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The Adenosine Antagonist Aminophylline Attenuates Pacing-Induced Coronary Functional Hyperemia
Left coronary blood flow (LCBF), left ventricular oxygen, extraction [(a-v)O₂ ], and myocardial oxygen consumption (MVO₂) were monitored in 10 dogs. HR was paced at 120 bpm and then increased to 180 bpm to elicit a hyperemic response (ΔLCBF). During the hyperemia, the vaso-dilatory response to exogenous adenosine (F_AD) was tested. Twenty min. after injection of aminophylline (100 mg/i.v.), HR was again increased. F_AD was again tested. The pacing-induced increase in MVO₂ (ΔMVO₂) was not affected by aminophylline (P>0.05). However, the slope ΔLCBF/ΔMVO₂ was decreased, and the slope (a-v)O₂ /ΔMVO₂ was increased. F_AD was also decreased and the magnitude of the reduction was correlated with the decrease in ΔLCBF/ΔMVO₂ (r=0.82). These results suggest that adenosine may play an role in coronary functional hyperemia induced by increases in heart rate.
Alpha-Adrenergic Modulation of Coronary Blood Flow and Cardiac Function During Exercise in Dogs
In the present study alpha-receptor modulation of coronary flow and cardiac function was examined in exercising dogs, chronically instrumented to measure: circumflex blood flow velocity (CFV), heart rate (HR), global left ventricular function (LVP and dP/dt Max) and regional left ventricular function (%SL and dL/dt (s)max). During exercise, local adrenergic blockade was produced by intracoronary injection of 1.0 mg phentolamine ( anon-specific alpha-antagonist) or .5 mp prazosin. Exercise significantly increased HR, LVP, dP/dt max, CFV, %SL and dL/dt (s)max. Neither alpha-antagonist produced changes in HR, LVP or %SL; however, both phentolamine and prazosin produced significant increses in dP/dtmax, CFV and dL/dt(s)max of the alpha-blocked region, when compared to their exercise level before alpha-blockade. It is suggested that an alpha1-adrenergic vasoconstriction limits coronary vasodilation and, thereby, cardiac function during exercise.
Characterization of the Molecular and Ionic Properties of the Histidine-Rich Protein Isolated From Newborn Rat Epidermis
Histidine-rich protein from newborn rat epidermis has been further characterized. Polyacrylamide gel electrophoresis in 8 M urea demonstrated dissociation of the protein, a possible oligomeric series, and one major band with two minor bands of the, pH 5.0 precipitate. Amino acid analysis correlated well with previous analyses (except for lower levels of histidine), while the amino acids of high content increased with purification. Sedimentation coefficients and molecular weights determined by ultracentribfugation of all monomers and the residual tissue in histidine-rich protein were in agreement with estimates from gel filtration chromatography. Lower values were obtained for keratohyalin granule proteins. Isoelectric focusing indicated diisoelectric properties of the protein. A molecular model of deamidation is presented in an attempt to explain this property.
Echocardiographic Assessment of the Left Ventricle in the Spinal Cord Injured Patient
Ten caucasian male quadriplegics were compared with eight sedentary caucasian male controls in regards to left ventricular dimensions and mass obtained from echocardiograrns. The interventricular septum (IVS), left ventricular posterior wall (LVPW) and left ventricular internal diameter (LVII) were within normal limits for both groups. However, the INS in the SCI were significantly thicker than controls (p <0.05). Myocardial thickness was larger in SCI subjects (p <0.05). Absolute left ventricular mass (LVM) and total left ventricular volume was not different ( p > 0.05), but SCI subjects had significantly greater LVM to lean body mass ratios. Echocardiographically, SCI patients demonstrate concentric hypertrophy. This suggests adaptive response to chronic increase in afterload pressure secondary to their daily activities and muscle spasticity.
Effects of Cigarette Smoke Condensates on Cultured Human Lymphocytes and Separation of Benzo-α-Pyrene Metabolites by High Pressure Liquid Chromatography
Cigarette smoke condensates from all cigarettes tested were found to be potent inducers of AHH enzyme in cultured human lymphocytes and, with the exception of Kent Lights and Carlton CSC's, all were found to be toxic under the experiment conditions. Most of the AHH inducing activity was found in basic and neutral fractions of the lAl standard cigarettes. A radiometric assay of BP metabolites in cultured human lymphocytes was developed in which we were able to separate the primary metabolites and the secondary metabolites from the parent compound (BP) by neutral alumnia HPLC. The primary metabolites were further separated by a selective enzyme hydrolysis and/or reverse phase HPLC.
Existence of an Alpha One-Adrenoceptor-Mediated Coronary Vasoconstrictor Reflex During Acute Systemic Hypoxia, in Anesthetized, Open-Chest Dogs
The presence of an alpha-adrenoceptor--mediated coronary vasoconstrictor reflex during acute systemic hypoxia was examined in thirteen chloralose-anesthetized dogs. Local vasodilator effects were avoided by perfusing the left common coronary artery (LCC) with normoxic blood, while the dogs were ventilated with 5% 02-95% N2 . Left ventricular afterload was held constant and positive cardiac inotropic responses and beta two-adrenoceptor-mediated coronary vasodilation were blocked by propranolol. Parasympatheticmediated bradycardia and coronary vasodilation were blocked with atropine. Systemic hypoxia decreased LCC flow to normoxic myocardium by 19.4+2.6 %. Although myocardial oxygen extraction increased 9.7+2.9 %, myocardial oxygen consumption decreased 16.5+2.6 %. Intracoronary prazosin prevented the reflex vasoconstriction during repeated hypoxia.
Exoprotease Production by Aeromonas hydrophila in a Chemically Defined Medium
Wretlind, Heden, and Wadstrom found ammonium sulfate to be inhibitory for the formation of extracellular protease in Aeromonas hydrophila grown in Brain Heart Infusion medium. They demonstrated by manipulating the iron and zinc content within their medium that it is possible to differentially affect the accumulation of hemolysin and protease by A. hydrophila grown in batch culture. Further manipulation of the composition of this medium was done in the present study to determine the effect of other components on the production of protease. The purpose of this study was to determine the factors affecting the level of A. hydrophila protease produced in a chemically defined medium.
The Fate of Benzo(a)pyrene in Tissues of Mice Exposed to Diesel Exhaust
Mice were exposed to diesel exhaust for 9 months prior to evaluation for benzo(a)pyrene disposition. On the last day of exposure the mice were instilled intratracheally with tritiated-benzo(a)pyrene ([3H]BP). The mice were sacrificed at intervals of 2, 24, and 168 hours. Disappearance of radioactivity from lungs and liver was rapid and essentially linear with time. In lungs, liver, and testes; [3H]BP metabolites were found mainly as conjugates, a form readily excretable. Clearance of the hydrocarbon from liver and testes in exposed mice was not markedly different from that in nonexposed mice. However, mice exposed to diesel exhaust had delayed [3H]BP clearance from lungs, possibly due to [3H]BP adsorption to diesel smoke particles.
Gold Compounds and Rheumatoid Arthritis Murine Studies of the Immune Response to Gold Sodium Thiomalate
Balb/c normal mice were used to study the effects of gold sodium thiomalate (GST) on intact, nonadherent, and adherent mononuclear spleen cells. The three populations were tested for the following aspects: in vitro effects of GST on the mitogen-triggered DNA synthesis; intracellular levels of cyclic AMP; and chemotaxis ability. These studies showed that GST inhibited the proliferative responses of all three populations as the concentration of GST increased. Cyclic AMP levels in the nonadherent population increased as the GST concentration increased. GST had a biphasic effect on the adherent population. At concentrations of 5 and 10 jag/ml, GST suppressed the cyclic AMP levels, and at concentration of 50 pg/ml it enhanced the cyclic AMP levels. GST had no effect on the cyclic AMP levels in the intact mononuclear spleen cells. GST appeared to have an inhibitory effect on the chemotaxis ability of all three populations of spleen cells.
An Investigation of the Ratio of Free to Bound Phenytoin in Overdose Cases
An investigation of the ratio of free to bound phenytoin in overdose cases was accomplished by three studies to answer these questions: 1. Will the free to bound ratio change with increasing total phenytoin concentration? 2. Will the free to bound ratio be altered with decreasing total protein concentration? 3. Do these results correlate with overdose cases? The results demonstrated that the ratio of free to bound phenytoin remains constant throughout the therapeutic range as long as a person has a normal total protein concentration. However, the free to bound ratio changes significantly when the total protein decreases by 25 per cent. This substantiates the importance of monitoring free and total phenytoin concentrations in hypoproteinemia.
Mast Cells in the Brains of Mice of Different Genotypes: A Histological Study
Histamine is present in the central nervous system and is believed to be derived from neurons (50 percent) and mast cells (50 percent). This experiment was designed to analyze histologically the numbers and distribution of brain-associated mast cells in normal (+/+), mast cell deficient (W/W^v) and heterozygote (W/+, W^v/+) mice of the WBB6F_1 /J strain. Significant variations in the number and distribution of mast cells between the various genotypes were found. Based on the results, a hypothesis is proposed to account for the observed genotypical differences in mast cell numbers and distribution. Based on the total number of mast cells and the content of histamine in a typical mast cell, it is apparent that the mast cell is not a major source of brain histamine, suggesting that another non-neuronal pool of histamine must be present in the brain.
A Model for Determining Induced Physiological Stress During Respirator Wear
A model was developed to predict the increased physiological effort of wearing a respiratory protective device. Specifically, the model was designed to predict the effects of varying ventilatory demands on eleven respiratory variables of the man-respirator system, breath frequency (f_b), tidal volume (V_t), inspiratory flow (dvi/dt), expiratory flow (dve/dt), inspiratory mask pressure (P_mi), expiratory mask pressure (P_me), inspiratory intrathoracic pressure (P_ii), expiratory intrathoracic pressure (P_ie), inspiratory mask work (W_mi), expiratory mask work (W_me), and mask leakage index (L_i). The model was tested by experiment in which three male subjects underwent maximal exercise testing with and without the "pressure-demand" respirator. The eleven variables were determined for each thirty second period utilizing on-line computer analysis. Application of the model to these experimental conditions resulted in significant (p<.001) relationships between each of the predicted and observed variables.
Partial Purification and Some Properties of Lipase From Pseudomonas Aeruginosa
Purification of lipase from Pseudomonas aeruginosa (from both a washed cell suspension and crude culture supernatant as the enzyme source) was performed utilizing affinity chromatography. Affinity chromatography was carried out using n-dodecylamine bound to Sepharose 4B. Chromatography of the concentrated crude culture supernatant resulted in a 65 to 95 fold purification with 5.8% recovery. Washed cells collected from a ten hour culture suspended in water also produced enzyme. Activity of the washed cell suspension supernatant was found to be 4.5 fold higher than the activity of the culture supernatant. A thirty percent recovery was obtained using the washed cell suspension supernatant. The washed cell suspension provides a cleaner preparation for use with the dodecylamine-agarose chromatography in purifying the enzyme.
Relationship of Estrous Cycle to Herpes Simplex Virus Type 2 Susceptibility in Female Mice
In CBA/NJ mice, splenic natural killer (NK) cell activity varies with stages of estrous. Susceptibility of ICR mice to intravaginal inoculation of herpes simplex virus type 2 (HSV-2) decreases with age. Susceptibility of female ICR and CBA/NJ mice to HSV-2 inoculated intravaginally and intraperitoneally was examined during the estrous cycle. In cycling ICR mice, greatest susceptibility to intravaginal inoculation was observed during diestrous and the least during metestrous. CBA/NJ mice were most susceptible to intravaginal inoculation of HSV-2 during diestrous. ICR mice were ovariectomized to mimic diestrous and found to be highly susceptible to intravaginal inoculation at all virus doses. No difference in susceptibility among phases of the estrous cycle was seen following intraperitoneal inoculation.
Serotonin, Norepinephrine, and the Hypothalamic Ventromedial Nucleus: a Proposed Mechanism Mediating Hyperphagia and Obesity
Serotonin has been implicated as a modulator of feeding behavior. This experiment was designed to alter brain serotonin levels through dietary means in hypothalamic ventromedial-lesioned and unlesioned rats. Daily food, water, and animal weights were measured. The purpose was to determine if VMH lesions altered the feeding pattern found in unlesioned rats. Although food intake for tryptophanenriched diets and tryptophan-deficient diets did not differ from their respective control groups, in some cases gross animal weights did differ significantly between experimental and control groups and between lesioned and unlesioned groups. A proposed model explains how a "low" energy signal and a "high" protein signal cycles amino acids through gluconeogenesis to comPensate for an energy deficit.
Tolerance to the Behavioral Effects of Methylphenidate
Thirty-one rats were trained on a differential reinforcement of low rate schedule. After responding had stabilized, animals were injected with methylphenidate, twice weekly, presession. Methylphenidate produced dose-dependent increases in response rates and decreases in reinforcements. Repetition of these doses produced a reduced drug effect, and a third administration of the 10 mg/kg dose further reduced the drug effect. Subsequently, the effects of daily and intermittent administration were determined for this dose. Daily methylphenidate, pre-session, produced tolerance to the behavioral effects of methylphenidate and cross-tolerance to the amphetamines. Twice-weekly methylphenidate, pre-session, produced partial tolerance to methylphenidate and partial cross-tolerance to the amphetamines. Thus, periodic exposure to the behaviorally disruptive effects of a drug of the amphetamine class reduces the effects of subsequent exposure.
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