Biomedical subjects

T D O'Brien

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

80 records · Page 5Linked to original sources

PubMedDate not supplied

Islet amyloid polypeptide (IAPP) competes for two binding sites of CGRP.

Two distinct binding sites for [125I]human calcitonin gene-related peptide (hCGRP) were found in rat brain, skeletal muscle, and liver. Each tissue had a high affinity site with an average Kd of 46 pM and a low affinity site with an average Kd of 22 nM. Islet amyloid polypeptide (IAPP), which has N- and C-terminal sequence homology to CGRP and is produced by islet beta-cells, bound to both sites but had a potency closer to that of CGRP at the low affinity binding site. A C-terminal fragment of IAPP competed for [125I]hCGRP binding at the low affinity site with potency comparable to that of hIAPP. No specific binding to membrane preparations was found in experiments using [125I]rIAPP, which was iodinated at the C-terminal tyrosyl residue. These results suggest that some of the previously reported biological effects occurring at nM or microM concentrations of IAPP may be mediated by IAPP binding to low affinity CGRP receptors. This study further indicates that the C-terminal region of IAPP is important for binding to low affinity CGRP receptors, and suggests that C-terminal fragments of IAPP may be of biological importance.

Amino Acid Sequence↗

PubMedDate not supplied

A beta-associated cerebral angiopathy and senile plaques with neurofibrillary tangles and cerebral hemorrhage in an aged wolverine (Gulo gulo).

In this study of an aged wolverine (Gulo gulo), we document neuropathologic lesions (cerebral amyloid angiopathy (CAA), neuritic plaques (NPs), neurofibrillary tangles (NFTs), and granulovacuolar degeneration strikingly similar to those present in aging and Alzheimer's disease (AD), with the additional finding of concurrent cerebral hemorrhage. A beta immunoreactive cerebral amyloid angiopathy and senile plaques (neuritic and diffuse) were present throughout the cerebral cortex and hippocampus. Ubiquitin immunoreactivity was noted in peripheral portions of some of the plaques. Argyrophilic intracellular neurofibrillary tangles containing abnormally phosphorylated (Ser 202) tau protein were present within cortical and hippocampal neurons. The wolverine should be added to the list of nonhuman species (dogs, nonhuman primates, polar bears) with amyloid deposits similar to those in aged humans and in humans with AD. The aged wolverine appears to be distinct from other nonhuman species in possessing plaques and NFTs, as well as other histologic cerebral lesions frequently associated with AD.

Aging↗

PubMedDate not supplied

Continent jejunal reservoir (Kock pouch) for urinary diversion in dogs.

Urinary diversion by transplantation of both ureters into a reservoir constructed from 60 cm of jejunum was performed in six clinically normal dogs. The reservoir was connected to a stoma on the abdominal wall through a valve constructed from a short segment of intussuscepted bowel to provide continence. The reservoir was emptied three times daily by catheterization. One dog did not survive the surgical procedure and two dogs died within 1 week of surgical complications. The postoperative capacity of the reservoir in surviving dogs was 100 to 200 mL; it increased during the first month to 600 to 750 mL. Continence was excellent in two dogs. One dog was continent until month 2, when partial slippage of the intussusception occurred. A reversible hyponatremic, hypochloremic, hypokalemic metabolic acidosis developed. Bacteriuria was not responsive to systemic or local instillation of antibiotics. Ascending pyelonephritis, hydroureter, and hydronephrosis occurred in two dogs. Struvite urinary calculi formed in one dog. The procedure as described would be unsuitable for clinical use in dogs.

Acidosis↗

PubMedDate not supplied

Correlation of urine protein/creatinine ratio and twenty-four-hour urinary protein excretion in normal cats and cats with surgically induced chronic renal failure.

Urine protein/creatinine (UP/C) ratios and 24-hour urinary protein excretion were compared in clinically normal cats and cats with surgically induced chronic renal failure (CRF). Mean 24-hour urinary protein excretion in 30 clinically normal cats fed a 28% protein diet (dry weight basis) was 4.93 mg/kg/24-hour (SD = 1.34) with a range of 2.99 to 8.88. Mean UP/C ratio in these cats was 0.134 (SD = 0.037) with a range of 0.073 to 0.239. Mean 24-hour urinary protein excretion in CRF cats was 10.49 mg/kg/24-hour (SD = 11.28) with a range of 2.16 to 62.93. Mean UP/C ratio in the CRF cats was 0.359 (SD = 0.374) with a range of 0.061 to 1.916. Linear regression showed high correlation (R2 = 0.973, P less than 0.001) between 24-hour urinary protein excretion and UP/C ratio in clinically normal cats and cats with surgically induced chronic renal failure. The regression equation for 24-hour urinary protein excretion versus UP/C ratio was: 24-hour urinary protein excretion = 29.39 (UP/C) + 0.18. Results of this study indicate that UP/C ratios are a valid estimate of 24-hour urinary protein excretion in clinically normal and CRF cats. Dietary protein intake significantly affected UP/C ratios in clinically normal cats and cats with surgically induced CRF. Therefore, the influence of dietary protein should be considered when interpreting UP/C ratios.

Animals↗

PubMedDate not supplied

Duplex Doppler estimation of Pourcelot resistive index in arcuate arteries of sedated normal cats.

Renal failure is an important cause of morbidity and mortality in feline patients. In human patients, intrarenal blood flow values obtained with duplex Doppler ultrasonography have been used to aid in the diagnosis and prognosis of renal failure. The purpose of this report is to present values for resistance to intrarenal blood flow in normal cats, derived by duplex Doppler ultrasonography. Ten mature clinically healthy conditioned domestic shorthaired cats were screened for normal renal anatomy and function by CBC, serum biochemical profile, urinalysis, urine protein/creatinine ratio, endogenous creatinine clearance, and renal B-mode ultrasonography; and for normal systemic blood pressure with Doppler pressure cuff measurement. Subsequently, the cats were sedated with ketamine hydrochloride, and values for mean intrarenal (arcuate artery) resistance to blood flow were determined by duplex Doppler ultrasonography, and expressed as the Pourcelot resistive index, a ratio of systolic to diastolic flow commonly used in duplex Doppler sonography in human patients. After duplex Doppler sonographic examination, histological normalcy of the kidneys was verified by evaluation of ultrasound-guided percutaneous renal biopsy. Based on the obtained resistive indices, 95% confidence intervals for normal values were calculated as follows: left kidney, 0.52 to 0.60; right kidney, 0.55 to 0.63. No statistically significant difference was noted between the values obtained for the right versus the left kidney.

Animals↗

PubMedDate not supplied

Evaluation of urine gamma-glutamyl transpeptidase-to-creatinine ratio as a diagnostic tool in an experimental model of aminoglycoside-induced acute renal failure in the dog.

The potential diagnostic utility of the urine gamma-glutamyl transpeptidase (GGT)-to-creatinine ratio was evaluated in an experimental canine model of aminoglycoside-induced nephrotoxicity. A therapeutic dosage of gentamicin resulted in a twofold increase in the mean urine GGT-to-creatinine ratio that was not associated with clinically significant nephrotoxicity. In dogs each given a nephrotoxic dosage of gentamicin, an increase in mean urine GGT-to-creatinine ratios approximately three times baseline values preceded clinically significant abnormalities in serum creatinine, urine specific gravity, and urine protein-to-creatinine ratio. The urine GGT-to-creatinine ratio appears superior as an early indicator of aminoglycoside-induced nephrotoxicity. Further studies in canine clinical cases are warranted.

Acute Kidney Injury↗

PubMedDate not supplied

Duplex Doppler estimation of resistive index in arcuate arteries of sedated, normal female dogs: implications for use in the diagnosis of renal failure.

The resistive index (RI), an ultrasonographic method of evaluating intrarenal resistance to blood flow, may be used to aid in diagnosis of renal failure. Values for arcuate artery RI, expressed as mean +/- two standard deviations, were obtained in clinically normal female dogs sedated with atropine, acepromazine maleate, diazepam, and ketamine hydrochloride. No statistically significant differences were noted between the values for the right kidney (0.33 to 0.57) versus the left kidney (0.32 to 0.56); however, the values were statistically significantly lower than values reported for nonsedated, normal dogs.

Acute Kidney Injury↗

PubMedDate not supplied

Resolution of superficial necrolytic dermatitis following excision of a glucagon-secreting pancreatic neoplasm in a dog.

An 11-year-old, neutered male standard poodle was diagnosed with superficial necrolytic dermatitis and a glucagon-secreting pancreatic islet neoplasm based on clinical, biochemical, histopathological, immunohistochemical, and hormonal findings. Hyperglucagonemia, hyperinsulinemia, and hypoaminoacidemia were observed on preoperative laboratory analysis. Abnormal laboratory values returned to normal, and complete resolution of skin lesions occurred after tumor excision. The dog has remained clinically normal for six months following surgery.

Amino Acids↗