Nonlinear dissipation effect in Brownian relaxation.

In an ensemble of noninteracting Brownian particles, a finite systematic average velocity may temporarily develop, even if it is zero initially. The effect originates from a small nonlinear correction to the dissipative force, causing the equation for the first moment of velocity to couple to moments of higher order. The effect may be relevant when a complex system dissociates in a viscous medium under strongly nonequilibrium conditions.

The N-linked oligosaccharides of the Fc epsilon receptors of rat basophilic leukemia cells.

This study was undertaken to investigate the nature and microheterogeneity of the carbohydrate moiety of the Fc epsilon receptors of RBL-CA10 and RBL-CA10.7 cells. Treatment using the glycosylation processing inhibitors, castanospermine (CN), 1-deoxymannojirimycin (DMJ), and swainsonine (SW) resulted in a decrease of the relative molecular mass (M(r)) of both the alpha-chain of the high affinity receptor for IgE, Fc epsilon RI(alpha), and the low affinity receptor for IgE, Fc epsilon RL. Exposure to DMJ had the greatest effect on the M(r), while CN seemed to lead to a decreased cell surface expression of Fc epsilon RI. Both receptors are largely resistant to endoglycosidase H as their M(r) decreased only by approximately 2 kDa. These results suggest that both receptors are composed primarily of complex oligosaccharides with a single high mannose, N-glycosylated site. Both Fc epsilon receptors become endoglycosidase H sensitive if first exposed to DMJ which indicates that the carbohydrate composition is indeed altered by this processing inhibitor presumably by blocking the formation of complex structures. When the Fc epsilon receptors were reduced and hydrolyzed by N-glycanase, the M(r) values for Fc epsilon RI(alpha) and Fc epsilon RL decreased to approximately 28 and 34-38 kDa respectively. In the case of Fc epsilon RI(alpha), this implies the presence of only a small amount of O-linked oligosaccharides.

The cross-reactivity of rat IgE and IgG with solubilized receptors of rat basophilic leukemia cells.

Normal rat IgG-Sepharose binds the same two receptors from solubilized rat basophilic leukemia (RBL) cells as are bound by rat IgE-Sepharose. These receptors have previously been designated R and H, and have apparent mol. wts of 45,000 and 55,000, respectively. Inhibition studies indicate that, although soluble deaggregated IgG is capable of interacting with both receptors, its affinity is higher for H than for R. Conversely, soluble IgE preferentially interacts with R, but its affinity for H is somewhat higher than that of rat IgG. Control studies show that IgG receptor interaction to be specific in that it is significantly stronger than that obtained with F(ab')2 fragments or a variety of proteins having pIs approximating that of IgG.

The interaction of IgG subclasses with solubilized Fc receptors of rat basophilic leukemia cells.

Rat basophilic leukemia (RBL) cells carry two surface glycoprotein molecules named R (or alpha) and H which, when detergent solubilized, bind to rat IgE-Sepharose. The same two molecules also bind to rat IgG-Sepharose but with a lower affinity. R is a component of the high affinity Fc receptor for IgE. In the present study the inhibition of the binding of R and H to rat IgG-Sepharose by various homologous and heterologous immunoglobulins was used to assess their relative affinities for the two receptor molecules. Ranking the rat immunoglobulins in order of their affinities for the R receptor yielded: IgE much greater than IgG2a greater than IgG1 greater than IgG2b; and for H: IgE greater than IgG2b greater than IgG1 greater than IgG2a. Rat IgG2c inhibited the binding of both R and H but a precise ranking could not be assigned. Conclusive evidence has been obtained for the Fc specificity of these interactions. The affinities of the mouse IgG subclass/R interactions can be ranked: IgG1 greater than IgG2a greater than IgG2b; and for the H receptor: IgG1 greater than IgG2b greater than IgG2a. All of the mouse proteins and other heterologous IgGs, such as those of sheep, goat, equine and rabbit origin, interacted considerably more strongly with H than with R. No interaction with mouse IgG3 could be detected under the conditions tested.

Suicide attempts in children and adolescents.

In a review of pediatric hospital emergency room admissions over 7 years, the authors found 505 children and adolescents who had attempted suicide. There were three times as many girls as boys, and the boys were significantly younger. Features that distinguished them from matched controls were religion, living situation, substance abuse, current psychiatric illness, prior psychotherapy, and current medical illness. Their families had more psychiatric illness (primarily drug or alcohol abuse), suicide, paternal unemployment, and paternal and maternal absence than the controls' families. The suicide attempts usually occurred in the winter, after school or in the evening, at home with someone nearby, and by drug overdose.

A microassay for studies of the interaction between Fc receptors and low affinity ligands.

A microassay using 10 microliter of a conjugate of rat IgG and Sepharose was developed for the study of the interaction between the solubilized receptors for IgE of rat basophilic leukemia (RBL) cells, designated H and R, and a variety of low affinity immunoglobulins. Rat IgG2a was used as the model of a low affinity ligand by serving as an inhibitor of the interaction between IgG-Sepharose and the receptors for IgE. Ligand concentrations 2.24 X 10(-7) to 5.37 X 10(-5) M were used along with detergent extracts of 2 X 10(5) RBL cells.

Emotional implications of primary familial hyperlipoproteinemia in childhood and adolescence.

To determine whether 43 patients and their 23 unaffected siblings were at increased risk for psychologic upset, 28 families of children being treated for primary familial hyperlipoproteinemia were studied. Nine fathers but no mothers had died of the disease. The families were interviewed for psychiatric assessment, and the parent(s) scored a questionnaire concerning eight behavioral factors. Male patients had significantly higher scores for impulsive hyperactive behavior than their male siblings. Fatherless female patients had the highest scores for perfectionism and the lowest scores for conduct problems and impulsive hyperactive behavior. Fatherless children scored lower for impulsive hyperactive behavior than children with fathers; fatherless male children were more anxious than fatherless female children. There were more significant differences in scores for children whose father was still alive vs those whose father had died than in scores for affected children vs unaffected siblings. Thus, the emotional impact of the premature death of an affected parent appears greater than that of having the disease. Therefore, one should be alert for changes in behavior in children with primary familial hyperlipoproteinemia when a parent dies of the disease and as the patients approach the age at which the parent died.

Proteolytic fragments of the receptors for IgE.

Partially purified IgE receptor(s) of rat basophilic leukemia cells (RBL) designated R and H and having apparent molecular weight of 45,000 and 55,000 daltons, respectively, were subjected to proteolysis with papain. Polyacrylamide gel electrophoresis of the digests in the presence of sodium dodecyl sulfate revealed a difference in the size and number of the fragments produced. These results suggest that these two receptor molecules are different with respect to amino acid composition and sequence. Whole Nonidet P-40 extracts of RBL cells were also subjected to digestions with papain, trypsin and chymotrypsin in an attempt to obtain receptor fragments still capable of binding to IgE-Sepharose. Treatment with papain produced a 38,000 dalton fragment of H but no fragments of R which retained the ability to bind to IgE. Tryptic and chymotryptic treatment produced a 41,000 dalton fragment of H with affinity for IgE. The IgE-binding site of R was either destroyed or not affected at all.

Factor-independent tissue cultured mast cells: establishment from rat peritoneal mast cells.

We report here that extended culture of purified rat peritoneal mast cells (RpMC), typical of the connective tissue-type (CTMC), gives rise to continuously proliferative cell lines without the requirement of exogenous growth factors such as IL-3 and IL-4 or accessory cells. Two of the cell lines established, RCMC1 and RCMC2, are described here. Both cell lines have been maintained in continuous culture in vitro for over a year. Although these cell lines were derived from CTMC, they exhibit phenotypic characteristics of mucosal-type mast cells, i.e., they contain rat mast cell protease II (RMCP II), low levels of histamine and stain alcian blue+/safranin-. Previous studies have identified both high and low affinity receptors for IgE, designated Fc epsilon RI and Rc epsilon RII, respectively, on RpMC and rat basophilic leukemia (RBL) cells. At the early stages of cell culture, RCMC1 expressed predominantly Fc epsilon RI and a gradual increase in the expression of Fc epsilon RII has been observed with time in culture. By comparison, RCMC2 expressed predominantly Fc epsilon RII throughout its entire period of cell culture.

Effect of graded erythrocythemia on cardiovascular and metabolic responses to exercise.

The effects of graded induced erythrocythemia on cardiovascular and metabolic responses to intense treadmill running were studied in four highly trained endurance runners. Three autologous infusions of 1 unit (U) whole blood (450 ml/U) were administered sequentially 2-7 days apart. Maximal O2 consumption (VO2max) increased from 5.04 l/min at control (C) to 5.24 l/min after 2 U (R2) and 5.38 l/min after 3 U (R3). Cardiac output during treadmill running at 91% control VO2max was 28.2 l/min at C, 29.8 l/min at R2, and 33.1 l/min at R3. Corresponding heart rates were unchanged, and stroke volume was increased at R3. Peak lactate concentration was reduced, and arterial acid-base status improved at R2 and R3 after standardized bouts of intense exercise. Arterial blood pressures and electrocardiograms during exercise were not affected by erythrocythemia. We conclude that the reinfusion of up to 3 U of autologous blood into highly trained endurance runners who have normal hematology does not adversely affect their cardiovascular response to maximal exercise. In addition, the increases in VO2max following reinfusion of 2 U, and again after 3 U, suggest that the aerobic power of the working muscles was not surpassed at these levels of erythrocythemia.

Lung volume recruitment during high-frequency oscillation in atelectasis-prone rabbits.

In diffuse lung injury, optimal oxygenation occurs with high-frequency oscillatory ventilation (HFO-A, where A is active expiratory phase) when sustained inflations (SI) are applied periodically to recruit lung volume. Theoretically pulsed pressures may be safer and more effective than static pressures for reexpanding alveoli. We compared the increases in lung volume and arterial PO2 (PaO2) induced by 30-s increases in mean airway pressure in six New Zealand White rabbits made atelectasis prone by saline lavage plus 1 h of conventional ventilation. Pulsatile SI's (HFO-A left on during increase in mean pressure) of delta PSI = 5, 10, and 15 cmH2O and static SI's (HFO-A off during SI) of delta PSI = 5, 10, 15, and 20 cmH2O were delivered in random order. Lungs were ventilated at 15 Hz, inspired fractional concentration of O2 = 1.0, and mean airway pressure 15-20 cmH2O between test periods and deflated to functional residual capacity before each SI to standardize volume history. With both maneuvers, increases in lung volume and PaO2 induced by SI's were proportional to the magnitude of the SI (P less than 0.001) in all cases. Pulsatile SI's consistently increased lung volume and PaO2 more than static SI's having the same delta PSI (P less than 0.005) such that any given target PaO2 or change in volume (delta V) was achieved at 5 cmH2O less mean pressure with the pulsatile maneuver. Respiratory system compliance increased after both types of SI. Oxygenation and lung volume changes at 5 min were related with r = 0.58 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung.

Both ventilator pattern and neutrophil activation influence lung injury in adult respiratory distress syndrome (ARDS). We therefore questioned whether ventilator pattern independently affects neutrophil accumulation and function in early ARDS. Thirty-five New Zealand White rabbits were anesthetized, paralyzed, and prepared using sterile techniques. Fifteen surfactant-depleted animals were randomized and ventilated for 4 h using high-frequency oscillatory ventilation (HFO) at 15 Hz with an inspired O2 fraction = 1.0 and arterial PO2 (PaO2) > 400 Torr (a pattern known to reverse atelectasis) or conventional mechanical ventilation (CMV) with PaO2 = 80-100 Torr (a pattern with some atelectasis despite positive end-expiratory pressure). Eight normal animals on CMV with PaO2 > 400 Torr served as a reference group (NorCMV). NorCMV animals progressively increased circulating polymorphonuclear neutrophil (PMN) numbers and had minor pressure-volume curve alterations but no other significant changes. Lavaged CMV animals developed the characteristic gas exchange and marked pressure-volume curve abnormalities of ARDS. Circulating PMNs remained constant but developed decreased chemotactic activity, whereas lung neutrophil numbers increased significantly (P = 0.0002) and had substantially enhanced chemiluminescence (P = 0.0003 vs. NorCMV animals). Although lavaged HFO animals accumulated an intermediate number of lung neutrophils (lung myeloperoxidase > NorCMV animals; P = 0.003), the chemiluminescence and chemotaxis of these PMNs were the same as in cells from NorCMV animals. We concluded that both the degree of neutrophil activation and lung injury can be minimized by preventing cyclic alveolar/airway expansion and collapse in the surfactant-deficient lung by use of appropriate ventilator patterns.

The influence of chronic cerebellar stimulation on respiratory muscle coordination in a patient with cerebral palsy.

The effect of chronic cerebellar stimulation on respiratory muscle coordination has been evaluated using a relatively simple and objective target breathing test on one patient. Seven normal subjects were used as controls. Magnetometer recordings were used to determine whether abdominal and rib cage expansion were in phase. Subjects were asked to match their breathing frequency to a metronome signal. Their ability to control respiratory timing voluntarily was assessed in terms of the coefficient of variation (CV) of inspiratory time (Ti) and of expiratory time (Te). The CV's of Ti and Te were much greater in the patient in the absence of cerebrellar stimulation than they were in normal subjects. Both at 3 weeks and 6 months after implantation of the stimulator, a significant improvement in the performance of the patient was demonstrable with the stimulator on, although normal values were never achieved. This demonstrable influence of chronic cerebellar stimulation on respiratory muscle coordination has important implications for both the avoidance of respiratory complications and the potential improvement of speech in patients with cerebral palsy.

Cerebellar stimulation in the management of cerebral palsy: clinical and physiological studies.

Cerebellar stimulators were inserted into seven children who had cerebral palsy and in whom extensive investigation, including computerized tomography, had revealed no structural brain abnormality. A team including physiotherapists, occupational therapists, speech pathologists, and respiratory physiologists assessed the children pre- and postoperatively; their somatosensory evoked potentials were also measured. The mean age at implantation was 8.6 yearsl follow-up has ranged from 8 to 23 months (mean, 17.3 months). No adverse effects of the cerebellar stimulation have been noted. Detailed case histories obtained from the parents, together with formal assessment scores, indicate good improvement in six patients and mild but significant improvement in the seventh. Clinically, there has been gradual improvement in all seven patients. The charge density range associated with clinical improvement was 0.8 to 2.1 muCi/cm2/phase. The stimulation equipment must be monitored very carefully to ensure that any variation from the desired output is acceptably small because it is probable that sizable deviation is a determining factor in lack of response to this therapy.

Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression.

The purpose of the present study was to examine the pattern of changes in respiratory system mechanics induced by dexamethasone (Dex) in infants with bronchopulmonary dysplasia (BPD) and to determine whether dosages that produce these changes induce adrenal suppression. We examined mechanics in seven ventilator-dependent premature infants (age, 33 +/- 4.8 days) with BPD, before and daily during Dex therapy. Dex (0.5 mg/kg/day) was given intravenously for 7 days unless complications necessitated early termination. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive expiratory flow-volume technique during the course of dexamethasone therapy or until extubation. Adrenocorticotrophic hormone (ACTH) stimulation tests were done at baseline and following Dex therapy to evaluate adrenal function. Dex therapy caused a 77 +/- 18% increase in Crs (from 0.97 +/- 0.09 SEM mL/cmH2O to 1.6 +/- 0.16 mL/cmH2O; P less than 0.025) and a 33 +/- 5% decrease in Rrs (from 0.20 +/- 0.02 cmH2O/mL/s to 0.14 +/- 0.01 cmH2O/mL/s; P less than 0.01). Concurrently, ventilator rate, mean airway pressure, and FIO2 all decreased significantly (P less than 0.025). Extubation occurred later in infants with the lowest Crs and highest Rrs at baseline. At extubation, all Crs values were greater than 1.33 mL/cmH2O and Rrs values were less than 0.15 cmH2O/mL/s. Systolic blood pressure increased from 61 +/- 6.3 mmHg to 84 +/- 17 mmHg, 72-96 h after the start of Dex (P less than 0.025). There were no episodes of culture-positive sepsis. Neither basal nor ACTH-stimulated levels of cortisol were suppressed as a result of Dex therapy (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of noninvasive maximal cardiac output measurement.

Due to the invasiveness of direct techniques and problems that constrain the use of popular indirect techniques during very heavy (non-steady-state) exercise, measurements of maximal cardiac output are seldom included in studies of exercise. The acetylene-rebreathing technique is well-suited for maximal exercise; however, until recent technological advances, difficulties involved in collecting and measuring alveolar acetylene samples have restricted its use. We compared cardiac output values measured via the acetylene-rebreathing technique (QA) (modified for use with a mass spectrometer) and the dye-dilution technique (QD) at rest and during light to maximal exercise in six moderately active males. Although QA consistently underestimated QD, the two techniques showed a significant correlation of 0.87 throughout all levels of exercise. During maximal exercise, QA and QD values were not significantly different (24.7 and 26.7 l X min-1, respectively). Modifications in the QA technique that reduce potential sources of error were also examined. We conclude that the acetylene-rebreathing technique, modified for use with a mass spectrometer, is a simple and valid procedure for measuring maximal cardiac output.

High frequency ventilation.

The potential role of HFV has yet to be fully defined. Its use should be approached with caution, ensuring that the possible benefits outweigh new hazards. Only further rigorously controlled trials, designed to make optimum use of the special features of HFV, will furnish the information we need.

Relational V-code conditions in a child and adolescent population do warrant treatment.

It is often argued that relational V-code conditions are less serious than classical psychiatric disorders, and that they should therefore receive lower clinical priority or diminished levels of treatment funding. Despite these common assertions, there have been virtually no studies that have used actual case data to evaluate whether such problems are in fact less serious and less worthy of treatment funding. We used actual case data from a universally funded child and family clinic to evaluate these questions. Results showed that both classical diagnoses and relational problems were significantly related to markers of clinical severity. As with previous research, family therapy was not differentially associated with a larger number of treatment sessions.

[Physiological basis for the use of muscarine antagonists in bronchopulmonary dysplasia]. / Bases physiologiques de l'utilisation des antagonistes muscariniques dans les dysplasies bronchopulmonaires.

The rationale for the use of muscarinic antagonists in bronchopulmonary dysplasia (BPD) is based on the physiology and pharmacology of airway smooth muscle, the pathology of BPD, and the response of infants with BPD to bronchodilators, in vivo and in vitro studies of airway smooth muscle of newborn animals and humans indicate that vagal efferent airway innervation and/or muscarinic receptors are functional at birth, as well as early in gestation. Current concepts regarding muscarinic receptor subtypes suggest that M3 receptors mediate airway smooth muscle contraction, M2 receptors are autoinhibitory and limit vagally-mediated bronchoconstriction, and M1 receptors may play a facilitatory role in ganglionic transmission. Muscarinic receptor subtypes appear to be functionally expressed at birth but may undergo developmental regulation. Infants with BPD have an elevated pulmonary resistance that is accompanied by hypertrophy of airway smooth muscle, b2-agonists cause bronchodilation in BPD as does atropine in infants recovering from severe BPD. The synthetic congener of atropine, ipratropium bromide (IPB) causes bronchodilation in ventilator-dependent infants with BPD in a dose-dependent fashion. Nebulized IPB causes a decrease in respiratory resistance that reaches a maximum of 20% at 175 mg. The bronchodilation seen with muscarinic antagonists suggests that part of the elevated resistance associated with BPD is due to increased muscarinic tone, presumably vagal in origin. When IPB is combined with salbutamol (0.04 mg) the response is increased in magnitude and duration; reaching a slightly larger decreases in resistance (26%) that is now accompanied by an increase in compliance (20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Sex differences in evaluating heterosexual and homosexual promiscuity.

Our research focused on men's and women's interpretations of homosexually and heterosexually promiscuous behavior. Study 1 involved 21 men and 21 women who rated perceived differences between homosexually and heterosexually promiscuous behavior following a discussion of impersonal sex in public restrooms. Men perceived the two types of promiscuous behavior as more different than did women. In Study 2, 41 men and 23 women rated their perceptions of the difference between homosexually and heterosexually promiscuous behavior without any prior discussion. No sex differences were found, though a significant correlation between age and rating was observed. Men and women may focus on different dimensions when evaluating sexual behavior.