Publications by authors named "Brenda Griffin"

23 Publications

  • Page 1 of 1

ANCA associated glomerulonephritis in tuberculosis: a paradoxical reaction.

BMJ Case Rep 2021 Jun 15;14(6). Epub 2021 Jun 15.

Department of Respiratory Medicine, St James's Hospital, Dublin, Ireland.

We present a case of antineutrophil cytoplasmic antibodies (ANCA)-associated rapidly progressive glomerulonephritis in the context of treatment of pulmonary tuberculosis (TB). A 42-year-old woman was treated for drug-susceptible pulmonary TB and represented with paradoxical worsening of symptoms and radiological features. She was HIV negative. A severe acute kidney injury with features of glomerulonephritis was evident on admission. Perinuclear ANCA and antimyeloperoxidase antibodies were present in serum and renal biopsy was consistent with ANCA-associated vasculitis. The patient was successfully treated with both antituberculous therapy and immunosuppression (corticosteroids and mycophenolate mofetil) with subsequent clinical improvement and amelioration of renal function. We propose this is the first case that describes the association between paradoxical reactions during TB treatment and ANCA-associated glomerulonephritis.
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http://dx.doi.org/10.1136/bcr-2021-241904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208009PMC
June 2021

Monogenic causes of chronic kidney disease in adults.

Kidney Int 2019 04 14;95(4):914-928. Epub 2019 Feb 14.

National Paediatric Haemodialysis Centre and Renal Transplant Unit, Temple Street Children's University Hospital, Dublin, Ireland.

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
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http://dx.doi.org/10.1016/j.kint.2018.10.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431580PMC
April 2019

Accuracy of a point-of-care luteinizing hormone test for help in distinguishing between sexually intact and ovariectomized or castrated domestic cats.

J Feline Med Surg 2018 10 3;20(10):955-961. Epub 2017 Nov 3.

3 Scott Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.

Objectives The aim of this study was to determine the accuracy of a commercial luteinizing hormone (LH) test as an aid in distinguishing between sexually intact and ovariectomized or castrated domestic cats. Methods Convenience serum samples collected from sexually intact female and male cats (n = 67) undergoing elective sterilization surgery and archived sera from ovariectomized and castrated cats (n = 54) were tested for LH using a commercial diagnostic assay. Test results were compared with the known reproductive status of the cats. Additionally, sera from sexually intact (n = 54) and ovariectomized (n = 94) queens were collected at specific times of the year to evaluate possible seasonal effects on test results. Results Overall test sensitivity was 89.3% (95% confidence interval [CI] 82.3-94.2%), specificity was 92.6% (95% CI 87.1-96.2%) and accuracy was 91.1%. Analysis of results of female cats (n = 216) - sexually intact (n = 87) and ovariectomized (n = 129) - yielded a test sensitivity of 90.8% (95% CI 82.7-96.0%), a specificity of 92.3% (95% CI 86.2-96.2%) and accuracy of 91.7%. Analysis of the results of male cats (n = 53) - sexually intact (n = 19) and neutered (n = 34) - yielded test a sensitivity of 85.3% (95% CI 68.9-95.1%), a specificity of 94.7% (95% CI 74.0-99.9%) and accuracy of 88.7%. The sera of 10 intact queens unexpectedly yielded positive LH results; two of these cats were in estrus, based on visual inspection at the time of ovariohysterectomy. Test accuracy was 94.6% for those 148 samples collected at specific times of the year, with two samples each over three, 3 month periods yielding false-positive results. Conclusions and relevance The commercial point-of-care LH test is a useful adjunct to historical and physical examination findings for determination of reproductive status in domestic cats. Repeat testing 24 h later should be considered for those female cats with signs of estrus and initial positive test results.
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http://dx.doi.org/10.1177/1098612X17738856DOI Listing
October 2018

Profibrotic IHG-1 complexes with renal disease associated HSPA5 and TRAP1 in mitochondria.

Biochim Biophys Acta Mol Basis Dis 2017 04 20;1863(4):896-906. Epub 2017 Jan 20.

Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address:

The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. Here we show that IHG-1 is solely expressed in mitochondria and localised to the inner mitochondrial membrane, the region where mitochondrial reactive oxygen species are generated. Chaperones HSPA5 and TRAP1 and cold shock protein YBX1 were identified as IHG-1 binding partners. All three proteins are important in the cellular response to oxidative stress and play important roles in mitochondrial transcription and DNA repair. Both redox imbalance and IHG-1 stimulate TGF-β signalling. IHG-1, HSPA5 and YBX1 all show increased expression in diabetic nephropathy, chronic kidney disease and in the Unilateral Ureteral Obstruction model of kidney fibrosis. Increased IHG-1 expression in UUO correlated with loss of TRAP1 expression. IHG-1 may target TRAP1 for degradation. When IHG-1 is no longer localised to mitochondria, it retains the ability to interact with the cold shock protein YBX1, facilitating anti-fibrotic actions in the nucleus. Targeting these proteins may offer alternative treatments for fibrotic kidney disease.
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http://dx.doi.org/10.1016/j.bbadis.2017.01.015DOI Listing
April 2017

The Association of Shelter Veterinarians' 2016 Veterinary Medical Care Guidelines for Spay-Neuter Programs.

J Am Vet Med Assoc 2016 Jul;249(2):165-88

As community efforts to reduce the overpopulation and euthanasia of unwanted and unowned cats and dogs have increased, many veterinarians have increasingly focused their clinical efforts on the provision of spay-neuter services. Because of the wide range of geographic and demographic needs, a wide variety of spay-neuter programs have been developed to increase delivery of services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, community cat programs, and services provided through private practitioners. In an effort to promote consistent, high-quality care across the broad range of these programs, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs. These guidelines consist of recommendations for general patient care and clinical procedures, preoperative care, anesthetic management, surgical procedures, postoperative care, and operations management. They were based on current principles of anesthesiology, critical care medicine, infection control, and surgical practice, as determined from published evidence and expert opinion. They represent acceptable practices that are attainable in spay-neuter programs regardless of location, facility, or type of program. The Association of Shelter Veterinarians envisions that these guidelines will be used by the profession to maintain consistent veterinary medical care in all settings where spay-neuter services are provided and to promote these services as a means of reducing sheltering and euthanasia of cats and dogs.
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http://dx.doi.org/10.2460/javma.249.2.165DOI Listing
July 2016

The Irish Kidney Gene Project--Prevalence of Family History in Patients with Kidney Disease in Ireland.

Nephron 2015 18;130(4):293-301. Epub 2015 Jul 18.

Department of Nephrology and Transplantation, Beaumont Hospital, Dublin, Ireland.

Background: The prevalence of kidney disease (KD) due to inherited genetic conditions in Ireland is unknown. The aim of this study was to characterise an adult kidney disease population in Ireland and to identify familial clusters of kidney disease within the population.

Methods: This was a multicenter cross-sectional study of patients with kidney disease in the Republic of Ireland, from January 2014 to September 2014, recruiting from dialysis units and out-patient renal departments. A survey was performed by collecting data on etiology of kidney disease and whether a family history of kidney disease exists. Medical records were cross-referenced to confirm the etiology of kidney disease.

Results: A total of 1,840 patients were recruited with a mean age of 55.9 years (range 17-94.5) and a male predominance (n = 1,095; 59.5%). A positive family history was reported by 629 participants (34.2%). Excluding polycystic kidney disease (n = 134, 7.3%), a positive family history was reported by 495 participants (26.9%). Kidney disease due to an unknown etiology was the commonest etiology in the non-polycystic kidney disease group with a positive family history (10.6%, n = 67). Kidney diseases that are not classically associated with familial inheritance including tubulo-interstitial kidney disease, congenital abnormalities of the kidney and urinary tract and glomerulonephritis demonstrated familial clustering.

Conclusion: In an Irish non-polycystic kidney disease population, 26.9% reports a positive family history. The commonest etiology of kidney disease in the positive family history cohort, excluding autosomal dominant polycystic kidney disease, was kidney disease due to unknown etiology. Examining families with kidney disease provides an opportunity to better understand disease pathogenesis and potentially identify genetic predispositions to kidney disease.
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http://dx.doi.org/10.1159/000436983DOI Listing
May 2016

A Friend in Need: Activated Protein C Stabilizes YB-1 during Renal Ischemia Reperfusion Injury.

J Am Soc Nephrol 2015 Nov 26;26(11):2605-7. Epub 2015 May 26.

School of Medicine, Conway Institute, University College Dublin, Belfield, Dublin, Ireland

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http://dx.doi.org/10.1681/ASN.2015040351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625685PMC
November 2015

IHG-1 increases mitochondrial fusion and bioenergetic function.

Diabetes 2014 Dec 9;63(12):4314-25. Epub 2014 Jul 9.

Diabetes Complications Research Centre, Conway Institute, University College Dublin, Belfield, Dublin, Ireland School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin, Ireland

Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-β1 signaling and increases mitochondrial biogenesis. Here we report that inhibition of endogenous IHG-1 expression results in reduced mitochondrial respiratory capacity, ATP production, and mitochondrial fusion. Conversely, overexpression of IHG-1 leads to increased mitochondrial fusion and also protects cells from reactive oxygen species-induced apoptosis. IHG-1 forms complexes with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding capacity of Mfn2, suggesting that IHG-1 acts as a guanine nucleotide exchange factor. IHG-1 must be localized to mitochondria to interact with Mfn1 and Mfn2, and this interaction is necessary for increased IHG-1-mediated mitochondrial fusion. Together, these findings indicate that IHG-1 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following oxidant stress. We propose that in diabetic kidney disease increased IHG-1 expression protects cell viability and enhances the actions of TGF-β, leading to renal proximal tubule dedifferentiation, an important event in the pathogenesis of this devastating condition.
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http://dx.doi.org/10.2337/db13-1256DOI Listing
December 2014

IHG-1 must be localised to mitochondria to decrease Smad7 expression and amplify TGF-β1-induced fibrotic responses.

Biochim Biophys Acta 2013 Aug 6;1833(8):1969-78. Epub 2013 Apr 6.

School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin, Ireland.

TGF-β1 is a prototypic profibrotic cytokine and major driver of fibrosis in the kidney and other organs. Induced in high glucose-1 (IHG-1) is a mitochondrial protein which we have recently reported to be associated with renal disease. IHG-1 amplifies responses to TGF-β1 and regulates mitochondrial biogenesis by stabilising the transcriptional co-activator peroxisome proliferator-activated receptor gamma coactivator-1-alpha. Here we report that the mitochondrial localisation of IHG-1 is pivotal in the amplification of TGF-β1 signalling. We demonstrate that IHG-1 expression is associated with repression of the endogenous TGF-β1 inhibitor Smad7. Intriguingly, expression of a non-mitochondrial deletion mutant of IHG-1 (Δmts-IHG-1) repressed TGF-β1 fibrotic signalling in renal epithelial cells. In cells expressing Δmts-IHG-1 fibrotic responses including CCN2/connective tissue growth factor, fibronectin and jagged-1 expression were reduced following stimulation with TGF-β1. Δmts-IHG-1 modulation of TGF-β1 signalling was associated with increased Smad7 protein expression. Δmts-IHG-1 modulated TGF-β1 activity by increasing Smad7 protein expression as it failed to inhibit TGF-β1 transcriptional responses when endogenous Smad7 expression was knocked down. These data indicate that mitochondria modulate TGF-β1 signal transduction and that IHG-1 is a key player in this modulation.
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http://dx.doi.org/10.1016/j.bbamcr.2013.03.027DOI Listing
August 2013

Prevalence of serum antibody titers against feline panleukopenia virus, feline herpesvirus 1, and feline calicivirus in cats entering a Florida animal shelter.

J Am Vet Med Assoc 2012 Nov;241(10):1320-5

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA.

Objective: To determine the proportion of cats entering a Florida animal shelter with serum antibody titers against feline panleukopenia virus (FPV), feline herpesvirus 1 (FHV1), and feline calicivirus (FCV) and to identify factors associated with seropositivity.

Design: Cross-sectional study.

Animals: 347 cats admitted to a Florida animal shelter.

Procedures: Within 24 hours after admission to the animal shelter, blood samples were collected from all cats ≥ 8 weeks of age. Serum antibody titers against FPV were determined via a hemagglutination inhibition assay, and those against FHV1 and FCV were determined via virus neutralization assays. Age, sex, environment (urban or rural), source (stray or previously owned), evidence of previous caregiving, health status (healthy or not healthy), and outcome (adoption, transfer, return to owner, or euthanasia) were evaluated as potential factors associated with antibody seropositivity.

Results: Of 347 cats, 138 (39.8%), 38 (11.0%), and 127 (36.6%) had antibody titers ≥ 40, ≥ 8, and ≥ 32 (ie, seropositive) against FPV, FHV1, and FCV, respectively. Factors associated with seropositivity included being neutered, age ≥ 6 months, and being relinquished by an owner. On multivariable analysis, health status at shelter admission, environment, vaccination at shelter admission, and outcome were not associated with seropositivity.

Conclusions And Clinical Relevance: Most cats were seronegative for antibodies against FPV, FHV1, and FCV at the time of admission to an animal shelter. These findings supported current guidelines that recommend vaccination of all cats immediately after admission to animal shelters, regardless of the source or physical condition.
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http://dx.doi.org/10.2460/javma.241.10.1320DOI Listing
November 2012

Effects of maternally-derived antibodies on serologic responses to vaccination in kittens.

J Feline Med Surg 2012 Feb;14(2):118-23

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, USA.

The optimal vaccination protocol to induce immunity in kittens with maternal antibodies is unknown. The objective of this study was to determine the effects of maternally-derived antibody (MDA) on serologic responses to vaccination in kittens. Vaccination with a modified live virus (MLV) product was more effective than an inactivated (IA) product at inducing protective antibody titers (PAT) against feline panleukopenia virus (FPV). IA vaccination against feline herpesvirus-1 (FHV) and feline calicivirus (FCV) was more effective in the presence of low MDA than high MDA. Among kittens with low MDA, MLV vaccination against FCV was more effective than IA vaccination. A total of 15%, 44% and 4% of kittens had insufficient titers against FPV, FHV and FCV, respectively, at 17 weeks of age. Serologic response to vaccination of kittens varies based on vaccination type and MDA level. In most situations, MLV vaccination should be utilized and protocols continued beyond 14 weeks of age to optimize response by all kittens.
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http://dx.doi.org/10.1177/1098612X11432239DOI Listing
February 2012

IHG-1 promotes mitochondrial biogenesis by stabilizing PGC-1α.

J Am Soc Nephrol 2011 Aug 22;22(8):1475-85. Epub 2011 Jul 22.

UCD Diabetes Research Centre, UCD Conway Institute, Ireland.

Increased expression of Induced-by-High-Glucose 1 (IHG-1) associates with tubulointerstitial fibrosis in diabetic nephropathy. IHG-1 amplifies TGF-β1 signaling, but the functions of this highly-conserved protein are not well understood. IHG-1 contains a putative mitochondrial-localization domain, and here we report that IHG-1 is specifically localized to mitochondria. IHG-1 overexpression increased mitochondrial mass and stabilized peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Conversely, inhibition of IHG-1 expression decreased mitochondrial mass, downregulated mitochondrial proteins, and PGC-1α-regulated transcription factors, including nuclear respiratory factor 1 and mitochondrial transcription factor A (TFAM), and reduced activity of the TFAM promoter. In the unilateral ureteral obstruction model, we observed higher PGC-1α protein expression and IHG-1 levels with fibrosis. In a gene-expression database, we noted that renal biopsies of human diabetic nephropathy demonstrated higher expression of genes encoding key mitochondrial proteins, including cytochrome c and manganese superoxide dismutase, compared with control biopsies. In summary, these data suggest that IHG-1 increases mitochondrial biogenesis by promoting PGC-1α-dependent processes, potentially contributing to the pathogenesis of renal fibrosis.
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http://dx.doi.org/10.1681/ASN.2010111154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148702PMC
August 2011

Use of a commercially available relaxin test for detection of pregnancy in cats.

J Am Vet Med Assoc 2010 Dec;237(11):1267-74

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA.

Objective: To determine the earliest day of gestation at which relaxin could be detected in pregnant queens by use of a commercially available point-of-care test designed for use in dogs, and to calculate sensitivity and specificity of the test for pregnancy detection on any specified day of gestation.

Design: Evaluation study.

Animals: 162 female cats (24 queens from a breeding colony, 128 stray and feral queens undergoing ovariohysterectomy, and 10 ovariohysterectomized cats).

Procedures: 24 queens were monitored for pregnancy. Blood samples were collected daily and tested for relaxin until 2 consecutive positive test results were obtained. The earliest day of pregnancy detection was estimated by counting backward from the day of parturition to the day of the first positive test. The uteri, ovaries, and any fetuses of 128 stray and feral queens undergoing ovariohysterectomy were examined grossly, and gestational day in pregnant queens was determined on the basis of fetal crown-rump length. Blood samples from these queens and from 10 cats ovariohysterectomized prior to the study were collected for relaxin testing.

Results: Pregnancy was detected by use of the relaxin test kit as early as gestational day 20; sensitivity of the test was 100% on and after gestational day 29. False-positive results were detected in 3 queens, 2 of which had large (approx 2×3-cm) ovarian cysts, resulting in a specificity of 95.9%.

Conclusions And Clinical Relevance: A commercially available relaxin test kit designed for use in dogs can be used to reliably detect pregnancy in cats.
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http://dx.doi.org/10.2460/javma.237.11.1267DOI Listing
December 2010

Giardia infection in cats.

Compend Contin Educ Vet 2010 Aug;32(8):E4

Animal Care and Control of New York City, USA.

The protozoon Giardia duodenalis is a common gastrointestinal parasite of cats. While most Giardia-infected cats are asymptomatic, acute small bowel diarrhea, occasionally with concomitant weight loss, may occur. Giardia poses a diagnostic challenge, but newer tests, including a commercially available ELISA kit, have improved clinicians' ability to obtain an accurate diagnosis. Several treatment options have been reported, and although none has been shown to be universally effective, most cases can be successfully managed with drug therapy, supportive measures, and environmental control. Current recommendations suggest that combination therapy with fenbendazole and metronidazole may be the safest, most effective treatment option for symptomatic cats.
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August 2010

Evaluation of collars and microchips for visual and permanent identification of pet cats.

J Am Vet Med Assoc 2010 Aug;237(4):387-94

Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.

Objective: To determine the percentage of pet cats still wearing collars and having functional microchips 6 months after application.

Design: Randomized controlled clinical trial.

Animals: 538 client-owned cats.

Procedures: Cats were randomly assigned to wear 1 of 3 types of collars: plastic buckle, breakaway plastic buckle safety, and elastic stretch safety. Each cat was fitted with the assigned collar, and a microchip was inserted SC between the scapulae. Owners completed questionnaires about their experiences and expectations of collars at enrollment and at the conclusion of the study.

Results: 391 of the 538 (72.7%) cats successfully wore their collars for the entire 6-month study period. Owners' initial expectations of the cats' tolerance of the collar and the number of times the collar was reapplied on the cats' necks were the most important factors predicting success. Type of collar likely influenced how often collars needed to be reapplied. Eighteen (3.3%) cats caught a forelimb in their collar or caught their collar on an object or in their mouth. Of the 478 microchips that were scanned at the conclusion of the study, 477 (99.8%) were functional.

Conclusions And Clinical Relevance: Most cats successfully wore their collars. Because even house cats can become lost, veterinarians should recommend that all cats wear identification collars since they are the most obvious means of identifying an owned pet. For some cats, collars may frequently come off and become lost; therefore, microchips are an important form of backup identification. Owners should select a collar that their cat will tolerate and should check it often to ensure a proper fit.
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http://dx.doi.org/10.2460/javma.237.4.387DOI Listing
August 2010

ZP-binding peptides identified via phage display stimulate production of sperm antibodies in dogs.

Anim Reprod Sci 2010 Jul 13;120(1-4):151-7. Epub 2010 Apr 13.

Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36830, USA.

Zona pellucida (ZP) glycoproteins play a central role in sperm-oocyte binding and fertilization. Sperm protein sequences that are involved in sperm-ZP recognition and have an important role in fertilization represent attractive targets for development of contraceptive vaccines, yet are currently unknown. To identify peptide sequences that recognize and bind to ZP proteins, we developed a novel selection procedure from phage display libraries that utilizes intact oocytes surrounded by ZP proteins. The major advantage of this procedure is that ZP proteins remain in their native conformation unlike a selection protocol previously published that utilized solubilized ZP on artificial solid support. Several peptides of 7 and 12 amino acids with binding specificity to canine ZP proteins were identified. Four of them (LNSFLRS, SSWYRGA, YLPIYTIPSMVY, and NNQSPILKLSIH) plus a control ZP-binding peptide (YLPVGGLRRIGG) from the literature were synthesized and tested for antigenic properties in dogs. NNQSPILKLSIH peptide stimulated production of anti-peptide antibodies. These antibodies bind to the acrosomal region of the canine sperm cell, demonstrating ability to act as sperm antibodies. The identified ZP-binding peptides (mimicking sperm cell surface antigens) may be useful in the design of immunocontraceptive agents for dogs.
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http://dx.doi.org/10.1016/j.anireprosci.2010.04.002DOI Listing
July 2010

The Association of Shelter Veterinarians veterinary medical care guidelines for spay-neuter programs.

J Am Vet Med Assoc 2008 Jul;233(1):74-86

Section of Pain Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

As efforts to reduce the overpopulation and euthanasia of unwanted and unowned dogs and cats have increased, greater attention has been focused on spay-neuter programs throughout the United States. Because of the wide range of geographic and demographic needs, a wide variety of programs have been developed to increase delivery of spay-neuter services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, feral cat programs, and services provided through private practitioners. In an effort to ensure a consistent level of care, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs. The guidelines consist of recommendations for preoperative care (eg, patient transport and housing, patient selection, client communication, record keeping, and medical considerations), anesthetic management (eg, equipment, monitoring, perioperative considerations, anesthetic protocols, and emergency preparedness), surgical care (eg, operating-area environment; surgical-pack preparation; patient preparation; surgeon preparation; surgical procedures for pediatric, juvenile, and adult patients; and identification of neutered animals), and postoperative care (eg, analgesia, recovery, and release). These guidelines are based on current principles of anesthesiology, critical care medicine, microbiology, and surgical practice, as determined from published evidence and expert opinion. They represent acceptable practices that are attainable in spay-neuter programs.
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http://dx.doi.org/10.2460/javma.233.1.74DOI Listing
July 2008

IHG-1 amplifies TGF-beta1 signaling and is increased in renal fibrosis.

J Am Soc Nephrol 2008 Sep 28;19(9):1672-80. Epub 2008 May 28.

UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

Induced in high glucose-1 (IHG-1) is an evolutionarily conserved gene transcript upregulated by high extracellular glucose concentrations, but its function is unknown. Here, it is reported that the abundance of IHG-1 mRNA is nearly 10-fold higher in microdissected, tubule-rich renal biopsies from patients with diabetic nephropathy compared with control subjects. In the diabetic nephropathy specimens, in situ hybridization localized IHG-1 to tubular epithelial cells along with TGF-beta1 and activated Smad3, suggesting a possible role in the development of tubulointerstitial fibrosis. Supporting this possibility, IHG-1 mRNA and protein expression also increased with unilateral ureteral obstruction. In the HK-2 proximal tubule cell line, overexpression of IHG-1 increased TGF-beta1-stimulated expression of connective tissue growth factor and fibronectin. IHG-1 was found to amplify TGF-beta1-mediated transcriptional activity by increasing and prolonging phosphorylation of Smad3. Conversely, inhibition of endogenous IHG-1 with small interference RNA suppressed transcriptional responses to TGF-beta1. In summary, IHG-1, which increases in diabetic nephropathy, may enhance the actions of TGF-beta1 and contribute to the development of tubulointerstitial fibrosis.
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http://dx.doi.org/10.1681/ASN.2007101080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518434PMC
September 2008

Prevalence of Anaplasma phagocytophilum in domestic felines in the United States.

Vet Parasitol 2007 Jun 9;147(1-2):194-8. Epub 2007 May 9.

Department of Pathobiology, 166 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, United States.

Anaplasma phagocytophilum is among the more common tick-borne disease agents in the United States. It is of veterinary and public health significance as dogs, cats, and human beings are known to be susceptible. A. phagocytophilum is transmitted trans-stadially by either nymphs or adults of either the black-legged tick (Ixodes scapularis) or the western black-legged tick (Ixodes pacificus). Little information is available regarding either the prevalence of this agent in cats or the dynamics of vector transmission. Four hundred and sixty feline blood samples from sites throughout the United States were assayed for antibodies to A. phagocytophilum using an indirect immunofluorescence assay (IFA). Results of the prevalence study showed that 20 samples (4.3%) were positive for A. phagocytophilum antibodies by IFA at a 1:50 dilution, however these results could not be confirmed by PCR analysis. PCR analysis for other cross-reacting Ehrlichia/Anaplasma spp. was also negative. These results demonstrate that natural infection of A. phagocytophilum in cats is uncommon.
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http://dx.doi.org/10.1016/j.vetpar.2007.03.028DOI Listing
June 2007

Prevalence of Bartonella species, haemoplasma species, Ehrlichia species, Anaplasma phagocytophilum, and Neorickettsia risticii DNA in the blood of cats and their fleas in the United States.

J Feline Med Surg 2006 Apr 14;8(2):85-90. Epub 2005 Nov 14.

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, 80523, USA.

Ctenocephalides felis were killed and collected from 92 cats in Alabama, Maryland, and Texas. The fleas and blood from the corresponding cat were digested and assessed in polymerase chain reaction assays that amplify DNA of Ehrlichia species, Anaplasma phagocytophilum, Neorickettsia risticii, Mycoplasma haemofelis, 'Candidatus M haemominutum' and Bartonella species. DNA consistent with B henselae, B clarridgeiae, M haemofelis, or 'Candidatus M haemominutum' was commonly amplified from cats (60.9%) and their fleas (65.2%). Results of this study support the recommendation to maintain flea control on cats in endemic areas.
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http://dx.doi.org/10.1016/j.jfms.2005.08.003DOI Listing
April 2006

Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis.

Acta Neuropathol 2005 Nov 1;110(5):443-50. Epub 2005 Oct 1.

Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5525, USA.

The G(M2) activator protein is required for successful degradation of G(M2) ganglioside by the A isozyme of lysosomal beta-N-acetylhexosaminidase (EC 3.2.1.52). Deficiency of the G(M2) activator protein leads to a relentlessly progressive accumulation of G(M2) ganglioside in neuronal lysosomes and subsequent fatal deterioration of central nervous system function. G(M2) activator deficiency has been described in humans, dogs and mice. This manuscript reports the discovery and characterization of a feline model of G(M2) activator deficiency that exhibits many disease traits typical of the disorder in other species. Cats deficient in the G(M2) activator protein develop clinical signs at approximately 14 months of age, including motor incoordination and exaggerated startle response to sharp sounds. Affected cats exhibit central nervous system abnormalities such as swollen neurons, membranous cytoplasmic bodies, increased sialic acid content and elevated levels of G(M2) ganglioside. As is typical of G(M2) activator deficiency, hexosaminidase A activity in tissue homogenates appears normal when assayed with a commonly used synthetic substrate. When the G(M2) activator cDNA was sequenced from normal and affected cats, a deletion of 4 base pairs was identified as the causative mutation, resulting in alteration of 21 amino acids at the C terminus of the G(M2) activator protein.
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http://dx.doi.org/10.1007/s00401-005-1040-6DOI Listing
November 2005

The use of fecal markers to facilitate sample collection in group-housed cats.

Authors:
Brenda Griffin

Contemp Top Lab Anim Sci 2002 Mar;41(2):51-6

Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Alabama 36841, USA.

The provision of proper social housing is a priority when designing an experiment using domestic cats as laboratory animals. When animals are group-housed, studies requiring analysis of stool samples from individual subjects pose difficulty in sample collection and identification. In this study, commercially available concentrated food colorings (known as bakers pastes) were used as fecal markers in group-housed cats. Cats readily consumed 0.5 ml of bakers paste food coloring once daily in canned cat food. Colorings served as fecal markers by imparting a distinct color to each cat s feces, allowing identification in the litter box. In addition, colored glitter (1/8 teaspoon in canned food) was fed to cats and found to be a reliable fecal marker. Long-term feeding of colorings and glitter was found to be safe and effective at yielding readily identifiable stools.
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March 2002

Vitamin A Homeostasis in the Diabetic Rat.

J Clin Biochem Nutr 1993;15(1):23-31

Alcon Laboratories, Inc., Fort Worth. Texas, U.S.A.

The concentrations of vitamin A (retinol) and retinyl ester in the plasma and liver of normal and diabetic rats were measured by HPLC (high-performance liquid chromatography). Diabetic rats had severe hyperglycemia, induced by a single streptozotocin injection 5 weeks prior to sampling. In the normal rats, plasma retinyl palmitate was very low, and the level was increased 10-fold by diabetes. Detailed time-course studies showed that rats became hyperglycemic within 48 h of streptozotocin injection, yet the plasma retinyl palmitate level was not elevated until some three weeks later. Severe diabetes did not significantly influence plasma retinol: however. free retinol in the liver was elevated within 10 days of initiation of the disease and continued to increase for the duration of the study. These results show that streptozotocin-induced diabetes significantly alters the concentrations of hepatic retinol and plasma retinyl ester. The biochemical mechanism(s) of this altered vitamin A homeostasis in diabetes and its possible relationship to tissue pathogenesis are not known at present.
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http://dx.doi.org/10.3164/jcbn.15.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307621PMC
January 1993
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