Pleuropulmonary blastoma with vascular invasion.
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Azygos Vein↗
Biomedical subjects
W H Johnson
Publications and source records attributed to W H Johnson.
Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans.
BACKGROUND: Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS: Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.
Adenosine↗
Production of four identical calves by the separation of blastomeres from an in vitro derived four-cell embryo.
The blastomeres of two in vitro derived four-cell embryos were separated and transferred individually into surrogate zonae pellucidae, then co-cultured with bovine oviductal epithelial cells for five days until blastulation. Pairs of the quarter blastocysts were co-transferred with trophoblastic vesicles into each of four synchronised Holstein heifers, three of which were diagnosed pregnant at 28 days gestation, carrying twin fetuses. Four genetically identical bull calves were delivered by elective caesarean section at term pregnancy. One pregnancy was terminated at 56 days.
Animals↗
Images in cardiovascular medicine. Coarctation of the aorta and ventricular septal defect.
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Aortic Coarctation↗
Sudden death in Marfan syndrome.
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Adolescent↗
Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.
In rheumatoid and osteoarthritis, degradation of articular cartilage is mediated by the matrix metalloproteinases collagenase, stromelysin and gelatinase. The key event in this process is the cleavage of triple helical collagen by collagenase. We have determined the crystal structure of the catalytic domain of human recombinant fibroblast collagenase complexed with a synthetic inhibitor at 2.2 A resolution. The protein fold is similar to the amino termini of the zinc endopeptidases astacin thermolysin and elastase despite a lack of primary sequence homology. The conformation of the bound inhibitor provides a molecular basis for the design of inhibitors of collagenase and other matrix metalloproteinases. Such inhibitors should be useful in the treatment of a variety of diseases including arthritis and cancer.
Amino Acid Sequence↗
A clinically applicable technique to study cytoskeletal dynamics in normal and abnormal polymorphonuclear leukocytes isolated from small volume blood samples.
Shape change and motility of polymorphonuclear leukocytes (PMNs) are essential for host defense and require dynamic reorganizations of microfilamentous cytoskeleton by reversible polymerization of G-actin into filaments (F-actin). Although clinical disorders of actin polymerization are rare, recently described simple methodologies for assaying actin dynamics in PMNs make the technique readily applicable to clinical studies. To develop a clinically useful F-actin assay, the authors investigated the optimal preparation conditions for PMN isolation that resulted in the least in vitro cytoskeletal activation and evaluated the variability in actin dynamics in acutely and chronically infected patients. Basal and chemotactic factor-activated PMN F-actin content was measured by a previously described flow cytometric technique in fixed, permeabilized, NBDphallacidin-stained PMNs isolated by centrifugation in Percoll or Ficoll-Hypaque density gradients or by countercurrent elutriation. F-actin content is expressed as mean fluorescent channel or relative fluorescence intensity. Basal F-actin in PMNs prepared from countercurrent elutriation (mean fluorescent channel = 79.0 +/- 4.5, n = 6) or by Ficoll Hypaque (82.0 +/- 3.5, n = 4) was significantly higher than endotoxin free, Percoll purified PMNs, whether purified in bulk (56.1 +/- 7.9, n = 8) or by the small volume modification applicable to clinical studies (53.3 +/- 8.7, n = 15). Basal Ficoll Hypaque purified PMNs have evidence of shape change, whereas endotoxin free, Percoll purified PMNs are smooth and round and represent the most basal cell equivalent in F-actin content to a circulating PMN.(ABSTRACT TRUNCATED AT 250 WORDS)
Actins↗
Intracoronary angiotensin-converting enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy.
BACKGROUND: There is increasing recognition of myocardial angiotensin-converting enzyme, which is induced with the development of left ventricular hypertrophy (LVH). The potential physiological significance of subsequent increased angiotensin I to II conversion in the presence of LVH is unclear but has been postulated to cause abnormal Ca2+ handling and secondary diastolic dysfunction. Accordingly, we hypothesized that acute angiotensin-converting enzyme inhibition would result in decreased production of angiotensin II and improved active (Ca(2+)-dependent) relaxation in patients with hypertensive LVH. METHODS AND RESULTS: Intracoronary (IC) enalaprilat was administered to 25 patients with and without LVH secondary to essential hypertension. Indexes of diastolic and systolic LV function were determined from pressure (micromanometer)-volume (conductance) analysis at steady state and with occlusion of the inferior vena cava. Patients were divided into those receiving high- (5.0 mg, n = 15) and low-dose (1.5 mg, n = 10) IC enalaprilat during a 30-minute infusion at 1 mL/min. The high-dose patients were further divided along the median normalized LV wall thickness of 0.671 cm/m2. The time constant of isovolumic relaxation (TauL) was prolonged at baseline in patients receiving high-dose enalaprilat with wall thickness > 0.671 cm/m2 (TauL, 56 +/- 2 versus 44 +/- 2 and 45 +/- 2 milliseconds, respectively, P < .01 by ANOVA) and shortened only in this patient group (TauL, 49 +/- 3 versus 46 +/- 2 and 43 +/- 2 milliseconds, respectively, P < .01 versus baseline and other groups by ANOVA). The improvement in TauL was directly proportional to the degree of LVH (r = .92, P < .001). Although there was a decrease in LV end-diastolic pressure (23 +/- 2 to 15 +/- 1 mm Hg, P < .01) and volume (86 +/- 8 to 67 +/- 9 mL/m2, P < .05) in those patients with a reduction in TauL, this is due to movement down a similar diastolic pressure-volume relation with no change in chamber elastic stiffness (0.023 +/- 0.002 to 0.025 +/- 0.004 mL-1, P = NS). CONCLUSIONS: Intracoronary enalaprilat resulted in an improvement in active (Ca(2+)-dependent) relaxation in those patients with more severe hypertensive LVH. The improvement in active relaxation was directly proportional to the severity of LVH. These results support the hypothesis that the cardiac renin-angiotensin system is an important determinant of active diastolic function in hypertensive LVH.
Adult↗
Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure.
Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.
Adrenergic beta-Antagonists↗
Motion sickness, vascular changes accompanying pseudo-coriolis-induced nausea.
We have previously shown that objective measurements of blood flow changes constitute a useful index in assessing susceptibility to nausea produced by cross-coupled angular accelerations (Coriolis stimulation). The findings of this study confirm the value of using the same technique for assessing the degree of nausea produced by pseudo-Coriolis effects.
Adult↗
Measurement of the cytotoxic effects of different strains of Mycoplasma equigenitalium on the equine uterine tube using a calmodulin assay.
The cytopathic effects induced by five strains of Mycoplasma equigenitalium for cells of equine uterine tube explants were tested by measuring changes in cellular and extracellular concentrations of calmodulin (CaM). Calmodulin concentrations in samples of total homogenate (TH) and total homogenate supernates (THS) of the infected equine uterine tube explants were significantly lower than respective measurements on noninfected controls. In tissue culture medium fractions (TCM) of some infected explants, CaM concentrations were significantly higher than noninfected controls (p > 0.95). The results suggest that M. equigenitalium colonization on ciliated cells of the equine uterine tube can affect the permeability of the cell membrane leading to leakage or release of CaM during cell breakdown. Measurement of CaM concentrations in samples of TH revealed significant differences in the cytotoxic effects induced by different strains of M. equigenitalium on the equine uterine tube (EUT). The data suggests that some strains of M. equigenitalium may have a role in reproductive failure in the mare. In addition comparisons of the means of the concentrations of CaM in samples of TH or THS in EUT explants from four mares in the follicular and four in the luteal phase of the estrous cycle were found to be not significantly different.
Animals↗
Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 4. Addition of chromone moiety enhances leukotriene D4 receptor binding affinity.
The combination of the benzopyran-4-one ring, a moiety found in the prototype leukotriene antagonist, FPL 55,712, with the (2-quinolinylmethoxy)phenyl group led to a significant increase in leukotriene receptor binding affinity. This modification resulted in a 10,000-fold improvement in binding affinity compared to FPL 55,712. Compound 7 (RG 12553), with a Ki value of 0.1 nM, has higher affinity than the natural agonist LTD4 and is one of the most potent LTD4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed.
Animals↗
Potent collagenase inhibitors prevent interleukin-1-induced cartilage degradation in vitro.
The matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysin, contribute to the destruction of articular cartilage which occurs during rheumatoid and osteoarthritis. Ro 31-4724, a substrate analogue containing a hydroxamic acid function, is a potent but non-selective inhibitor of all three MMPs (I50, collagenase = 10 nM), whereas Ro 31-7467, a phosphinic acid transition-state analogue, shows 14-fold and 12-fold selectivity for collagenase (I50 = 17 nM) over gelatinase and caseinase (stromelysin) respectively. The effects of these inhibitors on interleukin-1-induced bovine nasal cartilage degradation were examined. The hydroxamate Ro 31-4724 inhibits proteoglycan and collagen loss, whereas the phosphinic acid Ro 31-7467 selectively inhibits collagen breakdown in this model. This represents the first demonstration of potent and selective inhibition of IL1-induced cartilage degradation in vitro by MMP inhibitors. These results suggest that collagenase is responsible for collagen loss and that a different enzyme, possibly stromelysin, is responsible for proteoglycan degradation in this model.
Animals↗
Developmental changes in ECG associated with heart rate are similar in squirrel monkey and human infants.
Interest in refining noninvasive methods of diagnosis and further characterization of squirrel monkeys (Saimiri sp.) as a model for pediatric cardiology studies led to this investigation of electrocardiogram (ECG) changes associated with changes in age and position. During a single delivery season, ECGs were performed at 1 day, 1 month, and 1 year of age. For each age group, ECGs were recorded with animals in dorsal, ventral, and right lateral recumbency. The 1-day-old group had the lowest heart rates (271 +/- 10, right lateral recumbency, mean +/- SEM) relative to the other age groups. One-year-old monkeys had heart rates of 333 +/- 18. One-month-old infants had rates significantly higher than the other two age groups (366 +/- 4). The QRS frontal-plane axis showed an age-related leftward change from 1 day (151 +/- 28 degrees) to 1 year of age (121 +/- 44 degrees) while the P-wave frontal plane axis remained nearly constant over a narrow range at all ages. The pattern of heart rate changes with age were similar to those in humans, although the ranges of absolute heart rates were markedly different. These data suggest that factors that influence maturational changes in heart rate, conduction time (as reflected by ECG intervals) and cardiac chamber size and position (inferred from axis and voltage) are similar among primates of widely variant body sizes.
Animals↗
Endometrial biopsy in Holstein-Friesian dairy cows. I. Technique, histological criteria and results.
Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. Sixty-two cows were biopsied at both day 26 and 40 postpartum, 23 cows at only day 26, and 12 at day 40 only. Subjective and quantitative histological criteria were assessed. Ninety-five percent of biopsies were adequate for at least subjective assessment. The distribution of criteria within each horn-day category, as well as combined readings by day and by gravid or nongravid horn were computed and significant differences noted. There was more severe inflammation and more segmented cells at day 26 than 40 postpartum, and in the gravid compared to the nongravid horn. The distribution patterns for the criteria examined provide an overview of histological characteristics in this group of postpartum cows.
Animals↗
Systemic heparinization does not prevent clot formation in coil embolization.
Therapeutic transcatheter closure with Gianturco-type steel coils has been applied to a variety of vascular communications in children with congenital heart disease. Vessel closure depends upon successful thrombus formation around the coil. Since systemic anticoagulation with heparin is commonly used during catheterization and cardiac surgery, we studied the effect of systemic heparinization on the efficiency of vessel occlusion by coil embolization in lambs. Catheters inserted in femoral arteries were used to arteriographically locate and size 36 systemic arteries in 9 lambs weighing 4.2 to 7.4 kg. Twenty-four vessels were embolized prior to heparinization with 400 u/kg heparin, IV. Effective anticoagulation was demonstrated by post-heparin activated clotting time (ACT) values greater than 300 sec. Seven vessels (29%) were not successfully coil-embolized because of inadequate coil position or distant embolization of the coil; 17 (71%) of these vessels were shown to be successfully occluded by arteriography 6 to 77 min later. After a period of systemic heparinization ranging from 71 to 159 min, 9/17 arteries remained occluded, 7/17 could not be examined arteriographically due to early demise of the animal, and only 1/17 showed recanalization. A second group of 12 vessels were embolized after heparinization. Eight (75%) were successfully occluded, and 4 (25%) were not successfully coil-embolized because of inadequate coil position or coil embolization to distant arteries. We conclude that systemic heparinization had no measurable effect on occlusion rates in coil-embolized systemic arteries in the lamb. These data support the use of systemic heparinization, when indicated, during or following therapeutic coil embolization in children.
Animals↗
Aortic thrombosis in a neonate with undetectable protein C.
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Aorta, Abdominal↗
Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships.
This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.
Animals↗