Medical Physiology Commons^™

Mindfulness-Based Stress Reduction And Transcendental Meditation: Current State Of Research, Adam Holt

Journal of Patient-Centered Research and Reviews

This article summarizes the current state of meditation research, specifically focusing on mindfulness-based stress reduction and transcendental meditation. Despite significant methodological problems with the studies reported to date on the subject, there is consistent evidence that meditation can produce changes in the nervous system and physiology of the meditator, and can help with various psychological markers of well-being. Regarding improvement in specific clinical diseases, research is generally mixed and preliminary. Strong recommendations cannot be made based on current evidence, and further studies are needed. In general, there is a stronger body of evidence supporting mindfulness-based stress reduction than for transcendental …

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …

Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) …

A Systems Approach To Stress, Stressors And Resilience In Humans, Barry S. Oken, Irina Chamine, Wayne W. Wakeland

Complex Systems Faculty Publications and Presentations

The paper focuses on the biology of stress and resilience and their biomarkers in humans from the system science perspective. A stressor pushes the physiological system away from its baseline state towards a lower utility state. The physiological system may return towards the original state in one attractor basin but may be shifted to a state in another, lower utility attractor basin. While some physiological changes induced by stressors may benefit health, there is often a chronic wear and tear cost due to implementing changes to enable the return of the system to its baseline state and maintain itself in …

Maternal Nicotine Exposure Leads To Impaired Disulfide Bond Formation And Augmented Endoplasmic Reticulum Stress In The Rat Placenta, Michael Wong, Catherine J. Nicholson, Alison C. Holloway, Daniwl Hardy

Physiology and Pharmacology Publications

Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation-a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar …

Exposure To Phthalates Affects Calcium Handling And Intercellular Connectivity Of Human Stem Cell-Derived Cardiomyocytes, Nikki G. Posnack, Rabia Idrees, Hao Ding, Rafael Jaimes Iii, Gulnaz Stybayeva, Zaruhi Karabekian, Michael A. Laflamme, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes.

Methods and Results

The …

Guidelines For Pre-Clinical Assessment Of The Acetylcholine Receptor-Specific Passive Transfer Myasthenia Gravis Model - Recommendations For Methods And Experimental Designs., Linda L. Kusner, Mario Losen, Angela Vincent, Jon Lindstrom, Socrates Tzartos, Konstantinos Lazaridis, Pilar Martinez-Martinez

Pharmacology and Physiology Faculty Publications

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer …

Voltage-Gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity And Invasion Via Persistent Mapk Signaling, Carrie D. House, Bi-Dar Wang, Kristin Ceniccola, Russell Williams, May Simaan, Norman H. Lee, +7 Additional Authors

Pharmacology and Physiology Faculty Publications

Functional expression of voltage-gated Na⁺ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using …

The Role Of Occupational Therapy In Primary Care, Priti Patel

Occupational Therapy Doctorate Capstone Projects

The Capstone Project is focused on communicating, influencing and educating other health care professionals regarding the role of occupational therapy in the future model of primary care delivery initiated by the adoption of the Affordable Care Act and the Triple Aim Initiative. Currently, primary care, the largest health care platform in United States, is not inclusive of occupational therapy services. Occupational therapists have the scope, knowledge and understanding to be part of the redesigned team model of primary care. Educating those currently working in primary care about adding occupational therapy services can have a significant impact on the profession of …

Risperidone And Its Deconstructed Analogs: Functional Effects On The 5ht2ar, Sneha Shah

Theses and Dissertations

G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that sense extracellular signal and activate intracellular signaling pathways. The serotonin 5HT2A receptor (or 2AR) is one of the GPCRs coupled to Gq proteins, activating PLC and hydrolyzing PIP2. This hydrolysis causes a diffusion of bound PIP2 away from the channel binding site resulting in G protein-gated inwardly rectifying K⁺ channel (GIRK) inhibition and a downstream stimulation of Ca²⁺ release from endoplasmic reticulum stores. Previous experiments have demonstrated that the serotonin 5HTA receptor is a target of serotonergic psychedelic drugs, such as LSD, and partially mediates the action of many …

Appropriate Timing Of Fluoxetine And Statin Delivery Reduces The Risk Of Secondary Bleeding In Ischemic Stroke Rats, Maria Helen Harley Balch, Moner A. Ragas, Danny Wright, Kenny Reynolds, Bryce Kerr, Adrian M. Corbett

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Ongoing clinical trials are testing the effect of fluoxetine delivered post-stroke where a majority of patients are taking statins. This study determined the influence of the timing of administration of fluoxetine and statin on the final infarct volume and the risk of secondary bleeding in an animal model of ischemic stroke.

Methods and findings: Ischemic strokes were induced by endothelin-1 injection into two cortical sites of 10-12 month old female rats, targeting the forelimb motor cortex. Combined medications (5 mg/kg fluoxetine and 1 mg/kg simvastatin) were orally administered either beginning 6-12 hours or 20-26 hours after stroke induction and …

The Skeletal Muscle Molecular Clock Regulates The Timing Of Substrate Metabolism And The Circadian Expression Of Titin-Cap, Brian A. Hodge

Theses and Dissertations--Physiology

Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. An intrinsic molecular clock mechanism exists within skeletal muscle that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by assaying gene …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

Dysregulation of dopaminergic homeostasis has been established as the primary source of numerous neurological disorders including Parkinson’s and drug addiction. A tonic increase of dopamine (DA) in the nucleus accumbens is required for associating everyday events and behaviors with rewards. Yet many addictive exogenous compounds such as amphetamine (AMPH) and cocaine (COC) produce a much greater augmentation of synaptic DA levels that are linked to euphoria and a shift in behavior towards drug seeking. The protein responsible for maintaining extracellular levels of DA is the dopamine transporter (DAT). It is primarily located in the perisynaptic area at terminals of pre-synaptic …

Inhibition Of Mtor Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction, Scott M. Filippone

Theses and Dissertations

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of …

Inverse Relationship Between Physical Activity, Adiposity And Arterial Stiffness In Healthy Middle-Aged Subjects, Oscar Mac Ananey, B Mc Loughlin, A Leonard, L Maher, P Gaffney, G Boran, V Maher

Articles

BACKGROUND:

Several obesity related factors are reported to exacerbate premature arterial stiffening, including inactivity and metabolic disarray. The aim of the present study was to investigate the relationship between physical activity, arterial stiffness and adiposity using objective methods. To further explore the role of adiposity in this complex process, obesity associated anthropometric and humoral biomarkers were measured.

METHODS:

Seventy-nine healthy, lifelong non-smoking, subjects were recruited. Habitual physical activity was measured using accelerometry. Arterial stiffness (augmentation index; AIx & pulse wave velocity; PWV), was measured using tonometry. Body composition was estimated using bioimpedence. Adipose associated biomarkers, leptin and adiponectin, were also …

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

Mapping The Spatial And Temporal Dynamics Of Sensorimotor Integration During The Perception And Performance Of Wallowing, Megan E. Cuellar

Theses and Dissertations (ETD)

Similar to other complex sequences of muscle activity, swallowing relies heavily upon ‘sensorimotor integration.’ It is well known that the premotor cortex and primary sensorimotor cortices provide critical sensorimotor contributions that help control the strength and timing of swallowing muscle effectors. However, the temporal dynamics of sensorimotor integration remains unclear, even when performed normally without neurological compromise. Recent advances in EEG analysis blind source separation techniques via independent component analysis offer a novel and exciting opportunity to measure cortical sensorimotor activity in realtime during swallowing, concurrently with muscle activity during swallow initiation. In the current study, mu components were identified, …

Central Role Of Carotid Body Chemoreceptors In Disordered Breathing And Cardiorenal Dysfunction In Chronic Heart Failure., Noah J. Marcus, Rodrigo Del Rio, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. …

Analysis For Co-Occurring Sequence Features Identifies Link Between Common Synonymous Variant And An Early-Terminated Npc1 Isoform, Mercedeh Movassagh, Prakriti Mudvari, Maria Kokkinaki, Nathan J. Edwards, Nady Golestaneh, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Direct assessment of allelic phase for DNA and RNA features of diploid genomes has been challenging for Sanger sequencing, due to its allele-conflating base-calling signal. Massively parallel sequencing technologies are based on the generation of a continuous copy of a single strand sequence segments, thus preserving the allelic relation between the features of the original molecules. We have performed a transcriptome-wide search for co-occurrence of variant nucleotides and exon-intron boundaries positioned within the length of a single sequencing read. Analysis of 75 human transcriptomes from retinal pigment epithelia (RPE), glioblastoma, low-grade brain tumor, breast cancer and colon cancer, have identified …

Visualization Of Oxytocin Release That Mediates Paired Pulse Facilitation In Hypothalamic Pathways To Brainstem Autonomic Neurons, Ramon A. Pinol, Heather Jameson, Anastas Popratiloff, Norman H. Lee, David Mendelowitz

Pharmacology and Physiology Faculty Publications

Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work …

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

Role Of Astrocyte Network In Edema After Juvenile Traumatic Brain Injury, Andrew Minoru Fukuda

Loma Linda University Electronic Theses, Dissertations & Projects

Juvenile traumatic brain injury (jTBI) is the leading cause of death and disability in young children and adolescents. Despite its lasting detrimental effects on the developing brain, no pharmacological treatment exists. One of the pathological hallmarks of jTBI is edema. Astrocytes play a key role in the edema process, and have been hypothesized that numerous astrocyte networks allow communication and propagation of edema and secondary injury spread. Two key astrocyte proteins are hypothesized to have a central role in the edema process: Aquaporin 4 (AQP4) and Connexin 43 (Cx43). AQP4 is expressed extensively in astrocyte endfeet, which surrounds the blood …

Cc2d1a Regulates Human Intellectual And Social Function As Well As Nf-Κb Signaling Homeostasis., M. Chiara Manzini, Lan Xiong, Ranad Shaheen, Dimira E Tambunan, Stefania Di Costanzo, Vanessa Mitisalis, +15 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons …

Effects Of Various Partial Body Cooling Techniques On Core Temperature During Recovery From Prolonged Cycling-Induced Heat Stress, Afton Danielle Seeley

Masters Theses

The purpose of this study was to investigate the effects of using an ice-vest and a palm cooling device on core and skin temperatures, heart rate, and perceived thermal comfort during a one hour recovery period following exercise in the heat. Ten recreationally active adults cycled for one hour at 50% V0₂ peak on a cycle ergometer while exposed to 36°C 45%relative humidity environmental conditions. Following exercise, each subjectwas exposed to an ice vest, a palm cooling device, or a non cooling control while seated in the environmental chamber for 60 more minutes. No significant differencewas found betweenany of …

Comparison Of Dual- And Tri-Axial Accelerometer Accuracy, Lindsay Powell Toth

Masters Theses

The purpose of this study was to investigate the accuracy of the Omron HJ-720ITC and the Fitbit Zip activity monitors with regard to step count, energy expenditure, and distance traveled measurements. The importance of this research rests in the success rates of pedometer-based physical activity interventions which have been shown to increase physical activity while also enabling weight loss and lowering blood pressure in the adult population. Activity monitors available for retail sale must be found accurate for proper participation in exercise interventions especially low-cost devices as used in this study.

In order to test the accuracy of the Omron …

Survivin As Potential Mediator To Support Autoreactive Cell Survival In Myasthenia Gravis: A Human And Animal Model Study, Linda Louise Kusner, Michael J. Ciesielski, Alexander Marx, Henry J. Kaminski, Robert A. Fenstermaker

Pharmacology and Physiology Faculty Publications

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer …

Kinase Insert Domain Receptor/Vascular Endothelial Growth Factor Receptor 2 (Kdr) Genetic Variation Is Associated With Ovarian Hyperstimulation Syndrome, Travis J. O'Brien, Arthur F. Harralson, Tuyen Tran, Ian Gindoff, Funda E. Orkunoglu-Suer, David Frankfurter, Paul Gindoff

Pharmacology and Physiology Faculty Publications

Background

The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).

Methods

This was a case-control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups.

Results

Patients who developed OHSS had significantly higher response markers (estradiol levels …

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw …

Ponatinib-Induced Adverse Effects: Thrombocytopenia, Pancreatitis And Hepatoxicity-- A Case Report, Saba Hasan, Crystal Fedorkiv, Naba Rahman, Jennifer Andres

Research Day

Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease that generates from malignant transformation of pluripotent hematopoietic stem cells. First line treatment for CML is the tyrosine kinase inhibitor (TKI), imatinib. For patients resistant or intolerant to imatinib, other TKIs, dasatinib, nilotinib, and ponatinib, are approved treatments. Patients who are resistant or intolerant to other agents are started on ponatinib as a last line option. Common adverse events of ponatinib are hypertension, dry skin, rash, abdominal pain, constipation, and nausea. More serious adverse effects include cardiovascular effects, fluid retention, pancreatitis, severe myelosuppression, and hepatotoxicity. Treatment for these adverse effects can …

Targeting Therapy To The Neuromuscular Junction: Proof Of Concept, Linda L. Kusner, Namita Satija, Georgiana Cheng, Henry J. Kaminski

Pharmacology and Physiology Faculty Publications

Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ.

Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG.

Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally …