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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
PubMed1993

Effects of dietary protein and calorie restriction in clinically normal cats and in cats with surgically induced chronic renal failure.

To determine the effects of long-term dietary protein restriction in cats with chronic renal failure (CRF), 4 healthy adult cats and 7 cats with surgically induced CRF were fed a high-protein (HP, 51.7% protein) diet and 4 healthy adult cats and 7 cats with surgically induced CRF were fed a low-protein (LP, 27.6% protein) diet for 1 year. Cats with induced CRF that were fed the LP diet had reduced serum urea nitrogen concentrations, despite lower glomerular filtration rates, compared with cats with CRF fed the HP diet. Despite five-sixths reduction in renal mass, reduced glomerular filtration rate, and azotemia, 13 of the 14 cats with induced CRF retained the ability to concentrate urine and produced urine with a specific gravity > 1.035. Cats fed the HP diet consumed significantly more calories than did cats fed the LP diet, presumably because the HP diet was more palatable. As a result of the lower caloric intake in cats fed the LP diet, these cats were protein and calorie restricted, compared with cats fed the HP diet. Cats fed the HP diet weighed significantly more than did cats fed the LP diet. Mean hematocrit and mean serum albumin concentration were significantly lower in control cats and in cats with CRF fed the LP diet, compared with control cats and cats with CRF fed the HP diet. Hypokalemia developed in 4 of 7 cats with CRF fed the HP diet (containing 0.3% potassium); hypokalemia did not develop in control cats fed the same diet or in cats with CRF fed the LP diet containing 0.4% potassium. Excessive kaliuresis, hypomagnesemia, and metabolic acidosis did not appear to contribute to the hypokalemia. Subsequent supplementation of the HP diet with potassium gluconate prevented hypokalemia in cats with CRF.

Acid-Base Equilibrium↗
PubMed1993

Clinical features of duodenal somatostatinomas.

BACKGROUND: Duodenal somatostatinomas are rare tumors that are often asymptomatic or present with local symptoms rather than with evidence of excess somatostatin production. To characterize the clinical presentation and management of these neoplasms we reviewed the course of four patients. METHODS: The records of three men and one woman with duodenal somatostatinomas, who were treated between 1988 and 1992, are reviewed. RESULTS: Three of the patients presented with vague gastrointestinal complaints, and one was free of symptoms. No patient had symptoms of somatostatinoma syndrome, nor did any have associated neurofibromatosis. Three patients were diagnosed after biopsy of a submucosal mass during upper endoscopy. Three patients with tumors that measured less than 2 x 2 cm underwent local resection. One patient with a large tumor and liver metastases underwent a Whipple's operation and resection of the liver lesions. Immunohistochemically all tumors predominantly contained somatostatin, although each had traces of other neuropeptides. All tumors contained psammoma bodies. Follow-up periods ranged from 1 to 4 years. CONCLUSIONS: Duodenal somatostatinomas often appear with only local symptoms or are completely asymptomatic. Small tumors may be locally excised. Intraarterial methylene blue injection may help localize very small tumors during operation. Larger tumors, including those with localized metastases, should also be resected when possible.

Aged↗
PubMed1992

Pulmonary vascular amyloidosis in aged dogs. A new form of spontaneously occurring amyloidosis derived from apolipoprotein AI.

The N-terminus of a mutant form of apolipoprotein AI [apoAI] has previously been shown to be the subunit protein of amyloid fibrils in a human kindred with a form of familial amyloid polyneuropathy (FAP, type III) and in a recently reported kindred with a form of non-neuropathic hereditary amyloidosis. In this study, we demonstrate by amino-acid sequence analysis, that a form of vascular amyloidosis occurring in the lungs of aged dogs is derived from a N-terminal fragment of apoAI and that no amino acid substitution is present in this confirmed sequence. This represents the first documentation of apoAI as a precursor for a form of amyloidosis in animals, and provides the first documentation of apoAI as a precursor for amyloid fibrils in a form of age-associated ("senile") amyloidosis. Secondary structure prediction analysis of the N-terminal regions of normal human and dog apoAI indicated a propensity for beta-pleated sheet conformation, and thus amyloidogenesis, in 40 and 45% of the respective sequences. These results suggest that apoAI (like transthyretin) may serve as an amyloid precursor protein for both familial and senile forms of amyloidosis. ApoAI should, therefore, be considered as a potential amyloid precursor when forms of human senile amyloidosis of unknown origin are evaluated.

Aging↗
PubMed1992

Islet amyloid polypeptide: mechanisms of amyloidogenesis in the pancreatic islets and potential roles in diabetes mellitus.

Amyloid deposits characteristically associated with pancreatic islets of those species (e.g., humans, cats, and monkeys) that develop age-associated forms of diabetes have been shown to represent a concentrated and polymerized form of a previously unknown islet-derived protein identified either as IAPP or amylin. IAPP, a highly conserved and carboxy-terminally amidated 37 amino acid polypeptide with approximately 45% amino acid sequence identity to CGRP, is produced by islet beta cells and is cosecreted with insulin in response to glucose and other secretagogues. Prepro-IAPP is synthesized in beta cells as an 89 to 93 amino acid molecule, and mature IAPP appears to be formed by enzymatic processing similar to that involved in the formation of insulin. Glucose-stimulated IAPP secretion generally parallels that of insulin and, on a molar basis, IAPP represents about 1% of the amount of insulin secreted. A significant dissociation of IAPP and insulin secretion (associated with relatively greater upregulation of IAPP secretion) is observed in response to marked hyperglycemia, suggesting that IAPP and insulin expression are differentially regulated. The amyloidogenicity of IAPP in only a very limited number of species is importantly related to the amino acid residues inherently found in the 20-29 region of IAPP from those species. The 25-28 region of human and cat IAPP is identical in structure and appears to be the most important amyloidogenic sequence common to the human and cat. In vitro fibrillogenesis studies have shown that amino acid substitutions in this region especially affect the amyloidogenicity of IAPP. Studies in dogs and cats suggest that aberrations in beta cell synthesis (or processing) of IAPP may lead to an increased concentration of IAPP in the local milieu, thus providing a second prerequisite for the self aggregation of IAPP to form islet amyloid. IAPP has been implicated to have physiological roles in glucose regulation, hemodynamics, calcium homeostasis, and as an anorectic agent. The major current interest in IAPP concerns its potential relationships to glucose metabolism and the development of type 2 diabetes. Evidence has been provided which indicates that IAPP can inhibit glucose-stimulated insulin secretion by beta cells, and that IAPP can also potentially contribute to the pathogenesis of type 2 diabetes by increasing hepatic glucose output and by inducing peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1991

Ultrasonographic features of testicular neoplasia in dogs: 16 cases (1980-1988).

For 16 dogs with testicular neoplasia (n = 19 tumors), ultrasonography was performed to determine whether a correlation exists between ultrasonographic features of testicular tumors and cell type. The echogenicity of the tumors varied depending on the size of the tumor and whether the tumor had focal or diffuse distribution within the testis. The ultrasonographic characteristics of Sertoli cell tumors were variable, with no predominant pattern. This variation may be related to tumor size, because 6 of 7 Sertoli cell tumors were greater than 5 cm in diameter. Focal seminomas and interstitial cell tumors less than 3 cm in diameter had hypoechoic texture. Focal seminomas and interstitial cell tumors greater than 3 cm in diameter had mixed echogenicity. Tumors of multiple cell types were greater than 5 cm in diameter and had mixed echogenicity. In valuable breeding dogs with a small (less than 3 cm) focal intrascrotal lesion, testicular ultrasonography would be of benefit for localization of the mass to the testis or epididymis for subsequent biopsy. In dogs with intraabdominal neoplastic testes, ultrasonography may be of benefit in determining intra-abdominal metastases and invasion of contiguous structures.

Animals↗
PubMed1991

Amyloid in the pancreatic islets of the cougar (Felis concolor) is derived from islet amyloid polypeptide (IAPP).

1. Islet amyloid isolated from the pancreas of a 20-year-old cougar (Felis concolor) was dissolved and purified by gel permeation and reversed phase HPLC for amino acid sequence analysis. 2. N-Terminal amino acid sequence analysis of the purified protein revealed a primary structure (positions 1-28) identical to islet amyloid polypeptide (IAPP) from domesticated cats. 3. IAPP from the cougar, like IAPP from the human and domesticated cat, incorporates an inherently amyloidogenic AILS sequence at positions 25-28.

Amino Acid Sequence↗
PubMed1991

Islet amyloid polypeptide and insulin secretion from isolated perfused pancreas of fed, fasted, glucose-treated, and dexamethasone-treated rats.

Rats from four experimental treatment groups, including fed controls, 24- to 30-h fasted, dexamethasone-treated, and intraperitoneal glucose-treated, were used to assess the effects of these treatments on the immunohistochemically detectable islet amyloid polypeptide (IAPP) content in the pancreatic islets. Isolated perfused pancreases from additional animals in these groups were used to assess insulin and IAPP secretion and relative amounts of these hormones secreted into the perfusate under low-glucose (2.75 mM) and high-glucose (16.7 mM) conditions. Insulin and IAPP concentrations in the perfusate were measured by radioimmunoassays. Titration of immunohistochemical staining revealed the highest levels of IAPP in the dexamethasone- and glucose-treated groups, followed by the fed controls; the least amount was observed in the fasted group. In the perfusion experiments, the dexamethasone-treated group had significantly higher IAPP secretion than did all of the other groups under stimulation with 16.7 mM glucose. In addition, both dexamethasone treatment and glucose treatment increased the relative amount of IAPP to insulin secretion during 16.7 mM glucose stimulation in comparison with fed controls and fasted groups. Fasting tended to have the opposite effect and significantly decreased the relative amount of IAPP to insulin secreted under stimulation with 16.7 mM glucose. In all groups, IAPP and insulin secretion were generally parallel, which is consistent with their colocalization in the beta-cell secretory vesicle and co-release after glucose stimulation. However, significant differences in the insulin-IAPP ratios between experimental groups is consistent with the hypothesis that production of IAPP and insulin are regulated differently in the beta-cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1991

Newly identified pancreatic protein islet amyloid polypeptide. What is its relationship to diabetes?

Islet amyloid polypeptide (IAPP) or amylin is a newly identified 37-amino acid COOH-terminal-amidated polypeptide that is the major protein constituent of amyloid deposits in insulinomas and amyloid deposits in pancreatic islets of non-insulin-dependent (type II) diabetic humans and adult diabetic cats. IAPP is stored with insulin in beta-cell secretory vesicles and is cosecreted with insulin in response to glucose and several secretagogues. IAPP has been demonstrated in normal pancreatic islets of many species, but IAPP-derived amyloid develops commonly in the islets of only a few species (e.g., humans and cats), especially in association with age-related diabetes. IAPP from the human and cat inherently contains a short amyloidogenic sequence that is not present in species that do not form islet amyloid. Studies in animals indicate that an aberration in the synthesis or processing of IAPP, leading to a local increase in concentration of IAPP in the islet, is also required to facilitate the conversion of IAPP to amyloid. The formation of islet amyloid may contribute to the development of type II diabetes by causing disruption of islet cells and by replacement of islets. It has also been proposed that an abnormality of IAPP homeostasis underlies the pathogenesis of type II diabetes. A significant causal relationship between IAPP and type II diabetes is based on reports that IAPP inhibits glucose-stimulated insulin release by beta-cells and that IAPP inhibits insulin-stimulated rates of glycogen synthesis and glucose uptake by skeletal muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1991

An electrodynographic study of foot function in shoes of varying heel heights.

Forty-three female test subjects had electrodynographic gait analysis performed in barefoot, low-heel shoe, and high-heel shoe conditions. Comparisons of segmental foot function, actual pressures, and pressure durations were determined. The findings suggest that an increased duration of forefoot loading, rather than an increased actual pressure, is responsible for pedal pathology secondary to wearing high-heel shoes. Contrary to previous reports in the literature, evidence of abnormal pronation in high heels was not found in this study.

Biomechanical Phenomena↗
PubMed1991

Comparison of fractional excretion and 24-hour urinary excretion of sodium and potassium in clinically normal cats and cats with induced chronic renal failure.

The influence of induced chronic renal failure on 24-hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P less than 0.0001) and sodium (P less than 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24-hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with 24-hour urinary excretion in clinically normal cats.

Animals↗
PubMed1990

Glucagon-producing pancreatic endocrine tumors in two dogs with superficial necrolytic dermatitis.

A newly recognized disease in dogs, ulcerative dermatosis associated with diabetes mellitus (diabetic dermatopathy), was diagnosed in 2 dogs with pancreatic endocrine tumors that had immunohistologic evidence of glucagon production. Dogs developed diabetes mellitus in the later stages of the illness, months after the skin disease was first observed. Liver disease was identified and characterized by high serum alkaline phosphatase and alanine transaminase activities. Clinically, erythema and crusting involved the footpads, the face, perioral and genital skin, and ventrum. Histologically, skin lesions were intercellular and intracellular edema and necrosis of the upper half of the epidermis and diffuse parakeratosis. Clinically and histologically, skin lesions closely resembled necrolytic migratory erythema of people, a skin disease that usually is associated with a glucagon-secreting pancreatic endocrine tumor and diabetes mellitus (glucagonoma syndrome): The morphologically descriptive term, superficial necrolytic dermatitis, was preferred over the previously proposed names hepatocutaneous syndrome and diabetic dermatopathy, which each connote only a single feature of the disease.

Animals↗
PubMed1990

Islet amyloid polypeptide (IAPP) does not inhibit glucose-stimulated insulin secretion from isolated perfused rat pancreas.

Islet amyloid polypeptide (IAPP) is a recently discovered pancreatic islet hormone which is stored with insulin in the secretory vesicles of beta cells. Several lines of evidence suggested that IAPP might affect glucose-stimulated insulin secretion and, therefore, might play a role in the development of impaired insulin secretion which is typical of type 2 diabetes. In this study, the effects of human IAPP (amide) on glucose-stimulated insulin secretion was evaluated in the isolated perfused rat pancreas. IAPP in concentrations from 5 x 10(-12) to 10(-7) M had no significant effects on insulin secretion. IAPP, therefore, does not appear to be a significant modulator of glucose-stimulated insulin secretion at concentrations that are physiologically relevant.

Amyloid↗
PubMed1990

Canine IAPP cDNA sequence provides important clues regarding diabetogenesis and amyloidogenesis in type 2 diabetes.

Islet amyloid polypeptide (IAPP) is a recently discovered pancreatic islet hormone which is stored with insulin in beta cell granules. IAPP may have a significant role in the development of Type 2 diabetes mellitus due to its propensity to form islet cell-disrupting amyloid deposits, and by opposing the action of insulin in peripheral tissues. Most evidence to-date suggests that an intrinsic structural motif of IAPP is linked to the amyloidogenicity of IAPP, and that this motif occurs only in those species (e.g., humans and cats) that also develop age-associated or Type 2 diabetes We utilized polymerase chain reaction methodology in this study to obtain the IAPP nucleotide and protein sequences of the dog, a species not known to develop islet amyloid. We show that dog IAPP contains the same putative amyloidogenic sequence (GAILS) at residues 24-28 as human and cat IAPP, and that although dogs do not develop islet amyloid they do develop IAPP-derived amyloid in association with neoplastic beta cells (i.e., insulinomas). These results provide strong evidence that the amyloidogenicity of IAPP is linked to at least two prerequisites: a species-specific amyloidogenic structural motif, and aberrations in the synthesis (or processing) of IAPP which leads to increased concentration of IAPP in the local milieau.

Amino Acid Sequence↗
PubMed1990

Amino acid sequence from degu islet amyloid-derived insulin shows unique sequence characteristics.

The main protein of enriched and purified amyloid from Octodon degus pancreatic islets was identified as insulin. The material was reduced and alkylated and the A- and the B-chain were separated by reversed phase chromatography and subjected to Edman degradation and amino acid analysis. It was shown that the A-chain contains two additional C-terminal amino acid residues (i.e. a total of 23 residues) and that the B-chain has a deletion in the C-terminal part (i.e. a total of 29 residues). The obtained sequence follows: A-chain: GIVDQCCNNICTFNQLQNYCNVP B-chain: YSSQHLCGSNLVEALYMTCGRSGFYRPHD.

Amino Acid Sequence↗
PubMed1990

The putative hormone islet amyloid polypeptide (IAPP) induces impaired glucose tolerance in cats.

Islet amyloid polypeptide (IAPP) has been implicated by in vitro studies as an inhibitor of insulin-stimulated glucose utilization by skeletal muscle cells and also as an inhibitor of insulin-stimulated insulin secretion by beta cells. Increased expression and production of IAPP by beta cells, as has been suggested to occur in cats with impaired glucose tolerance, could thus contribute substantially to the development of the insulin resistance and impaired insulin release which are the hallmarks of Type 2 diabetes mellitus. The effects of IAPP with respect to glucose metabolism in living animals, however, have not been previously reported. In the present in vivo study we show that synthetic amidated IAPP induced impaired glucose tolerance in each of the 3 cats studied, with dramatic impairment (increases in glucose to T1/2 values of 124% and 234%) in 2 of the 3 cats. Impaired insulin responses were also evident in the 2 cats with the most dramatic states of glucose intolerance. These results provide the most direct evidence to-date that IAPP may have an important role in the development of Type 2 diabetes mellitus.

Amyloid↗
PubMed1990

Islet amyloid polypeptide and calcitonin gene-related peptide immunoreactivity in amyloid and tumor cells of canine pancreatic endocrine tumors.

Seven canine pancreatic endocrine tumors were evaluated immunohistochemically for the presence of islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), and several other pancreatic hormones. Four tumors contained cells with IAPP immunoreactivity, and four had cells with CGRP immunoreactivity. IAPP and CGRP immunoreactivities were localized to distinctly different cell populations in three tumors in which both peptides were detected; however, IAPP immunoreactivity consistently was found in cells that also contained insulin immunoreactivity. Amyloid deposits, which were found in three of the seven tumors, showed strong immunoreactivity with antiserum against IAPP and weaker immunoreactivity with antiserum to CGRP. These results indicate that amyloid deposits in canine pancreatic endocrine tumors are likely derived from IAPP, as is amyloid found in human pancreatic endocrine tumors and pancreatic islet amyloid in aged and diabetic persons and cats.

Amyloid↗
PubMed1990

Structure of cat islet amyloid polypeptide and identification of amino acid residues of potential significance for islet amyloid formation.

Cats and humans, unlike most rodent species, develop amyloid in the islets of Langerhans in conjunction with non-insulin-dependent diabetes mellitus. The amyloid consists of a 37-amino acid polypeptide referred to as islet amyloid polypeptide (IAPP). The primary structures of IAPP from human and three rodent species have previously been determined. Sequence divergence was seen in the region corresponding to amino acid residues 20-29, which in human IAPP has been suggested to confer the amyloidogenic properties to the molecule. Using polymerase chain-reaction methodology, we determined the primary sequence of cat IAPP. Amino acid region 20-29 shows specific similarities and differences compared with human and rodent IAPP, respectively. A synthetic cat IAPP20-29 decapeptide formed amyloid fibrils spontaneously in vitro. Comparison between the structure and amyloid fibril-forming activity of various synthetic peptides suggests that the amino acid residues at positions 25-26 in mature IAPP are important for the amyloidogenic properties of the molecule.

Amino Acid Sequence↗