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Biomedical subjects

C A Brown

Publications and source records attributed to C A Brown.

At least 91 records · Page 5Linked to original sources
PubMed1997

Malignant cauda equina paraganglioma in a cat.

An 11-year-old spayed female domestic long-haired cat presented for surgical removal of a slowly growing and deeply invasive 2.5 x 3.5-cm mass cranial to the base of the tail. Light microscopic examination of surgical biopsy specimens revealed an encapsulated mass composed of packets of polygonal cells of various sizes separated by a delicate fibrovascular stroma. Gömöri's reticulum stain revealed a characteristic endocrine or "Zellballen" pattern. Tumor cells contained diffuse positive reactivity to synaptophysin and neuron-specific enolase, reactions consistent with a neuroendocrine neoplasm. S-100 protein-positive cells reminiscent of sustentacular (support) cells occurred singly or in small clusters within tumor packets. At postmortem examination 3 months later, a 9- x 5- x 4-cm multinodular raised tan mass involving the caudal pelvis, sacrum, and tail-head regions was found. The base of this neoplastic mass originated within the cauda equina region and involved approximately five caudal nerve roots. Numerous 1-3-mm metastatic nodules were identified disseminated throughout the pulmonary parenchyma. The tumor was diagnosed as a malignant paraganglioma of the cauda equina region with pulmonary metastasis.

Animals↗
PubMed1997

Effects of parathyroidectomy on induced renal failure in dogs.

OBJECTIVE: To determine the effects of parathyroid hormone (PTH) depletion on dogs with induced chronic renal failure. ANIMALS: 2 groups of 26 mixed-breed dogs of both sexes (13 were parathyroidectomized [PTX] and 13 had sham surgery). PROCEDURE: After surgical reduction of renal mass and PTX, dogs were selected for a 24-month period of study and monitored for clinical, hematologic, blood biochemical, and organ function status. On development of uremia or after 24 months, dogs were euthanatized, and tissues were examined. RESULTS: Higher survival rate and smaller decrement in renal function (glomerular filtration rate) were observed in PTX dogs, compared with those that had sham surgery, but values did not reach statistical significance. The PTX dogs remained hypocalcemic during the study and had lower serum Ca2+ X P product values. Regardless of parathyroid state, survivors and fatalities could be separated on the basis of serum Ca2+ X P product values. Parathyroidectomy did not prevent renal deposition of calcium, and renal lesions were poorly correlated with renal cortical calcium concentration. Abnormalities reported in dogs with renal failure, which were attributed to PTH (glucose intolerance, pulmonary hypertension), were not observed in PTX dogs or those that had sham surgery. CONCLUSIONS AND CLINICAL RELEVANCE: PTX had beneficial effects, but these were mediated via changes in mineral homeostasis rather than via direct effects of PTH. Results attributable to PTX were similar to those previously obtained by dietary restriction of phosphate intake.

Acidosis↗
PubMed1997

Mitogenic effects of epidermal growth factor and platelet-derived growth factor on canine and equine mesangial cells in vitro.

OBJECTIVE: To evaluate the effects of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) on canine and equine mesangial cell (MC) proliferation in vitro. SAMPLE POPULATION: Third- through eighth-passage canine and equine MC were obtained from explant outgrowth after differential sieving of glomeruli isolated from the kidneys of clinically normal dogs and horses. PROCEDURE: Mitogenic effects of serum, insulin, EGF, and PDGF were evaluated in MC by induction of DNA synthesis, measured as stimulation of [3H]thymidine incorporation and increase in cell numbers. RESULTS: Epidermal growth factor was a potent mitogen in canine and equine MC, stimulating dose-dependent increases in [3H]thymidine incorporation and moderate increase in cell numbers. Although PDGF alone did not significantly stimulate [3H]thymidine incorporation in canine MC, PDGF was synergistic with EGF in stimulation of [3H]thymidine incorporation in canine and equine MC, and PDGF significantly stimulated [3H]thymidine incorporation in equine MC. CONCLUSIONS: Both EGF and PDGF are important mediators of canine and equine MC proliferation. CLINICAL RELEVANCE: Our results are consistent with the hypothesis that growth factors have a role in the progression of glomerular disease in dogs and horses. These findings could prove to be of diagnostic, prognostic, and therapeutic value in the management of spontaneous renal disease in these species.

Animals↗
PubMed1996

P2 purinoceptor-stimulated conversion of arginine to citrulline in bovine endothelial cells is reduced by inhibition of protein kinase C.

Bovine aortic endothelial cells contain two coexisting receptors for extracellular ATP, named the P2Y and P2U purinoceptors. Previous studies have shown that these receptors are linked to phospholipase C in a manner that is modulated in part by protein kinase C (PKC). In this study, we investigate the influence of PKC in the regulation of endothelial nitric oxide synthase (NOS) by these two purinoceptors. Activation of either P2Y or P2U purinoceptors by either 2-methylthio-ATP or UTP, respectively, stimulated the formation of [3H]-citrulline in [3H]-arginine-labelled cells in a concentration-dependent manner. This stimulation was sensitive to inhibition by NG-nitro-L-arginine. Ten minutes of pretreatment with the PKC activator tetradecanoyl phorbol acetate (TPA) failed to affect NOS activity, either alone or when stimulated with 2-methylthio-ATP or UTP. However, under these conditions TPA caused almost complete translocation of PKC-alpha from the cytosol to the membrane. Ten minutes of pretreatment with the PKC inhibitor Ro 31-8220 significantly inhibited the agonist-induced stimulation of NOS. These results show that both P2Y and P2U purinoceptors stimulate endothelial NOS in a manner that is dependent on PKC activity.

Animals↗
PubMed1996

Leptospira interrogans serovar grippotyphosa infection in dogs.

Leptospirosis attributed to infection with serovar grippotyphosa was diagnosed in 11 dogs. In naturally and experimentally infected dogs, a stereotypic serologic response to infection with Leptospira serovar grippotyphosa was detected. Although the highest serum antibody titers developed against serovar grippotyphosa, most dogs also had lower titers against serovars bratislava and pomona. Acute renal failure was evident in 10 dogs. One dog died prior to initiation of treatment; the remaining 10 dogs were treated with antibiotics and fluids. Two dogs were euthanatized, 2 dogs recovered without clinical or biochemical evidence of residual renal dysfunction, and 6 dogs recovered but had varying degrees of renal insufficiency. Hepatic involvement appeared to be a minor component of the disease in these dogs. Our results indicate that Leptospira serovar grippotyphosa infection is an important problem in dogs and should be considered when evaluating a dog with renal failure.

Acute Kidney Injury↗
PubMed1996

Tissue-specific methylation differences and cognitive function in fragile X premutation females.

Tissue-specific variation in (CGG)n repeat size and methylation status of the FMR1 gene was investigated in 17 female premutation carriers. Minor variation in premutation repeat size among leukocyte, lymphoblast, and fibroblast tissues was noted in some subjects. One subject exhibited a premutation size allele of (CGG)64 in leukocyte and fibroblast tissues by polymerase chain reaction analysis but a normal-size allele of (CGG)46 in lymphoblast cells, suggesting low-level mosaicism in blood and clonality of the lymphoblast cell line. Six subjects exhibited differences in methylation pattern between leukocytes and lymphoblasts but not between leukocytes and fibroblasts, whereas 2 subjects showed large differences in methylation pattern between leukocytes and fibroblasts. Cognitive function was studied in 14 subjects using the Wechsler Adult Intelligence Scale-Revised. Mean Verbal and Performance IQs were well within the average range as was the mean Full Scale IQ; nevertheless, a trend toward lower Performance IQ compared with Verbal IQ was observed. No significant correlation was apparent between Full Scale IQ and (CGG)n repeat size; however, a significant positive correlation was observed between Full Scale IQ and the proportion of the active X carrying the normal FMR1 allele in fibroblasts but not in leukocytes or lymphoblasts.

Adult↗
PubMed1996

Salicylate-induced changes in auditory thresholds of adolescent and adult rats.

Shifts in auditory intensity thresholds after salicylate administration were examined in postweanling and adult pigmented rats at frequencies ranging from 1 to 35 kHz. A total of 132 subjects from both age levels were tested under two-way active avoidance or one-way active avoidance paradigms. Estimated thresholds were inferred from behavioral responses to presentations of descending and ascending series of intensities for each test frequency value. Reliable threshold estimates were found under both avoidance conditioning methods, and compared to controls, subjects at both age levels showed threshold shifts at selective higher frequency values after salicylate injection, and the extent of shifts was related to salicylate dose level.

Acoustic Stimulation↗
PubMed1996

Does modifying dietary lipids influence the progression of renal failure?

Recent studies have identified important effects of dietary fatty acid composition in animals with chronic renal disease, particularly in dogs. The theoretic basis for these effects provides a rationale for the use of diets enriched with omega-3 (but not omega-6) polyunsaturated fatty acids. A therapeutic trial with a diet enriched with omega-3 polyunsaturated fatty acids should be considered as a maneuver designed to slow the rate of progression of chronic renal disease in dogs.

Animals↗
PubMed1996

Does dietary trans fatty acid intake relate to the prevalence of coronary heart disease in Scotland?

Reports of the effects of trans fatty acids on coronary heart disease are inconsistent. Trans fatty acids may particularly influence coronary risk when linoleic acid levels are low, a situation which occurs in Scotland where prevalence of coronary heart disease is also very high. The link between trans fatty acid intake and prevalent coronary heart disease was therefore investigated in the Scottish Heart Health Study population. Trans fatty acid intakes were calculated from 10/359 sets of food-frequency questionnaire data obtained from the cross-sectional survey of men and women aged 40-59 years. Logistic regression analysis was used to calculate the odds ratios for prevalent coronary heart disease by fifths of dietary intake of total, natural and commercial hydrogenation-derived trans fatty acid. The group who had undiagnosed coronary heart disease at the time of survey was the pertinent group for examining the possible causative effects of trans fatty acid intake. After adjustment for the confounding factors (i.e. age, weight, height, smoking, level of physical activity, blood pressure, total energy intake and intakes of saturated fat, linoleic acid and the antioxidant vitamins) the odds of undiagnosed coronary heart disease for men, relative to the lowest intake fifth, did not differ significantly from unity by total or commercially-derived trans fatty acid intake. Odds were around 35% smaller in the higher intake fifths of naturally-derived trans fatty acids. For women, the odds of undiagnosed coronary heart disease tended to be greater in the higher fifths of total (odds ratio 1.36 (95% confidence interval 0.94, 1.89)) and hydrogenated (1.26 (0.92, 1.72)) trans fatty acid relative to the lowest fifth, but only reached significance in the third fifth of total trans fatty acid (1.36 (1.01, 1.83)). Dietary total and commercially-derived trans fatty acids failed to influence the odds of coronary heart disease for men, even though a significant increase in the ratio of low density plus very low density lipoprotein to high density lipoprotein-cholesterol occurred with trans fatty acid intake. The results, therefore, do not support a major effect of dietary trans fatty acid from commercial hydrogenation on coronary heart disease risk in these Scottish men. The results for women are less clear, and the possibility remains that individuals at the high extreme of trans fatty acid intake, who may be essential fatty acid deficient, are at enhanced risk of coronary heart disease.

Adult↗
PubMed1996

Implications of the Myocarditis Treatment Trial for clinical practice.

Active myocarditis, a common precursor of dilated cardiomyopathy, is defined as myocardial inflammation and injury in the absence of ischemia. Many agents may cause myocarditis and the exact manifestation of the disease depends on the interplay between the inciting agent and host response. Widespread belief that myocarditis is an autoimmune disorder has led to the possible overuse of endomyocardial biopsy and immunosuppressive agents. Their use is further complicated by the observation that many patients improve with conservative management alone. The Myocarditis Treatment Trial was designed to address the role of immunosuppression in the treatment of myocarditis, define the natural history of the disease, and increase understanding of the immunologic mechanisms involved in the pathogenesis of the disease. Enrollment began in October 1986 and was completed in October 1990 with follow-up completed in 1991. The study failed to show a significant benefit for immunosuppressive agents. Conventional medical regimens should be used to alleviate symptoms and immunosuppressive agents should be reserved for patients with progressive deterioration and biopsy-proven disease.

Adult↗
PubMed1996

PPADS and suramin as antagonists at cloned P2Y- and P2U-purinoceptors.

1. The effect of suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on the stimulation of phospholipase C in 1321N1 cells transfected with the human P2U-purinoceptor (h-P2U-1321N1 cells) or with the turkey P2Y-purinoceptor (t-P2Y-1321N1 cells) was investigated. 2-Methylthioadenosine triphosphate (2MeSATP) was used as the agonist at t-P2Y-1321N1 cells and uridine triphosphate (UTP) at h-P2U-1321N1 cells. 2. Suramin caused a parallel shift to the right of the concentration-response curves for 2MeSATP in the t-P2Y-1321N1 cells, yielding a Schild plot with a slope of 1.16 +/- 0.08 and a pA2 value of 5.77 +/- 0.11. 3. Suramin also caused a shift to the right of concentration-response curves for UTP in the h-P2U-1321N1 cells, and on Schild plots gave a slope different from unity (1.57 +/- 0.19) and an apparent pA2 value of 4.32 +/- 0.13. Suramin was therefore a less potent antagonist at the P2U-purinoceptor than the P2Y-purinoceptor. 4. In the presence of the ectonucleotidase inhibitor, ARL 67156 (6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP) there was no significant difference in the EC50 or shapes of curves with either cell type, and no difference in pA2 values for suramin. 5. PPADS caused an increase in the EC50 for 2MeSATP in the t-P2Y-1321N1 cells. The Schild plot had a slope different from unity (0.55 +/- 0.15) and an X-intercept corresponding to an apparent pA2 of 5.98 +/- 0.65. 6. PPADS up to 30 microM had no effect on the concentration-response curve for UTP with the h-P2U-1321N1 cells. 7. In conclusion, suramin and PPADS show clear differences in their action at the 2 receptor types, in each case being substantially more effective as an antagonist at the P2Y-purinoceptor than at the P2U-purinoceptor. Ectonucleotidase breakdown had little influence on the nature of the responses at the two receptor types, or in their differential sensitivity to suramin.

Cell Line↗
PubMed1996

Cloned and transfected P2Y4 receptors: characterization of a suramin and PPADS-insensitive response to UTP.

The P2Y family of receptors are G protein-coupled receptors for ATP, ADP, UTP and UDP. Recently several members of this family have been cloned, including the P2Y4, which is activated by UTP but not by ATP. In the present report, using receptors stably transfected into 1321N1 cells, we show that suramin acts as an antagonist at cloned P2Y1 and (less potently) P2Y2 receptors, but not at the cloned P2Y4 receptor. Furthermore, PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid), a potent antagonist at the P2Y1 receptor, is a relatively inneffective antagonist at the cloned P2Y4 receptor. This work moves us closer to the goal of classifying the native P2Y receptors on the basis of agonist and antagonist profiles.

Cell Line↗
PubMed1996

Use of speech-modulated noise adds strong "bottom-up" cues for phonemic restoration.

When deleted segments of speech are replaced by extraneous sounds rather than silence, the missing speech fragments may be perceptually restored and intelligibility improved. This phonemic restoration (PhR) effect has been used to measure various aspects of speech processing, with deleted portions of speech typically being replaced by stochastic noise. However, several recent studies of PhR have used speech-modulated noise, which may provide amplitude-envelope cues concerning the replaced speech. The present study compared the effects upon intelligibility of replacing regularly spaced portions of speech with stochastic (white) noise versus speech-modulated noise. In Experiment 1, filling periodic gaps in sentences with noise modulated by the amplitude envelope of the deleted speech fragments produced twice the intelligibility increase obtained with interpolated stochastic noise. Moreover, when lists of isolated monosyllables were interrupted in Experiment 2, interpolation of speech-modulated noise increased intelligibility whereas stochastic noise reduced intelligibility. The augmentation of PhR produced by modulated noise appeared without practice, suggesting that speech processing normally involves not only a narrowband analysis of spectral information but also a wideband integration of amplitude levels across critical bands. This is of considerable theoretical interest, but it also suggests that since PhRs produced by speech-modulated noise utilize potent bottom-up cues provided by the noise, they differ from the PhRs produced by extraneous sounds, such as coughs and stochastic noise.

Attention↗