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Articles 41731 - 41760 of 45185

Full-Text Articles in Medicine and Health Sciences

Effects Of Altered Superoxide Dismutase Expression On Age-Related Functional Declines And Survival In Drosophila, Ian Martin Apr 2008

Effects Of Altered Superoxide Dismutase Expression On Age-Related Functional Declines And Survival In Drosophila, Ian Martin

Theses and Dissertations

Most organisms experience progressive declines in physiological function as they age. A number of studies in a variety of species support a strong link between oxidative damage, age-related functional declines and life span determination. Here, manipulating the expression levels of superoxide dismutase (SOD) isoenzymes SOD1 and SOD2, resulted in altered functional senescence and survival characteristics in Drosophila. Overexpression of cytosolic Sod1 using the yeast GAL4/UAS system conferred a 30-34% increase in mean life span and resulted in an attenuated senescence of odor avoidance behavior in aging flies. Tissue-specific Sod1 overexpression selectively in the nervous system or muscle failed to reproduce …


A Luteinizing Hormone Receptor Intronic Variant Is Significantly Associated With Decreased Risk Of Alzheimer's Disease In Males Carrying An Apolipoprotein E Epsilon 4 Allele, Ryan J. Haasl, M Reza Ahmadi, Sivan Vadakkadath Meethal, Carey E. Gleason, Sterling C. Johnson, Sanjay Asthana, Richard L. Bowen, Craig S. Atwood Apr 2008

A Luteinizing Hormone Receptor Intronic Variant Is Significantly Associated With Decreased Risk Of Alzheimer's Disease In Males Carrying An Apolipoprotein E Epsilon 4 Allele, Ryan J. Haasl, M Reza Ahmadi, Sivan Vadakkadath Meethal, Carey E. Gleason, Sterling C. Johnson, Sanjay Asthana, Richard L. Bowen, Craig S. Atwood

Research outputs pre 2011

Genetic and biochemical studies support the apolipoprotein E (APOE) ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH)-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB) and its receptor (LHCGR) have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the …


A Central Function For Perlecan In Skeletal Muscle And Cardiovascular Development, Jason J. Zoeller, Angela Mcquillan, John Whitelock, Shiu-Ying Ho, Renato V. Iozzo Apr 2008

A Central Function For Perlecan In Skeletal Muscle And Cardiovascular Development, Jason J. Zoeller, Angela Mcquillan, John Whitelock, Shiu-Ying Ho, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Perlecan's developmental functions are difficult to dissect in placental animals because perlecan disruption is embryonic lethal. In contrast to mammals, cardiovascular function is not essential for early zebrafish development because the embryos obtain adequate oxygen by diffusion. In this study, we use targeted protein depletion coupled with protein-based rescue experiments to investigate the involvement of perlecan and its C-terminal domain V/endorepellin in zebrafish development. The perlecan morphants show a severe myopathy characterized by abnormal actin filament orientation and disorganized sarcomeres, suggesting an involvement of perlecan in myopathies. In the perlecan morphants, primary intersegmental vessel sprouts, which develop through angiogenesis, fail …


Susceptibility Of Chlamydia Trachomatis To The Excipient Hydroxy-Ethylcellulose: Ph And Concentration Dependence Of Antimicrobial Activity, Ali A. Abdul-Sater, David M. Ojcius, M. P. Meyer Apr 2008

Susceptibility Of Chlamydia Trachomatis To The Excipient Hydroxy-Ethylcellulose: Ph And Concentration Dependence Of Antimicrobial Activity, Ali A. Abdul-Sater, David M. Ojcius, M. P. Meyer

All Dugoni School of Dentistry Faculty Articles

Hydroxyethyl cellulose (HEC) is used as a neutral excipient in microbicides used against sexually transmitted pathogens. However, HEC inhibits the infection of cervical epithelial cells by Chlamydia trachomatis at pH 5 in a concentration-dependent manner. At pH 7, infection is inversely dependent on the concentration of HEC, possibly due to pH-dependent calcium sequestration.


Changing The Rules At The Drop Of A Hat: An Erp Study Of Preschoolers' Set-Shifting Ability, Sandra A. Wiebe, Daniel J. Carroll, Megan Herrington, Sari Raber, Kimberly A. Espy Apr 2008

Changing The Rules At The Drop Of A Hat: An Erp Study Of Preschoolers' Set-Shifting Ability, Sandra A. Wiebe, Daniel J. Carroll, Megan Herrington, Sari Raber, Kimberly A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

We examined the neural correlates of set-shifting in 5-year-old children and examined whether the ease of switching was affected by varying the number of non-switch trials preceding a switch.


A Distinct Role For B1b Lymphocytes In T Cell-Independent Immunity, Kishore R. Alugupalli Apr 2008

A Distinct Role For B1b Lymphocytes In T Cell-Independent Immunity, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell …


Drd2 Genotype And Prenatal Exposure To Tobacco Interact To Influence Infant Attention And Reactivity, Sandra A. Wiebe, Kimberly A. Espy, Christian Stopp, Jennifer Respass, Travis Jameson, Jodi Huggenvik Apr 2008

Drd2 Genotype And Prenatal Exposure To Tobacco Interact To Influence Infant Attention And Reactivity, Sandra A. Wiebe, Kimberly A. Espy, Christian Stopp, Jennifer Respass, Travis Jameson, Jodi Huggenvik

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

The present study examined the effects of dopamine receptor D2 genotype and PTE status on early infant neurobehavior.


Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh Apr 2008

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

Publications and Research

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …


Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh Apr 2008

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8-19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI(2) microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …


Drug Resistance In Malaria: A Peruvian Research Experience, Ryan Haley Apr 2008

Drug Resistance In Malaria: A Peruvian Research Experience, Ryan Haley

Inquiry Journal 2008

No abstract provided.


17beta-Estradiol Increases Basal But Not Bradykinin-Stimulated Release Of Active T-Pa In Young Postmenopausal Women, Mias Pretorius, Gary Van Guilder, Raul J Guzman, James M Luther, Nancy J Brown Apr 2008

17beta-Estradiol Increases Basal But Not Bradykinin-Stimulated Release Of Active T-Pa In Young Postmenopausal Women, Mias Pretorius, Gary Van Guilder, Raul J Guzman, James M Luther, Nancy J Brown

Health and Nutritional Sciences Faculty Publications

Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17beta-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2+/-2.3 years) who were randomized to receive 17beta-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before …


Disruption Of C-Jun Reduces Cellular Migration And Invasion Through Inhibition Of C-Src And Hyperactivation Of Rock Ii Kinase., Xuanmao Jiao, Sanjay Katiyar, Manran Liu, Susette C Mueller, Michael P. Lisanti, Anping Li, Timothy G Pestell, Kongming Wu, Xiaoming Ju, Zhiping Li, Erwin F Wagner, Tatsuo Takeya, Chenguang Wang, Richard G Pestell Apr 2008

Disruption Of C-Jun Reduces Cellular Migration And Invasion Through Inhibition Of C-Src And Hyperactivation Of Rock Ii Kinase., Xuanmao Jiao, Sanjay Katiyar, Manran Liu, Susette C Mueller, Michael P. Lisanti, Anping Li, Timothy G Pestell, Kongming Wu, Xiaoming Ju, Zhiping Li, Erwin F Wagner, Tatsuo Takeya, Chenguang Wang, Richard G Pestell

Kimmel Cancer Center Faculty Papers

The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding member of the activator protein-1 family and is required for cellular proliferation and DNA synthesis in response to oncogenic signals and plays an essential role in chemical carcinogenesis. The role of c-Jun in cellular invasion remains to be defined. Genetic deletion of c-Jun in transgenic mice is embryonic lethal; therefore, transgenic mice encoding a c-Jun gene flanked by LoxP sites (c-jun(f/f)) were used. c-jun gene deletion reduced c-Src expression, hyperactivated ROCK II signaling, …


Trail Mediates Liver Injury By The Innate Immune System In The Bile Duct-Ligated Mouse., Alisan Kahraman, Fernando J. Barreyro, Steven F. Bronk, Nathan W. Werneburg, Justin L. Mott, Yuko Akazawa, Howard C Masuoka, Charles L Howe, Gregory J. Gores Apr 2008

Trail Mediates Liver Injury By The Innate Immune System In The Bile Duct-Ligated Mouse., Alisan Kahraman, Fernando J. Barreyro, Steven F. Bronk, Nathan W. Werneburg, Justin L. Mott, Yuko Akazawa, Howard C Masuoka, Charles L Howe, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL(+/-)), and TRAIL knockout (TRAIL(-/-)) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by >80% in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL(-/-) animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.


Solid Serous Adenoma Of The Pancreas: A Rare Form Of Serous Cystadenoma, Madhusudhan R. Sanaka, Thomas E. Kowalski, Corey Brotz, Charles J. Yeo, Peter Mccue, Juan Palazzo Mar 2008

Solid Serous Adenoma Of The Pancreas: A Rare Form Of Serous Cystadenoma, Madhusudhan R. Sanaka, Thomas E. Kowalski, Corey Brotz, Charles J. Yeo, Peter Mccue, Juan Palazzo

Department of Medicine Faculty Papers

Serous cystadenomas (SC) of the pancreas are uncommon benign cystic neoplasms that were first differentiated from mucinous cystadenomas in 1978 by Compagno and Oertel (1-3). Serous cystadenomas characteristically have a spongy gross appearance and are composed of innumerable tiny cysts lined by flattened cuboidal or polygonal cells with clear to pale eosinophilic cytoplasm atop of thin fibrous septae. Since 1978, five unique SC subtypes have been identified (4-5). Here we report a case of a solid serous adenoma, a rare serous cystadenoma subtype.


Nucleoplasmic And Cytoplasmic Degradation Of Telomerase: Implications Toward Telomerase-Based Cancer Therapy, Binh Nguyen Mar 2008

Nucleoplasmic And Cytoplasmic Degradation Of Telomerase: Implications Toward Telomerase-Based Cancer Therapy, Binh Nguyen

Theses and Dissertations

Telomerase is a ribonucleoprotein that is reactivated in cancer cells to allow for continuous cellular division and indefinite growth. With telomerase being expressed in more than 85% of all cancer, it is imperative that we understand how to selectively inactivate and degrade this unique DNA polymerase. In doing so, we can specifically target tumor cells to erode their telomeres so that they will undergo apoptosis or senescence. Through this research, we have learned that telomerase can be degraded in the nucleoplasm by Hsp90 chaperone inhibition and in the cytoplasm by the dominant negative mutant, D712A V713I. These findings should guide …


Using Confirmatory Factor Analysis To Understand Executive Control In Preschool Children: I. Latent Structure, Sandra A. Wiebe, Kimberly A. Espy, David Charak Mar 2008

Using Confirmatory Factor Analysis To Understand Executive Control In Preschool Children: I. Latent Structure, Sandra A. Wiebe, Kimberly A. Espy, David Charak

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

*This article may not exactly replicate the final version published in the APA journal. It is not the copy of record. http://content.apa.org/journals/0012-1649 Although many tasks have been developed recently to study executive control in the preschool years, the constructs that underlie performance on these tasks are poorly understood. In particular, it is unclear whether executive control is comprised of multiple, separable cognitive abilities (e.g., inhibition and working memory) or whether it is unitary in nature. A sample of 243 normally developing children between 2.25 and 6 years of age completed a battery of ageappropriate executive control tasks. Confirmatory factor analysis …


Health State Valuation In Mild To Moderate Cognitive Impairment: Feasibility Of Computer-Based, Direct Patient Utility Assessment, Neal V. Dawson, Mendel E. Singer, Marian B. Patterson, Susie A. Sami, Iahn Gonsenhouser, Heather A. Lindstrom, Kathleen A. Smyth, Melissa Barber Butson, Peter J. Whitehouse Mar 2008

Health State Valuation In Mild To Moderate Cognitive Impairment: Feasibility Of Computer-Based, Direct Patient Utility Assessment, Neal V. Dawson, Mendel E. Singer, Marian B. Patterson, Susie A. Sami, Iahn Gonsenhouser, Heather A. Lindstrom, Kathleen A. Smyth, Melissa Barber Butson, Peter J. Whitehouse

Faculty Scholarship

Background. Most patients with dementia will, at some point, need a proxy health care decision maker. It is unknown whether persons with various degrees of cognitive impairment can reliably report their health-related preferences. Methods. The authors performed health state valuations (HSVs) of current and hypothetical future health states on 47 pairs of patients with mild to moderate cognitive impairment and their caregivers using computer-based standard gamble, time tradeoff, and rating scale techniques. Results. Patients' mean (SD) age was 74.6 (9.3) years. About half of the patients were women (48%), as were most caregivers (73%), who were on average younger (mean …


Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole Mar 2008

Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole

Dartmouth Scholarship

We reported previously that low concentrations of sodium citrate strongly promote biofilm formation by Staphylococcus aureus laboratory strains and clinical isolates. Here, we show that citrate promotes biofilm formation via stimulating both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm formation is independent of the ica locus, and in fact, citrate represses polysaccharide adhesin production. We show that fibronectin binding proteins FnbA and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB gene expression, are required for citrate's positive effects on biofilm formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm formation is also stimulated by several …


Functional Imaging Of The Auditory Processing Applied To Speech Sounds, Roy D Patterson, Ingrid Johnsrude Mar 2008

Functional Imaging Of The Auditory Processing Applied To Speech Sounds, Roy D Patterson, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

In this paper, we describe domain-general auditory processes that we believe are prerequisite to the linguistic analysis of speech. We discuss biological evidence for these processes and how they might relate to processes that are specific to human speech and language. We begin with a brief review of (i) the anatomy of the auditory system and (ii) the essential properties of speech sounds. Section 4 describes the general auditory mechanisms that we believe are applied to all communication sounds, and how functional neuroimaging is being used to map the brain networks associated with domain-general auditory processing. Section 5 discusses recent …


Hpr6 Mutants And Uses Thereof, Rolf Joseph Craven Mar 2008

Hpr6 Mutants And Uses Thereof, Rolf Joseph Craven

Pharmacology and Nutritional Sciences Faculty Patents

Methods and agents that interfere with Hpr6 function in non-sarcoma tumor cells are disclosed. Anti-Hpr6 agents are used to enhance the killing effect of anti-cancer agents in non-sarcoma tumor cells and to teat non-sarcoma tumors.


Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty Mar 2008

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …


Clinical And Microbiological Aspects Of Linezolid Resistance Mediated By The Cfr Gene Encoding A 23s Rrna Methyltransferase, Cesar A Arias, Martha Vallejo, Jinnethe Reyes, Diana Panesso, Jaime Moreno, Elizabeth Castañeda, Maria V Villegas, Barbara E Murray, John P Quinn Mar 2008

Clinical And Microbiological Aspects Of Linezolid Resistance Mediated By The Cfr Gene Encoding A 23s Rrna Methyltransferase, Cesar A Arias, Martha Vallejo, Jinnethe Reyes, Diana Panesso, Jaime Moreno, Elizabeth Castañeda, Maria V Villegas, Barbara E Murray, John P Quinn

Faculty, Staff and Student Publications

The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), …


Insights Into Morphological Nature Of Precipitation Of Cholesterol, Vuk Uskoković Mar 2008

Insights Into Morphological Nature Of Precipitation Of Cholesterol, Vuk Uskoković

Pharmacy Faculty Articles and Research

Additional effects on the previously reported procedure of precipitation of narrowly dispersed and well-defined, brick-shaped cholesterol particles, including non-solvent addition rate, temperature, solvent purity, aging treatments, ultrasound agitation and fine mechanical effects were investigated. Based on the presented results, significant morphological sensitivity of cholesterol precipitation processes upon variations from the standard established procedure of crystallization is induced. However, the tendency of cholesterol to crystallize in the form of biaxially grown particles was evidenced as dominating the precipitation processes, irrespective of any modifications of experimental parameters involved in the preparation procedure investigated hereby. Prolonged aging time and temperature effects lead to …


Functional Interactions Of Alcohol-Sensitive Sites In The N-Methyl-D-Aspartate Receptor M3 And M4 Domains, Hong Ren, Abdelghaffar K. Salous, Jaclyn M. Paul, Kaitlin A. Lamb, Donard S. Dwyer, Robert W. Peoples Mar 2008

Functional Interactions Of Alcohol-Sensitive Sites In The N-Methyl-D-Aspartate Receptor M3 And M4 Domains, Hong Ren, Abdelghaffar K. Salous, Jaclyn M. Paul, Kaitlin A. Lamb, Donard S. Dwyer, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-d-aspartate receptor is an important mediator of the behavioral effects of ethanol in the central nervous system. Previous studies have demonstrated sites in the third and fourth membrane-associated (M) domains of the N-methyl-d-aspartate receptor NR2A subunit that influence alcohol sensitivity and ion channel gating. We investigated whether two of these sites, Phe-637 in M3 and Met-823 in M4, interactively regulate the ethanol sensitivity of the receptor by testing dual substitution mutants at these positions. A majority of the mutations decreased steady-state glutamate EC50 values and maximal steady-state to peak current ratios (Iss/I …


Psychiatric Outcomes In A Resident-Run Multidisciplinary Hepatitis C Clinic, Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md Mar 2008

Psychiatric Outcomes In A Resident-Run Multidisciplinary Hepatitis C Clinic, Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md

Department of Medicine

No abstract provided.


Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez Mar 2008

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …


Gating Charge Immobilization In Kv4.2 Channels: The Basis Of Closed-State Inactivation., Kevin Dougherty, Jose A De Santiago-Castillo, Manuel Covarrubias Mar 2008

Gating Charge Immobilization In Kv4.2 Channels: The Basis Of Closed-State Inactivation., Kevin Dougherty, Jose A De Santiago-Castillo, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Kv4 channels mediate the somatodendritic A-type K+ current (I(SA)) in neurons. The availability of functional Kv4 channels is dynamically regulated by the membrane potential such that subthreshold depolarizations render Kv4 channels unavailable. The underlying process involves inactivation from closed states along the main activation pathway. Although classical inactivation mechanisms such as N- and P/C-type inactivation have been excluded, a clear understanding of closed-state inactivation in Kv4 channels has remained elusive. This is in part due to the lack of crucial information about the interactions between gating charge (Q) movement, activation, and inactivation. To overcome this limitation, we engineered a charybdotoxin …


Incorporating Ethnicity Into Genetic Risk Assessment For Alzheimer Disease: The Reveal Study Experience, Peter J. Whitehouse, Melissa Barber Butson Mar 2008

Incorporating Ethnicity Into Genetic Risk Assessment For Alzheimer Disease: The Reveal Study Experience, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

PURPOSE: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. METHODS: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. RESULTS: Review of epidemiological data suggested notable differences in risk between African …


Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole Feb 2008

Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Oral delivery is the most common and preferred route of drug administration although the digestive tract exhibits several obstacles to drug delivery including motility and intraluminal pH profiles. The gut milieu represents the largest mucosal surface exposed to microorganisms with 1010-12 colony forming bacteria/g of colonic content. Approximately, one third of fecal dry matter is made of bacteria/ bacterial components. Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers (polysaccharides) and fermentation of short chain fatty acids such as acetate and butyrate that provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD) results …


Method For Treating A Viral Infection Related Or A Chemical Toxin Related Hepatic Injury With Deltorphin D, Peter R. Oeltgen, Paul D. Bishop, Craig J. Mcclain, Shirish Barve Feb 2008

Method For Treating A Viral Infection Related Or A Chemical Toxin Related Hepatic Injury With Deltorphin D, Peter R. Oeltgen, Paul D. Bishop, Craig J. Mcclain, Shirish Barve

Pathology and Laboratory Medicine Faculty Patents

A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed.