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Biomedical subjects

L M Fox

Publications and source records attributed to L M Fox.

At least 55 records · Page 3Linked to original sources
PubMed1989

Quantification of plasma cortisol levels in ascorbic acid studies using guinea pigs implanted with ACTH pellets.

A method is described that permits multiple blood collections from unanesthetized, unrestrained guinea pigs with minimal disruption to the animal, as verified by plasma cortisol (PC) levels. Blood (100-200 microliters) was collected from the lateral metatarsal vein using a vacuum-assisted method. Using this method, the effect of subcutaneously-implanted slow-releasing ACTH versus placebo pellets on PC levels was determined. A small, but significant, increase in PC concentration occurred in the control group, reflecting the stress of handling and the implant procedure. In contrast, the peak concentration of PC after implantation of a pellet containing ACTH was 20 times the starting level and occurred within 4 hr. However, the PC level was not correlated with the content of ACTH in the pellet because a similar level was achieved with 0.125 or 8 mg/pellet. A decline in Pc to pre-treatment levels occurred within 24 to 48 hr. The results indicate that administration of ACTH by pellet, although intended to achieve a sustained elevation in PC level, is not suitable for maintaining elevated PC levels.

Adrenocorticotropic Hormone↗
PubMed1989

The influence of anesthesia and surgery on plasma cortisol and tissue ascorbic acid levels in the guinea pig.

The influence of methoxyflurane anesthesia alone compared to anesthesia and laparotomy surgery on plasma cortisol (PC) levels and tissue ascorbic acid (AA) levels was examined in adult male albino guinea pigs (485 +/- 7 g) consuming 500 mg AA/kg diet. Anesthesia resulted in a 60% decrease in food intake on day 1 after treatment, while surgery resulted in a 71% decrease. By day 4, food intake for both groups was equal to that of control animals. Body weight decreased 5-7% on day 1 after both treatments; recovery of body weight to pre-treatment levels was slowest in the animals exposed to surgery. After anesthesia alone, PC levels were twice that of controls by 1 hr and the five-fold higher peak PC level was observed at 9 hr. Surgery induced a more immediate five-fold rise in PC level that plateaued at 1 hr. PC levels decreased to levels similar to the control animals after 72 hr after both treatments. Weight, percent water, and AA levels of tissues examined at seven days after treatment were similar among groups. The results indicate that the adrenal cortical response to surgery is of the same magnitude as for anesthesia alone, although the peak PC level is more quickly achieved. Tissue AA levels are similar seven days after surgery or anesthesia alone even though elevated PC levels sustained for several days.

Abdomen↗
PubMed1988

Day-night variability in acid phosphatase activity of pineal gland macrophages.

Acid phosphatase (ACP) activity was investigated in the photoreceptive pineal gland of the goldfish by both light and electron microscopy. Intraluminal macrophages exhibited the greatest ACP reactivity that was generally confined to lysosomal bodies containing membranous debris. Quantitative light microscopic evaluation revealed significantly higher ACP reactivity in animals collected at mid-light compared to those collected at mid-dark suggesting that functional activities of macrophages in this photoneuroendocrine organ are cyclical over the 24-h photoperiod. Day-night differences in macrophage ACP activity may reflect rhythmic renewal and shedding of photoreceptor outer segment membranes.

Acid Phosphatase↗
PubMed1987

Electrophysiology and ultrastructure of eustachian ridge from cat right atrium: a comparison with SA node.

Intracellular microelectrode and electron microscopic techniques were used to investigate and correlate the electrophysiology of subsidiary pacemaker activity with the presence of cells having ultrastructural characteristics of pacemaker cells i.e. P cells, in Eustachian ridge tissue isolated from cat right atrium. In addition, the electrophysiological characteristics of subsidiary pacemaker activity and the ultrastructural characteristics of P cells in Eustachian ridge were compared to those of SA node obtained from the same hearts. Action potential recordings and morphological analysis were restricted to the endocardial site of earliest activation. Electrophysiological recordings revealed that spontaneously active Eustachian ridge tissues generate slow response action potentials with pacemaker characteristics similar, although not identical, to those of SA node. These included a relatively steep diastolic slope, low maximum diastolic potential (-70 mV), rate of rise (5.5 V/s), take-off potential (-52.5 mV), a relatively large overshoot potential (+7.7 mV) and a spontaneous cycle length (948 ms) about twice as long as SA node (434 ms). Morphological analysis revealed cells with ultrastructural characteristics of P cells, that were restricted to the endocardial site of earliest pacemaker activation. Morphological measurements indicate that Eustachian ridge P cells are not significantly different from P cells in SA node of the same hearts. However, Eustachian ridge P cells exhibit a unique apposition of subsarcolemmal cisternae between cells not seen in SA node. We conclude that pacemaker cells within the Eustachian ridge generate stable, spontaneous activity via slow response pacemaker action potentials. Cells responsible for this subsidiary pacemaker activity are most likely P cell types that are similar, although not identical, to P cells in SA node.

Action Potentials↗
PubMed1987

Pinealocyte dense-cored vesicles and synaptic ribbons: a correlative ultrastructural-biochemical investigation in rats and mice.

Dense-cored vesicles (DCV) and synaptic ribbons (SR) were quantified in the pineal gland of the rat (Sprague-Dawley) and mouse (Sasco/ICR strain), and day/night differences in frequency of these organelles correlated with levels of indoles determined by high performance liquid chromatography (HPLC). There were significant day/night differences in levels of serotonin (5HT), 5-hydroxyindole acetic acid (5HIAA), N-acetyl-5HT, and melatonin in the rat gland. Melatonin and N-acetyl-5HT were not detectable in the mouse gland sampled every 4 h over the light:dark cycle. The concentrations of 5HT and 5HIAA (ng/microgram protein) were similar in light-adapted rats and mice, but these indoles did not exhibit a circadian rhythm in the mouse gland. Correlative ultrastructural/biochemical results suggest that DCV do not contain physiologically important stores of 5HT since 1) the mouse gland contains the same number of DCV as the rat during the daytime, but only one-tenth the levels of 5HT, 2) day/night 5HT levels do not vary in the mouse gland, but there is a significant nocturnal decline in DCV numbers, and 3) 5HT levels in the rat gland decline at night when DCV numbers increase. Numbers of SR were significantly elevated at night in the rat and mouse, and the frequency of this organelle was similar in both species. However, ribbon-type SR predominated in rat pinealocytes, whereas SR in the mouse were almost exclusively spherical in shape. Day/night differences in SR numbers in the mouse gland suggest that cellular mechanisms regulating the frequency of this organelle do not involve factors related to indole metabolism. Because of the lack of photoperiodic effects on indole metabolism in the mouse pineal gland, this species is a potentially important model to study the functional relationship of pinealocyte organelles to cyclical changes in pineal products other than indoles (e.g., peptide/protein factors).

Animals↗
PubMed1986

The assessment of contractile reserve after thrombolytic therapy for acute myocardial infarction.

"Stunned" myocardium prevents the assessment of myocardial salvage after streptokinase. In order to unmask "stunning," we sought to evaluate left ventricular inotropic contractile reserve of patients after streptokinase. Radionuclide ventriculograms were obtained in 75 consecutive patients 2 weeks after myocardial infarction, at rest and during intravenous isoproterenol infusion. Resting and isoproterenol-stressed ejection fractions were compared in the patent and closed-infarct vessel groups. Although there was no difference in the resting ejection fractions between the patent group (0.48 +/- 0.02) and the closed group (0.48 +/- 0.02), isoproterenol increased the ejection fractions in the patent group (increase 0.14 +/- 0.01) significantly more than in the closed group (increase 0.06 +/- 0.01) (p less than 0.0001). Thus, despite identical resting ventricular function, the greater inotropic contractile reserve in the patent infarct vessel group suggests that restoration of blood flow in acute myocardial infarction salvages myocardium.

Adult↗
PubMed1984

Temperature dependence of protein transport across lymphatic endothelium in vitro.

The purpose of the work was to develop an in vitro model for the study of lymphatic endothelium and to determine, using this model, whether or not a cytoplasmic process may be involved in transendothelial transport. Segments of canine renal hilar lymphatics were dissected clean, cannulated at both ends, and transferred to a perfusion chamber for measurement of transendothelial protein transport and for ultrastructural tracer studies. The segments were subsequently processed for light and electron microscopy. By both structural and functional criteria the lymphatics were judged to have retained their integrity. At 37 degrees C, 36 lymphatics showed a mean rate of protein transport of 3.51 +/- 0.45 (SEM) micrograms/min per cm2 of lymphatic endothelium. The rate was influenced by the temperature of the system, being significantly reduced by 49% +/- 4.8, 31% +/- 5.3, and 29% +/- 3.9 when the temperature was lowered to 4 degrees, 24 degrees, and 30 degrees C, respectively. When the temperature was raised to 40 degrees C, the rate was significantly increased by 48% +/- 12.2. The vesicular system and the intercellular regions in vessels with increased or reduced rates of transport were analyzed quantitatively to ascertain whether the rate changes could be correlated with ultrastructurally demonstrable changes in either of these postulated pathways. No significant changes in junctional or vesicular parameters were found between the control lymphatics and those perfused at 24 degrees, 30 degrees, and 40 degrees C. At 4 degrees C, the temperature at which the rate of protein transport was maximally reduced, vesicular size decreased, and the number of free cytoplasmic vesicles increased, whereas the number associated with the abluminal and luminal surfaces decreased. We concluded that isolated perfused lymphatic segments transport protein at a relatively constant rate under control conditions, and that this transendothelial transport comprises both temperature-dependent and temperature-independent mechanisms. The findings were considered in terms of the different theories of lymph formation and were interpreted as providing support for the vesicular theory.

Animals↗
PubMed1982

The morphology of canine lymphatic valves.

The architecture of 60 valves from thoracic ducts and from renal hilar and mesenteric collecting lymph vessels of dogs were studied by scanning electron microscopy as well as by light and transmission electron microscopy. All of the valves seen in hilar and mesenteric lymph vessels and most of those studied in the thoracic duct were bicuspid. An occasional tricuspid and one monocuspid valve was seen in the thoracic duct. The semilunar cusps of the valves extended from the vessel wall, to which they were attached, towards the valve outlet where adjacent cusps fused. Coincident to the area of fusion was the formation of mesenteric-like folds or buttresses that anchored the cusps to the vessel wall. These folds extended 50-100 micrometers beyond the cusp margins on the outflow side of the valve. The attachments of the cusps, buttresses, and vessel wall to one another resulted in the formation of postvalvular sinuses, such that raised intraluminal pressure downstream to valve areas would distend the sinuses, causing leaflet apposition and hence valvular closure. The morphology of the valves was such that they were not considered to provide any significant impediment to the antegrade flow of lymph.

Animals↗
PubMed1982

Capacity of deoxycytidine to selectively antagonize cytotoxicity of 5-halogenated analogs of deoxycytidine without loss of antiherpetic activity.

Enzyme kinetic studies from this laboratory (M. Dobersen and S. Greer, Biochemistry 17:920-928, 1978) suggested that deoxycytidine could antagonize the toxicity of 5-halogenated analogs of deoxycytidine without interfering with their antiviral activity. Antagonism by deoxycytidine of the toxicity of 5-chlorodeoxycytidine without impairing its anti-herpes simplex virus type 2 activity is demonstrated in the present studies. Tetrahydrouridine, an inhibitor of cytidine deaminase, was utilized. The high Km for deoxycytidine (0.6 mM) with respect to the herpes pyrimidine nucleoside kinase as compared with the low Km for 5-chlorodeoxycytidine (1.1 microM) accounts for the absence of antagonism of the antiviral activity. The high Km for 5-chlorodeoxycytidine (56 microM) as compared with the low Km of deoxycytidine (2 microM) with respect to mammalian deoxycytidine kinase accounts, in great part, for the antagonism of toxicity. In addition, antagonism of toxicity by deoxycytidine is the result of factors other than the kinetic parameters of nucleoside kinases, as indicated by its antagonism of the cytotoxicity of 5-chlorodeoxyuridine. This may be attributed to replenishment of low dCTP pools, diminished because of effector inhibition of ribonucleoside diphosphate reductase by Cl-dUTP. Resistance of the herpes-encoded enzymes to effector control may also play a role in the selective antagonism. Cell culture studies with high concentrations of tetrahydrouridine and 2'-deoxytetrahydrouridine suggest that competition by deoxycytidine for deaminases may not play a major role. The fact that deoxycytidine antagonizes the toxicity of chlorodeoxyuridine also argues against competition for the deaminases as a major reason for its effect. Limited studies with a topical herpes simplex virus type 2 infection system indicate heightened efficacy of 5-chlorodeoxycytidine (and tetrahydrouridine) when deoxycytidine is coadministered. The concepts of selective antagonism of a chemotherapeutic agent derived from these studies may be applied to other approaches that extent beyond viral chemotherapy.

Animals↗
PubMed1980

Left ventricular function in sickle cell anemia: a noninvasive evaluation.

There is controversy in the medical literature regarding the significance of "sickle cell cardiomyopathy." In an attempt to clarify this, we studied 14 patients with sickle cell anemia (age range 16 to 36 years) using simultaneous echocardiography and phonocardiography. The values of systolic time intervals and echocardiographic indices of left ventricular performance were similar to those reported for normal subjects and those with comparable degrees of anemia. We confirm a previous report of normal left ventricular function at rest in patients with sickle cell anemia and concur with the suggestion that a concomitant heart disease be considered in these patients when cardiac failure supervenes.

Adolescent↗
PubMed1979

Effects of antihypertensive therapy on cardiovascular response to exercise.

The effects of alpha methyldopa and hydrochlorothiazide therapy on exercise induced changes in arterial pressure, heart rate, rate-pressure product and total duration of exercise were evaluated with graded treadmill exercise. Although both agents were equally effective in reducing resting arterial pressure, alpha methyldopa appeared to provide slower build-up, a lower ceiling and more rapid recovery of arterial pressure in response to exercise stress than did hydrochlorothizide. Alpha methyldopa significantly reduced the degree of rise of the rate-pressure product (an index of myocardial oxygen consumption) during the exercise and recovery phases, whereas hydrochlorothiazide failed to do so. The total duration of exercise (an index of work capacity) was unchanged with either hydrochlorothiazide or alpha methyldopa. Therapy with alpha methyldopa presumably reduced myocardial oxygen demand without reducing work capacity.

Adult↗
PubMed1979

Right-sided infective endocarditis: an echocardiographic study.

Echocardiographic observations are described in 10 patients with right-sided bacterial endocarditis. Six of the nine patients with tricuspid regurgitation had shaggy echoes on the tricuspid valve, which were confirmed to be vegetations on autopsy in two patients. In six patients, right ventricular dilatation was present, and paradoxic septal motion was seen in four. In one of the patients with pulmonic valve endocarditis, the pulmonic valve and right ventricular outflow tract revealed the shaggy echoes in diastole, along with systolic fluttering of the pulmonic valve, right ventricular dilatation and paradoxic septal motion. When the findings are supplemented to the clinical picture, echocardiography is found to be a useful noninvasive adjunct in the diagnosis of acute vegetative bacterial endocarditis involving the right side of the heart, especially if other clinical features, e.g., fever, leukocytosis and positive blood cultures are absent.

Adult↗
PubMed1977

Echocardiographic observations in opiate addicts with active infective endocarditis. Frequency of involvement of the various values and comparison of echocardiographic features of right- and left-sided cardiac valve endocarditis.

Echocardiographic observations are described in 25 opiate addicts with active infective endocarditis involving apparently previously normal valves. Infective endocarditis was isolated to the tricuspid valve in 11 patients, involved both right- (tricuspid valve) and left-sided valves in 7 and was isolated to the left-sided valves in 7 (mitral valve in 6). Twenty patients (80%) had tricuspid valve regurgitation, 12 had mitral regurgitation, 3 had aortic regurgitation and none had pulmonary valve regurgitation. Considering the 75 cardiac valves (excluding the pulmonary) in the 25 patients, echocardiographic abnormalities consistent with active infective endocarditis were detected in 26 (74%) of the 35 clinically incompetent valves but in none of the 40 competent valves. Comparison of the 20 incompetent tricuspid valves with the 12 incompetent mitral valves indicated that (1) the echocardiogram was less sensitive in detecting tricuspid valve lesions, (2) rupture of tricuspid valve chordae tendineae was absent or not detectable, and (3) tricuspid valve vegetations tended to be larger.

Adult↗