Early neurophysiological biomarkers and spinal cord pathology in inherited prion disease
Peter Rudge Zane Jaunmuktane Harpreet Hyare Matthew Ellis Martin Koltzenburg John Collinge Sebastian Brandner Simon Mead Brain, awy358, https://doi.org/10.1093/brain/awy358
Published: 28 January 2019 Article history
Abstract A common presentation of inherited prion disease is Gerstmann-Sträussler-Scheinker syndrome, typically presenting with gait ataxia and painful dysaesthesiae in the legs evolving over 2–5 years. The most frequent molecular genetic diagnosis is a P102L mutation of the prion protein gene (PRNP). There is no explanation for why this clinical syndrome is so distinct from Creutzfeldt-Jakob disease, and biomarkers of the early stages of disease have not been developed. Here we aimed, first, at determining if quantitative neurophysiological assessments could predict clinical diagnosis or disability and monitor progression and, second, to determine the neuropathological basis of the initial clinical and neurophysiological findings. We investigated subjects known to carry the P102L mutation in the longitudinal observational UK National Prion Monitoring Cohort study, with serial assessments of clinical features, peripheral nerve conduction, H and F components, threshold tracking and histamine flare and itch response and neuropathological examination in some of those who died. Twenty-three subjects were studied over a period of up to 12 years, including 65 neurophysiological assessments at the same department. Six were symptomatic throughout and six became symptomatic during the study. Neurophysiological abnormalities were restricted to the lower limbs. In symptomatic patients around the time of, or shortly after, symptom onset the H-reflex was lost. Lower limb thermal thresholds were at floor/ceiling in some at presentation, in others thresholds progressively deteriorated. Itch sensation to histamine injection was lost in most symptomatic patients. In six patients with initial assessments in the asymptomatic stage of the disease, a progressive deterioration in the ability to detect warm temperatures in the feet was observed prior to clinical diagnosis and the onset of disability. All of these six patients developed objective abnormalities of either warm or cold sensation prior to the onset of significant symptoms or clinical diagnosis. Autopsy examination in five patients (including two not followed clinically) showed prion protein in the substantia gelatinosa, spinothalamic tracts, posterior columns and nuclei and in the neuropil surrounding anterior horn cells. In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. Neuro-physiological measures become abnormal around the time of symptom onset, prior to diagnosis, and may be of value for improved early diagnosis and for recruitment and monitoring of progression in clinical trials.
P102L, GSS, sensory symptoms, spinal cord
Issue Section: Original Article
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
here is the latest;
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge). To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip...see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry
Prion 2017 Conference Abstracts
CWD 2017 PRION CONFERENCE
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes.
Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product.
Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain).
Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments.
We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem.
Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes.
All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.
Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing.
Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years.
Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017
DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE
DECIPHERING NEURODEGENERATIVE DISORDERS
VIDEO PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
*** PRION 2017 CONFERENCE VIDEO
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. <***
ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION
10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question...
''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II)
EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors
also, see;
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
snip...
The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
REVIEW
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
Thursday, March 8, 2018
Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein
MONDAY, NOVEMBER 23, 2015
Blood transmission studies of prion infectivity in the squirrel monkey (Saimiri sciureus): the Baxter study
ORIGINAL RESEARCH
Blood transmission studies of prion infectivity in the squirrel monkey (Saimiri sciureus): the Baxter study
Diane L. Ritchie1,*, Susan V. Gibson2,†, Christian R. Abee3, Thomas R. Kreil4, James W. Ironside1 and Paul Brown5 Article first published online: 23 NOV 2015 DOI: 10.1111/trf.13422 © 2015 AABB
Issue Cover image for Vol. 55 Issue 11 Transfusion Early View (Online Version of Record published before inclusion in an issue)
Abstract
BACKGROUND Four secondary transmissions of variant Creutzfeldt-Jakob disease (vCJD) infectivity have been associated with the transfusion of nonleukoreduced red blood cells collected from vCJD patients during the asymptomatic phase of the disease. Establishing efficient experimental models for assessing the risk of future transmissions of vCJD infectivity via blood transfusion is of paramount importance in view of a study of archived appendix samples in which the prevalence of asymptomatic vCJD infection in the United Kingdom was estimated at approximately 1 in 2000 of the population. In this study, we investigated transmission of vCJD and sporadic CJD (sCJD) infectivity from blood using the squirrel monkey, which is highly susceptible to experimental challenge with human prion disease.
STUDY DESIGN AND METHODS Whole blood collected from vCJD- and sCJD-infected squirrel monkeys was transfused at multiple time points into recipient squirrel monkeys. Blood recipients were euthanized approximately 7 years after their first blood transfusion.
RESULTS No clinical or pathologic signs of a prion disease were observed in either the sCJD- or the vCJD-transfused monkeys, and immunohistochemistry and biochemical investigations showed no PrPTSE in central nervous system or lymphoreticular tissues. Similarly, monkeys inoculated intracerebrally (IC) and intravenously (IV) with either buffy coat or plasma from vCJD and sCJD patients failed to develop disease. However, white blood cells from a chimpanzee-passaged strain of human Gerstmann-Sträussler-Scheinker (GSS) disease transmitted autopsy-proven disease to two IC-inoculated monkeys after incubation periods of 34 and 39 months.
CONCLUSION Blood transmits GSS but not sCJD or vCJD infectivity to IC- or IV-inoculated squirrel monkeys within a 7-year observation period.
2015 PRION CONFERENCE
*** RE-P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study
***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD.
*** P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study
Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA
Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.
ran across an old paper from 1984 ;
***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent. ***
From: Terry S. Singeltary Sr.
Sent: Saturday, November 15, 2014 9:29 PM
To: Terry S. Singeltary Sr.
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984 THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984
snip...
THE BAXTER STUDY...SEE MORE HERE ;
Saturday, May 30, 2015
PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS
FRIDAY, JANUARY 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???
MONDAY, DECEMBER 03, 2018
Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients
SUNDAY, DECEMBER 09, 2018
Creutzfeldt Jakob Disease CJD, BSE, Scrapie, CWD, TSE Prion Annual Report December 14, 2018
MONDAY, JANUARY 21, 2019
Bovine Spongiform Encephalopathy BSE TSE Prion Surveillance FDA USDA APHIS FSIS UPDATE 2019
Wednesday, January 23, 2019
CFIA SFCR Guidance on Specified risk material (SRM) came into force on January 15, 2019
FRIDAY, JANUARY 25, 2019
Mad cow testing in Alabama halted by government shutdown while mad deer disease CWD is spreading in the USA like wildfire
A collaborative program between the Alabama Department of Agriculture and Industries and the U.S. Department of Agriculture to sample cows that die of unknown causes for bovine spongiform encephalopathy [BSE], also called mad cow disease, has been suspended since the federal government shutdown began in December.
CWD TSE PRION FROM TEXAS TO MISSISSIPPI WITH LOVE?
''On January 21, 2017 a tornado took down thousands of feet of fence for a 420-acre illegal deer enclosure in Lamar County that had been subject to federal and state investigation for illegally importing white-tailed deer into Mississippi from Texas (a CWD positive state). Native deer were free to move on and off the property before all of the deer were able to be tested for CWD. Testing will be made available for a period of three years for CWD on the property and will be available for deer killed within a 5-mile radius of the property on a voluntary basis. ''
Texas Chronic Wasting Disease CWD TSE Prion Symposium 2018 posted January 2019 VIDEO SET 18 CLIPS
See Wisconsin update...terrible news, right after Texas updated map around 5 minute mark...
WISCONSIN CWD CAPTIVE CWD UPDATE VIDEO
cwd update on Wisconsin from Tammy Ryan...
Wyoming CWD Dr. Mary Wood
''first step is admitting you have a problem''
''Wyoming was behind the curve''
wyoming has a problem...
SATURDAY, JANUARY 19, 2019
Texas Chronic Wasting Disease CWD TSE Prion Symposium 2018 posted January 2019 VIDEO SET 18 CLIPS
TUESDAY, JANUARY 29, 2019
TEXAS REPORTS 2 MORE CWD TSE PRION ALL WILD CERVID TOTAL TO DATE 141
***> This is very likely to have parallels with control efforts for CWD in cervids.
Rapid recontamination of a farm building occurs after attempted prion removal
Kevin Christopher Gough, BSc (Hons), PhD1, Claire Alison Baker, BSc (Hons)2, Steve Hawkins, MIBiol3, Hugh Simmons, BVSc, MRCVS, MBA, MA3, Timm Konold, DrMedVet, PhD, MRCVS3 and Ben Charles Maddison, BSc (Hons), PhD2
Abstract
The transmissible spongiform encephalopathy scrapie of sheep/goats and chronic wasting disease of cervids are associated with environmental reservoirs of infectivity.
Preventing environmental prions acting as a source of infectivity to healthy animals is of major concern to farms that have had outbreaks of scrapie and also to the health management of wild and farmed cervids.
Here, an efficient scrapie decontamination protocol was applied to a farm with high levels of environmental contamination with the scrapie agent.
Post-decontamination, no prion material was detected within samples taken from the farm buildings as determined using a sensitive in vitro replication assay (sPMCA).
A bioassay consisting of 25 newborn lambs of highly susceptible prion protein genotype VRQ/VRQ introduced into this decontaminated barn was carried out in addition to sampling and analysis of dust samples that were collected during the bioassay.
Twenty-four of the animals examined by immunohistochemical analysis of lymphatic tissues were scrapie-positive during the bioassay, samples of dust collected within the barn were positive by month 3.
The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.
snip...
As in the authors' previous study,12 the decontamination of this sheep barn was not effective at removing scrapie infectivity, and despite the extra measures brought into this study (more effective chemical treatment and removal of sources of dust) the overall rates of disease transmission mirror previous results on this farm. With such apparently effective decontamination (assuming that at least some sPMCA seeding ability is coincident with infectivity), how was infectivity able to persist within the environment and where does infectivity reside? Dust samples were collected in both the bioassay barn and also a barn subject to the same decontamination regime within the same farm (but remaining unoccupied). Within both of these barns dust had accumulated for three months that was able to seed sPMCA, indicating the accumulation of scrapie-containing material that was independent of the presence of sheep that may have been incubating and possibly shedding low amounts of infectivity.
This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapiepositive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.
Acknowledgements The authors thank the APHA farm staff, Tony Duarte, Olly Roberts and Margaret Newlands for preparation of the sheep pens and animal husbandry during the study. The authors also thank the APHA pathology team for RAMALT and postmortem examination.
Funding This study was funded by DEFRA within project SE1865.
Competing interests None declared.
Saturday, January 5, 2019
Rapid recontamination of a farm building occurs after attempted prion removal
***> NORWAY CWD UPDATE December 2018
Report from the Norwegian Scientific Committee for Food and Environment (VKM) 2018: 16
Factors that can contribute to spread of CWD – an update on the situation in Nordfjella, Norway
Opinion of Panel on biological hazards of the Norwegian Scientific Committee for Food and Environment
13.12.2018
ISBN: 978-82-8259-316-8
ISSN: 2535-4019
Norwegian Scientific Committee for Food and Environment (VKM)
Po 222 Skøyen
0213 Oslo
Norway
FRIDAY, DECEMBER 14, 2018
Norway, Nordfjella VKM 2018 16 Factors that can contribute to spread of CWD TSE Prion UPDATE December 14, 2018
THURSDAY, OCTOBER 25, 2018
***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion
new link;
THURSDAY, JANUARY 31, 2019
Mississippi Chronic Wasting Disease Cases Almost Doubles to 11 Cases Confirmed To Date
Terry S. Singeltary Sr.
