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Biomedical subjects

D C Ferguson

Publications and source records attributed to D C Ferguson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effect of dexamethasone on triiodothyronine production in the perfused rat liver and kidney.

Dexamethasone administration to rats decreases T4-5'-deiodinase activity in liver homogenates and slices and in isolated rat renal tubules. To determine if this decreased T4-5'-deiodinase activity results in decreased T3 production, rat livers and kidneys of control and dexamethasone-treated rats were perfused with medium containing free T4 concentrations approximating euthyroid rat serum, and net T3 production was measured by RIA. Dexamethasone administration decreased body weight by 14% but did not affect liver weight, kidney weight, or serum concentrations of T4 or T3. When livers were perfused with T4 concentrations of 10 micrograms/dl (free T4 = 6.5 ng/dl), hepatic T3 production, T4 uptake, and the conversion of T4 to T3 were similar in dexamethasone-treated rats and saline-treated controls. However, when livers were perfused at a T4 concentration of 125 micrograms/dl (free T4 = 81 ng/dl), dexamethasone-treated livers produced significantly less T3 than controls because of decreased conversion of T4 to T3. Hepatic deiodination of T3 and excretion of T3 into bile were not affected by dexamethasone. Renal T3 production, T4 uptake, and conversion of T4 to T3 was likewise unaffected by dexamethasone treatment when kidneys were perfused at near-normal free T4 concentrations. These studies indicate that dexamethasone treatment does not alter T3 production in the perfused liver and kidney and underscore the importance of using free T4 concentrations approximating physiologic levels when studying regulation of T3 production in individual organs.

Animals↗
PubMed1984

Pharmacological modifications of insulin release in vitro from fuel-responsive transplantable insulinomas.

The response of insulinoma tissue to glucose, alpha-ketoisocaproate, and the modifiers of insulin release, tolbutamide, isoproterenol, and acetylcholine, was studied. Tumor tissue was transplanted under the kidney capsule of 14 rats, and the tumor-bearing kidneys were perfused in vitro about 8 weeks later. The plasma glucose concentration of these animals was 85.0 +/- 7.0 mg/dl, while the plasma insulin concentration was 13.8 +/- 1.5 ng/ml (normal, 180.5 +/- 7.0 mg/dl and 2.6 +/- 0.5 ng/ml, respectively; n = 26). Glucose (30 mM) evoked a 3- to 5-fold increase in insulin secretion, similar to the increase seen when either 100 micrograms/ml tolbutamide or 0.5 micrograms/ml isoproterenol were added to the perfusion medium containing 5 mM glucose. Propranolol at 50 micrograms/ml, but not at 20 micrograms/ml, inhibited insulin release stimulated by isoproterenol. Acetylcholine (10 or 100 microM) did not stimulate insulin secretion. alpha-Ketoisocaproate caused the highest insulin release of all stimuli studied. Glucagon or somatostatin release was not seen in any of the experiments. These results show that the tumor tissue transplanted under the kidney capsule responds not only to model fuels, but also to the sulfonylurea class of drugs and to adrenergic agents.

Acetylcholine↗
PubMed1984

Fuel-induced insulin release in vitro from insulinomas transplanted into the rat kidney.

We studied the release of insulin, glucagon, and somatostatin in response to glucose, glyceraldehyde (GA), and alpha-ketoisocaproate (KIC) from rat kidneys containing transplanted insulinomas. Kidneys were perfused about 11 wk after transplantation when the plasma glucose concentration of the fed animals had decreased from 180 +/- 7 to 95.1 +/- 9.9 mg/dl and plasma insulin concentrations had increased from 2.6 +/- 0.5 to 14.2 +/- 2.0 ng/ml. The insulin content of the tumor-containing kidney ranged from 40 to 679 micrograms; the glucagon and somatostatin concentrations ranged from undetectable levels to 3.7 micrograms and 248 ng, respectively. The average response to 30 mM glucose and 10 mM GA was a four- to fivefold increase in insulin secretion, whereas 30 mM KIC caused a 16- to 28-fold increase. In vitro stimulation of the insulinoma with 30 mM glucose primed the beta-cell response to a second stimulus following a short rest period. Cytochalasin B did not enhance this primed glucose response. Diazoxide inhibited glucose, GA, and KIC-stimulated insulin release. Glucose, GA, and KIC stimulated glucagon release in 2 of 17 insulinomas studied here. Somatostatin release was not seen in any of the experiments. These findings show that this islet cell tumor transplanted under the kidney capsule releases insulin in response to physiologic and model fuel substances. Thus, this particular transplantable tumor offers an opportunity to study the biochemistry and biophysics that underlie fuel-stimulated insulin release.

Adenoma, Islet Cell↗
PubMed1984

Effects of spontaneous hyperadrenocorticism on serum thyroid hormone concentrations in the dog.

Serum thyroid hormone concentrations were evaluated in 124 dogs with untreated spontaneous hyperadrenocorticism either by measuring basal thyroxine (T4) and triiodothyronine (T3) concentrations (102 dogs) or by assessing the T4 response to exogenous thyroid-stimulating hormone (TSH) administration (22 dogs). Reduced basal serum concentrations of T4 and of T3 were found in 58 (57%) and 53 (52%), respectively, of the 102 dogs with hyperadrenocorticism; of these, 42 dogs had low values for both T4 and T3, 16 had decreased T4 concentrations alone, and 11 had only decreased T3 concentrations. In 20 dogs that had basal serum thyroid hormone concentrations determined before and after control of hyperadrenocorticism, mean concentrations of both T4 and T3 increased significantly (P less than 0.05). Serum T4 and T3 concentrations normalized in all but 1 of the 20 dogs. In the 22 dogs with hyperadrenocorticism given TSH, mean serum concentrations of T4 at both basal and post-TSH administration times were significantly decreased (P less than 0.01) compared with the results obtained in 18 normal dogs. Nevertheless, a significant increase (P less than 0.001) in mean T4 concentration occurred in these dogs; T4 concentrations after TSH was given were at least 2-fold greater than basal values. The T4 response to exogenous TSH was less in the 13 dogs with low basal T4 concentrations than in the 9 dogs that had resting T4 values within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1983

Feline hyperthyroidism: pretreatment clinical and laboratory evaluation of 131 cases.

Hyperthyroidism was diagnosed in 131 cats during a 3 1/2-year period. The cats ranged in age from 6 to 20 years; there was no breed or sex predilection. The most frequent clinical signs included weight loss, polyphagia, increased activity, polydipsia, polyuria, and vomiting. Common serum biochemical abnormalities included high values for alkaline phosphatase activity (75%), lactate dehydrogenase activity (66%), aspartate transaminase activity (66%), and alanine transaminase activity (54%). Electrocardiographic changes included tachycardia (greater than or equal to 240 beats/min) and increased R-wave amplitude in lead II (greater than or equal to 0.9 mV) in 66% and 29% of the 131 cats, respectively. Thoracic radiography in 82 cats revealed cardiomegaly in 40 (49%) of these cats; 16 cats with congestive heart failure also had pulmonary edema or pleural effusion. In 5 cats with markedly increased fecal volume, mean 48-hour fecal fat content was significantly greater than normal, with daily fat excretion 2 to 15 times the upper limit of normal. Base-line serum thyroxine concentrations were increased above normal range in all cats, whereas triiodothyronine concentrations were increased in 127 (97%) of the 131 cats. In 11 cats tested, mean thyroxine concentration did not increase significantly after thyroid-stimulating hormone administration. Mean 24-hour percentage of thyroid radioiodine uptake in 32 hyperthyroid cats was significantly higher (39.1%) than normal (9.2%). Thyroid scans, performed on 126 cats, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 36 (29%) and both lobes in 90 (71%) of the cats.

Adenocarcinoma↗
PubMed1983

Regulation of conversion of thyroxine to triiodothyronine in perfused rat kidney.

The factors regulating the renal uptake of thyroxine (T4), its conversion to 3,5,3'-triiodothyronine (T3), and the urinary iodothyronine excretion were studied in the perfused rat kidney. Increasing the perfusate free T4 (FT4) concentration from 1 to 11.5 times that of euthyroid rat serum resulted in a linear increase in T4 uptake and T3 production that was not saturated at the highest dose. When FT4 concentrations were increased by decreasing the perfusate albumin concentration from 7.5 to 2.5 g/dl, T4 uptake and T3 production increased in proportion to the FT4 concentration. Propylthiouracil (PTU), a 5'-deiodinase inhibitor, decreased renal T3 production by 60.5% without affecting tissue T4 uptake. In the absence of glomerular filtration, T4 uptake and T3 production were unchanged, indicating that T4 is extracted by the contraluminal surface of the renal tubule. However, probenecid, an inhibitor of contraluminal organic acid uptake, did not decrease but increased T4 uptake and T3 production by increasing the perfusate FT4 fraction in the perfusate. There was no net renal 3,3',5'-triiodothyronine (rT3) production from T4, and degradation and urinary excretion of T3 were negligible. The urinary excretion of T4 and T3 correlated closely with the degree of proteinuria.

Animals↗
PubMed1983

Assessment of thyroid functional reserve in the cat by the thyrotropin-stimulation test.

Serum thyroxine (T4) concentrations before and after various IV doses of bovine thyrotropin (TSH) were measured over a 48-hour period in 19 healthy cats. Base-line T4 values, as measured by radioimmunoassay, varied greatly. The peak T4 concentration occurred 6 hours after TSH injection, and there was an increase in post-TSH serum T4 concentration that was linearly related to the logarithm of the dose. Greatest stimulation was seen with the highest dose used (1 U of TSH/kg of body weight), and 6 hours after administration of this dose, the serum T4 concentration range was 4.1 to 8.4 micrograms/dl. The post-TSH serum T4 concentration and the absolute increase in serum T4 concentration after TSH administration correlated more closely with the TSH dose than did the ratio of post-TSH serum T4 concentration to base-line T4 concentration. Therefore, in cats with normal thyroid-binding protein concentrations, the former indices should represent the most reliable assessment of thyroid functional reserve.

Animals↗
PubMed1982

Electrocardiographic findings in 45 cats with hyperthyroidism.

Electrocardiographic (ECG) abnormalities were recorded in 36 (80%) of 45 cats with untreated hyperthyroidism caused by hyperfunctioning thyroid adenomas (adenomatous hyperplasia). Tachycardia (greater than or equal to 240/min) and increased R-wave amplitude in lead II (greater than or equal to 0.9 mV) were the most frequent abnormalities recorded (62% and 49%, respectively). Other abnormalities included atrial and ventricular arrhythmias (20%), prolonged QRS duration (16%), shortened Q-T interval (11%), intraventricular conduction disturbances (3%), and ventricular pre-excitation (1%). In 17 cats, repeat ECG were recorded 6 months after hemi- or total thyroidectomy; resolution of tachycardia, increased R-wave amplitudes, shortened Q-T intervals, and atrial and ventricular arrhythmias had occurred in all cats. It was concluded that many of the ECG changes associated with feline hyperthyroidism are similar to those associated with primary myocardial disease in cats; however, the ECG abnormalities and associated cardiovascular signs of hyperthyroidism generally resolve after successful treatment of the hyperthyroid state.

Adenoma↗
PubMed1979

Behavioral medicine approaches to hypertension: an integrative analysis of theory and research.

This article compares behavioral and biological approaches to hypertension, highlights some of the practical, semantic, and theoretical issues involved, and attempts a constructive, behavioral medicine integration of these approaches. The major behavioral approaches to hypertension are described, with a focus on their conceptual limitations as stimulants to research into psychobiological mechanisms. A biobehavioral systems analysis of hypertension is outlined, emphasizing the role of the central nervous system as a common pathway relating environmental and behavioral factors to cardiovascular regulatory dynamics and disease. Schwartz's concept of blood pressure disregulation is discussed, by which behavioral "feedback loops" may be included in the pathogenesis of homeostatic disorders. A detailed discussion of concepts underlying the clinical pharmacological approach to hypertension is provided; parallels are drawn between the conceptual framework and the theoretical and practical questions facing behavioral researchers concerned with hypertension. Synergistic interactive effects of drug and behavioral treatments are proposed. A biobehavioral overview, which links pressor and depressor stimulus patterns to both pathogenesis and therapy, can serve to integrate the previous biobehavioral systems analysis, the conceptual framework of clinical pharmacology, and the notion of biobehavioral disregulation of blood pressure. Implications for future behavioral medicine research in hypertension are provided.

Antihypertensive Agents↗
PubMed1979

Regulation of the conversion of thyroxine to triiodothyronine in the perfused rat liver.

This study was undertaken to determine what factors control the conversion of thyroxine (T(4)) to triiodothyronine (T(3)) in rat liver under conditions approximating those found in vivo. Conversion of T(4) to T(3) was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T(4) from perfusion medium and converted it to T(3). Production of T(3) by the perfused liver was a function of the size of the liver, the uptake of T(4) by the liver, and the presence of T(4)-5'-deiodinase activity. Production of T(3) was increased by increasing the uptake of T(4) by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T(4) concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T(4) to T(3). The liver had a large capacity for extracting T(4) and for T(4)-5'-deiodination to T(3), which was not saturated at a T(4) concentration of 60 mug/dl. Production of T(3) was decreased by inhibiting hepatic T(4)-5'-deiodinase with propylthiouracil, which decreased T(3) production by decreasing the conversion of T(4) to T(3). Propylthiouracil did not alter hepatic T(4) uptake. Fasting resulted in a progressive decrease in hepatic T(4) uptake to 42% of control levels by the 3rd d of fasting; this was accompanied by a proportionate decrease in T(3) production. The rate of conversion of T(4) to T(3) did not change during fasting. When T(4) uptake in 2-d-fasted rat livers was raised to levels found in fed rats by increasing the perfusate T(4) concentration from 10 to 30 mug/dl, T(3) production returned to normal. Again, no change in the rate of conversion of T(4) to T(3) was observed. These results indicate that the decreased hepatic T(3) production during fasting primarily results from decreased hepatic uptake of T(4), rather than from changes in T(4)-5'-deiodinase activity. Thus, these studies have delineated a new mechanism that functions independently of enzyme quantity or activity whereby production of T(3) from T(4) is regulated.

Animals↗