Biomedical subjects
Publications and source records attributed to R W Lee.
Examination of the larval stage of the tapeworm, Taenia crassiceps, by 31P NMR spectroscopy revealed the presence of a major phosphoglyceride component. However, using saturation transfer, no exchange between glycerophosphorylcholine and phosphoglyceride or any other NMR-detectable phosphorus metabolites was detected.
Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.
The 31P NMR spectrum of the adult tapeworm, Hymenolepis diminuta, at 37 degrees C during perfusion with physiological saline was composed of 10 peaks. Based on chemical shifts and analysis of worm extracts, the phosphorus components included glucose-6-phosphate, fructose-6-phosphate, phosphorylcholine, glycerophosphoryl choline and -ethanolamine, nucleotide monophosphate-diphosphate and -triphosphate, nicotinamide adenine dinucleotide and uridine diphosphate glucose. The mean level of nucleotide triphosphate was 0.86 nmol (mg fresh weight)-1 and the nucleotide triphosphate/-diphosphate ratio 3.9. Based on the nucleotide triphosphate level, worms were viable for at least 3 h and the intracellular pH was maintained constant at approximately 6.7. Short-term exposure to mebendazole perfused at 11 or 27 microM solubilized in physiological saline containing 0.5% Tween 80 or 0.1% dimethyl sulphoxide had little effect on the nucleotide triphosphate level. Some cytological changes, however, were evident following perfusion of mebendazole. In contrast, exposure to 2,4-dinitrophenol caused a rapid decline in nucleotide triphosphate level. It was concluded that mebendazole does not exert its primary effect on oxidative phosphorylation.
The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 micrograms/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 +/- 2.0 to 57.6 +/- 2.7 mm Hg (p less than 0.01). Central blood volume decreased from 21.1 +/- 1.4 to 15.9 +/- 1.1 ml/kg (p less than 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 +/- 0.14 to 2.32 +/- 0.16 ml/mm Hg per kg (p less than 0.01) and arterial compliance 33% from 0.049 +/- 0.007 to 0.065 +/- 0.007 ml/mm Hg per kg (p less than 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 +/- 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p less than 0.02) to 0.050 +/- 0.006 and 1.50 +/- 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout.(ABSTRACT TRUNCATED AT 250 WORDS)
The inheritance of six polymorphic loci mapping in the rRNA-encoding (rDNA) region of the inverted repeat sequence of chloroplast DNA (cpDNA) was scored in hybrid subclones derived from reciprocal interspecific crosses between the green algae Chlamydomonas eugametos and Chlamydomonas moewusii. In order to enhance the detection of cells that had undergone recombination between parental cpDNAs, hybrids were selected that inherited a chloroplast antibiotic-resistance marker contributed by the mating-type-minus(mt(-)) parent, the parent that normally contributes fewer cpDNA molecules. The major findings of this study can be summarized as follows. (i) The majority of the hybrids (14/17) were recombinant for cpDNA markers in the 10-kilobase-pair rDNA region under study. (ii) Only one allele of each polymorphic cpDNA locus was ever detected in the hybrids, thus suggesting that newly recombined rDNA sequences in one copy of the inverted repeat are rapidly spread to the other by a copy-correction mechanism. (iii) Chloroplast streptomycin-resistance (sr-2) and erythromycin-resistance (er-nM1) loci, although showing little or no genetic linkage, were mapped to the 16S and 23S rRNA gene regions of the cpDNA, respectively, by virtue of their perfect coinheritance with polymorphic markers within these genes. (iv) cpDNA markers associated with a putative intron of the C. eugametos 23S rRNA gene were inherited by all 17 hybrids. Such a result is similar to that observed for certain alleles of the large rRNA gene of yeast mitochondria in crosses between omega(+) and omega(-) strains.
The mechanisms responsible for maintenance of the high-output state associated with thyrotoxicosis have been investigated by measurement of cardiac-function curves and venous compliance during ganglionic blockade with trimethaphan. Thirteen calves were injected daily with L-thyroxine (200 micrograms/kg) for 12-14 days. Thyroxine treatment increased heart rate (70%), left ventricular systolic pressure (22%), cardiac output (120%), left ventricular maximum rate of pressure development (dP/dt) (56%), and total blood volume (18%) and decreased systemic vascular resistance (39%). These hemodynamic changes persisted during ganglionic blockade or autonomic blockade with atropine and propranolol. Cardiac-function curves in conscious thyrotoxic calves were displaced upward and to the left. Mean circulatory filling pressure (MCFP), measured during anesthesia, was increased from 8 +/- 1 to 12 +/- 1 mmHg. During autonomic and ganglionic blockade MCFP remained elevated after treatment with thyroxine. Venous compliance decreased from 2.1 +/- 0.2 to 1.3 +/- 0.1 ml X mmHg-1 X kg-1 after thyroxine. Unstressed vascular volume was increased from 52.3 +/- 1.1 to 67.1 +/- 0.9 ml/kg. Thus the elevated cardiac output and new cardiac-function curve in thyrotoxicosis are associated with a combination of increased inotropic state, increased blood volume, and decreased venous compliance. These effects are not the result of autonomic influences and may represent direct actions of thyroid hormone on the heart and peripheral venous circulation.
To determine whether changes in the venous circulation were responsible for preload-afterload mismatch with angiotensin, we examined the changes in the heart and the peripheral circulation in six splenectomized dogs after ganglion blockade during an angiotensin infusion to increase mean aortic pressure 25 and then 50%. The peripheral circulation was evaluated by measuring mean circulatory filling pressure (MCFP), arterial compliance, and venous compliance. A 25% increase in mean aortic pressure increased MCFP from 6.2 +/- 0.3 to 7.6 +/- 0.3 mmHg (P less than 0.001) but did not change cardiac output, heart rate, or stroke volume. Systemic vascular resistance increased (P less than 0.01) from 0.50 +/- 0.02 to 0.59 +/- 0.03 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.03 to 0.06 +/- 0.03 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.6 +/- 0.1 ml X mmHg-1 X kg-1, respectively. A 50% elevation in mean aortic pressure increased MCFP from 7.1 +/- 0.4 to 9.5 +/- 0.9 mmHg (P less than 0.001) but did not change heart rate. At this level of aortic pressure, cardiac output and stroke volume decreased (P less than 0.01) 12 and 19%, respectively, whereas systemic vascular resistance increased (P less than 0.001) from 0.48 +/- 0.03 to 0.83 +/- 0.05 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.01 to 0.05 +/- 0.01 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.4 +/- 0.1 ml X mmHg-1 X kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Two experiments were conducted to determine how varying the proportion of wheat (W) and high-moisture sorghum grain (SG) in 80% grain dies would affect ruminal fermentation, liquid and solid flow, site and extent of digestion (Exp. 1) and feeding performance of cattle (Exp. 2). In Exp. 1, three ruminal, duodenal and ileal cannulated steers (average weight 295 kg), fed at 1.54% of body weight, were used in a six-period crossover design. Treatments were: W, 50W:50SG (W:SG) and SG. Increasing wheat level decreased ruminal pH, molar proportion of acetate, and acetate:propionate ratio (P less than .05) and increased (P less than .05) L-lactate concentration, molar proportions of propionate and valerate and total volatile fatty acid concentration. Ruminal liquid dilution and outflow rates were faster (P less than .05) and retention time was shorter (P less than .05) for the W diet. Duodenal and ileal liquid flow increased (P less than .05), and solid flow decreased (P less than .05), as dietary level of wheat increased. Apparent ruminal digestion (% of intake) of dry matter (DM) and organic matter (OM) was greater (P less than .01) with the wheat-containing diets. Intestinal DM and OM digestion (percent of intake) was higher (P less than .05) with the SG and W:SG diets. Ruminal, small intestine, large intestine and total tract starch digestion (percent of intake) was 93.5, 5.6, .7, 99.8, 71.5, 20.4, 5.7, 97.6; and 48.0, 32.5, 10.5, 91.0 with the W, W:SG and SG diets, respectively. In Exp. 2, group-fed (24 pens) steers (avg initial weight 341 kg) were fed ad libitum once daily for 121 d. Treatments were: W, 67W:33SG, 33W:67SG and SG. Rates of gain (kg/d) with the W (1.32), 67W:37SG (1.33) and 33W:67SG (1.30) diets were similar (P greater than .05), but faster (P less than .05) than those with the SG diet (1.16). Feed intake was lower (P less than .01) with the W and 67W:33SG diets, but the wheat-containing diets were utilized more efficiently (P less than .01). Increasing the proportion of wheat in sorghum grain feedlot diets improved cattle performance by optimizing ruminal and post-ruminal digestion.
Three experiments utilizing three Holstein steers (235 and 299 kg avg body weight for Exp. 1 and 2, respectively) were conducted to evaluate the effects of decoquinate, a synthetic coccidiostat, on ruminal fermentation, diet digestibility and performance of steers fed a finishing diet containing monensin and tylosin. Experiment 1 utilized a 70% forage diet, whereas Exp. 2 utilized a 20% forage diet. Each experiment was a 3 X 3 Latin-square design with treatments being 0, .5 and 5 mg decoquinate/kg body weight. Ruminal fermentation characteristics, water kinetics and blood constituents were measured on d 11 of each period, and zero-time volatile fatty acid (VFA) production was measured at 3 and 6 h post-feeding on d 12 to 14. No changes were seen in plasma glucose or L-lactate, ruminal pH, NH3-N or ruminal L-lactate for either experiment. Dry matter digestibility was depressed (P less than .05) at the .5- and 5-mg levels of decoquinate in Exp. 1, but dry matter digestibility was not affected in Exp. 2. No changes were seen in ruminal volume, outflow or total VFA concentration for either experiment. Molar proportions of VFA were not affected in Exp. 1, but the proportions of isobutyrate and butyrate decreased (P less than .05) at the 5-mg level of decoquinate in Exp. 2. Volatile fatty acid production was not changed in Exp. 1, but butyrate production was decreased (P less than .05) at the 5-mg level in Exp. 2. Experiment 3 involved 135 crossbred steers (259 kg avg initial wt), which were stratified by weight into 12 pens.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of beta-2 adrenoceptor stimulation on the peripheral circulation in 10 dogs were evaluated. All studies were done during ganglion blockade with hexamethonium. Venous capacitance was assessed by measuring mean circulatory filling pressure, venous compliance and unstressed vascular volume. Beta-2 stimulation was achieved with terbutaline (27 micrograms/min) after beta-1 blockade with metoprolol (0.75 mg/kg). At a dose of terbutaline that decreased mean aortic pressure from 80.4 +/- 3.5 to 58.9 +/- 1.9 mm Hg (P less than .01), there was no change in cardiac index (155.8 +/- 10.5 vs. 161.1 +/- 9.1 ml/kg/min) despite an increase in heart rate from 118.6 +/- 5.2 to 132.6 +/- 5.0 beats/min. Right atrial pressure, left ventricular end-diastolic pressure and dP/dt did not change. Systemic vascular resistance decreased from 0.52 +/- 0.02 to 0.39 +/- 0.03 mm Hg . min . kg . ml (P less than .01). Arterial compliance increased from 0.067 +/- 0.003 to 0.088 +/- 0.007 ml/mm Hg/kg and the volume of blood shifted out of the larger arteries was 1.8 +/- 0.4 ml/kg. Mean circulatory filling pressure did not change but venous compliance decreased from 1.90 +/- 0.04 to 1.47 +/- 0.06 ml/mm Hg/kg and unstressed vascular volume increased from -14.5 +/- 0.5 to -8.4 +/- 0.5 ml/kg. Central blood volume increased from 22.8 +/- 1.1 to 27.4 +/- 2.2 ml/kg. There was an increase in total blood volume from 81.1 +/- 2.7 to 90.5 +/- 3.7 ml/kg. To determine the extent to which changes in the spleen were responsible for these observations, five dogs were studied 2 weeks after splenectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
To study the effects of an inotropic agent, milrinone, on the entire cardiovascular system, we developed an intact dog model to assess the responses of the heart, arterial and venous circulations. At a dose that increased left ventricular dP/dt by 30% (P less than .001) from 2033 +/- 133 to 2688 +/- 140 mm Hg/sec, milrinone caused a decrease (P less than .001) in mean aortic pressure from 88.4 +/- 3.5 to 73.1 +/- 3.0 mm Hg and cardiac output from 148.0 +/- 14.6 to 134.5 +/- 13.9 ml/kg/min. Heart rate increased (P less than .01) from 124 +/- 8 to 135 +/- 8 beats/min. Systemic vascular resistance did not change. Right atrial pressure and left ventricular end-diastolic pressure decreased (P less than .01). Total blood volume did not change but central blood volume decreased (P less than .01) from 26.1 +/- 0.9 to 22.3 +/- 0.5 ml/kg. After milrinone administration, mean circulatory filling pressure decreased (P less than .01) by 30% from 7.4 +/- 0.4 to 5.0 +/- 0.2 mm Hg. Vascular or venous compliance increased (P less than .05) slightly from 1.96 +/- 0.4 to 2.20 +/- 0.1 ml/mm Hg/kg. This was accompanied by an increase (P less than .01) in unstressed vascular blood volume of 3.3 +/- 0.6 ml/kg. Arterial compliance also increased (P less than .05). In summary, milrinone produces an increase in inotropy, arterial vasodilatation and venodilatation as evidenced by the increased venous compliance and unstressed vascular volume.(ABSTRACT TRUNCATED AT 250 WORDS)
The 31P nuclear magnetic resonance (NMR) spectrum of the digestive gland-gonad complex (DGG) of the schistosome vector Biomphalaria glabrata was characterized and the effects of infection by Schistosoma mansoni noted. The in vivo spectrum was comprised of 11 peaks, 5 downfield and 6 upfield of an external 85% phosphoric acid standard. Based on a variety of analytical procedures, the upfield peaks from the standard were demonstrated to be composed of carbamoyl phosphate + a mixture of 3 phosphatides and sphingomyelin, the gamma + beta phosphorus resonances of nucleotide triphosphate (NTP) and nucleotide diphosphate (NDP), respectively, the alpha phosphorus resonances of NTP + NDP, NAD(H) + the phosphorus resonance of uridine phosphate from uridine diphosphoglucose (UDPG), the phosphorus resonance of glucose phosphate from UDPG and, last, the beta phosphorus resonance of NTP. The downfield peaks were assigned as glycerophosphoryl choline, intracellular inorganic phosphate (Pi), sugar phosphates + phosphoryl choline, aminoethyl phosphonate (AEP), and ceramide AEP. T1 values for the in vivo NMR components were determined by inversion recovery. Infection produced distinct alterations in the levels of nonnucleotide components of the in vivo 31P NMR spectrum and the spectra of tissue extracts. Specifically, the levels of phosphonate, phospholipids, and carbamoyl phosphate were markedly reduced, and the relative level of Pi was increased. The potential significance of these changes to the parasite-host relationship was discussed. In contrast, starvation resulted in a decreased level of phosphonate only. The pH of the intact DGG was estimated by titrating the inorganic phosphate component of tissue extracts. The mean pH was 6.9 for both control and infected material.
The efficacy of trioxifene mesylate, a new antiestrogen, in the management of advanced breast cancer was evaluated in 69 patients. Fifty-two patients were randomly allocated to dose schedules of 5 mg, 10 mg, and 20 mg orally twice daily. There were five complete responders (10%), 22 partial responders (42%), and 9 patients (17%) with no change in disease. The median time to progression was 12 months (range, 4-27+). Positive estrogen receptor status, long disease-free interval, and low tumor burden (with fewer sites of disease) correlated with higher response rates. Higher doses did not result in better responses. Another group of 17 patients who responded to prior tamoxifen administration, upon failure, were treated with trioxifene. Two (12%) had partial remission with time to progression of 3 and 10 months, respectively. Side effects were mild and generally well-tolerated, with hot flashes being most common (20%). These results suggest that trioxifene mesylate is an active agent, and has similar therapeutic efficacy and toxicity compared with those reported for tamoxifen. In a small fraction of patients treated after tamoxifen therapy was received, objective response was also observed. This observation requires further evaluation.
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Pacemaker malfunction manifested as a runaway circuitry occurred in two patients after they received radiation therapy for treatment of carcinoma. Both pacemakers were programmable atrioventricular sequential units (DVI) with complementary metal oxide semiconductor circuitry. One pacemaker was directly in the radiation field, whereas the other was not directly within the radiation port. Thus, direct irradiation of an implanted pacemaker should be avoided. It is advisable that a pacemaker be shielded even when the pacemaker is not in the direct field of radiation.
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The peripheral circulatory effects of alpha 1-adrenoceptor stimulation with methoxamine hydrochloride were compared with those of alpha 2-stimulation with UK 14304-18 in 12 intact dogs. Doses of each agent were infused to increase systemic vascular resistance and arterial pressure 50 and then 100% above control. Heart rate was controlled with atropine. At the higher dose, methoxamine increased mean aortic pressure (PAo) from a control of 77.3 +/- 1.6 to 152.9 +/- 3.2 mmHg, mean circulatory filling pressure (MCFP) from 8.0 +/- 0.4 to 13.3 +/- 1.3 mmHg, and central blood volume (CBV) from 21.3 +/- 1.1 to 25.9 +/- 1.5 ml X kg-1, whereas cardiac output did not change. UK 14304-18 increased PAo from 78.1 +/- 2.6 to 148.9 +/- 2.7 mmHg, MCFP from 7.9 +/- 0.4 to 10.6 +/- 0.4 mmHg, and CBV from 21.0 +/- 1.1 to 24.1 +/- 1.5 ml X kg-1, whereas cardiac output decreased from 151.7 +/- 9.4 to 126.3 +/- 5.8 ml X kg-1 X min-1. Mean circulatory filling pressure and CBV were higher with methoxamine than with UK 14304-18. Effective vascular compliance, determined by serial measurements of MCFP during ganglionic blockade after rapid changes in blood volume, decreased from a control value of 1.9 +/- 0.1 to 1.3 +/- 0.3 ml X mmHg-1 X kg-1 with methoxamine, but did not change with UK 14304-18 (1.9 +/- 0.1 ml X mmHg-1 X kg-1). At any given change in blood volume, there was a higher MCFP with alpha 1-stimulation compared with alpha 2-stimulation. Both agents decreased unstressed vascular volume.(ABSTRACT TRUNCATED AT 250 WORDS)