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- Type:
- Dataset
- Description/Abstract:
- ABSTRACT Purpose: Tongue manometry (i.e. tongue pressure measurement) is a commonly used assessment for patients with suspected oral-motor involvement in swallowing disorders. Availability of lingual manometry has changed in recent years, with the introduction of the TongueometerTM device being a more affordable tongue manometry system. The purpose of this study was to test concurrent (criterion) validity of the TongueometerTM compared to the current standard reference device, the Iowa Oral Performance Instrument, IOPI®. Method: Adults without dysphagia were recruited for participation in this study. Standard lingual measurements (swallowing-related pressures, maximum isometric pressure (MIP), and maximum isometric endurance) were recorded, with the bulb anteriorly placed, with both devices, in a randomized order. The Bland-Altman method was used to determine concurrent (criterion) validity of these measurements compared to the clinical standard IOPI® device. A recently available suggested corrective value by Curtis and colleagues (2023) was also applied, with comparisons made between devices both with and without the Curtis correction. Results: The final sample included 70 adult participants aged 20-89 years (average age 52.3 years). Measures with the TongueometerTM device were significantly lower when compared with the same measures taken using the IOPI® (p<0.01) for all measures including MIP, endurance, and swallow pressures. The correction suggested by Curtis and colleagues did not ameliorate these differences. Conclusions: The TongueometerTM lingual measurements were consistently lower compared to the IOPI®. Clinical use of values taken with the TongueometerTM device should be compared to normative data published for each specific device. Available features of each device (e.g. display, bulb texture, technology/application) should be considered when selecting which device to use with an individual patient.
- Creator/Author:
- Krekeler, Brittany
- Submitter:
- Brittany Krekeler
- Date Uploaded:
- 01/26/2024
- Date Modified:
- 01/26/2024
- Date Created:
- 2020-01-01
- License:
- Open Data Commons Public Domain Dedication and License (PDDL)
- Type:
- Dataset
- Description/Abstract:
- Retrospective chart review project of subjects receiving lumbar epidural steroid injections for low back pain associated with degenerative disc disease. The primary objective was to compare the efficacy of two different steroids used during the time period studied, methylprednisolone and triamcinolone.
- Creator/Author:
- Strong, Judith
- Submitter:
- Judith Strong
- Date Uploaded:
- 08/24/2023
- Date Modified:
- 08/15/2024
- Date Created:
- 2023-08
- License:
- Open Data Commons Public Domain Dedication and License (PDDL)
- Type:
- Dataset
- Description/Abstract:
- Data from qualitative study "Employing Strategies to Address Implicit Racial Bias in the Home Visit Setting" Includes: written reflections by FM residents, resident focus group data, commitments-to-change, and 3-month follow up survey data
- Creator/Author:
- Goroncy, Anna
- Submitter:
- Anna Goroncy
- Date Uploaded:
- 03/03/2023
- Date Modified:
- 03/03/2023
- Date Created:
- 2020-01
- License:
- Open Data Commons Attribution License (ODC-By)
- Type:
- Document
- Description/Abstract:
- This is a preprint of a to be submitted paper that demonstrates that: (1) many important food allergens (eggs, milk, peanuts, tree nuts) induce the unfolded protein response (UPR) in intestinal epithelial cells; (2) induction of the UPR, in turn, stimulates the expression of pro-Th2 cytokines (IL-25, IL-33, TSLP) that are required for the induction of food allergy by these cytokines; (3) egg allergy is suppressed in mouse models by the UPR inhibitor, metformin (a drug widely used to treat diabetes mellitus); and (4) metformin appears to have a protective effects in humans who have alpha-gal syndrome, which is a form of food allergy.
- Creator/Author:
- Finkelman, Fred
- Submitter:
- Fred Finkelman
- Date Uploaded:
- 06/02/2020
- Date Modified:
- 06/02/2020
- Date Created:
- 2020-06-02
- License:
- Open Data Commons Attribution License (ODC-By)
- Type:
- Document
- Description/Abstract:
- This presentation represents Panelists 3 and 4 as a joint presentation and This talk was the third panelist in the Health Equities and Disparities Session for the 4th Annual UC Data Day Conference hosted by UC Libraries. Joint Talk with Dr. Pickle and Stef Murwsky – Title: Developing Best Practices to Address LGBTQ and Health Disparities Sarah Pickle, MD (she/her/hers), Associate Professor, University of Cincinnati Department of Family and Community Medicine. Dr. Pickle and her colleagues are studying best practices for training future generations of health care professionals in transgender medicine. University of Cincinnati College of Medicine is one of the only US Medical Schools to have a nationally published, dedicated transgender medicine curriculum. Stef Murawsky, MA, WGSS, Ph.D. Candidate, Sociology Pronouns: they/them/theirs University of Cincinnati Department of Sociology I am currently completing a qualitative dissertation that explores transgender patient experiences of navigating and managing a stigmatized gender identity in biomedical contexts. I plan to generate a critical analysis of stigma in healthcare that demonstrates how structural, interpersonal and individual level transgender healthcare experiences are gendered and racialized.
- Creator/Author:
- Murawsky, Stef and Pickel, Sara
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 04/12/2019
- Date Modified:
- 04/12/2019
- Date Created:
- 2019-04-01
- License:
- Attribution-NonCommercial 4.0 International
- Type:
- Document
- Description/Abstract:
- This talk was the second panelist in the Health Equities and Disparities Session for the 4th Annual UC Data Day Conference hosted by UC Libraries. Tammy Mentzel, MPH, Assistant Director for Programs and Projects, University of Cincinnati, Academic Health Center, Cincinnati Cancer Center Talk Title(s): Understanding Health Disparities and Perceptions of Discrimination in Greater Cincinnati Tammy served as the Program Director for the Transformation of Mission-based Health Care through Diversity, Equity, and Inclusion project aimed at bolstering diversity in the health care workforce and eliminating health disparities in urban communities by identifying, testing and adopting evidence-based strategies and tools. Tammy was formerly in the College of Nursing at UC where she was a Research Associate and Program Director providing leadership and support on six funded research projects totaling over $4.6 million.
- Creator/Author:
- Mentzel, Tammy
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 04/12/2019
- Date Modified:
- 04/12/2019
- Date Created:
- 2019-04-01
- License:
- Attribution-NonCommercial 4.0 International
- Type:
- Dataset
- Description/Abstract:
- ABSTRACT Helicobacter pylori (H. pylori) is the major risk factor for the development of gastric cancer. Our laboratory has reported that the Sonic Hedgehog (Shh) signaling pathway is an early response to infection that is fundamental to the initiation of H. pylori-induced gastritis. H. pylori also induces programmed death ligand 1 (PD-L1) expression on gastric epithelial cells, yet the mechanism is unknown. We hypothesize that H. pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Shh signaling pathway during infection. To identify the role of Shh signaling as a mediator of H. pylori-induced PD-L1 expression, human gastric organoids generated from either induced pluripotent stem cells (HGOs) or tissue (huFGOs) were microinjected with bacteria and treated with Hedgehog/Gli inhibitor GANT61. Gastric epithelial monolayers generated from the huFGOs were also infected with H. pylori and treated with GANT61 to study the role of Hedgehog signaling as a mediator of induced PD-1 expression. A patient-derived organoid/autologous immune cell co-culture system infected with H. pylori and treated with PD-1 inhibitor (PD-1Inh) was developed to study the protective mechanism of PD-L1 in response to bacterial infection. H. pylori significantly increased PD-L1 expression in organoid cultures 48 hours post-infection when compared to uninfected controls. The mechanism was cytotoxic associated gene A (CagA) dependent. This response was blocked by pretreatment with GANT61. Anti-PD-L1 treatment of H. pylori infected huFGOs, co-cultured with autologous patient cytotoxic T lymphocytes and dendritic cells, induced organoid death. H. pylori-induced PD-L1 expression is mediated by the Shh signaling pathway within the gastric epithelium. Cells infected with H. pylori that express PD-L1 may be protected from the immune response, creating premalignant lesions progressing to gastric cancer.
- Creator/Author:
- Zavros, Yana
- Submitter:
- Yana Zavros
- Date Uploaded:
- 12/21/2018
- Date Modified:
- 12/21/2018
- Date Created:
- License:
- All rights reserved
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-12 to 2012-01-28 at the East Liverpool Water Treatment Plant, in East Liverpool, Ohio (40.639501 , -80.523561). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - EastLiverpool_WaterTreatmentPlant_Raw.csv . Aggregated monthly averages of the raw data - EastLiverpool_WaterTreatmentPlant_Processed.csv. How the raw data are processed into monthly averages - Marietta_EastLiverpool_WaterTreatmentPlant_WorkingFile.xlsx. How the video is generated- EastLiverpool_WaterTreatmentPlant.ppt. Video - EastLiverpool_WaterTreatmentPlant- generated from EastLiverpool_WaterTreatmentPlant.ppt.
- Creator/Author:
- Yao, Zhiyuan; Hilbert, Tim, and Haynes, Erin
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/27/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-01 to 2018-04
- License:
- CC0 1.0 Universal
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-12 to 2012-01-28 at the East Liverpool East Elementary School, in East Liverpool, Ohio (40.635093 , -80.545558). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese. The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - EastLiverpoolEastElementarySchool_Raw.csv . Aggregated monthly averages of the raw data - EastLiverpoolEastElementarySchool_Processed.csv. How the raw data are processed into monthly averages - Marietta_EastLiverpoolEastElementarySchool_WorkingFile.xlsx. How the video is generated- EastLiverpoolEastElementarySchool.ppt. Video - EastLiverpoolEastElementarySchool- generated from EastLiverpoolEastElementarySchool.ppt.
- Creator/Author:
- Yao, Zhiyuan; Hilbert, Tim, and Haynes, Erin
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/27/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-08-12 to 2012-01-28
- License:
- CC0 1.0 Universal
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-17 to 2012-02-25 at the Ohio Valley Educational Service Center in Marietta, Ohio (39.443477 , -81.452199). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - Marietta_OhioValleyEducationalServiceCenter_Raw.csv . Aggregated monthly averages of the raw data - Marietta_OhioValleyEducationalServiceCenter_Processed.csv. How the raw data are processed into monthly averages - Marietta_OhioValleyEducationalServiceCenter_WorkingFile.xlsx. How the video is generated- Marietta_OhioValleyEducationalServiceCenter.ppt. Video - Marietta_OhioValleyEducationalServiceCenter - generated from Marietta_OhioValleyEducationalServiceCenter.ppt.
- Creator/Author:
- Yao, Zhiyuan; Hilbert, Tim, and Haynes, Erin
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/27/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-08-17 to 2012-02-25
- License:
- CC0 1.0 Universal
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-17 to 2012-02-25 at the Warren Elementary School in Marietta, Ohio (39.393536, -81.554015). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese. The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - Marietta_WarrenElementraySchool_Raw.csv . Aggregated monthly averages of the raw data - Marietta_WarrenElementraySchool_Processed.csv. How the raw data are processed into monthly averages - Marietta_WarrenElementraySchool_WorkingFile.xlsx. How the video is generated- Marietta_WarrenElementraySchool.ppt. Video - Marietta_WarrenElementraySchool.mp4 - generated from Marietta_WarrenElementraySchool.ppt.
- Creator/Author:
- Erin Hayes; Zhiyuan Yao, and Tim Hilbert
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/26/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-08-17 to 2012-02-25
- License:
- CC0 1.0 Universal
- Type:
- Image
- Description/Abstract:
- The Retrosplenial Cortex (RSC) has a persistent role in the establishment of spatial and contextual memory, with also the connections between visuo-spatial association cortices. The RSC’s ability to form afferent and efferent connections with the Parahippocampal areas of the brain allow it to be another prime location in the brains of both rodents and humans where multiple cues are linked together in memory formation, storage and retrieval of Long Term Memories. Due to the high nature of memory formation and retrieval, the RSC has become a section of the brain that in recent years has been more heavily focused on for the research of Alzheimer’s and Dementia. The RSC has not been examined fully in previous studies with examination of the expression of the apolipoprotein E (APOE) gene along with other genetic and regulatory factors. There are 3 major alleles of the APOE gene (APOE2, APOE3, and APOE4), with APOE4 having the greatest risk for AD. In this research, I identify the relative connection between DEK the proto-oncogene and APOE3 and APOE4 in a rodent model, looking specifically at the RSC and how it affects spatial memory with an induced model of chronic stress.
- Creator/Author:
- Solomon, Matia B.; Balmer, Nikolaus J.; Selmanovic, Din; Nguyen, Elizabeth T., and Ghisays, Valentina
- Submitter:
- Din Selmanovic
- Date Uploaded:
- 06/27/2018
- Date Modified:
- 06/27/2018
- Date Created:
- 2018-04-13
- License:
- Public Domain Mark 1.0
- Type:
- Student Work
- Description/Abstract:
- Summary: The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of possible sarcoidosis patients. Biopsy confirmed sarcoidosis patients seen during a seven-month time period at the University of Cincinnati Sarcoidosis clinic were prospectively identified. Non-sarcoidosis patients seen at the same clinic were used as controls. Using a modified WASOG organ assessment instrument, we scored all patients for presence of biopsy, one or more highly probable symptom, and one or more at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy).The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 biopsy confirmed sarcoidosis, 150 controls) to establish cut-off values for SDS biopsy and SDS clinical and a validation cohort of 380 patients (103 biopsy confirmed sarcoidosis patients and 277 controls). The best cutoff value for SDS biopsy was > 6 (sensitivity =99.3%; specificity=100%). For the total the 980 patients, an SDS clinical > 3 had a sensitivity of 94.2%, specificity of 88.8%, and a likelihood ratio of 7.9. An SDS clinical score > 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%). For sarcoidosis, the presence of specific clinical features, especially multi-organ involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis. Awards/Publications: Published in CHEST Journal 2018 Oral presentation at the 2018 American Thoracic Society Conference
- Creator/Author:
- Lower, Elyse E., M.D.; Baughman, Robert P., M.D., and Bickett, Alexandra
- Submitter:
- Alexandra Bickett
- Date Uploaded:
- 05/24/2018
- Date Modified:
- 05/24/2018
- Date Created:
- 2018-04-15
- License:
- Attribution-ShareAlike 4.0 International
14. ELISA_QC
- Type:
- Student Work
- Description/Abstract:
- This program is meant to batch process ELISA standard curve data to generate Levey-Jennings control charts and report values that fall outisde of 2 and 3 standard deviations of the mean. The Instruction Manual contains a detailed guide on usage.
- Creator/Author:
- Wetzel, Hanna
- Submitter:
- Hanna Wetzel
- Date Uploaded:
- 04/21/2017
- Date Modified:
- 04/21/2017
- License:
- All rights reserved
- Type:
- Dataset
- Description/Abstract:
- Scanning electron microscopy (SEM) images of the surfaces of porcine and human clots, at 800x, 3500x, and 7000x magnification.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 04/11/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Article
- Description/Abstract:
- Background: Acid -glucosidase is trafficked to the lysosome by LIMP-2. Results: A unique 11-amino acid sequence on acid -glucosidase was critical for its LIMP-2-dependent targeting to the lysosome. Conclusion: This sequence is essential for oligosaccharide-independent targeting of synthesized acid -glucosidase to the lysosome. Significance: Modification of this sequence has basic/therapeutic implications for Gaucher disease and its comorbidities (e.g. Parkinson disease).
- Creator/Author:
- Grabowski, Gregory A.; Haffey, Wendy D.; Greis, Kenneth D., and Llou, Benjamin
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2014-09
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS-proteins for detecting activity of LN over time. Using surface-enhanced or matrix assisted laser desorption/ ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalintype prostaglandin-D synthetase (L-PGDS), albumin and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African-American) and 30 controls with juvenile idiopathic arthritis. All urinary PS-proteins were significantly higher with active versus inactive LN or in patients without LN (all p<0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 months before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001) and L-PGDS (p < 0.01) occurred, indicating that these PS-proteins are biomarkers of LN activity and may help anticipate the future course of LN. Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune disease and lupus nephritis (LN) is one of the main determinants of poor prognosis (1). Currently, LN is gauged by measuring circulating and excreted indicators of renal dysfunction, with supporting information from kidney biopsies. The latter constitute the current standard for diagnosing LN, providing a direct assessment of the presence, severity and activity of LN, and the degree of renal damage (2). Due to the invasive nature of kidney biopsies, clinicians base LN activity and its therapy on the results of urinary protein excretion, urinary sediment, creatinine clearance and serum albumin. These traditional markers are not accurate in assessing whether active LN is present or not, and none of them is predictive, i.e. can anticipate the course of LN. Using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF MS) technology, we previously identified a LN urinary protein signature (PS), consisting of eight candidate biomarkers at the mass-to-charge ratios (m/z) of 2.763, 22, 23, 44, 56, 79, 100, and 133 kDa (3). In this study, we present the identification of the specific proteins contained in this PS of children with LN. We further assayed plasma and urine samples of SLE patients and controls with juvenile idiopathic arthritis (JIA) to investigate the concurrent and predictive validity of the PS-proteins to serve as biomarkers of LN activity.
- Creator/Author:
- Tucker, Lori; Brunner, Hermine I.; Wiers, Kristina; Olson, Judyann; Suzuki, Michiko; Onel, Karen; Ying, Jun; Greis, Kenneth D.; Devarajan, Prasad; Haines, Kathleen; O'Neil, Kathleen M.; Silverman, Earl D.; Klein-Gitelman, Marisa S., and Brooks, Elizabeth B.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2009-02
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- OBJECTIVE: Damage to hair from UV exposure has been well reported in the literature and is known to be a highly complex process involving initiation via absorption of UV light followed by formation and propagation of reactive oxygen species (ROS). The objective of this work was to understand these mechanisms, explain the role of copper in accelerating the formation of ROS and identify strategies to reduce the hair damage caused by these reactive species. METHODS: The location of copper in hair was measured by Transmission electron microscopy–(TEM) X-ray energy dispersive spectroscopy (XEDS) and levels measured by ICP-OES. Protein changes were measured as total protein loss via the Lowry assay, and MALDI ToF was used to identify the biomarker protein fragments. TBARS assay was used to measure lipid peroxide formation. Sensory methods and dry combing friction were used to measure hair damage due to copper and UV exposure and to demonstrate the efficacy of N,N’ ethylenediamine disuccinic acid (EDDS) and histidine chelants to reduce this damage. RESULTS: In this work, a biomarker protein fragment formed during UV exposure is identified using mass spectrometry. This fragment originates from the calcium-binding protein S100A3. Also shown is the accelerated formation of this peptide fragment in hair containing low levels of copper absorbed from hair during washing with tap water containing copper ions. Transmission electron microscopy (TEM) X-ray energy dispersive spectroscopy (XEDS) studies indicate copper is located in the sulphur-poor endo-cuticle region, a region where the S100A3 protein is concentrated. A mechanism for formation of this peptide fragment is proposed in addition to the possible role of lipids in UV oxidation. A shampoo and conditioner containing chelants (EDDS in shampoo and histidine in conditioner) is shown to reduce copper uptake from tap water and reduce protein loss and formation of S100A3 protein fragment. In addition, the long-term consequences of UV oxidation and additional damage induced by copper are illustrated in a fourmonth wear study where hair was treated with a consumer relevant protocol of hair colouring treatments, UV exposure and regular shampoo and conditioning. CONCLUSIONS: The role of copper in accelerating UV damage to hair has been demonstrated as well as the ability of chelants such as EDDS and histidine in shampoo and conditioner products to reduce this damage.
- Creator/Author:
- McComb, D. W.; Marsh, J. M.; Sun, Y.; Chaudhary, T.; Flagler, M. J.; Coderch, L.; Mamak, M.; Greis, Kenneth D.; Rubio, L.; Williams, R. E. A., and Davis, M. G.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2015-04
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- In the pharmaceutical industry, there is a tremendous need for qualitative and quantitative analysis of target analytes such as peptides, proteins, drugs, metabolites, biomarkers, impurities, and degradation products in various mixtures including synthetic reactions, in vitro cultures, biological fluids, drug substances, finished products, and many others. To provide adequate specificity for analysis in these complex mixtures, multidimensional analytical techniques are required. Mass spectrometry plays a central role in many of these multidimensional approaches to mixture analysis because it provides an unparalleled combination of sensitivity and specificity that is useful for both molecular identification and quantitative applications. Recent innovations in mass spectrometry and industrial implementation of these advances have transformed many aspects of pharmaceutical research and development. Data that were previously unattainable, or were not collected due to exorbitant cost or time constraints, can now be obtained using mass spectrometry-based technologies. The impact of these innovations has been most dramatically felt in early stages of discovery, as more data are available to make critical decisions, such as selecting compounds for advancement to costly preclinical and clinical trials. New MS technologies have also accelerated the progression of drug candidates through development and toward regulatory approval. Here, five major categories of pharmaceutical applications of mass spectrometry are reviewed. They are new chemical entity characterization, biomacromolecule characterization, bioanalytical quantitation, metabolite identification, and impurity and degradation product identification. A brief historical perspective and evolution of technologies for each application area are presented. Those discussions are followed with a description of the current strategies for implementation of the tremendous capabilities of the state-of-the-art approaches, along with representative applications. In addition, emerging technologies for each application area are presented to indicate the future directions of instrumentation for mixture analysis in the pharmaceutical industry. (Int J Mass Spectrom 212 (2001) 135–196) © 2001 Elsevier Science B.V.
- Creator/Author:
- Harbol, Kevin L.; Greis, Kenneth D.; Hoke, Steven H.; Morand, Kenneth L.; Baker, Timothy R., and Dobson, Roy L. M.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2001-11
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequencebased search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms.
- Creator/Author:
- Andes, David R.; Lu, Jason Long; Tan, Queenie K., G.; Hostetter, Margaret K.; Greis, Kenneth D.; Zhang, Minlu; Orsborn, Kris I.; Porollo, Alexey, and Green, Julianne V.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2013-07
- License:
- All rights reserved
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