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Biomedical subjects

G A Padgett

Publications and source records attributed to G A Padgett.

At least 37 records · Page 2Linked to original sources
PubMed1983

Comparative pathology of connective tissue diseases.

Selected examples of animal models for human connective tissue diseases are reviewed, with emphasis on those which can be verified by genetic, immunologic, and biochemical studies. Desnick et al. have stated that the study of animal models in inborn errors of metabolism will "have a dramatic impact on the future development and evaluation of effective therapies for a variety of human enzyme diseases." It is hoped that these discussions, including comments on the importance of animal models for specific human diseases of the connective tissue, will yield significant benefits in human health.

Animals↗
PubMed1982

Dwarfism in Alaskan malamutes: a disease resembling metaphyseal dysplasia in human beings.

In a study of 300 Alaskan Malamutes, dwarfism was shown to be an autosomal recessive inherited disease with complete penetrance that resulted in disturbed endochondral bone formation. Osseous growth disturbance was manifest at the metaphyses of tubular bones. Clinical and radiographic changes were very similar to those of rickets, although appositional bone formation rates were normal. Serum calcium, phosphorus, and alkaline phosphatase were within normal limits. Urinary excretion of calcium, phosphate, and amino acids were normal. Excess matrix was formed in the zone of cartilage cell proliferation, and the matrix persisted in the growth plate. Normal stresses resulted in microfractures in the metaphyses with subsequent interference of vascular penetration into the zone of degenerated cartilage cells.

Alkaline Phosphatase↗
PubMed1980

Prolonged bleeding time in Aleutian mink associated with a cyclo-oxygenase-independent aggregation defect and nucleotide deficit in blood platelets.

A prolonged mean template bleeding time of 13 minutes was present in nine Aleutian mink affected with Chediak-Higashi syndrome (CHS) compared with 4 minutes in dark control mink. The concentrations of blood platelets in normal and affected animals did not differ significantly. However, in mink with CHS, a marked disturbance of platelet response to collagen was present. Administration of aspirin and indomethacin completely blocked CH platelet response to collagen. Blood platelet adenosine triphosphate and adenosine diphosphate values from mink with CHS were significantly less than those of normal mink, and the platelet adenosine triphosphate/adenosine diphosphate ratios were 10.31 in affected mink and 2.74 in normal mink. These findings are consistent with our previous investigations in affectd cattle and persons and indicate that a "storage pool disease" of platelets exist in the mink with CHS.

Adenine Nucleotides↗
PubMed1976

Inherited progressive epilepsy of the dog with comparisons to Lafora's disease of man.

A familial progressive form of epilepsy in the beagle dog is clinically characterized by intermittent seizures, often of grand mal type. If not properly treated, the seizures may lead to status epilepticus. The seizures are often elicited by external stimuli, especially a change in noise or light in the surroundings. Histologically, intracytoplasmic inclusions, 2-10 mum in diameter, occur in glial and neuronal cells in the brain, especially the thalamus. The inclusions are strongly positive for carbohydrate stains, weakly metachromatic, and lipid negative. They are spherical with a dense core and an often radiating, less dense periphery. Histologic changes in other organs include basophilic myocardial degeneration, degeneration and variation in diameter size of skeletal muscle fibers, and deposition of periodic acid-Schiff positive material in the cytoplasm of reticuloendothelial cells of the liver, spleen, and lymph nodes. Based on clinical and morphologic manifestations, the beagle disorder resembles Lafora's disease of man. This disorder will provide a useful model for comparative studies with progressive myoclonic epilepsy (Lafora's disease) of man and for defining the pathomechanisms of other forms of epilepsy.

Animals↗
PubMed1976

Muscular dystrophy of mink: a new animal model.

Muscular dystrophies comprise an important group of inherited disorders of man. Although the disease has been studied extensively, little is known about the underlying primary pathomechanisms. Consequently, treatment of patients is difficult and prognosis is poor. An animal model of muscular dystrophy is a useful research tool for approaching the basic problems of pathogenesis in muscle diseases. An inherited progressive muscular dystrophy of mink which resembles the amyotonic forms of human muscular dystrophy is currently under study. Clinically, the earliest sign is progressive muscular weakness and atrophy. Muscle enzyme activities in serum are usually elevated to pathologic levels. Urinary creatine/creatinine ratio is elevated. Pathologic changes are limited to skeletal muscle and are typical of those seen in amyotonic forms of human muscular dystrophy. These changes include variation in diameter size of muscle fibers, centralized nuclei, floccular and hyaline degeneration of scattered muscle fibers, increase in connective tissue in endomysial and perimysial areas, and regenerative attempts. Both type I and type II muscle fibers are involved in the disease process. Genetic studies indicate an autosomal recessive mode of inheritance. Although the primary defect in muscular dystrophy is traditionally thought to reside in skeletal muscle, recent studies have produced theories of primary involvement of other tissues and organ systems. These theories are presented and relationships to the traditional theory are discussed.

Animals↗
PubMed1976

Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets.

Prolonged mean template bleeding time of 14 min observed in seven cattle with the Chediak-Higashi syndrome (CHS) prompted the examination of platelet function in these animals. There was no distinguishable difference in concentration of circulating platelets between CHS and control cattle. CHS bovine platelets failed to aggregate in vitro in response to concentrations of acid-soluble collagen which induced aggregation in all normal samples. The primary platelet response to 5 muM ADP was normal in CHS cattle. A markedly decreased amount of serotonin (1.2% of normal) was detected in CHS bovine platelets. Bovine CHS platelet ATP and ADP contents were significantly less than normal, and the ATP/ADP ratios were 5.04 in normal and 29.38 in CHS platelets. Results of these animal investigations prompted a similar study of two patients with CHS. In humans, an increased bleeding time greater than 15 min and an in vitro impaired aggregation response to acid-soluble collagen and 5 muM adrenaline were discovered. Both ATP and ADP were reduced in CHS human platelets, and the ATP/ADP ratio was 3.96, compared to a ratio of 1.52 for platelets of two normal subjects. These findings suggested the presence of a "storage pool disease" of CHS platelets.

Adenosine Diphosphate↗
PubMed1975

Ataxia, depression, and dermatitis associated with the use of dichlorvos-impregnated collars in the laboratory cat.

Ataxia and depression developed in 21 of 50 (42%) laboratory cats wearing flea collars impregnated with 2,2-dichlorovinyl dimethyl phosphate (dichlorvos or DDVP) in a warm dry environment. Five (10%) of the cats died. Whole blood cholinesterase (ChE) activity was significantly (P smaller than 0.001) reduced in all cats and cervical dermatitis occurred in 37 (74%) of them.

Alanine Transaminase↗
PubMed1975

Defective mononuclear leukocyte chemotaxis in the Chediak-Higashi syndrome of humans, mink, and cattle.

Chemotaxis of mononuclear leukocytes from humans, mink, and cattle was evaluated in vitro using a morphologic Boyden chamber technique and a new 51-Cr-labeled mononuclear radioassay with a double micropore filter system. Significantly decreased mononuclear leukocyte chemotactic response were noted when human, mink, or cattle Chediak-Higashi cells were tested using autologous serum or endotoxin-activated autolotous serum. A similar Chediak-Higashi mononuclear leukocyte defect was noted in humans when kallikrein or dialyzable transfer factor were used as the chemotactic stimulus. Studies using smaller pore filters in the chemotactic chamber exaggerated the chemotactic defect. Serum from Chediak-Higashi subjects had normal chemotactic activity. Additional studies on the spontaneous (random) locomotion of Chediak-Higashi mononuclear leukocytes revealed normal results when a capillary tube assay system was used, but abnormal results were obtained when a Boyden chamber micropore filter assay was used, demonstrating fundamental differences in these two assays of random locomotion. It is clear from these studies that defective mononuclear leukocyte chemotaxis is another feature of the imparied host defenses in the Chediak-Higashi syndrome that may contribute to the marked susceptibility to pyogenic infections so characteristic of this dease.

Animals↗
PubMed1975

Feline congenital erythropoietic porphyria associated with severe anemia and renal disease. Clinical, morphologic, and biochemical studies.

A feline erythropoietic porphyria was studied in an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia, hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries) and ischemic tubular injury. There was thickening of tubular basement membranes and tubular epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter in cytoplasmic and extracellular locations.

Anemia, Hypochromic↗
PubMed1974

Leukocyte dysfunction in the bovine homologue of the Chediak-Higashi syndrome of humans.

The increased susceptibility to pyogenic infections noted in cattle with the Chediak-Higashi syndrome trait has been related to an impairment of leukocyte function at the cellular level. Investigations of the relationship of abnormal granule formation to increased susceptibility to infection, conducted with cell suspensions containing high concentrations of polymorphonuclear leukocytes, revealed a bactericidal defect that was associated with abnormal intracellular killing and not due to defective particle ingestion. The in vitro bactericidal defect was associated with a metabolic anomaly in the hexose monophosphate shunt, but not with an alteration in the capacity to reduce nitroblue tetrazolium dye. Ultrastructural histochemical studies of phagocytosis and phagolysosome formation in polymorphonuclear leukocytes suggest that the impairment in bactericidal capacity is correlated also with either a delay or failure of primary granules to degranulate.

Animals↗