Morphological Aspects Of Atrium Development
Research & Experimental Medicine
Linz D; Gilloteaux J J
Clinical Research
1987
1987-09
Journal Article or Conference Abstract Publication
n/a
An Inservice Examination For Internal-medicine Residents
Research & Experimental Medicine
Levy R P; Newcomb J L; Stickley W T
Clinical Research
1987
1987-04
Journal Article or Conference Abstract Publication
n/a
Targeted Extended Cystic Fibrosis Mutation Testing On Known And At-risk Patients And Relatives
blood; cftr mutations; early-diagnosis; experience; Genetics & Heredity; immunoreactive trypsinogen; midlands; newborn; outcomes; Research & Experimental Medicine; vas-deferens; west; wisconsin
This paper reports mathematically derived residual risks of being a carrier or being affected with cystic fibrosis following various screening scenarios to assist in interpreting test results and advising patients. While parental screening with 23 American College of Medical Genetics (ACMG) cystic fibrosis mutations defines the 64% of affected U. S. Caucasian fetuses with two detectable mutations, newborn screening for elevated immunoreactive trypsinogen (IRT) and sweat chloride identifies an additional 36% of affected newborns with zero or one detected mutation. The relatives of these affected newborns with less than two detectable mutations have higher posterior (after) 23 mutation-negative test risks of carrying undetected mutations. These calculations emphasize how knowledge of the mutations in the related affected patient substantially improves upon the quality of after-test advice to patients. Furthermore, negative tests of the partner without a family history and/or more extensive cystic fibrosis transmembrane conductance regulator (CFTR) gene testing also increases the likelihood that a negative report is truly negative. When a newborn patient with zero or one detected CFTR mutation has an inconclusive sweat test result, the sweat test should be repeated before ordering additional often unnecessary CFTR gene sequencing. Given the same composite mutation panel test accuracy, a higher proportion of reported test results would be correct during parental screening than when testing at-risk fetuses or symptomatic newborns. Prenatal and newborn screening would be enhanced substantially by medical professionals offering copies of all positive parental and newborn test reports to the parents to share with their relatives. These principles are likely to be applicable to other genetic diseases as the most common mutation frequencies are reported.
Lebo R V; Omlor G J
Genetic Testing
2007
2007-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1089/gte.2007.0050" target="_blank" rel="noreferrer noopener">10.1089/gte.2007.0050</a>
Variable Penetrance And Expressivity Of The Splice Altering 5t Sequence In The Cystic Fibrosis Gene
cftr gene; congenital bilateral absence; disease; Genetics & Heredity; males; messenger-rna; mutations; polymorphism; repeat; Research & Experimental Medicine; risk; vas-deferens
This manuscript reviews the frequencies, symptoms, testing, and reporting of genotypes with the 5T poly-thymidine tract which reduces splicing efficiency in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene in congenital bilateral absence of the vas deferens (CBAVD) patients and in patients and fetuses with cystic fibrosis-like symptoms. The 5T sequence has not been included in the American College of Medical Genetics (ACMG) CFTR mutation panel recommended for screening pregnant women for an increased fetal risk of cystic fibrosis (CF; MIM 219700) because finding this allele would raise concern for possible CFTR gene-related symptoms in many fetuses, even though only a fraction inheriting 5T and another major CFTR mutation would develop CF-like symptoms. In contrast, 40-80% of the symptomatic patients with CBAVD (MIM 277180) are compound heterozygotes for the 5T sequence. This submission provides template report summaries for CBAVD patient results for the 5T allele when tested along with the 23 most common ACMG mutation panel. If CBAVD patients were also tested with the remaining 16 most common reported mutations in CBAVD, the derived proportion of patients with at least one CFTR mutant allele is predicted to increase from 63% to 97%. Testing for the 5T sequence in symptomatic patients and reflex 5T testing in fetuses found to carry a major CF allele are discussed because finding the 5T sequence in these patients lowers the risk of typical severe symptoms. Additional reflex testing for the number of TG repeats adjacent to a 5T allele further modifies the predicted long-term severity of disease symptoms in patients and fetuses that are compound heterozygotes for a major CF mutation and the 5T sequence. Even though patient advice can be modified currently based upon the adjacent TG-repeat number, the final most accurate risk frequencies with different 5T + TG-repeat alleles are likely to become available only after a larger patient population is completed with multiple well-defined clinical and mutation categories.
Lebo R V; Grody W W
Genetic Testing
2007
2007-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1089/gte.2006.9997" target="_blank" rel="noreferrer noopener">10.1089/gte.2006.9997</a>
Testing And Reporting Acmg Cystic Fibrosis Mutation Panel Results
congenital bilateral absence; Genetics & Heredity; nonpaternity; population; Research & Experimental Medicine; vas-deferens
Testing strategies and summary reports for pregnant patients and symptomatic patients being tested for cystic fibrosis (CF; MIM 219700) were developed based upon calculated after (posterior) test risk tables incorporating patient and family histories, ethnicities, and prior testing status. This manuscript defines the proportion of all mutations detected by the American College of Medical Genetics (ACMG)-recommended 23-mutation cystic fibrosis transmembrane conductance regulator (CFTR) gene core panel when testing all patient categories with severe symptoms, including pregnant couples with no family history as well as CF patients, their partners, and other family members. Reference tables incorporate prior and posterior test risks sufficient to complete > 99% of all tested cases and to report the results according to HIPAA guidelines. These tables were calculated based on the assumption that all patient samples have been collected, labeled, analyzed, and reported correctly, including the patient's reported relationship to a known affected or carrier relative, even though the template letter states that the likelihood is about 99% that each reported result is accurate. Pedigrees and tables with the prior (before; a priori) test risks of patients offered CF screening with a family history of a CF patient and/or a known carrier patient are provided for ready reference with each risk frequency, dependent upon the assumption that the patient's pedigree reflects familial relationships correctly. Comparison of tables emphasizes the value of asking the tested partner to ask a relative known to have CF or who tested positive for a CF mutation to donate a sample as a DNA test control and/or to obtain a copy of a prior molecular test result and/or extracted DNA sample. These tables posterior test risks also indicate that when one partner with no family history tests negative for the 23 mutation panel, no further prenatal testing is indicated.
Lebo R V; Grody W W
Genetic Testing
2007
2007-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1089/gte.2006.9996" target="_blank" rel="noreferrer noopener">10.1089/gte.2006.9996</a>
One Multiplex Control For 29 Cystic Fibrosis Mutations
gene; Genetics & Heredity; Research & Experimental Medicine
A simple approach is described to synthesize and clone an inexhaustible supply of any homozygous and/ or heterozygous controls diluted with yeast genomic DNA to mimic human genome equivalents for use throughout the entire multiplex mutation assay. As a proof of principle, the 25 cystic fibrosis mutation panel selected by the American College of Medical Genetics and four additional mutant sequences were prepared as a single control mixture. The 29 CFTR mutations were incorporated into 17 gene fragments by PCR amplification of targeted sequences using mutagenic primers on normal human genomic DNA template. Flanking primers selected to bind beyond all published PCR primer sites amplified controls for most assay platforms. The 17 synthesized 433-933-bp CFTR fragments each with one to four homozygous mutant sequences were cloned into nine plasmid vectors at the multiple cloning site and bidirectionally sequenced. Miniplasmid preps from these nine clones were mixed and diluted with genomic yeast DNA to mimic the final nucleotide molar ratio of two CFTR genes in 6 x 10(9) bp total human genomic DNA. This mixture was added to control PCR reactions prior to amplification as the only positive control sample. In this fashion <200 multiplex clinical PCR analyses of > 4,000 clinical patient samples have been controlled simultaneously for PCR amplification and substrate specificity for 29 tested mutations without cross contamination. This clinically validated multiplex cystic fibrosis control can be modified readily for different test formats and provides a robust means to control for all mutations instead of rotating human genomic controls each with a fraction of the mutations. This approach allows scores of additional mutation controls from any gene loci to be added to the same mixture annually.
Lebo R V; Bixler M; Galehouse D
Genetic Testing
2007
2007
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1089/gte.2007.9994" target="_blank" rel="noreferrer noopener">10.1089/gte.2007.9994</a>
Tissue Engineering A Model For The Human Ear: Assessment Of Size, Shape, Morphology, And Gene Expression Following Seeding Of Different Chondrocytes
auricular reconstruction; bone sialoprotein; cartilage tissue; Cell Biology; cells; costal cartilage; culture; Dermatology; growth-plate; in-vitro; regeneration; Research & Experimental Medicine; Surgery; transplantation
This study examines the tissue engineering of a human ear model through use of bovine chondrocytes isolated from four different cartilaginous sites (nasoseptal, articular, costal, and auricular) and seeded onto biodegradable poly(l-lactic acid) and poly(l-lactide-epsilon-caprolactone) (50 : 50) polymer ear-shaped scaffolds. After implantation in athymic mice for up to 40 weeks, cell/scaffold constructs were harvested and analyzed in terms of size, shape, histology, and gene expression. Gross morphology revealed that all the tissue-engineered cartilages retained the initial human auricular shape through 40 weeks of implantation. Scaffolds alone lost significant size and shape over the same period. Quantitative reverse transcription-polymerase chain reaction demonstrated that the engineered chondrocyte/scaffolds yielded unique expression patterns for type II collagen, aggrecan, and bone sialoprotein mRNA. Histological analysis showed type II collagen and proteoglycan to be the predominant extracellular matrix components of the various constructs sampled at different implantation times. Elastin was also present but it was found only in constructs seeded with auricular chondrocytes. By 40 weeks of implantation, tissue-engineered cartilage of costal origin became calcified, marked by a notably high relative gene expression level of bone sialoprotein and the presence of rigid, nodular protrusions formed by mineralizing rudimentary cartilaginous growth plates. The collective data suggest that nasoseptal, articular, and auricular cartilages represent harvest sites suitable for development of tissue-engineered human ear models with retention over time of three-dimensional construct architecture, gene expression, and extracellular matrix composition comparable to normal, nonmineralizing cartilages. Calcification of constructs of costal chondrocyte origin clearly shows that chondrocytes from different tissue sources are not identical and retain distinct characteristics and that these specific cells are inappropriate for use in engineering a flexible ear model.
Kusuhara H; Isogai N; Enjo M; Otani H; Ikada Y; Jacquet R; Lowder E; Landis W J
Wound Repair and Regeneration
2009
2009-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1111/j.1524-475X.2008.00451.x" target="_blank" rel="noreferrer noopener">10.1111/j.1524-475X.2008.00451.x</a>
Behavioral Suppression Following 3,4-methylenenedioxymethamphetamine
Pharmacology & Pharmacy; Research & Experimental Medicine
Kulmala H K; Boja J W; Schechter M D
Life Sciences
1987
1987-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0024-3205(87)90618-7" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(87)90618-7</a>
Aging Changes In The Hamster Adrenal Glomerulosa
Research & Experimental Medicine
Kingsley E; Gilloteaux J J
Clinical Research
1987
1987-09
Journal Article or Conference Abstract Publication
n/a
The Ph-dependence Of Herpes-simplex Type-1 Penetration
Research & Experimental Medicine
Killius J G; Hodnichak C M; Rosenthal K S
Clinical Research
1986
1986-10
Journal Article or Conference Abstract Publication
n/a
The Medical Humanities - Introduction
History & Philosophy of Science; Research & Experimental Medicine
Jones T; Wear D
Perspectives in Biology and Medicine
2007
2007
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1353/pbm.2007.0030" target="_blank" rel="noreferrer noopener">10.1353/pbm.2007.0030</a>
Enhancement Of The Antiviral Activity Of Poly R(a-u) By Ametantrone And Mitoxantrone
Pharmacology & Pharmacy; Research & Experimental Medicine
Jamison J M; Krabill K; Flowers D G; Tsai C C
Life Sciences
1990
1990
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0024-3205(90)90134-d" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(90)90134-d</a>
Enhancement Of The Antiviral And Interferon-inducing Activities Of Poly-r(a-u) By Carminic Acid
Pharmacology & Pharmacy; Research & Experimental Medicine
Jamison J M; Flowers D G; Jamison E; Kitareewan S; Krabill K; Rosenthal K S; Tsai C C
Life Sciences
1988
1988
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0024-3205(88)90058-6" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(88)90058-6</a>
Physical-examination In An Ambulatory Care Setting - An Assessment Of Resident Performance
Research & Experimental Medicine
Illera V A; Blend D; Jarjoura D; Cugino A E; Whittier F C
Clinical Research
1988
1988-10
Journal Article or Conference Abstract Publication
n/a
Famotidine Compatibility With 3-in-1 Total Parenteral-nutrition Solutions
Research & Experimental Medicine
Heiselman D E; Malik A M
Clinical Research
1989
1989-04
Journal Article or Conference Abstract Publication
n/a
The Effect Of Intravenous Metoclopramide Upon Enteral Feeding Tube Placement In Intensive-care Patients
Research & Experimental Medicine
Heiselman D E; Hofer T; Vidovich R R
Clinical Research
1994
1994-04
Journal Article or Conference Abstract Publication
n/a
Predicted Vs Measured Energy-expenditure In Critically Ill Mechanically Ventilated Patients
Nutrition & Dietetics; Research & Experimental Medicine
Heiselman D E; Beckner J; Black L; Bredle D L
Clinical Research
1994
1994-10
Journal Article or Conference Abstract Publication
n/a
Acute Cardiovascular-response To A Single Large Intravenous Dose Of Methylprednisolone And Its Effects On The Responses To Norepinephrine And Isoproterenol
Research & Experimental Medicine
Hall E D; Plaster M; Braughler J M
Proceedings of the Society for Experimental Biology and Medicine
1983
1983
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.3181/00379727-173-41653" target="_blank" rel="noreferrer noopener">10.3181/00379727-173-41653</a>
Hepatic Neuregulin 4 Signaling Defines An Endocrine Checkpoint For Steatosis-to-nash Progression
alpha-induced apoptosis; association; brown; fatty liver-disease; Inflammation; mice; necroptosis; necrotic cell-death; nonalcoholic steatohepatitis; pathogenesis; Research & Experimental Medicine
Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury.
Guo L; Zhang P; Chen Z M; Xia H J; Li S M; Zhang Y Q; Kobberup S; Zou W P; Lin J D
Journal of Clinical Investigation
2017
2017-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1172/jci96324" target="_blank" rel="noreferrer noopener">10.1172/jci96324</a>
Ace2 Overexpression Inhibits Hypoxia-induced Collagen Production By Cardiac Fibroblasts
angiotensin-converting enzyme 2 (ACE2); angiotensin-converting enzyme-2; collagen; cross-talk; expression; fibroblast; growth-factor-beta; heart failure; hypoxia; Myocardial infarction; myofibroblast differentiation; oxidative stress; pathways; rat; remodelling; Research & Experimental Medicine; signaling; transforming growth factor beta (TGF beta)
Cardiac remodelling is a key risk factor for the development of heart failure in the chronic phase following myocardial infarction. Our previous studies have shown an anti-remodelling role of ACE2 (angiotensin-converting enzyme 2) in vivo during hypertension and that these protective effects are mediated through increased circulating levels of Ang-(1-7) [angiotensin-(1-7)]. In the present study, we have demonstrated that cardiac myocytes have modest ACE2 activity, whereas cardiac fibroblasts do not: exhibit any endogenous activity. As fibroblasts are the major cell type found in an infarct zone following a myocardial infarction, we examined the effects of ACE2 gene delivery to cultured cardiac fibroblasts after acute hypoxic exposure. Cardiac fibroblasts from 5-day-old Sprague-Dawley rat hearts were grown to confluence and transduced with a lentiviral vector containing murine ACE2 cDNA under transcriptional control by the EFI alpha (elongation factor I alpha) promoter (lenti-ACE2). Transduction of fibroblasts with lenti-ACE2 resulted in a viral dose-dependent increase in ACE2 activity. This was associated with a significant attenuation of both basal and hypoxia/re-oxygenation-induced collagen production by the fibroblasts. Cytokine production, specifically TGF beta (transforming growth factor beta), by these cells was also significantly attenuated by ACE2 expression. Collectively, these results indicate that: (i) endogenous ACE2 activity is observed in cardiac myocytes, but not in cardiac fibroblasts; (ii) ACE2 overexpression in the cardiac fibroblast attenuates collagen production; and (iii) this prevention is probably mediated by decreased expression of cytokines. We conclude that ACE2 expression, limited to cardiac fibroblasts, may represent a novel paradigm for in vivo therapy following acute ischaemia.
Grobe J L; Der Sarkissian S; Stewart J M; Meszaros J G; Raizada M K; Katovich M J
Clinical Science
2007
2007-10
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1042/cs20070160" target="_blank" rel="noreferrer noopener">10.1042/cs20070160</a>
Effectiveness And Safety Of Augmentin In The Management Of Pneumonia Of Infants And Children
Pharmacology & Pharmacy; Research & Experimental Medicine
Gooch W M; Congeni B L; Swenson E; Snellman L W
Current Therapeutic Research-Clinical and Experimental
1985
1905-06
Journal Article or Conference Abstract Publication
n/a
Targeted Liquid Chromatography-mass Spectrometry Analysis Of Serum Acylcarnitines In Acetaminophen Toxicity In Children
-oxidation; acetaminophen; acute liver-failure; acylcarnitine; biomarker; clinical; clofibrate; hepatic; hepatotoxicity; induced; induced hepatic-necrosis; metabolism; metabolomics; mice; multicenter; overdose; protein adducts; Research & Experimental Medicine; toxicity
Aim: Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose (overdose' or toxic ingestion) exposure to APAP. Materials & methods: The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography-triple-quadrupole mass spectrometry. Results: Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. Conclusion: Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the -oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity.
Bhattacharyya S; Yan K; Pence L; Simpson P M; Gill P; Letzig L G; Beger R D; Sullivan J E; Kearns G L; Reed M D; Marshall J D; Van Den Anker J N; James L P
Biomarkers in Medicine
2014
2014-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.2217/bmm.13.150" target="_blank" rel="noreferrer noopener">10.2217/bmm.13.150</a>
Sentinel Role Of Langerhans' Cells In Cervical Cancer
Pathology; Research & Experimental Medicine
Marty J J
Laboratory Investigation
1997
1997-01
Journal Article or Conference Abstract Publication
n/a
Recent Findings And Future Directions In Breast Cancer Chemoprevention
Pharmacology & Pharmacy; Research & Experimental Medicine
Mamounas E P
Biomedicine & Pharmacotherapy
2005
2005-10
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/s0753-3322(05)80067-8" target="_blank" rel="noreferrer noopener">10.1016/s0753-3322(05)80067-8</a>
Nsabp Adjuvant Trial On The Use Of Cox-2 Inhibition In Breast Cancer
Pharmacology & Pharmacy; Research & Experimental Medicine
Mamounas E P
Biomedicine & Pharmacotherapy
2005
2005-10
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/s0753-3322(05)80060-5" target="_blank" rel="noreferrer noopener">10.1016/s0753-3322(05)80060-5</a>
Place Preference And Microdialysis Studies With Two Derivatives Of Methylphenidate
abuse; affinity; binding; cocaine; dependence; dopamine; methylphenidate; microdialysis studies; pharmacology; Pharmacology & Pharmacy; place preference; Research & Experimental Medicine; transporters
Gatley S J; Meehan S M; Chen R; Pan D F; Schechter M D; Dewey S L
Life Sciences
1996
1996-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0024-3205(96)00222-6" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(96)00222-6</a>
Group-b Streptococcal Bacteremia In A Community-teaching Hospital
Research & Experimental Medicine
Gallagher P G; Watanakunakorn C
Clinical Research
1985
1985
Journal Article or Conference Abstract Publication
n/a
Pseudomonas Bacteremia In A Community-teaching Hospital, 1980-1984
Research & Experimental Medicine
Gallagher P G; Cmolik B; Watanakunakorn C
Clinical Research
1988
1988-10
Journal Article or Conference Abstract Publication
n/a
Clinical Implications Of 750mg, 5-day Levofloxacin For The Treatment Of Community Acquired Pneumonia
adults; antimicrobial therapy; community-acquired pneumonia; controlled-trial; critical pathway; early switch; General & Internal Medicine; guidelines; levofloxacin; management; oral antibiotics; Research & Experimental Medicine; resolution; short-course; symptom
File T M; Milkovich G; Tennenberg A M; Xiang J X; Khashab M M; Zadeikis N
Current Medical Research and Opinion
2004
2004-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1185/030079904x2558" target="_blank" rel="noreferrer noopener">10.1185/030079904x2558</a>
Rat Mesenchymal Stem Cell Secretome Promotes Elastogenesis And Facilitates Recovery From Simulated Childbirth Injury
Cell Biology; Elastin; Electromyography (EMG); expression; External urethral sphincter (EUS); female; female rats; mice; Paracrine factors; protection; Research & Experimental Medicine; Stress urinary incontinence (SUI); stress urinary-incontinence; stromal cells; tissue; transplantation; transplantation; Urethra; urethral sphincter; vaginal distension
Dissaranan C; Cruz M A; Kiedrowski M; Balog B M; Gill B C; Penn M S; Goldman H B; Damaser M S
Cell Transplantation
2014
2014
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.3727/096368913x670921" target="_blank" rel="noreferrer noopener">10.3727/096368913x670921</a>
Bile Synthesis In Rat Models Of Inflammatory Bowel Diseases
acid synthesis; acute-phase response; acute-phase response; bile synthesis; cholesterol 7-alpha hydroxylase; cholesterol 7-alpha-hydroxylase gene; colitis; crohns-disease; experimental; General & Internal Medicine; inflammatory bowel disease; intestinal inflammation; messenger-rna; nitric-oxide; Research & Experimental Medicine; sulfonic-acid; ulcerative-colitis
Dikopoulos N; Schmid R M; Bachem M; Buttenschoen K; Adler G; Chiang J Y L; Weidenbach H
European Journal of Clinical Investigation
2007
2007-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1111/j.1365-2362.2007.01779.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2362.2007.01779.x</a>
Trpv1 Residues Vital To Protection Against 4-hne Modification, Prservation Of Channel Activity And Microvascular Function
General & Internal Medicine; Research & Experimental Medicine
DelloStritto D J; Connel P; Bratz I; Geldenhuys O W
Journal of Investigative Medicine
2015
2015-04
Journal Article or Conference Abstract Publication
n/a
Targeted Liquid Chromatography-mass Spectrometry Analysis Of Serum Acylcarnitines In Acetaminophen Toxicity In Children
-oxidation; acetaminophen; acute liver-failure; acylcarnitine; biomarker; clinical; clofibrate; hepatic; hepatotoxicity; induced; induced hepatic-necrosis; metabolism; metabolomics; mice; multicenter; overdose; protein adducts; Research & Experimental Medicine; toxicity
Bhattacharyya S; Yan K; Pence L; Simpson P M; Gill P; Letzig L G; Beger R D; Sullivan J E; Kearns G L; Reed M D; Marshall J D; Van Den Anker J N; James L P
Biomarkers in Medicine
2014
2014-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.2217/bmm.13.150" target="_blank" rel="noreferrer noopener">10.2217/bmm.13.150</a>
MELANOTIC SCHWANNOMA OF THE ACOUSTIC NERVE
Medical Laboratory Technology; Pathology; Research & Experimental Medicine
Miller R T; Sarikaya H; Sos A
Archives of Pathology & Laboratory Medicine
1986
1986-02
Journal Article or Conference Abstract Publication
n/a
miR-145 is differentially regulated by TGF-ss 1 and ischaemia and targets Disabled-2 expression and wnt/ss-catenin activity
gene-expression; Myocardial infarction; Cell Biology; Myocardial infarction; Research & Experimental Medicine; stem-cells; binding; pathway; cytokines; growth factors; c-myc; cell-differentiation; dab2; epithelial ovarian-cancer; myosin-vi; nasopharyngeal carcinoma
The effect of wnt/beta-catenin signalling in the response to acute myocardial infarction (AMI) remains controversial. The membrane receptor adaptor protein Disabled-2 (Dab2) is a tumour suppressor protein and has a critical role in stem cell specification. We recently demonstrated that down-regulation of Dab2 regulates cardiac protein expression and wnt/beta-catenin activity in mesenchymal stem cells (MSC) in response to transforming growth factor-beta 1 (TGF-beta 1). Although Dab2 expression has been shown to have effects in stem cells and tumour suppression, the molecular mechanisms regulating this expression are still undefined. We identified putative binding sites for miR-145 in the 3'-UTR of Dab2. In MSC in culture, we observed that TGF-beta 1 treatment led to rapid and sustained up-regulation of primiR-145. Through gain and loss of function studies we demonstrate that miR-145 up-regulation was required for the down-regulation of Dab2 and increased beta-catenin activity in response to TGF-beta 1. To begin to define how Dab2 might regulate wnt/beta-catenin in the heart following AMI, we quantified myocardial Dab2 as a function of time after left anterior descending ligation. There was no significant Dab2 expression in sham-operated myocardium. Following AMI, Dab2 levels were rapidly up-regulated in cardiac myocytes in the infarct border zone. The increase in cardiac myocyte Dab2 expression correlated with the rapid and sustained down-regulation of myocardial primiR-145 expression following AMI. Our data demonstrate a novel and critical role for miR-145 expression as a regulator of Dab2 expression and beta-catenin activity in response to TGF-beta 1 and hypoxia.
Mayorga M E; Penn M S
Journal of Cellular and Molecular Medicine
2012
2012-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1111/j.1582-4934.2011.01385.x" target="_blank" rel="noreferrer noopener">10.1111/j.1582-4934.2011.01385.x</a>
PRIMARY CARE PHYSICIAN TRAINING IN THE NURSING-HOME - A NATIONAL SURVEY OF INTERNAL-MEDICINE AND FAMILY-PRACTICE PROGRAMS
Research & Experimental Medicine
Counsell S R; Katz P R; Karuza J
Clinical Research
1993
1993-04
Journal Article or Conference Abstract Publication
n/a
CEL-1000 - a peptide with adjuvant activity or Th1 immune responses
Research & Experimental Medicine; Immunology; cytokines; antibodies; beta-2-microglobulin; vaccines; dna; antigens; CEL-1000; epitope; gamma interferon; IgG2a antibodies; liposomes
CEL-1000 (derG, DGQEEKAGVVSTGLIGGG) is a small immunomodulatory peptide which delivers demonstrated protective activity in two infectious disease challenge models (HSV and malaria) and an allogenic tumor vaccine model. CEL-1000 and other activators (defensin-beta, CpG ODN, and imiquimod) of the innate immune system promote IFN-gamma-associated protective responses. CEL-1000 is an improved form of peptide G (a peptide from human MHC II beta chain second domain, aa 135-149) known to enhance immune responses of other immunogenic peptides. Since defensin-P, CpG ODN, and imiquimod have been shown to possess adjuvant activity, we investigated the adjuvant effect of peptide G and CEL-1000 as conjugates with HIV and malaria peptides. Antibody titers and isotypes were evaluated on serum taken from select days following immunization. Results for CEL-1000 and G peptide conjugates were compared with results for KLH conjugates of the same HIV peptide from the p 17 molecule (87-116) referred to as HGP-30. Studies demonstrated that comparable titers were seen on day 28, 42, 63, and 77 with either G or KLH-HGP-30 peptide conjugates. In another study, CEL-1000 conjugates (CEL-1000-HGP-30) demonstrated a 4-10-fold higher titer antibody response than seen with several other peptide conjugates of the same HGP-30 peptide. Improved adjuvant activity of CEL-1000 in peptide conjugates was also demonstrated by a shift in the antibody isotypes toward a Th1 response (IgG2a). The IgG2a/IgG1, ratio for G-HGP-30 HIV or KLH-HGP-30 HIV conjugates were lower than for the CEL-1000-HGP-30 HIV conjugate. A similar favoring of the IgG2a/IgG1 ratio was seen for a malaria peptide conjugate (CEL-1000-SF/GF) compared to the un-conjugated peptide (SF-GF). CEL-1000 also showed adjuvant activity in an allogenic tumor vaccine model. As expected for an adjuvant, CEL-1000 or G does not induce detectable self-directed or cross reactive antibodies. CEL-1000 is currently being investigated for use as an adjuvant with conventional vaccines. It is expected that IgG2a antibodies would be preferably generated by CEL-1000 adjuvancy and could enhance in vivo clearance of antigens or pathogens. (C) 2004 Elsevier Ltd. All rights reserved.
Charoenvit Y; Goel N; Whelan M; Rosenthal K S; Zimmerman D H
Vaccine
2004
2004-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.vaccine.2003.11.062" target="_blank" rel="noreferrer noopener">10.1016/j.vaccine.2003.11.062</a>
Kallistatin is a potent new vasodilator
Research & Experimental Medicine; expression; purification; endothelium; vasopressin; inhibitor; bradykinin; blood pressure; human tissue kallikrein; hypertensive rats; kallikrein; kallikrein-binding protein; kallistatin; kinins; renal pressure; vasorelaxation
Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity, The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmoVkg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B-2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor N-omega-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney, Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a K-d of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.
Chao J L; Stallone J N; Liang Y M; Chen L M; Wang D Z; Chao L
Journal of Clinical Investigation
1997
1997-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1172/jci119502" target="_blank" rel="noreferrer noopener">10.1172/jci119502</a>
The additive effects of carnitine and ascorbic acid on distally burned dorsal skin flap in rats
ischemia; prevention; ultrastructure; Research & Experimental Medicine; model; metabolism; skeletal-muscle; vitamin C; burn; carnitine; skin flap; thermal-injury
Background: The purpose of this study was to determine the effects of combined use of L-carnitine and vitamin C on partially burned skin flap in an experimental rat model. Material/Methods: In the rat dorsal skin, a 10x3 cm flap was marked. The most distal 3x3 cm part was burned to full thickness. Twenty-four rats were randomized into four groups with 6 animals in each. Group 1 was simply followed tip. Group 2 was given 0.5 mg/kg vitamin C per day for 7 days, group 3 100 mg/kg carnitine per day for 7 days, and group 4 both carnitine and vitamin C. On the eighth postoperative day, the animals were sacrificed and examined. The surviving and necrotic areas were determined by macroscopic examination and measured with a planimeter. Results: The areas of flap necrosis were measured. The median surviving areas and areas of flap necrosis, respectively, of the groups were: group 1, 16.0 cm(2) and 14.0 cm(2); group 2, 18.25 cm(2) and 11.75 cm(2); group 3, 20.0 cm(2) and 10 cm(2); and group 4, 23.75 cm(2) and 6.25 cm(2). The surviving areas of the groups were found to be significantly different (p=0.000).
Arslan E; Basterzi Y; Aksoy A; Majka C; Unal S; Sari A; Demirkan F
Medical Science Monitor
2005
2005-06
Journal Article or Conference Abstract Publication
n/a
ENDOCRINE STATUS OF RECENTLY ABSTINENT ALCOHOLIC MEN
Research & Experimental Medicine
Aftab D; Levy R P; Jarjoura D; Pittman R; Karl R
Clinical Research
1990
1990-10
Journal Article or Conference Abstract Publication
n/a