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Biomedical subjects

T D O'Brien

Publications and source records attributed to T D O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1990

Clinicopathologic analysis of herpesvirus-induced urinary tract infection in specific-pathogen-free cats given methylprednisolone.

The clinicopathologic manifestations of bovid herpesvirus-4 (BHV-4; FCAHV strain)-induced infection of the lower portion of the urinary tract were characterized in 12 adult neutered male and 6 female specific-pathogen-free cats, and were compared with those in 12 neutered male control cats. Six neutered male and 6 female cats were given immunosuppressive doses of methylprednisolone acetate prior to inoculation of their urinary bladders with BHV-4. Six neutered male control cats were given immunosuppressive doses of methylprednisolone acetate prior to inoculation of their urinary bladders with uninfected tissue culture control inoculum. Six additional neutered male control cats were exposed only to uninfected tissue culture control inoculum. All cats were observed for 90 days following inoculation. Dysuria and gross hematuria were observed in only 1 BHV-4-exposed cat. Radiographic abnormalities of the lower portion of the urinary tract were not observed. Microscopic hematuria, crystalluria, and lipiduria were identified with similar frequency in BHV-4-exposed and control cats. Results of urine culturing for bacteria, mycoplasma, ureaplasma, and viruses were negative. Viruses were not isolated from blood leukocytes collected from exposed or control cats. Three to 6 weeks after inoculation, high concentrations of BHV-4 serum antibodies were detected in all exposed cats by an indirect fluorescent antibody test. Light microscopic examination of the urinary tract revealed multifocal lymphoid cystitis in 2 BHV-4-exposed cats. Except for suppurative bronchitis in 1 BHV-4-exposed cat given glucocorticoids, morphologic differences in urinary and extraurinary tissues were not observed. In urinary bladder tissue collected 90 days after inoculation, BHV-4 was reisolated from urinary bladder explants of all but 1 exposed cat. Virus was also isolated from a kidney explant of 1 exposed male cat, and spleen cell co-cultures of 1 exposed female cat given glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Clinicopathologic and pathologic findings of herpesvirus-induced urinary tract infection in conventionally reared cats.

Clinicopathologic manifestations of induced infection of the feline lower urinary tract with bovid herpesvirus-4 (BHV-4, strain FCAHV) were characterized in 6 conventionally reared adult cats (2 sexually intact males, 2 castrated males, and 2 females). Two additional control cats were exposed with noninfected cell culture control inoculum. Clinical and radiographic signs of lower urinary tract disease were not observed in exposed or control cats. Microscopic hematuria was detected in urine samples collected by cystocentesis from 4 to 6 exposed cats and 1 of 2 control cats. Results of culture of urine for bacteria, mycoplasmas, ureaplasmas, and viruses were consistently negative. Low titer of serum BHV-4 (strain FCAHV)-neutralizing antibodies was detected in 4 of 6 exposed cats, but not in controls. Gross abnormalities of the urinary tract were not observed in any cat. Light microscopic examination of serial sections of the lower urinary tract revealed mild focal lymphoid cystitis in 2 of 6 exposed cats, one of which also had increased amounts of connective tissue and proliferation of blood vessels in the urinary bladder lamina propria. Ninety days after initial exposure, BHV-4 (strain FCAHV) was reisolated from explanted urinary bladder tissues of 5 of 6 exposed cats. Virus was not isolated from tissues of control cats. It was concluded that BHV-4 (strain FCAHV) establishes persistent urinary tract infection in conventionally reared adult male and female cats. However, persistent BHV-4 infection in cats may remain clinically inapparent.

Animals↗
PubMed1990

Prophylactic use of mexiletine in the elderly with acute myocardial infarction.

A double blind randomised study comparing the effects of oral mexiletine and placebo given to elderly patients (65 years and older) immediately following hospital admission with suspected myocardial infarction (MI) is described. The study comprised one hundred and fifty-four patients of which 74 had confirmed myocardial infarction according to the diagnostic criteria of the study. Eighty patients without definite evidence of myocardial infarction were subsequently excluded from the study. Thirty-three patients (44.5%) with confirmed MI treated with mexiletine, compared with 41 (51%) in the placebo group showed no significant difference in mortality at 48 hours and 14 days. The mexiletine treated group showed a significant reduction (p less than 0.05) in certain forms of ventricular dysrhythmias. Six of these patients (18%) taking mexiletine had the drug withdrawn because of possible adverse drug reactions compared with two (4.8%) of the placebo group. None of the patients withdrawn because of possible adverse drug reactions had any long term side effect. Mild confusion observed in one patient was reversed after withdrawal of therapy. Results of this study indicate the safety of mexiletine as an anti-arrhythmic drug and its efficacy in suppression of certain ventricular dysrhythmias in the elderly with acute myocardial infarction. The overall mortality rate in both groups (mexiletine and placebo) remained unchanged.

Administration, Oral↗
PubMed1989

Islet amyloid, islet-amyloid polypeptide, and diabetes mellitus.

Islet-amyloid deposits, which are a common feature of Type II diabetes mellitus, are derived from the polymerization of a putative hormone identified as IAPP. IAPP is synthesized by normal islet beta cells and probably is cosecreted with insulin. Although the physiologic function of IAPP and its role in the pathogenesis of Type II diabetes mellitus are just beginning to be unraveled, IAPP may play an important part in the development of this most common form of diabetes mellitus by opposing the action of insulin in peripheral tissues. The polymerization of IAPP to form extracellular islet-amyloid deposits may further contribute to the development of Type II diabetes mellitus by destroying islet cells and by disrupting the passage of glucose and hormones to and from them. Substantial evidence indicates that the propensity of IAPP to polymerize and form extracellular amyloid deposits in only certain species (e.g., humans, cats, and raccoons) is directly associated with an intrinsically amyloidogenic part of the molecule--i.e., positions 20 through 29 of IAPP. The inherent amyloidogenicity of IAPP in these species may be further facilitated by increased beta-cell production of IAPP, leading to a high local concentration that predisposes to polymerization. The latter possibility is supported by studies demonstrating that IAPP production by islet beta cells is increased in normoglycemic cats with impaired glucose tolerance. Although increased production of IAPP may initially cause insulin resistance, prolonged overproduction of IAPP may ultimately impair insulin secretion by leading to the progressive deposition of insoluble islet amyloid, a finding apparent in most subjects with overt diabetes. If, as these studies suggest, increased IAPP production is linked to the development of Type II diabetes mellitus, further studies must address the genetic and nongenetic factors that influence this important biologic change in humans and some animal species.

Amino Acid Sequence↗
PubMed1989

Amino acid sequence variations in protein AA of cats with high and low incidences of AA amyloidosis.

1. Amyloid isolated from the liver of a domestic short-haired (DSH) cat was dissolved and purified by gel filtration for amino acid sequence analysis. 2. Sequences of two major peptides corresponding to positions 18-23 and 25-75 of human amyloid protein AA were obtained when cyanogen bromide-cleaved protein was applied to an amino acid sequenator. 3. Comparison of these regions of amyloid protein from the Abyssinian cat (high incidence of AA amyloidosis) and DSH cat (low incidence of AA amyloidosis) revealed three amino acid differences, two of which occurred within regions that are completely conserved in the Abyssinian cat and all other species. 4. Secondary prediction plots showed less potential for amyloidogenicity (i.e., less beta-sheet conformation) in protein AA of the DSH cat as compared to the Abyssinian cat and other animal species. 5. These differences in protein AA of the DSH cat may, therefore, be linked to the comparatively uncommon occurrence of AA amyloidosis in the DSH cat as compared to the Abyssinian cat and other animals species.

Amino Acid Sequence↗
PubMed1989

Dietary management of canine and feline chronic renal failure.

Nutritional therapy is the mainstay of management of chronic renal failure in dogs and cats. Diets designed for use in renal failure are typically reduced in protein, phosphorus, and sodium content. These and other dietary modifications are designed to prevent or ameliorate clinical signs of uremia, minimize disturbances associated with excesses or losses of electrolytes and minerals, arrest or retard progression of renal failure, and maintain adequate nutrition.

Animal Nutritional Physiological Phenomena↗
PubMed1989

Relationship of nutritional factors to the cause, dissolution, and prevention of feline uroliths and urethral plugs.

Feline lower urinary tract disease is often associated with uroliths and urethral plugs. Uroliths and urethral plugs are composed of variable quantities of matrix and a variety of minerals (including struvite, calcium oxalate, ammonium urate, calcium phosphate, and cystine). Knowledge of nutritional factors associated with the pathophysiology of uroliths and urethral plugs facilitates the modification of diets for the dissolution of several minerals contained within them.

Animals↗
PubMed1989

Impaired glucose tolerance is associated with increased islet amyloid polypeptide (IAPP) immunoreactivity in pancreatic beta cells.

Adult cats determined by clinical laboratory evaluations to be normal, impaired glucose tolerant, or overtly diabetic were used to explore prospectively the relationships among pancreatic beta cell islet amyloid polypeptide (IAPP) immunoreactivity, islet amyloid (IA) deposition, and diabetogenesis. IAPP-derived IA was found in 11 of 14 (79%) diabetic cats, in four of nine (44%) impaired glucose tolerant cats, and in two of eight (25%) normal adult cats. The presence of IA even in very small amounts, therefore, predicts a very high probability (88%) that an animal has either impaired glucose tolerance or overt DM. Although all overtly diabetic cats had a marked decrease or absence of beta cell IAPP immunoreactivity, six of six cats with impaired glucose tolerance retained IAPP immunoreactivity with 1:15,000 dilutions of antisynthetic IAPP 7-17, whereas only one of seven normal cats had IAPP immunoreactivity beyond 1:10,000 dilutions. These findings suggest that increased IAPP production preceding the development of overt DM is linked to the progressive formation of insoluble IA deposits that are apparent in most overtly diabetic individuals. Of most importance, in that IAPP has been reported to inhibit both basal and insulin-stimulated rates of glycogen synthesis, is the possibility that increased production and release of IAPP by pancreatic beta cells plays a key role in the development of the insulin resistance and impaired glucose tolerance, both of which occur in Type 2 DM.

Amyloid↗
PubMed1988

Applications of ultrasonography in the diagnosis of parenchymal kidney disease in cats: 24 cases (1981-1986).

Renal sonograms from 24 cats with confirmed parenchymal kidney disease and from 1 cat with radiographic and palpable evidence of renal enlargement (but without identifiable histologic abnormalities) were evaluated to describe the ultrasonographic appearance of feline renal diseases and to determine the role of ultrasonographic examination in the clinical evaluation of these cases. In all cats with radiographic evidence of abnormal renal size or contour and when poor intraabdominal radiographic contrast precluded visualization of the kidneys, ultrasonography provided complementary information pertaining to location (cortical/medullary), extent, and distribution (focal/multifocal/diffuse) of disease. Ultrasonography also characterized these lesions as cystic (cavitating) or solid. The echo patterns were most specific for renal cysts. Infiltrative diseases did not have consistent patterns. Multifocal hypoechoic nodules, diffuse cortical hyper-echogenicity, and normal-appearing parenchyma were identified. In these instances, however, ultrasonography did define the extent of disease and narrowed the spectrum of differential considerations.

Animals↗
PubMed1988

Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques.

A novel putative polypeptide hormone identified as islet amyloid polypeptide (IAPP) was recently purified from islet amyloid (IA) of diabetic humans and cats, and also from amyloid of a human insulinoma. Although the function of IAPP is yet unknown, its occurrence in pancreatic endocrine tissue and its partial amino acid sequence identity with calcitonin gene-related peptide (CGRP) suggests an endocrine regulatory effect. In the present investigation, the authors utilized antisera to insulin, glucagon, somatostatin, pancreatic polypeptide, synthetic human CGRP, and a synthetic human IAPP (7-17) undecapeptide to immunohistochemically (PAP technique) document the presence of IAPP immunoreactive cells in the islets of the cat, dog, mouse, and rat, but not in the islets of the horse or calf. In serial sections of islets from these species it was shown that IAPP immunoreactivity occurred in insulin-reactive beta cells. This observation was confirmed immunocytochemically in cat islets by means of protein A-gold probes. With protein A-gold labeling techniques, IAPP immunoreactivity was localized to the outer lucent compartment of the beta cell secretory granule, whereas insulin immunoreactivity was associated with the electron-dense core. These findings provide strong evidence that IAPP or an IAPP precursor is synthesized by beta cells and is stored in beta cell granules for subsequent co-secretion with insulin. The conservation of IAPP in humans and multiple animal species and the localization of IAPP to pancreatic beta cells provide further evidence that IAPP has an important endocrine regulatory function. The propensity of IAPP to polymerize and form IA fibrils in diabetes associated with aging may indicate that IAPP is in some way also linked to the development of Type 2 diabetes.

Amyloid↗
PubMed1987

Urologic disorders of immature cats.

Numerous inherited and congenital disorders may affect the urinary system of cats. Those associated with clinical signs include renal dysplasia, renal hypoplasia, polycystic kidneys, ectopic ureters, urachal anomalies, and fistulas between the lower urinary tract and other structures. Acquired disorders of the urinary system of immature cats have been uncommonly recognized. Further studies are warranted to better define their prevalence in immature cats.

Animals↗
PubMed1987

Etiopathogenesis and biological behavior of feline vesicourachal diverticula. Don't just do something--stand there.

Asymptomatic microscopic urachal remnants located at the vertex of the urinary bladder are common in cats. Because they reduce the tensile strength of the bladder wall at this location, they represent risk factors for development of acquired macroscopic diverticula in cats with lower urinary tract disorders. Elimination of the underlying cause of lower urinary tract disease is frequently associated with resolution of acquired macroscopic vesicourachal diverticula.

Animals↗
PubMed1987

Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.

Amyloid deposits localized to the islets of Langerhans are typical of non-insulin-dependent human diabetes mellitus and of diabetes mellitus in adult cats. Amyloid deposits also commonly occur in insulin-producing pancreatic tumors. We have purified a major protein--insulinoma or islet amyloid polypeptide (IAPP)--from human and cat islet amyloid and from amyloid of a human insulinoma. IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da. The amino acid sequence is unique but has greater than 40% identity with the human calcitonin gene-related peptide. A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions. An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells. The significance of this pancreatic neuropeptide-like protein is unknown, but it is suggested that it may exert an important endocrine regulatory effect.

Adenoma, Islet Cell↗
PubMed1987

Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid.

Thirty-one primary canine pancreatic endocrine tumors and their metastases were studied histologically and immunohistochemically for the presence of insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, and adrenocorticotrophic hormone (ACTH). Tumors were also evaluated for the presence of amyloid. The cytoarchitectural pattern of 25 of 31 primary tumors was predominantly solid, whereas three tumors were mostly glandular, two were unclassified, and one had a gyriform pattern. Cells with insulin immunoreactivity were found in 30 of 31 tumors and were found in all cases in which there was clinical evidence of inappropriate insulin secretion. Insulin was the only hormone demonstrable in three of the 30 tumors, but cells immunoreactive for other hormones were also present in various combinations in most tumors [i.e., glucagon (13 of 30), somatostatin (17 of 30), PP (25 of 30), and gastrin (2 of 30)]. One tumor contained only cells with glucagon and PP immunoreactivity. Amyloid was found in ten of 31 primary tumors but was not detected in metastases. Cells with insulin immunoreactivity were the only cell type consistently present in tumors containing amyloid. Amyloid deposits did not immunoreact with any of the antisera. Seventeen of 31 dogs had metastasis of the pancreatic endocrine tumor to regional lymph nodes, liver, or both. All metastases available for study (15 of 17) contained cells with insulin immunoreactivity and some contained cells with PP or somatostatin immunoreactivity. No statistically significant (P greater than 0.05) differences in tendency to metastasize were found when pancreatic endocrine tumors were compared by region of origin, cytoarchitectural pattern, presence of amyloid, or by number of hormones contained within the tumor.

Adrenocorticotropic Hormone↗
PubMed1987

Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone.

Amyloid deposition is a very typical alteration in the islets of Langerhans in human Type 2 (non-insulin-dependent) diabetes mellitus and in feline diabetes mellitus. Amyloid infiltration is also commonly found in insulin-producing pancreatic tumors. It was shown recently that amyloid purified from an insulinoma was composed mainly of a novel polypeptide (insulinoma amyloid polypeptide, IAPP), which had partial identity with the neuropeptide calcitonin gene-related peptide (CGRP). Cat islet amyloid contained a similar polypeptide. This finding is verified in the present study, and it is shown that the cat IAPP differs from the human peptide only in two of the 16 elucidated amino acid residues. The authors now also show by N-terminal amino acid sequence analysis that human islet amyloid is of IAPP origin. Although the significance of IAPP is unknown, its occurrence in pancreatic endocrine tissue and partial identity with a known neuropeptide suggests an endocrine regulatory function.

Amino Acid Sequence↗