Hantavirus cardiopulmonary syndrome: immune response and pathogenesis

Hantaviruses are emerging viruses in the Americas that cause cardiopulmonary syndrome with high lethality. The intense cellular immune response to hantavirus alters normal endothelial cell barrier functions and seems to be harmful to the host. On the other hand, the humoral immune response seems to be essential for recovery from infection.     

Hippocampus and context in classical conditioning.

Recent evidence suggests that contextual learning encompasses a variety of changes in learning and performance processes. Only some of these changes depend on the hippocampus. Specialized functions proposed for the hippocampus in contextual learning include the construction and consolidation of contextual memory representations, incidental contextual learning, and inhibitory contextual learning.     

Appraisal of pediatric cardiopulmonary resuscitation.

Sixty-six patients more than 30 days and less thant 16 years of age suffering an unexpected cardiac arrest in an 18-month period were included in a study of resuscitative measures in children. Six children survived to be discharged from hospital. Respiratory disease accounted for most (29%) of the cardiac arrests, but it also had the most favourable prognosis, 21% of the 19 patients surviving. None of the patients survived whose cardiac arrest was secondary to sepsis or trauma, even when the resuscitative efforts were initially successful. Only 1 of the 41 patients who had a cardiac arrest outside of hospital survived, and only 1 of the 34 patients who presented with asystole survived, and then with considerable damage to the central nervous system. The interval between cardiac arrest and application of basic life support was substantially shorter among the survivors. Also, most of the survivors did not present with asystole. The results of this study suggest that survival among resuscitated children is no better than that among adults but can be improved with early recognition and monitoring of children at risk. earlier application of basic and advanced life support, improved education of medical and lay personnel, and further research into pediatric resuscitative techniques.     

A comparison of the effects of vicariously instigated classical conditioning and direct classical conditioning procedures.

Two groups of Ss received either two or 16 paired classical conditioning trails beyond the peak CR. A third group received the same stimuli as the 16 postpeak condition but in an unpaired and random order. The stimuli in all three groups were delivered directly to S. Subsequently, all three groups, including a fourth which was not given any prior direct classical conditioning, were exposed to vicariously instigated classical conditioning. This consisted of having S observe someone (model) employed by E who received the same CS as was delivered during direct conditioning. The CS was paired with the feigned arm movement of the model, simulating a reaction to shock. This vicarious classical conditioning procedure when compared to direct classical conditioning resulted in smaller GSR magnitudes for both the CRs and UCRs. Previous experience with direct classical conditional seems to have had an attenuating effect on GSR magnitude during the vicarious situation. A postexperimental questionnaire tended to support the results, and the relationship between the present study and current classical conditioning theory is discussed.     

动物的经典条件反射和操作条件反射学习行为

概述了经典条件反射和操作条件反射的特征、形成过程和适应意义。     

Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndrome

Hantavirus cardiopulmonary syndrome (HCPS) is a life-threatening respiratory disease characterized by profound pulmonary edema and myocardial depression. Most cases of HCPS in North America are caused by Sin Nombre virus (SNV), which is carried asymptomatically by deer mice (Peromyscus maniculatus). The underlying pathophysiology of HCPS is poorly understood. We hypothesized that pathogenic SNV infection results in increased generation of reactive oxygen/nitrogen species (RONS), which contribute to the morbidity and mortality of HCPS. Human disease following infection with SNV or Andes virus was associated with increased nitrotyrosine (NT) adduct formation in the lungs, heart, and plasma and increased expression of inducible nitric oxide synthase (iNOS) in the lungs compared to the results obtained for normal human volunteers. In contrast, NT formation was not increased in the lungs or cardiac tissue from SNV-infected deer mice, even at the time of peak viral antigen expression. In a murine (Mus musculus) model of HCPS (infection of NZB/BLNJ mice with lymphocytic choriomeningitis virus clone 13), HCPS-like disease was associated with elevated expression of iNOS in the lungs and NT formation in plasma, cardiac tissue, and the lungs. In this model, intraperitoneal injection of 1400W, a specific iNOS inhibitor, every 12 h during infection significantly improved survival without affecting intrapulmonary fluid accumulation or viral replication, suggesting that cardiac damage may instead be the cause of mortality. These data indicate that elevated production of RONS is a feature of pathogenic New World hantavirus infection and that pharmacologic blockade of iNOS activity may be of therapeutic benefit in HCPS cases, possibly by ameliorating the myocardial suppressant effects of RONS.     

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders.

When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 +/- 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 +/- 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure.     

Operant conditioning and behavioral analyses using a minicomputer.

An operant conditioning and data analysis software system was developed for use on a PDP-12A minicomputer. The operant software functions in quasi time-sharing fashion to control and acquire data from any peripheral device that operates in the binary mode. In addition to independently running different experiments in near simultaneous fashion, the program also provides information on the current status of each experiment using a cathode ray-tube display. Response data from each experimental subject is stored on magnetic tape and analyzed, off-line, by the data analysis portion of the software system. A discussion of the operation of this system is given for one possible application: visual discrimination training.     

Transswitching and contextual conditioning. Relevant aspects of time

An empirical evaluation of temporal aspects of contextual conditioning was conducted in relation to Asratyan's (1965) theory of transswitching and to an alternative explanation that was partly stimulated by the Rescorla-Wagner model (Rescorla and Wagner 1972). On the basis of a human electrodermal conditioning preparation suggested by Kimmel and Ray (1978), five groups with 12 subjects each were run. The results indicated that the basic phenomena of transswitching are robust and therefore could be replicated; but the Asratyan theory was rejected. All the results supported an alternative explanation: in contextual conditioning, duration of contextual stimuli is less important than order. Phasic switching is due to simultaneous occurrence of stimuli (differential compound conditioning) and is therefore compatible with the Rescorla-Wagner model. Tonic switching is due to signals that occur before a marked sequence of conditioning trials, in part a challenge to the Rescorla-Wagner model. Long delays between critical events can perhaps be compensated for by mediating memory processes.     

The Pavlovian analysis of instrumental conditioning.

An account was given of the development within the Russian literature of a uniprocess formulation of classical and instrumental conditioning, known as the bidirectional conditioning hypothesis. The hypothesis purports to offer a single set of Pavlovian principles to account for both paradigms, based upon a neural model which assumes that bidirectional (forward and backward) connections are formed in both calssical and instrumental conditioning situations. In instrumental conditioning, the bidirectional connections are hypothesized to be simply more complex than those in classical conditioning, and any differences in empirical functions are presumed to lie not in difference in mechanism, but in the strength of the forward and backward connections. Although bidirectional connections are assumed to develop in instrumental conditioning, the experimental investigation of the bidirectional conditioning hypothesis has been essentially restricted to the classical conditioning operations of pairing two CSs (sensory preconditioning training), a US followed by a CS (backward conditioning training) and two USs. However, the paradigm involving the pairing of two USs, because of theoretical and analytical considerations, is the one most commonly employed by Russian investigators. The results of an initial experiment involving the pairing of two USs, and reference to the results of a more extensive investigation, leads us to tentatively question the validity of the bidirectional conditioning account of instrumental conditioning.     

Familial aggregation of nasal conditioning capacity.

In our previous studies on nasal conditioning, we observed a large variability among individuals to condition inspired air. Although we previously investigated various physiological parameters (age, sex, nasal mucosal temperature, heart rate, blood pressure, and nasal volume) that might underlie these differences, we have been unable to explain this variability. Many proteins and molecules, which are under genetic control and could affect nasal conditioning, are involved in water transport,. In this study, we hypothesized that familial factors may contribute to the differences in nasal conditioning capacity (NCC). We performed a prospective study of 47 sibling pairs. Cold dry air was delivered to the nose, and the total water gradient (TWG) was calculated to determine the NCC. We found a highly significant intraclass correlation of 0.53 (P < 0.0001) between sibling pairs for the TWG. These results suggest that there is a familial basis for nasal conditioning and a large enough genetic component to search for genes explaining the observed correlation.