Lipid-laden alveolar macrophage and lactose assay as markers of aspiration in neonates with lung disease.
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Gastroesophageal Reflux↗
Biomedical subjects
S M Block
Publications and source records attributed to S M Block.
Uterine metabolism of the pregnant guinea pig as a function of gestational age.
During the last half of pregnancy, the fetal guinea pig grows exponentially at 7.1%/day. In order to define the metabolic requirements of the gravid uterus during this period of rapid growth, catheters were placed in the femoral artery and uterine vein of guinea pigs at gestational ages ranging from 40 days to term (68 days). The animals were studied in the unstressed state after full recovery from surgery and anesthesia. Arterial and venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, and acetate were measured, and metabolic quotients and coefficients of extraction were calculated. The glucose/oxygen quotient did not change significantly in the last half of pregnancy averaging 1.26, while the lactate/oxygen quotient remained unchanged at -0.42, and the (glucose + lactate)/oxygen quotient remained unchanged at 0.82. Coefficients of extraction of glucose and oxygen increased linearly with gestational age. The increase in supply of substrates for the rapid growth of the conceptus toward the end of gestation is accounted for by increasing extraction of substrate and by greatly increasing blood flow with increasing gestation. While glucose remains the major metabolic fuel of the guinea pig conceptus and acetate is consistently taken up by the uterus, these substrates alone cannot account for the metabolic fate of the oxygen taken up and fall far short of the predicted nutritional requirements of the fetus for both oxidative metabolism and growth.
3-Hydroxybutyric Acid↗
Movement of myosin fragments in vitro: domains involved in force production.
We have used the Nitella-based movement assay to localize the site of force production in myosin. Methods were developed to use nonfilamentous myosin or proteolytic fragments of myosin in place of the thick filaments used in the original assay. In the experiments described here, the tail of myosin or its subfragments is anchored via antibodies to the surface of small particles. Nonfilamentous myosin or its subfragments move along Nitella actin cables at speeds similar to those obtained with filamentous myosin. We generated short HMM, a myosin fragment containing the heads and only 400 A of the tail. Although short HMM lacks the "hinge" region proposed by Harrington to be the site of force generation, and is incapable of forming thick filaments, it moves along actin at speeds above 1 micron/sec. Therefore, neither a thick filament nor the carboxy-terminal 1100 A of the tail is required for movement along actin. The results indicate that force production occurs in or near the myosin heads.
Actins↗
C-reactive protein: a limited test for managing patients with preterm labor or preterm rupture of membranes?
C-reactive protein has been used to identify patients at high risk for infectious morbidity with preterm labor or preterm rupture of membranes. In this article we report on 104 patients with preterm labor symptoms (n = 45) or preterm rupture of the membranes (n = 59) and serial evaluations of C-reactive protein measured by latex agglutination and laser nephelometry. The simple, inexpensive latex method appears comparable to the laser method in predicting infectious morbidity and can be used clinically. Elevated C-reactive protein values before delivery predict infectious morbidity in only 8% to 29% of patients, and up to 18% of patients with serious infections may be misdiagnosed as having normal C-reactive protein values before delivery.
C-Reactive Protein↗
Prophylactic treatment of asymptomatic patent ductus arteriosus in premature infants with respiratory distress syndrome.
Early treatment of premature infants with indomethacin has been proposed as a means of reducing the morbidity associated with respiratory distress syndrome complicated by symptomatic patent ductus arteriosus. We identified 26 infants less than 48 hours old with severe respiratory distress syndrome who had an asymptomatic patent ductus arteriosus. These infants were treated with either indomethacin or placebo. There was a significant difference in the frequency of ductal closure after receiving indomethacin treatment. No significant difference was observed in the time required for mechanical ventilation, time receiving supplemental oxygen, or time in the hospital, and there were no significant differences in the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, or death between the two groups.
Clinical Trials as Topic↗
Responses to converting-enzyme inhibition and hemorrhage in newborn lambs and adult sheep.
We compared the cardiovascular and hormonal responses to angiotensin converting enzyme inhibition and hemorrhage of 20% of blood volume in chronically instrumented unanesthetized newborn lambs and adult sheep. Administration of the nonsulfhydryl-containing converting-enzyme inhibitor enalapril reduced mean arterial pressure in the newborn but not in the adult animals. Blood pressure fell in both age groups after hemorrhage, and the hemorrhage-induced fall in blood pressure, integrated over the period of hypovolemia, was more pronounced when converting-enzyme inhibition was present in the lambs. This was not observed in the adults. Cardiac output fell following hemorrhage in both age groups, and the fall was greater when enalapril was present in the lambs, but this was not the case in the adults. Hemorrhage increased plasma renin activity in both groups, and enalapril augmented this increase. Plasma concentrations of vasopressin and catecholamines increased following hemorrhage within and between groups. Taken together these data suggest that the renin-angiotensin system plays a more important role in the maintenance of cardiovascular homeostasis in newborn lambs than it does in adult sheep, and catecholamine and vasopressin responses to volume loss can occur in the presence of blockade of the renin-angiotensin system.
Angiotensin-Converting Enzyme Inhibitors↗
Cardiovascular and endocrine response to hemorrhage after alpha 1-blockade in lambs and ewes.
To evaluate the role of the alpha 1-adrenergic system in the response to hemorrhage during development, lambs and adult sheep were chronically catheterized and hemorrhaged after pretreatment with prazosin or vehicle. The adults became markedly more hypotensive after alpha 1-blockade and hemorrhage than after vehicle and hemorrhage (26.1 +/- 4 vs. 10.7 +/- 2%, P less than 0.0001), whereas the lambs were no more hypotensive when hemorrhaged after prazosin (21.5 +/- 3.2 vs. 23.1 +/- 4.4%, P greater than 0.05). In the adults and the lambs, hemorrhage produced elevations in plasma renin activity and arginine vasopressin. However, after prazosin, the adults had a far greater increase in arginine vasopressin levels than after vehicle treatment (1,970 +/- 820 vs. 320 +/- 273%).
Adrenergic alpha-Antagonists↗
Buffy coat transfusions in neonates with sepsis and neutrophil storage pool depletion.
A randomized study was initiated in neonates with neutropenia (absolute peripheral neutrophil count less than 1,500/microL) and suspected bacterial infection. Twenty infants with proven infection were enrolled, nine of whom had depletion of bone marrow stores of maturing neutrophils (less than or equal to 7% metamyelocyte, band and mature forms per 100 nucleated cells). These nine were randomized to receive 15 mL/kg of either buffy coat transfusions (group 2) or plasma and blood products (group 3). The remaining 11 (group 1) were observed. Peripheral neutrophil counts were monitored to determine the neutrophil response to transfusions. There were ten of 11 patients in group 1, two of four in group 2, and two of five in group 3 who lived at least seven days. No complications of transfusion were noted. No difference in the rate of peripheral neutrophil increase was found among the three groups. The study was stopped when it became clear that sufficient numbers of patients could not be entered into the study, in a reasonable period of time, to prove or disprove a clinically significant improvement in outcome. Although in vitro testing of the buffy coat preparations showed normal function in three of four cases, the clinical quality of the buffy coats may have been inadequate because of poor availability of whole fresh blood less than 24 hours old. The role of neutrophil transfusions in these patients remains unclear.
Agranulocytosis↗
Uterine metabolism of the pregnant rabbit under chronic steady-state conditions.
The study of uterine metabolism in pregnancy under chronic steady-state conditions has been confined to large mammals and, more recently, to the guinea pig. The pregnant rabbit is of interest because of its short gestation and large litter size. We developed an indirect approach involving retrograde catheterization of the uterine venous drainage, permitting measurement of both uterine metabolic quotients and uterine uptakes. Radioactive microspheres were used to measure blood flow. A large lactate and ammonia efflux from the uterus was found. In the fed state, ketogenic substrates were taken up in small amounts. However, during starvation a significant increase in ketoacid uptake was observed with a concurrent fall in acetate uptake. There was a large glucose/oxygen quotient across the uterus, but the glucose plus lactate/oxygen quotient was comparable to that found in the sheep and guinea pig (0.6 +/- 0.1). It is apparent that in all three species studied under chronic steady-state conditions (sheep, guinea pig, and rabbit) there is a large glucose uptake associated with a net lactate production, and fuels other than glucose and lactate must be used by the uterus.
Acetates↗
Myosin movement in vitro: a quantitative assay using oriented actin cables from Nitella.
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Actins↗
Temporal comparisons in bacterial chemotaxis.
Responses of tethered cells of Escherichia coli to impulse, step, exponential-ramp or exponentiated sine-wave stimuli are internally consistent, provided that allowance is made for the nonlinear effect of thresholds. This result confirms that wild-type cells exposed to stimuli in the physiological range make short-term temporal comparisons extending 4 sec into the past: the past second is given a positive weighting, the previous 3 sec are given a negative weighting, and the cells respond to the difference. cheRcheB mutants (defective in methylation and demethylation) weight the past second in a manner similar to the wild type, but they do not make short-term temporal comparisons. When exposed to small steps delivered iontophoretically, they fail to adapt over periods of up to 12 sec; when exposed to longer steps in a flow cell, they partially adapt, but with a decay time of greater than 30 sec. cheZ mutants use a weighting that extends at least 40 sec into the past. The gain of the chemotactic system is large: the change in occupancy of one receptor molecule produces a significant response.
Bacterial Proteins↗
Metabolic quotients of the gravid uterus of the chronically catheterized guinea pig.
The uptake of substrates by the pregnant uterus defines the "diet" of the uterus and conceptus. In order to determine the uterine substrate uptake, catheters were placed in the femoral artery and uterine veins of guinea pigs at 40-49 days gestation. After at least 2 days recovery from perioperative stress, systemic arterial and uterine venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, acetate, and free fatty acids were measured and metabolic quotients were calculated. The glucose/O2 quotient was 1.22 +/- 0.07 (mean +/- SEM), the lactate/O2 quotient was -0.40 +/- 0.09, the acetoacetate/O2 quotient was 0.03 +/- 0.02, the beta-hydroxybutyrate/O2 quotient was 0.01 +/- 0.006, the acetate/O2 quotient was 0.03 +/- 0.01, and the free fatty acid/O2 quotient was 0.24 +/- 0.21. Among the substrates measured, glucose appears to be the major metabolic fuel of the pregnant guinea pig uterus, but does not account for all of the oxygen consumed by the uterus if adjusted for lactate production, since lactate is produced within the gravid uterus in large quantities. Acetoacetate and beta-hydroxybutyrate are utilized in negligible amounts.
Animals↗
A miniature flow cell designed for rapid exchange of media under high-power microscope objectives.
The design, fabrication and use of a flow cell that allows rapid displacement of media viewed by short working distance, high power objectives are described. The cell has a small internal depth (about 0.04 cm), small volume (about 0.05 ml), and is chemically inert. It has been tested extensively in studies of tethered bacteria.
Bacterial Physiological Phenomena↗
Light and dark adaptation in Phycomyces light-growth response.
Sporangiophores of the fungus Phycomyces exhibit adaptation to light stimuli over a dynamic range of 10(10). This range applies to both phototropism and the closely related light-growth response; in the latter response, the elongation rate is modulated transiently by changes in the light intensity. We have performed light- and dark-adaptation experiments on growing sporangiophores using an automated tracking machine that allows a continuous measurement of growth velocity under controlled conditions. The results are examined in terms of the adaptation model of Delbrück and Reichardt (1956, Cellular Mechanisms in Differentiation and Growth, 3-44). The "level of adaptation," A, was inferred from responses to test pulses of light by means of a series of intensity-response curves. For dark adaptation to steps down in the normal intensity range (10(-6)-10(-2) W/m2), A decays exponentially with a time constant b = 6.1 +/- 0.3 min. This result is in agreement with the model. Higher-order kinetics are indicated, however, for dark adaptation in the high-intensity range (10(-2)-1 W/m2). Adaptation in this range is compared with predictions of a model relating changes in A to the inactivation and recovery of a receptor pigment. In response to steps up in intensity in the normal range, A was found to increase rapidly, overshoot the applied intensity level, and then relax to that level within 40 min. These results are incompatible with the Delbrück-Reichardt model or any simple generalizations of it. The asymmetry and overshoot are similar to adaptation phenomena observed in systems as diverse as bacterial chemotaxis and human vision. It appears likely that light and dark adaptation in Phycomyces are mediated by altogether different processes.
Adaptation, Biological↗
Adaptation kinetics in bacterial chemotaxis.
Cells of Escherichia coli, tethered to glass by a single flagellum, were subjected to constant flow of a medium containing the attractant alpha-methyl-DL-aspartate. The concentration of this chemical was varied with a programmable mixing apparatus over a range spanning the dissociation constant of the chemoreceptor at rates comparable to those experienced by cells swimming in spatial gradients. When an exponentially increasing ramp was turned on (a ramp that increases the chemoreceptor occupancy linearly), the rotational bias of the cells (the fraction of time spent spinning counterclockwise) changed rapidly to a higher stable level, which persisted for the duration of the ramp. The change in bias increased with ramp rate, i.e., with the time rate of change of chemoreceptor occupancy. This behavior can be accounted for by a model for adaptation involving proportional control, in which the flagellar motors respond to an error signal proportional to the difference between the current occupancy and the occupancy averaged over the recent past. Distributions of clockwise and counterclockwise rotation intervals were found to be exponential. This result cannot be explained by a response regular model in which transitions between rotational states are generated by threshold crossings of a regular subject to statistical fluctuation; this mechanism generates distributions with far too many long events. However, the data can be fit by a model in which transitions between rotational states are governed by first-order rate constants. The error signal acts as a bias regulator, controlling the values of these constants.
Aspartic Acid↗
Coordination of flagella on filamentous cells of Escherichia coli.
Video techniques were used to study the coordination of different flagella on single filamentous cells of Escherichia coli. Filamentous, nonseptate cells were produced by introducing a cell division mutation into a strain that was polyhook but otherwise wild type for chemotaxis. Markers for its flagellar motors (ordinary polyhook cells that had been fixed with glutaraldehyde) were attached with antihook antibodies. The markers were driven alternately clockwise and counterclockwise, at angular velocities comparable to those observed when wild-type cells are tethered to glass. The directions of rotation of different markers on the same cell were not correlated; reversals of the flagellar motors occurred asynchronously. The bias of the motors (the fraction of time spent spinning counterclockwise) changed with time. Variations in bias were correlated, provided that the motors were within a few micrometers of one another. Thus, although the directions of rotation of flagellar motors are not controlled by a common intracellular signal, their biases are. This signal appears to have a limited range.
Cell Division↗
Impulse responses in bacterial chemotaxis.
The chemotactic behavior of Escherichia coli has been studied by exposing cells tethered by a single flagellum to pulses of chemicals delivered iontophoretically. Normally, wild-type cells spin alternately clockwise and counterclockwise, changing their direction on the average approximately once per second. When cells were exposed to a very brief diffusive wave of attractant, the probability of spinning counterclockwise quickly peaked, then fell below the prestimulus value, returning to baseline within a few seconds; repellent responses were similar but inverted. The width of the response indicates that cells integrate sensory inputs over a period of seconds, while the biphasic character implies that they also take time derivatives of these inputs. The sensory system is maximally tuned to concentration changes that occur over a span of approximately 2 sec, an interval over which changes normally occur when cells swim in spatial gradients; it is optimized to extract information from signals subject to statistical fluctuation. Impulse responses of cells defective in methylation were similar to those of wild-type cells, but did not fall as far below the baseline, indicating a partial defect in adaptation. Impulse responses of cheZ mutants were aberrant, indicating a serious defect in excitation.
Chemotaxis↗
Lomotil poisoning in children: two case reports.
Lomotil is a proprietary antidiarrhoeal agent in common use. Two cases of Lomotil poisoning, one of them fatal, are described. Symptoms are those of central nervous system depression and atropinism. Treatment consists of gastric emptying, administration of specific narcotic antagonists, cathartics and activated charcoal.
Atropine↗