Henry J Baker

Henry J Baker
Auburn University | AU · Department of Pathobiology

DVM

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131
Publications
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Publications

Publications (131)
Article
Objective: GM2 gangliosidosis is usually fatal by 5 years of age in its two major subtypes, Tay-Sachs and Sandhoff disease. First reported in 1881, GM2 gangliosidosis has no effective treatment today, and children succumb to the disease after a protracted neurodegenerative course and semi-vegetative state. This study seeks to further develop adeno...
Article
Rabies is the deadliest viral infection known, with no reliable treatment, and although it is entirely preventable, rabies continues to kill more than 60,000 people every year, mostly children in countries where dog rabies is endemic. America is only 1 generation away from the time when rabies killed more than 10,000 animals and 50 Americans every...
Article
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Sandhoff disease (SD) is an autosomal recessive lysosomal storage disease caused by defects in the β-subunit of β-N-acetylhexosaminidase (Hex), the enzyme that catabolizes GM2 ganglioside. Hex deficiency causes neuronal storage of GM2 and related glycoconjugates, resulting in progressive neurodegeneration and death, typically in infancy. No effecti...
Article
GM1 gangliosidosis is a fatal neurodegenerative disease that affects individuals of all ages. Favorable outcomes using adeno-associated viral (AAV) gene therapy in GM1 mice and cats have prompted consideration of human clinical trials, yet there remains a paucity of objective biomarkers to track disease status. We developed a panel of biomarkers us...
Article
Sandhoff disease (SD) is a lysosomal storage disorder characterized by the absence of hydrolytic enzyme β-N-acetylhexosaminidase (Hex), which results in storage of GM2 ganglioside in neurons and unremitting neurodegeneration. Neuron loss initially affects fine motor skills, but rapidly progresses to loss of all body faculties, a vegetative state, a...
Article
Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme β-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnor...
Article
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Sandhoff disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the gene for the β-subunit of β-N-acetylhexosaminidase (Hex), resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2, primarily in the central nervous system....
Article
Sandhoff disease (SD) is caused by deficiency of N-acetyl-β-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) ge...
Article
Full-text available
The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective...
Article
Progressive debilitating neurological defects characterize feline GM1 gangliosidosis, a lysosomal storage disease caused by deficiency of lysosomal β-galactosidase. No effective therapy exists for affected children, who often die before age 5 years. An adeno-associated viral vector carrying the therapeutic gene was injected bilaterally into two bra...
Article
Full-text available
Salutary responses to adeno-associated viral (AAV) gene therapy have been reported in the mouse model of Sandhoff disease (SD), a neurodegenerative lysosomal storage disease caused by deficiency of β-N-acetylhexosaminidase (Hex). While untreated mice reach the humane endpoint by 4.1 months of age, mice treated by a single intracranial injection of...
Article
Contents Overpopulation of cats and dogs is a serious worldwide problem that demands novel, safe and cost‐effective solutions. The objective of this study was to generate and characterize phage‐peptide conjugates with gonadotropin‐releasing hormone ( G n RH ) for potential use as an immunocontraceptive. A filamentous phage vector f5‐8 with wild‐typ...
Article
Full-text available
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. Evaluation study. 162 female cats (24 queens from a breed...
Article
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...
Article
GM2 gangliosidosis is a fatal, progressive neuronopathic lysosomal storage disease resulting from a deficiency of β-N-acetylhexosaminidase (EC 3.2.1.52) activity. GM2 gangliosidosis occurs with varying degrees of severity in humans and in a variety of animals, including cats. In the current research, European Burmese cats presented with clinical ne...
Article
Lysosomal beta-galactosidase is required for the degradation of GM1 ganglioside and other glycolipids and glycoproteins with a terminal galactose moiety. Deficiency of this enzyme leads to the lysosomal storage disorder, GM1 gangliosidosis, marked by severe neurodegeneration resulting in premature death. As a step towards preclinical studies for en...
Article
G(M1) gangliosidosis is an inherited, fatal neurodegenerative disease caused by deficiency of lysosomal beta-d-galactosidase (EC 3.2.1.23) and consequent storage of undegraded G(M1) ganglioside. To characterize the genetic mutation responsible for feline G(M1) gangliosidosis, the normal sequence of feline beta-galactosidase cDNA first was defined....
Article
To evaluate neural stem/progenitor cell (NPC) transplantation therapy in cat models of neurodegenerative diseases, we have isolated, expanded and characterized feline NPCs (fNPCs) from normal fetal cat brain. Feline NPCs responsive to both human epidermal growth factor (hEGF) and human fibroblast growth factor 2 (hFGF2) proliferated as neurospheres...
Article
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Conditionally replicative adenoviruses (CRAds) are engineered to replicate only in the target tissue and destroy tumor through their cytopathic effect. Because of restricted in vivo replication, it is difficult to model behavior of human Ad5-based vectors in animal subjects. To circumvent this, we developed a "syngeneic" canine CRAd based on canine...
Chapter
This chapter traces the biomedical history including the early events and personalities involved in establishment of Rattus norvegicus as a leading laboratory animal. With the coming of modern civilization, a suitable ecological niche became available to the species as an economic pest, allowing its numbers to increase rapidly and spread over the w...
Article
Few diseases of laboratory animals have been as troublesome to research projects or as enigmatic to microbiologists as murine mycoplasma respiratory disease. Its entire history has been characterized by continuing disagreement about possible etiologies and endless proliferation of new terms for its pathological identification. Its ubiquity as an in...
Article
Full-text available
Molecular Therapy (2006) 13, S342|[ndash]|S342; doi: 10.1016/j.ymthe.2006.08.978 889. Adeno-Associated Virus Gene Therapy of Feline Gangliosidosis Douglas R. Martin1, Begona Cachon-Gonzalez2, Miguel Sena-Esteves3, Misako Hwang1, Atoska S. Gentry1, Nancy E. Morrison1, Nancy R. Cox1, Timothy M. Cox2 and Henry J. Baker11Scott-Ritchey Research Center,...
Patent
Full-text available
A diagnostic technique for matching anti-cancer peptide drugs to the molecular profiles of individual cancer tumors, and a method using the technique for a patient-specific treatment of tumors in mammals. This strategy matches anti-cancer peptide drugs to the molecular profiles of individual tumors, and includes the development of two banks, both o...
Article
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 s...
Article
Full-text available
Deficiency of lysosomal -galactosidase causes GM1 gangliosidosis, an inherited, progressive neurological disorder in which GM1 ganglioside accumulates in all tissues, including thymus, liver and brain. In addition to abnormal neuronal histology and function, gangliosidosis pathology involves a significant inflammatory component and therefore is sim...
Article
We have developed a gene delivery system that utilizes a cell-binding helper phage preselected from a landscape phage display library, and a phagemid harboring a marker gene and all regulatory elements (origins of replication and promoter-enhancer cassettes) necessary for replication of the phagemid and expression of the marker gene in the targeted...
Article
Full-text available
Cell-binding ligands for RG2 rat glioma were identified in our recent study from a library of peptides that are displayed as fusion molecules on phage particles. Here, one of the phage clones was used to affinity purify those cell membrane components to which the displayed peptides bind. This phage clone, displaying the ELRGDSLP peptide, was shown...
Article
In G(M2) gangliosidosis variant 0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase (EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside and severe neurodegeneration. Distinct feline models of G(M2) gangliosidosis variant 0 have been described in both domestic shorthair and Korat cats. In this study, we determined th...
Article
Unmethylated CpG dinucleotides have been found to stimulate general immune responses in mammals. CpG motifs have further been shown to be potent adjuvants when used in conjunction with vaccines for viral and bacterial organisms. It was necessary to determine whether these CpG motifs will also enhance immune responses in parasitic diseases. We there...
Article
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Early diagnosis and effective treatment of malignant gliomas, which are heterogeneous brain tumors with variable expression of cell surface markers, are inhibited by the lack of means to characterize and target tumor-selective molecules. To create molecular profiles for RG2 rat glioma cells, we used phage display technology, an approach capable of...
Article
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Oncolytic adenoviruses, which selectively replicate in and subsequently kill cancer cells, have emerged as a promising approach for treatment of tumors resistant to other modalities. Although preclinical results have been exciting, single-agent clinical efficacy has been less impressive heretofore. The immunogenicity of adenoviruses, and consequent...
Article
Full-text available
The mucosal delivery of antigens requires an effective adjuvant to induce mucosal immunity. Current mucosal adjuvants include cholera toxin (CT) and Escherichia coli heat-labile toxin. Unmethylated CpG immunostimulatory oligodeoxynucleotides (ODNs) have been proposed as novel mucosal adjuvants. In this study, mice were immunized with sonicated Heli...
Article
Background: Breast cancer represents one of the most significant health risks in the human female population due both to its frequency and metastatic potential. Current therapies, while improving the overall survival rate of women with mammary neoplasias, have not eliminated this disease as an important cause of morbidity and mortality. Materials...
Article
Although several types of stem cells have been isolated from rodent and human tissues, very few data exist on stem cell isolation from nonrodent animals, which seriously limits the advancement of stem cell biology and its ultimate translation to human clinical applications. Domestic cats are used frequently in biomedical research and are the prefer...
Article
To study the musculoskeletal development of Great Dane puppies fed various dietary concentrations of calcium (Ca) and phosphorus (P) in fixed ratio by use of dual energy x-ray absorptiometry (DEXA), determination of serum insulin-like growth factor 1 and parathyroid hormone concentrations, radiography, and blood chemistry analysis results. 32 pureb...
Article
Full-text available
Screening with a 7-mer phage display peptide library, a panel of cell-targeting peptides for the murine microglial cell line, EOC 20, was recognized. A number of similar, but not identical, sets of sequences representing more than 75% of all the cell line-binding clones were identified. Comparative analysis indicated that motif S/(T) F T/(X) Y W is...
Article
Oligodeoxynucleotides (ODNs) with unmethylated CpG dinucleotide motifs may be useful as non-specific immune system stimulants and adjuvants for protein or nucleic acid vaccines in humans and other primates. They may also be useful in cancer immunotherapy and in the modulation of allergic responses or mucosal immunity. To begin to determine the pote...
Article
To determine quantitative values for components of body composition in clinically normal dogs of various breeds by use of dual energy x-ray absorptiometry (DEXA) and validate the precision and accuracy of DEXA technology in dogs. 103 clinically normal sexually intact adult dogs. In a cross-sectional study, Beagles, Pembroke Welsh Corgis, Golden Ret...
Article
Full-text available
Total body scans were performed on 89 domestic cats of various ages, using dual energy x-ray absorptiometry (DEXA) to determine body composition, including fat, lean, and bone mineral content. Bone mineral density results from scans also are presented. This cross sectional study included data for cats from a closed colony and from privately owned c...
Article
Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between...
Article
Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between...
Article
Full-text available
A nucleic acid vaccine encoding human carcinoembryonic antigen (CEA) was administered to 10 juvenile dogs, 10-15 weeks of age, by four parenteral routes. The routes tested were intramuscular injection using a needle and syringe, intramuscular injection using the Biojector needleless injection device, intradermal injection or intravenous injection....
Article
To ascertain the effects of dietary omega-3 (n-3) fatty acids on biochemical and histopathologic components of the inflammatory stage of wound healing. 30 purpose-bred Beagles. Dogs were allotted to 5 groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n-3--diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; a...
Article
GM1 gangliosidosis is an inherited metabolic disease characterized by progressive neurological deterioration with premature death seen in children and numerous animals, including cats. We have observed that thymuses from affected cats greater than seven months of age (GM1 mutant cats) show marked thymic reduction compared to age-matched normal cats...
Article
Nucleic acid vaccines (NAVs) use expression vectors encoding one or more antigen genes to transfect host cells inducing both humoral and cellular immunity against the expressed antigen. NAV offers major advantages over conventional vaccines for the protection of humans and animals. This study shows that a plasmid DNA (pGT36VP1) encoding the full le...
Article
Monosialogangliosides, normal components of cell membranes, regulate cell development and differentiation in several organs. Our previous observation of dramatic premature thymic involution in cats with feline GM1 gangliosidosis, whose thymocytes have abnormally high cell surface gangliosides, suggested that excess GM1 ganglioside (GM1) could modul...
Article
To determine which electrodiagnostic tests yield abnormal findings in cats with GM1 gangliosidosis, and to determine the approximate age of onset of electrodiagnostic abnormalities. Cats (28 to 335 days old) affected with GM1 gangliosidosis (n = 11) and unaffected controls (n = 14). Cats were grouped by age: group 1, < or = 90 days, group 2, 91 to...
Article
Thirty-nine Great Dane puppies from 5 litters were studied from 2 through 12 months of age Puppies were divided into three groups and fed diets identical in protein and fat (27% and 14% respectively), but differing in calcium and phosphorus. The diets consisted of 0.48% Ca: 0.4% P (Low) (n=12), 0.8% Ca: 0.67% P (Med) (n=12), or 2.7% Ca: 2.2% P (Hig...
Article
Full-text available
Phosphoinositide-specific phospholipase C and adenylyl cyclase were studied in brain cortical membranes from cats with GM1 and GM2 gangliosidosis. In contrast to brain cortical membranes from unaffected control cats, phospholipase C acting against exogenously supplied phosphoinositide substrates did not respond to stimulation by GTP gamma S, carbac...
Article
The formation of focal granular enlargements within axons (axonal spheroids or "torpedoes"; neuroaxonal dystrophy) is a well known phenomenon occurring in a variety of neurological diseases. The relative susceptibility of different types of neurons to this kind of axonal pathology, however, is largely unknown. An immunocytochemical study directed a...
Article
The pathogenesis of neuronal dysfunction in the gangliosidoses is poorly understood. Studies of the feline gangliosidoses and in vitro experiments implicate ganglioside inhibition of protein kinase C (PKC) in the pathogenesis of these neurological diseases. Therefore, in the present study, the binding of [3H]phorbol-12, 13 dibutyrate was measured t...
Article
Golgi and combined Golgi-electron microscopic (EM) studies were carried out on cats in the terminal stages of GM2 ganglioside storage disease and the resulting data were compared with those from similar studies of other neuronal storage diseases in cats, including GM1 gangliosidosis. The results support the view that only limited types of neurons a...
Article
The incidence of cortical pyramidal neurons displaying meganeurites or enlarged axon hillocks with ectopic spines and neurites was evaluated developmentally using feline models of GM1 and GM2 gangliosidosis. Results of these studies demonstrated that the onset of ectopic neurite growth occurred after the elaboration of dendrites on cortical pyramid...
Article
Ca2+ transport was studied in synaptosomes prepared from normal cats and cats with GM1 gangliosidosis. The influx of Ca2+ was found to be a biphasic process in synaptosomes from both GM1 mutant and normal cats. Both the fast and slow phases of voltage-dependent Ca2+ uptake were significantly reduced in cats with the lysosomal storage disease, howev...
Article
Full-text available
A 7-month-old Balinese cat with progressive neurological dysfunction had histopathological lesions of brain, liver, kidney, spleen, and lung consistent with a lysosomal storage disease. Ultrastructural examination revealed lysosomal hypertrophy with membranous inclusions. Hepatic sphingomyelin and cholesterol were elevated 10 times normal, and tota...
Article
Ceroid-lipofuscinosis is described in Australian Cattle dogs. Lesions included storage of ceroid-lipofuscin in most tissues with characteristic ultrastructural inclusion body patterns in neurons and other cells. Dolichol concentration of the affected dog's brain was similar to those in age-matched control dog brains. However, concentrations in brai...
Article
Cholinergic processes were measured in motor cortex, hippocampus, and striatum of cats in the terminal stages of GM1 gangliosidosis and compared to those of control cats. The greatest difference observed was elevation in the rate of K+-stimulated release of acetylcholine (ACh) from brain slices prepared from affected cats. The K+-stimulated release...
Article
Acetylcholine metabolism was studied in cats with Gm1 gangliosidosis. Marked increases in acetylcholine synthesis (130% of controls) and K+-stimulated release of ACh (142-165% of controls) were observed in cortical and hippocampal brain slices of diseased cats. Cortical synaptosomes prepared from affected cats had significantly elevated rates of hi...
Article
Neurochemical studies were performed on synaptosomal membranes from cats with GM1 or GM2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal fu...
Article
Full-text available
An inherited neurological disorder characterized by sustained twisting movements during waking has been discovered in Sprague-Dawley rats. The mutation follows an autosomal recessive pattern of inheritance and has been named dystonic (dt). The rat mutants are indistinguishable from normal littermates in open field behavior and climbing activity pri...
Article
Alterations in neuronal geometry in a feline model of sphingomyelin lipidosis were evaluated using Golgi staining. Neurons in cerebral cortex, basal ganglia, amygdala, thalamus, and cerebellum were impregnated and many were found to possess conspicuous enlargements at the axon hillock-initial segment region (meganeurites) and/or to sprout secondary...
Article
Assays for synaptosomal high-affinity uptake activity (glutamate, gamma-aminobutyric acid, norepinephrine), neurotransmitter synthesizing enzymes (choline acetyltransferase, glutamate decarboxylase, tyrosine hydroxylase), and endogenous neurotransmitters were performed in cats with advanced inherited GM1 gangliosidosis. A significant reduction in u...
Article
To assess the feasibility of enzyme therapy in human Gm2 gangliosidosis, hampered by hepatic uptake of, and blood-brain barrier (BBB) impermeability to exogenous Hex A, kittens with Gm2 gangliosidosis (a model for human Sandhoff disease) were injected IV or intracarotid (IC) with ~5 mg purified human placental Hex A. Hepatic uptake was reduced with...

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