Digital Commons Network^™

Pegylated Interferon 2a And 2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Hiv Infected Patients., Ravinder Dhillon, Simona Rossi, Steven K Herrine

Department of Medicine Faculty Papers

Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA …

Structures And Functions Of The Normal And Injured Human Olfactory Epithelium, Jonathan P Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E Gimenez, Suping Jin, Alexander B Taylor, Borries Demeler, Kevin A Morano, P John Hart, Jose M Valpuesta, Eileen M Lafer, Rui Sousa

Faculty, Staff and Student Publications

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of …

Manipulations Of Macrophage Activation Through Targeted Delivery Of Interferon Regulatory Factor Genes Mediated By Recombinant Adenovirus-Conjugated Zymosan, Mengmeng Zhang

All Theses

According to the different phenotypes and distinct patterns of gene expression, macrophages can be subdivided into two types: M1 and M2. The M1 macrophages, which are activated through the classical pathway, have a proinflammatory characteristic, providing an in-front defense line against different kinds of pathogens as well as malignant cells. On the other hand, the M2 macrophages are immunosuppressive and instead can promote tumor growth and dissemination. The solid tumor tissues are often infiltrated with a large number of macrophages, the so-called tumor-associated macrophages (TAMs). TAMs, which are polarized into M2 phenotype under the tumor microenvironment, promote tumor progression by …

Drug-Prescribing Patterns During Pregnancy In The Tertiary Care Hospitals Of Pakistan: A Cross Sectional Study., Dileep K Rohra, Nirmal Das, Syed I Azam, Nazir A Solangi, Zahida Memon, Abdul M Shaikh, Nusrat H Khan

Department of Biological & Biomedical Sciences

Background: The rationale for use of drugs during pregnancy requires a careful assessment as in addition to the mother, the health and life of her unborn child is also at stake. Information on the use of drugs during pregnancy is not available in Pakistan. The aim of this study was to evaluate the patterns of drug prescriptions to pregnant women in tertiary care hospitals of Pakistan. Methods: This was a cross-sectional study conducted at five tertiary care hospitals of Pakistan. Copies of outPatient medicinal prescriptions given to pregnant Patients attending the antenatal clinics were collected. The drugs were classified according …

Effects Of Early Gestation Gh Administration On Placental And Fetal Development In Sheep., Casey D Wright, Ryan J Orbus, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Ovine GH (oGH) is synthesized in placental tissue during maximal placental growth and development. Our objectives were to localize oGH mRNA in the placenta, and study the impact of exogenous GH on twin pregnancies during the normal window (35-55 days of gestational age; dGA) of placental expression. In situ hybridization localized oGH mRNA in uterine luminal epithelium but not in tissues of fetal origin. While maternal GH and IGF-I concentrations were increased (P

Brain Fiber Tract Plasticity In Experimental Spinal Cord Injury: Diffusion Tensor Imaging, Jaivijay Ramu, Juan Herrera, Raymond Grill, Tobias Bockhorst, Ponnada Narayana

Faculty, Staff and Student Publications

Diffusion tensor imaging (DTI) and immunohistochemistry were performed in spinal cord injured rats to understand the basis for activation of multiple regions in the brain observed in functional magnetic resonance imaging (fMRI) studies. The measured fractional anisotropy (FA), a scalar measure of diffusion anisotropy, along the region encompassing corticospinal tracts (CST) indicates significant differences between control and injured groups in the 3 to 4 mm area posterior to bregma that correspond to internal capsule and cerebral peduncle. Additionally, DTI-based tractography in injured animals showed increased number of fibers that extend towards the cortex terminating in the regions that were activated …

The Temporal Relationship Between The Coronavirus Disease 2019 (Covid-19) Pandemic And Preterm Birth, Harold E Bedell, Mahalakshmi Ramamurthy, Saumil S Patel, Shobana Subramaniam, Lan-Phuong Vu-Yu, Jianliang Tong

Faculty, Staff and Student Publications

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment …

In Vivo Murine Melanoma Tumor Responses To Nanosecond Pulsed Electric Field Treatment, Xinhua Chen

Theses and Dissertations in Biomedical Sciences

High intensity nanosecond pulsed electric fields (nsPEF) were applied to melanoma tumors to observe functional and structural biological changes and to investigate the possible molecular mechanisms responsible. An animal model was set up by injecting B16F10 mouse melanoma cells into SKH-1 mice. A treatment (Tx) of 100 pulses: 300 nanosecond duration; 40 kV/cm field strength; at 0.5 Hz rate were delivered to melanoma tumors in 120 mice. The nsPEF Txcaused tumor self-destruction with sharply decreased cell volumes and shrunken nuclei. The apoptotic biochemical tests confirmed nsPEF Tx induced apoptosis in a time-dependent manner. Examination of gross vessel and micro-vessel density …

Nanosecond Pulsed Electric Fields Induce A Mitochondria-Independent Apoptosis In B16f10 Melanoma Cells In Vitro, Wentia Elissa Ford

Theses and Dissertations in Biomedical Sciences

Nanosecond pulsed electric fields (nsPEFs) are ultra-short pulses that induce direct electric field and biological effects that initiate apoptosis. Here the application of ten 300ns pulses ranging in electric fields from 12kV/cm-60kV/cm was administered to determine the effects on B16F10 melanoma cells evaluated by in vitro studies. Initial application of nsPEFs demonstrated apoptosis induction in an electric field- and pulse number-dependent manner measured by caspase activation that correlated with decrease in cell viability 24hr post pulse. In addition caspase activity was shown to be independent of calcium mobilization though ions may play a part in other aspects of apoptosis. The …

Water-Soluble Fullerene (C60) Derivatives As Nonviral Gene-Delivery Vectors, Balaji Sitharaman, Tatiana Y Zakharian, Anita Saraf, Preeti Misra, Jared Ashcroft, Su Pan, Quynh P Pham, Antonios G Mikos, Lon J Wilson, David A Engler

Faculty, Staff and Student Publications

A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green …

Synaptotagmin-2 Controls Regulated Exocytosis But Not Other Secretory Responses Of Mast Cells*, Qun-Fang Wan, Alejandro Vila, Zhen-Yu Zhou, Ruth Heidelberger

Faculty, Staff and Student Publications

To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time …

Obesity And Cardiac Metabolism In Women, Heinrich Taegtmeyer, Mohamed F Algahim

Faculty, Staff and Student Publications

No abstract provided.

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Fluorescence Tomography Characterization For Sub-Surface Imaging With Protoporphyrin Ix, Dax Kepshire, Scott C. Davis, Hamid Dehghani, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

Optical imaging of fluorescent objects embedded in a tissue simulating medium was characterized using non-contact based approaches to fluorescence remittance imaging (FRI) and sub-surface fluorescence diffuse optical tomography (FDOT). Using Protoporphyrin IX as a fluorescent agent, experiments were performed on tissue phantoms comprised of typical in-vivo tumor to normal tissue contrast ratios, ranging from 3.5:1 up to 10:1. It was found that tomographic imaging was able to recover interior inclusions with high contrast relative to the background; however, simple planar fluorescence imaging provided a superior contrast to noise ratio. Overall, FRI performed optimally when the object was located on or …

Spinal Cord Stimulation For Control Of Pain, Stephen Falowski Md

JHN Journal

Spinal cord stimulation (SCS) is an adjustable, non-destructive procedure which delivers therapeutic doses of electrical current to the spinal cord for the management of neuropathic pain. The most common indications include post-laminectomy (“failed back surgery”) syndrome, complex regional pain syndrome (CRPS), ischemic limb pain, and angina. Other reported applications include visceral/abdominal pain, cervical neuritis pain, spinal cord injury pain, post-herpetic neuralgia, and neurogenic thoracic outlet syndrome.

Nerve Growth Factor Regulation Of Cyclin D1 In Pc12 Cells Through A P21ras Extracellular Signal-Regulated Kinase Pathway Requires Cooperative Interactions Between Sp1 And Nuclear Factor-Kappab., Francesco Marampon, Mathew C Casimiro, Maofu Fu, Michael J Powell, Vladimir M Popov, Jaime Lindsay, Bianca M Zani, Carmela Ciccarelli, Genichi Watanabe, Richard J Lee, Richard G Pestell

Department of Cancer Biology Faculty Papers

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF …

Skeletal Abnormalities In Mice Lacking Extracellular Matrix Proteins, Thrombospondin-1, Thrombospondin-3, Thrombospondin-5, And Type Ix Collagen, Karen L Posey, Kurt Hankenson, Alka C Veerisetty, Paul Bornstein, Jack Lawler, Jacqueline T Hecht

Faculty, Staff and Student Publications

Thrombospondin-5 (TSP5) is a large extracellular matrix glycoprotein found in musculoskeletal tissues. TSP5 mutations cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia; both show a characteristic growth plate phenotype with retention of TSP5, type IX collagen (Col9), and matrillin-3 in the rough endoplasmic reticulum. Whereas most studies focus on defining the disease process, few functional studies have been performed. TSP5 knockout mice have no obvious skeletal abnormalities, suggesting that TSP5 is not essential in the growth plate and/or that other TSPs may compensate. In contrast, Col9 knockout mice have diminished matrillin-3 levels in the extracellular matrix and early-onset osteoarthritis. …

Triple Test Assessment And A Scoring System To Predict The Presence Of Breast Cancer At Aga Khan University Hospital, Nairobi, Aideed A. Kahie

Master of Medicine in General Surgery

Background: Breast cancer is an emerging health concern in Africa. It is the most common female cancer in Kenya. The accuracy of the diagnostic modalities in our institution has not been previously assessed, especially in cases where components of the Triple Test (TT) are non-concordant. Objectives: To retrospectively evaluate the accuracy of TT, its components and its modification; the Triple Test Score when the components are nonconcordant at Aga Khan University Hospital, Nairobi. Methods: Using ICD9 611.72 we identified patients with breast lump or mass in the period between January 2000 and July 2007. One hundred and thirty nine patients …

Response Of Endothelial Cells To Stressors: The Impact Of Aging And Diabetes, Katie Mclellan

Loma Linda University Electronic Theses, Dissertations & Projects

Preliminary research indicates there is some impairment of the endothelial cells to respond to single stressors such as local heat, shear stress, and global heat in older people and people who have diabetes. The response of the skin blood flow to local heat is an indicator of the endothelial cells ability to cope with stress. In addition, factors such as thicker subcutaneous fat and skin moisture may impair the skin’s ability to dissipate heat. For older people and people with diabetes, this endothelial dysfunction may cause an even more diminished response to multiple stressors. However, no studies have examined the …

Factors That Affect Performance On Executive Functioning After Coronary Artery Bypass Grafting, Sapna Mahesh Patel

Loma Linda University Electronic Theses, Dissertations & Projects

Research suggests that individuals who undergo coronary artery bypass grafting (CABG) experience declines in neuropsychological functioning post-operatively. This decline has been observed in up to 80% of patients early after surgery, and in up to 30% of patients after six months. Many studies have examined the potential effects of CABG on neuropsychological functioning in general, and numerous studies have found that executive functions are impaired in particular. However, none have examined what factors contribute to observed executive dysfunction after CABG. This study investigated the role of memory functions on executive functions in a selected sample of patients undergoing CABG. This …

Neuronal Connections From The Cervix To The Spinal Cord Before Parturition, Mary Medina Groves

Loma Linda University Electronic Theses, Dissertations & Projects

By the day before birth, the density of nerve fibers in the cervix has increased compared to earlier in pregnancy or in nonpregnant mice. Similar findings are reported in parturient women. To test the hypothesis that connections between the cervix and spinal cord are enhanced by term, the cervix of nonpregnant and time-dated pregnant mice (day 15 or 18 post-breeding) was injected with pseudorabies virus (PRV), a trans-synaptic retrograde neural tract tracer. Mice were euthanized and perfused 5 days later. The spinal cord and cervix were removed and postfixed overnight, immersed in sucrose, and cryostat sections through the thoracic to …

Mechanisms Of T Helper Cell Modulation In A Simulated Space Radiation Environment, Asma Rizvi

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation …

Understanding Neurosurgery Through Experimental And Computer Models, Ciro Randazzo Md, Aditya S. Pandey Md, Erol Veznedaroglu Md

JHN Journal

Endovascular neurosurgery is an evolving field, with the goal of treating neurological disease with minimal invasion of the body. The current approach is to deliver focused therapies via catheters traveling through the vascular tree. Refinement and advancement of these techniques requires not just new ideas, but new ideas that hold up when tested through the scientific method.

Before clinical trials can begin, ethics and law demand that the ideas are tested first under experimental models. One benefit of these pre-clinical tests is the early identification of side effects. Another is the opportunity to practice and polish surgical technique in advance …

Jhn Journal (Download The Full Pdf Of This Issue), Robert H. Rosenwasser Md

JHN Journal

Complete JHN Journal Issue, Vol. 4, Issue 1, June 2008.

A New Model For Hemoglobin Ingestion And Transport By The Human Malaria Parasite Plasmodium Falciparum., Michelle D Lazarus, Timothy G Schneider, Theodore F Taraschi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuole (FV) of the parasite are poorly understood. Because actin dynamics play key roles in vesicle formation and transport in endocytosis, we used the actin-perturbing agents jasplakinolide and cytochalasin D to investigate the role of parasite actin in hemoglobin ingestion and transport to the FV. In addition, we tested the current hemoglobin trafficking model through extensive analysis of serial …

Usefulness Of Baseline Lipids And C-Reactive Protein In Women Receiving Menopausal Hormone Therapy As Predictors Of Treatment-Related Coronary Events., Paul Bray, Joseph C Larson, Andrea Z Lacroix, Joann Manson, Marian C Limacher, Jacques E Rossouw, Norman L Lasser, William E Lawson, Marcia L Stefanick, Robert D Langer, Karen L Margolis

Cardeza Foundation for Hematologic Research

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen …

Radioactive Seed Immobilization Techniques For Interstitial Brachytherapy, K. Yan, T. Podder, I. Buzurovic, Y. Hu, E. Messing, D. Rubens, A. Dicker, R. Valicenti, N. Sarkar, W. Ng, Y. Yu

Department of Radiation Oncology Faculty Papers

Purpose In prostate brachytherapy, seeds can detach from their deposited sites and move locally in the pelvis or migrate to distant sites including the pulmonary and cardiac regions. Undesirable consequences of seed migration include inadequate dose coverage of the prostate and tissue irradiation effects at the site of migration. Thus, it is clinically important to develop seed immobilization techniques.

Methods We first analyze the possible causes for seed movement, and propose three potential techniques for seed immobilization: (1) surgical glue, (2) laser coagulation and (3) diathermy coagulation. The feasibility of each method is explored. Experiments were carried out using fresh …

Feedback From Horizontal Cells To Rod Photoreceptors In Vertebrate Retina., Wallace B. Thoreson, Norbert Babai, Theodore M M. Bartoletti

Journal Articles: Ophthalmology

Retinal horizontal cells (HCs) provide negative feedback to cones, but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (I(Ca)) that do not always generate detectable depolarizing responses. We therefore recorded I(Ca) directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage-clamped HCs while simultaneously recording from rods in …

388 A Structure Of Cytoplasmic Polyhedrosis Virus By Cryo-Electron Microscopy, Xuekui Yu, Lei Jin, Z Hong Zhou

Faculty, Staff and Student Publications

Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription. Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation. Here we report the three-dimensional structure of CPV at 3.88 A resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of alpha-helices, the strand separation in beta-sheets, and densities for loops and many bulky …

Bovine Oocytes And Early Embryos Express Staufen And Elavl Rna-Binding Proteins., M D Calder, P Madan, A J Watson

Obstetrics & Gynaecology Publications

RNA-binding proteins (RBP) influence RNA editing, localization, stability and translation and may contribute to oocyte developmental competence by regulating the stability and turnover of oogenetic mRNAs. The expression of Staufen 1 and 2 and ELAVL1, ELAVL2 RNA-binding proteins during cow early development was characterized. Cumulus-oocyte complexes were collected from slaughterhouse ovaries, matured, inseminated and subjected to embryo culture in vitro. Oocyte or preimplantation embryo pools were processed for RT-PCR and whole-mount immunofluorescence analysis of mRNA expression and protein distribution. STAU1 and STAU2 and ELAVL1 mRNAs and proteins were detected throughout cow preimplantation development from the germinal vesicle (GV) oocyte to …