that WSI can be effectively utilized in subspecialty diagnostic cases where a minimum amount of tissue is available.
    Human pathology 01/2014; · 3.03 Impact Factor
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    ABSTRACT: Acute respiratory infections are a significant concern throughout the world, contributing to 4.25 million deaths annually. One such pathogen, H5N1 avian influenza, has the potential to become the next pandemic threat. While currently not transmitted human-to-human, recent cases of H5N1 have been shown to result in a 60% fatality rate and an increasing resistance to antiviral treatments. However, because of the rapid mutation rate of RNA viruses like influenza, it is likely that human-to-human transmission is imminent, motivating the need for efficacious vaccines against pandemic influenzas. Polyanhydride nanovaccines have been shown to be a versatile platform for the delivery of subunit vaccines. Nanoparticles composed of sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy) hexane (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), and their copolymers have been shown to sustain the release of encapsulated proteins while enhancing internalization by antigen presenting cells. Polyanhydride nanovaccines have also been shown to have immunomodulatory capabilities inducing both high avidity antibody titers as well as cell-mediated immune responses. Previously, we have demonstrated that polyanhydride nanoparticles are capable of stably releasing recombinant H5 hemagglutinin, an antigen for H5N1 influenza. In this work, we characterized the in vivo immune responses generated by polyanhydride-based subunit nanovaccines. Polyanhydride nanovaccine formulations encapsulating rH5 were found to elicit high antigen-specific antibody titers as well as virus-neutralizing antibody titers. Likewise, enhanced T cell memory responses were observed at 63 days post immunization. Finally, the efficacy of a nanovaccine formulation was evaluated using a live viral challenge. All these studies together indicate that polyanhydride nanovaccines offer a patient-friendly and efficacious platform for next generation influenza A vaccines.
    13 AIChE Annual Meeting; 11/2013
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    ABSTRACT: PURPOSE: A comprehensive strategy was developed and validated for the identification of pathogens from closely-related near neighbors using both chromosomal and protein biomarkers, with emphasis on distinguishing Yersinia pestis from the ancestral bacterium Yersinia pseudotuberculosis. EXPERIMENTAL DESIGN: Computational analysis was used to discover chromosomal targets unique to Y. pestis. Locus identifier YPO1670 was selected for further validation and PCR was used to confirm that this biomarker was exclusively present in Y. pestis strains, while absent in other Yersinia species. RT-PCR and western blot analyses were utilized to evaluate YPO1670 expression and multiple-reaction monitoring mass spectrometry (MRM MS) was performed to identify the YPO1670 protein within cell lysates. RESULTS: The described study validated that YPO1670 was exclusive to Y. pestis. PCR confirmed the locus to be unique to Y. pestis. The associated transcript and protein were produced throughout growth with the highest abundance occurring in stationary phase and MRM MS conclusively identified the YPO1670 protein in cell extracts. CONCLUSIONS AND CLINICAL RELEVANCE: These findings validated YPO1670 as a reliable candidate biomarker for Y. pestis and that a dual DNA and protein targeting approach is feasible for the development of next generation assays to accurately differentiate pathogens from near neighbors.
    PROTEOMICS - CLINICAL APPLICATIONS 02/2013; · 1.81 Impact Factor
  • Steven H Hinrichs, Patina Zarcone
    Public Health Reports 01/2013; 128(Suppl 2):7-9. · 1.42 Impact Factor
  • Walter S Campbell, Kirk W Foster, Steven H Hinrichs
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    ABSTRACT: The ability to transfer image markup and annotation data from one scanned image of a slide to a newly acquired image of the same slide within a single vendor platform was investigated. The goal was to study the ability to use image markup and annotation data files as a mechanism to capture and retain pathologist knowledge without retaining the entire whole slide image (WSI) file. Accepted mathematical principles were investigated as a method to overcome variations in scans of the same glass slide and to accurately associate image markup and annotation data across different WSI of the same glass slide. Trilateration was used to link fixed points within the image and slide to the placement of markups and annotations of the image in a metadata file. Variation in markup and annotation placement between WSI of the same glass slide was reduced from over 80 μ to less than 4 μ in the x-axis and from 17 μ to 6 μ in the y-axis (P < 0.025). This methodology allows for the creation of a highly reproducible image library of histopathology images and interpretations for educational and research use.
    Journal of pathology informatics. 01/2013; 4:2.
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    ABSTRACT: We describe the transfer of bla(KPC-4) from Enterobacter cloacae to Serratia marcescens in a single patient. DNA sequencing revealed that bla(KPC-4) was encoded on an Inc L/M plasmid pNE1280 highly related to pCTX-M360. Further analysis found that bla(KPC-4) was encoded within a novel Tn4401 element (Tn4401f) containing a truncated tnpA and lacking tnpR, ISKpn7 left and Tn4401 IRL-1 that are conserved in other Tn4401 transposons. This study highlights the continued evolution of Tn4401 transposons and movement to multiple plasmid backbones that results in acquisition by multiple species of gram-negative bacilli.
    Antimicrobial Agents and Chemotherapy 10/2012; · 4.57 Impact Factor
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    Scott A Koepsell, Steven H Hinrichs, Peter C Iwen
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    ABSTRACT: A real-time PCR assay to detect Histoplasma capsulatum in formalin-fixed, paraffin-embedded (FFPE) tissue is described. The assay had an analytical sensitivity of 6 pg/μl of fungal DNA, analytical specificity of 100%, and clinical sensitivity of 88.9%. This proof-of-concept study may aid in the diagnosis of histoplasmosis from FFPE tissue.
    Journal of clinical microbiology 08/2012; 50(10):3395-7. · 4.16 Impact Factor
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    ABSTRACT: The aim of this study was to demonstrate a prototype tool for measuring infectivity of an aerosolized human pathogen - influenza A/PR/8/34 (H1N1) virus - using a small-animal model in the Controlled Aerosol Test System (CATS). Intranasal inoculation of nonadapted H1N1 virus into C57BL, BALB/c and CD-1 mice caused infection in all three species. Respiratory exposure of CD-1 mice to the aerosolized virus at graduated doses was accomplished in a modified rodent exposure apparatus. Weight change was recorded for 7 days postexposure, and viral populations in lung tissue homogenates were measured post mortem by DNA amplification (qRT-PCR), direct fluorescence and microscopic evaluation of cytopathic effect. Plots of weight change and of PCR cycle threshold vs delivered dose were linear to threshold doses of ~40 TCID(50) and ~12 TCID(50) , respectively. MID(50) for inspired H1N1 aerosols in CD-1 mice is between 12 and 40 TCID(50) ; proportionality to dose of weight loss and viral populations makes the CD-1 mouse a useful model for measuring infectivity by inhalation. In the CATS, this mouse-virus model provides the first quantitative method to evaluate the ability of respiratory protective technologies to attenuate the infectivity of an inspired pathogenic aerosol.
    Journal of Applied Microbiology 07/2012; 113(4):767-78. · 2.20 Impact Factor
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    ABSTRACT: We investigated the use of whole-genome mapping and pulsed-field gel electrophoresis (PFGE) with isolates from an outbreak of Salmonella enterica serotype Saintpaul. PFGE and whole-genome mapping were concordant with 22 of 23 isolates. Whole-genome mapping is a viable alternative tool for the epidemiological analysis of Salmonella food-borne disease investigations.
    Journal of clinical microbiology 06/2012; 50(9):3063-5. · 4.16 Impact Factor
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    ABSTRACT: The use of high-resolution digital images of histopathology slides as a routine diagnostic tool for surgical pathology was investigated. The study purpose was to determine the diagnostic concordance between pathologic interpretations using whole-slide imaging and standard light microscopy. Two hundred fifty-one consecutive surgical pathology cases (312 parts, 1085 slides) from a single pathology service were included in the study after cases had been signed out and reports generated. A broad array of diagnostic challenges and tissue sources were represented, including 52 neoplastic cases. All cases were digitized at ×20 and presented to 2 pathologists for diagnosis using whole-slide imaging as the sole diagnostic tool. Diagnoses rendered by the whole-slide imaging pathologists were compared with the original light microscopy diagnoses. Overall concordance between whole-slide imaging and light microscopy as determined by a third pathologist and jury panel was 96.5% (95% confidence interval, 94.8%-98.3%). Concordance between whole-slide imaging pathologists was 97.7% (95% confidence interval, 94.7%-99.2%). Five cases were discordant between the whole-slide imaging diagnosis and the original light microscopy diagnosis, of which 2 were clinically significant. Discordance resulted from interpretive criteria or diagnostic error. The whole-slide imaging modality did not contribute to diagnostic differences. Problems encountered by the whole-slide imaging pathologists primarily involved the inability to clearly visualize nuclear detail or microscopic organisms. Technical difficulties associated with image scanning required at least 1 slide be rescanned in 13% of the cases. Technical and operational issues associated with whole-slide imaging scanning devices used in this study were found to be the most significant obstacle to the use of whole-slide imaging in general surgical pathology.
    Human pathology 05/2012; 43(10):1739-44. · 3.03 Impact Factor
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    ABSTRACT: Staphylococcus aureus is a major human pathogen that is capable of producing an expansive repertoire of cell surface-associated and extracellular virulence factors. Herein we describe an S. aureus regulatory RNA, SSR42, which modulates the expression of approximately 80 mRNA species, including several virulence factors, in S. aureus strains UAMS-1 and USA300 (LAC) during stationary-phase growth. Mutagenesis studies revealed that SSR42 codes for an 891-nucleotide RNA molecule and that the molecule's regulatory effects are mediated by the full-length transcript. Western blotting and functional assays indicated that the regulatory effects of SSR42 correlate with biologically significant changes in corresponding protein abundances. Further, in S. aureus strain LAC, SSR42 is required for wild-type levels of erythrocyte lysis, resistance to human polymorphonuclear leukocyte killing, and pathogenesis in a murine model of skin and soft tissue infection. Taken together, our results indicate that SSR42 is a novel S. aureus regulatory RNA molecule that contributes to the organism's ability to cause disease.
    Journal of bacteriology 04/2012; 194(11):2924-38. · 3.94 Impact Factor
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    ABSTRACT: This study evaluated the filtration performance of four commercially available models of National Institute of Occupational Safety and Health (NIOSH)-certified filtering facepiece respirators (FFR) against both biological and inert aerosols at a flow rate of 85 L/min. Conventional N95 and P100 FFRs and two antimicrobial (AM)-treated FFRs (an N95 and a P95, both with iodine-based AM treatments) were tested for both physical penetration (PEN(P)) and viable penetration (PEN(V)) with three different bioaerosols, including MS2 bacteriophage virus, and the spores and vegetative cells of Bacillus atrophaeus bacteria, in addition to inert sodium chloride (NaCl) aerosol. For each FFR model, the PEN(P) measured with NaCl was predictive of its MS2 PEN(P), and it was observed that spores and bacteria aerosols were also filtered similarly to the inert aerosol. For both conventional FFRs, up to a 1-log reduction in PEN(V) in comparison with PEN(P) was observed and attributed to the experimental variability of the test system. For both models of AM-FFRs, no statistically significant differences between PEN(V) and PEN(P) for any of the three different bioaerosol challenges were observed. Thus, no bioaerosol filtration enhancement over the conventional FFRs was detected for either iodine-based AM-FFR. In the absence of any standardized test methods, we recommend that future studies evaluating the filtration performance of AM-treated FFRs incorporate the experimental best practices described herein.
    Journal of Occupational and Environmental Hygiene 02/2012; 9(2):69-80. · 1.28 Impact Factor
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    ABSTRACT: Acinetobacter baumannii has emerged as a bacterial pathogen of considerable healthcare concern. Yet, little is known about the organism's basic biological processes and the regulatory networks that modulate expression of its virulence factors and antibiotic resistance. Using Affymetrix GeneChips , we comprehensively defined and compared the transcriptomes of two A. baumannii strains, ATCC 17978 and 98-37-09, during exponential and stationary phase growth in Luria-Bertani (LB) medium. Results revealed that in addition to expected growth phase-associated metabolic changes, several putative virulence factors were dramatically regulated in a growth phase-dependent manner. Because a common feature between the two most severe types of A. baumannii infection, pneumonia and septicemia, includes the organism's dissemination to visceral organs via the circulatory system, microarray studies were expanded to define the expression properties of A. baumannii during growth in human serum. Growth in serum significantly upregulated iron acquisition systems, genes associated with epithelial cell adherence and DNA uptake, as well as numerous putative drug efflux pumps. Antibiotic susceptibility testing verified that the organism exhibits increased antibiotic tolerance when cultured in human serum, as compared to LB medium. Collectively, these studies provide researchers with a comprehensive database of A. baumannii's expression properties in LB medium and serum and identify biological processes that may contribute to the organism's virulence and antibiotic resistance.
    FEMS Immunology & Medical Microbiology 12/2011; 64(3):403-12. · 2.68 Impact Factor
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    ABSTRACT: Filtering facepiece respirators (FFRs) are recommended for use as precautions against airborne pathogenic microorganisms; however, during pandemics demand for FFRs may far exceed availability. Reuse of FFRs following decontamination has been proposed but few reported studies have addressed the feasibility. Concerns regarding biocidal efficacy, respirator performance post decontamination, decontamination cost, and user safety have impeded adoption of reuse measures. This study examined the effectiveness of three energetic decontamination methods [ultraviolet germicidal irradiation (UVGI), microwave-generated steam, and moist heat] on two National Institute for Occupational Safety and Health-certified N95 FFRs (3M models 1860s and 1870) contaminated with H5N1. An aerosol settling chamber was used to apply virus-laden droplets to FFRs in a method designed to simulate respiratory deposition of droplets onto surfaces. When FFRs were examined post decontamination by viral culture, all three decontamination methods were effective, reducing virus load by > 4 log median tissue culture infective dose. Analysis of treated FFRs using a quantitative molecular amplification assay (quantitative real-time polymerase chain reaction) indicated that UVGI decontamination resulted in lower levels of detectable viral RNA than the other two methods. Filter performance was evaluated before and after decontamination using a 1% NaCl aerosol. As all FFRs displayed <5% penetration by 300-nm particles, no profound reduction in filtration performance was caused in the FFRs tested by exposure to virus and subsequent decontamination by the methods used. These findings indicate that, when properly implemented, these methods effectively decontaminate H5N1 on the two FFR models tested and do not drastically affect their filtering function; however, other considerations may influence decisions to reuse FFRs.
    Annals of Occupational Hygiene 08/2011; 56(1):92-101. · 2.16 Impact Factor
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    ABSTRACT: Tularemia is a potentially fatal disease that is caused by the highly infectious and zoonotic pathogen Francisella tularensis. Despite the monomorphic nature of sequenced F. tularensis genomes, there is a significant degree of plasticity in the organization of genetic elements. The observed variability in these genomes is due primarily to the transposition of direct repeats and insertion sequence (IS) elements. Since current methods used to genotype F. tularensis are time-consuming and require extensive laboratory resources, IS elements were investigated as a means to subtype this organism. The unique spatial location of specific IS elements provided the basis for the development of a differential IS amplification (DISA) assay to detect and distinguish the more virulent F. tularensis subsp. tularensis (subtypes A.I and A.II) and subsp. holarctica (type B) strains from F. tularensis subsp. novicida and other near neighbors, including Francisella philomiragia and Francisella-like endosymbionts found in ticks. Amplicon sizes and sequences derived from DISA showed heterogeneity within members of the subtype A.I and A.II isolates but not the type B strains. These differences were due to a 312-bp fragment derived from the IS element ISFtu1. Analysis of wild-type F. tularensis isolates by DISA correlated with pulsed-field gel electrophoresis genotyping utilizing two different restriction endonucleases and provided rapid results with minimal sample processing. The applicability of this molecular typing assay for environmental studies was demonstrated by the accurate identification and differentiation of tick-borne F. tularensis. The described approach to IS targeting and amplification provides new capability for epidemiological investigations and characterizations of tularemia source outbreaks.
    Journal of clinical microbiology 05/2011; 49(8):2786-97. · 4.16 Impact Factor

Publication Stats

4k Citations
857.87 Total Impact Points

Institutions

  • 2009–2014
    • The Nebraska Medical Center
      Omaha, Nebraska, United States
  • 1991–2014
    • University of Nebraska Medical Center
      • Department of Pathology and Microbiology
      Omaha, Nebraska, United States
  • 1996–2013
    • University of Nebraska at Omaha
      • • Department of Pathology and Microbiology
      • • Department of Computer Science
      • • Department of Internal Medicine
      Omaha, Nebraska, United States
  • 2006–2011
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan
  • 2007–2010
    • University of Nebraska at Lincoln
      • • Department of Electrical Engineering
      • • Department of Computer and Electronics Engineering
      • • Department of Chemistry
      Lincoln, NE, United States
  • 2007–2009
    • University of Nottingham
      • School of Chemistry
      Nottingham, ENG, United Kingdom
  • 1999
    • University of Virginia
      Charlottesville, Virginia, United States
  • 1988–1992
    • National Cancer Institute (USA)
      • Laboratory of Molecular Biology
      Maryland, United States