Myths & facts about nosocomial infections.
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Biomedical subjects
Publications and source records attributed to J Farley.
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Cumulative depolarization of Hermissenda type B photoreceptors, a short-term neural correlate of associative learning, was produced by simulating associative training in the isolated nervous system (in vitro conditioning). This simulation entailed stimulation and recording from three classes of neurons normally affected by the associative training procedure: a type B photoreceptor, the silent/excitatory (S/E) optic ganglion cell, and a statocyst caudal hair cell. Exposure of the isolated nervous system to five simultaneous pairings of light and current-induced impulse activity of the caudal hair cell resulted in an average 10-mV depolarization of type B cells. Cumulative depolarization was found to be pairing specific, to occur with a minimal number of training trials, and was paralleled by short-term pairing-specific changes in phototactic behavior for the intact animal. Two important determinants of cumulative depolarization were found to be the magnitude and duration of the long-lasting depolarization (LLD) response of type B cells to light, and a pairing-specific synaptic facilitation of the LLD response. The synaptic facilitation arose from two distinct sources: increased excitatory postsynaptic potential (EPSP) feedback on B cells following light and caudal hair cell stimulation pairings, and disinhibition of the type B photoreceptor following pairings. The S/E optic ganglion cell was found to be a potent regulator of B cell EPSPs. Cumulative depolarization was substantially reduced when the S/E cell was hyperpolarized throughout the course of pairings. Conversely, pairings of light with depolarizing current stimulation of the S/E cell were sufficient to produce cumulative depolarization of B cells. Precluding disinhibition of the B cell from the caudal hair cell was also found to attenuate cumulative depolarization. Additional constraints, inherent to the neural organization of the visual and statocyst neural systems were found to further limit the degree of cumulative depolarization. Among the most important of these were the interpairing interval and light intensity. Exposure of intact animals of five pairings of light and rotation resulted in short-term suppression of phototactic behavior. Like the cumulative depolarization of B cells with in vitro conditioning procedures, these changes were relatively pairing specific and persisted for comparable durations of time. Cumulative depolarization of B cells appears to be an important initial step in the production of long-term associative neural and behavioral changes in Hermissenda.
Bilateral palmar skin conductance and heart rate were measured throughout a series of psychological tests and during both sitting and ambulant social interactions in 14 right-handed men with chronic schizophrenic disorder and 12 healthy volunteers matched for age and handedness. Miniature radio telemetry equipment was used to collect the physiological data. The schizophrenic group was effectively unresponsive to 70-dB auditory stimuli, while all but one of the control group responded and habituated to a nil response by the tenth tone in sequence. The schizophrenic group showed some evidence of increased skin conductance activity at rest, and in socially demanding conditions skin conductance level and variability were increased in the right hand. The present group of electrodermal 'non-responders' was not in general autonomically under-active. Asymmetry of skin conductance activity during social interaction may be a characteristic of chronic schizophrenic disorder.
Reaction time, set index, critical flicker frequency, two-flash threshold, a sustained performance task and psychophysiological parameters from people with chronic schizophrenic disorder (n = 14) and a control group (n = 12) were analysed to assess the association between arousal, attentional dysfunction and social dysfunction in schizophrenia. Shorter reaction time, rated ability to mime and, in the schizophrenic group, scores on Venable's ward activity scale correlated with each other. In the schizophrenic group, prolonged reaction time latency correlated positively with skin conductance level in the right hand and negatively with skin conductance variability in the left hand, the latter being in the opposite direction to that for the control group. The results may provide support for the hypothesis that lateralised cerebral dysfunction is associated with performance deficits in people with chronic schizophrenic symptoms.
In order to investigate the mechanism(s) of electric field-stimulated osteogenesis, we have developed an in vitro model in which embryonic chick tibiae have consistently demonstrated increased bone matrix formation in response to a low amplitude (estimated 10(-5) V/m in the serum-free culture medium), capacitively coupled, 10 Hz sinusoidal electric field. Initial applications of this model revealed that 72 h of continuous exposure to the electric field increased tibial collagen production by 29% compared to untreated controls, P less than 0.01. Additional studies further revealed: (a) that when electric field exposure was limited to 30 min/day during the 72 h in vitro incubation, embryonic bone matrix formation was increased by 83%, compared to non-treated controls (P less than 0.001), suggesting an inductive mechanism; (b) that the osteogenic response to electric field exposure in vitro was not unique to embryonic chick tibiae, since a similar response was also seen with newborn mouse calvaria (+133%, P less than 0.02); (c) that electric field-exposure-stimulated chick bone matrix formation was associated with increased bone cell proliferation; and (d) that this mitogenic response to in vitro electric field exposure could also be observed with embryonic chick calvarial cells in monolayer, serum-free cultures.
Preputial smegma samples from 195 beef bulls were collected repeatedly and cultured for Tritrichomonas foetus. Seventy-five (38.5%) of these bulls were positive for trichomonads on at least 1 culture. Sensitivity of the culture procedure (number of positive cultures/number of total cultures from known-positive bulls) was 81.6%. Storage of preputial smegma in lactated Ringer's solution at 5 C for 24 hours resulted in a 14% loss of sensitivity. Seventy-three of the 75 infected bulls were available for treatment and were alloted randomly to 2 groups. Bulls in both groups were treated with procaine penicillin (7,000 IU/kg, IM) for 2 days before ipronidazole treatment. Thirty grams of ipronidazole powder was dissolved in 60 ml of sterile water, and was given IM to group 1 bulls. Group 2 bulls were given a similar 30-g ipronidazole solution IM on day 1, and were given 15 g of ipronidazole dissolved in 30 ml of sterile water on days 2 and 3. Efficacy of treatment (ie, negative cultures of preputial smegma for trichomonads for 6 consecutive weeks after treatment) was 92.8% for the 42 bulls treated once and 100% for the 31 bulls treated 3 times.
A single identified neuron, the medial type B photoreceptor, was isolated by axotomy from the nervous systems of nudibranch molluscs (Hermissenda) which had been exposed to three different training experiences. Paired animals had been trained with repeated paired presentations of light and rotation and random animals with randomized light and rotation; naive animals had no training. A two-microelectrode voltage clamp of axotomized type B somata (separated from all synaptic interactions and impulse activity) was used to measure, with a blind procedure, three distinct ionic currents at least 24 h after the training experience. An early K+ current, IA, and a Ca2+-dependent K+ current, ICa2+-K+, but not a light-induced inward Na+ current, were significantly reduced for the paired as compared to the random and naive animals. The magnitude of ICa2+-K+ reduction was related (again measured blindly) to the degree of training-induced suppression of phototaxis (a measure of the learned behavior) for the paired animals. These data are consistent with previous observations indicating that changes of intrinsic type B membrane properties are an important means for encoding the acquisition and retention of Hermissenda associative learning.
Eight independent recombinant Epstein-Barr virus genomes, each of which was a transforming strain, were made by superinfecting cell lines containing Epstein-Barr virus DNA (Raji or B95-8 strain) with a nontransforming virus (P3HR1 strain). A knowledge of the constitution of each transforming recombinant allowed the localization of the defect in the genome of the nontransforming parent to a 12-megadalton sequence within the EcoRI A fragment. Within this region, the nontransforming virus has a deletion of the BamHI Y fragment and about half of the sequences in the adjacent BamHI H fragment. The present data suggest that this deletion is responsible for the nontransforming phenotype. Furthermore, mapping a deletion in one of the recombinant genomes allowed the conclusion that a sequence (comprising about 20% of the Epstein-Barr virus genome) from the center of BamHI-D to BamHI-I' is not necessary for the maintenance of transformation by Epstein-Barr virus.
In Table 1, we summarize what is convincingly demonstrated to date for the major vertebrate and invertebrate model systems attempting to elucidate cellular mechanisms of associative learning. Two major concerns are the adequacy of the behavioral demonstrations and the completeness and extent of the accompanying neurophysiology. In addressing the issue of behavior, it is important to define clearly which criteria are both necessary and sufficient to infer the involvement of an associative-learning process. Similarly, it is also important to distinguish among those primary characteristics of associative learning in general, and those secondary or tertiary features that serve to define various subclasses. In our view, it would be unreasonable to require that any given preparation exhibit all the defining features of classical conditioning, for example, in order to qualify as a "legitimate" instance of associative learning. This is especially true if the goal is to understand the more general, rather than the specific, mechanisms involved in associative learning. Hence, we emphasize the following as primary features of learned behavior: pairing specificity, stimulus specificity, long-term retention (arbitrarily defined as lasting for at least 24 hr), a moderate degree of reversibility by subsequent experience (e.g. extinction), and demonstrations that nonassociative-learning processes cannot account for features a-c. Where appropriate, we also identified other interesting features of the learned behavior. It is apparent from the table that a major unresolved issue for most of the preparations is the extent to which the behavioral changes are exclusively associative. This is no less true for the vertebrate preparations than it is for the invertebrates. The clearest example of an exclusively associative behavioral change is the rabbit NMR. The learning-produced changes in the invertebrate preparations were all shown, to varying degrees, to be pairing specific. Yet a major unresolved issue is the degree to which apparent examples of associative-learning reflect complex interactions among basically nonassociative-learning processes. The core issue is really quite simple: Does the associative training procedure result in the acquisition of new or qualitatively different behavior; and is there a strict requirement for an associative relation? In addressing the adequacy of the neurophysiological analyses, the major issue is that of localization. Logically, there are two components to this.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of systemic calcium regulating hormones have been studied extensively, yet mechanisms of bone volume regulation at the local level are poorly understood. Our laboratory has reported evidence for two locally mediated processes of bone volume regulation which function independently of systemic control: (1) coupling of bone formation and resorption and (2) repletion of resorbed bone. These local regulatory mechanisms have been shown to occur in vivo and in vitro. We have reported that embryonic chick tibiae in culture, stimulated to resorb, release a factor in the serum-free culture medium that stimulates bone cell proliferation and bone matrix formation in vitro. We have postulated that this factor could be involved in the coupling mechanism. Subsequently, a similar factor which stimulates bone cell proliferation, collagen synthesis and bone formation in vitro was extracted from embryonic and adult bones. The factor partially purified from human bone, designated as human skeletal growth factor, has molecular weight, heat sensitivity and biological activity similar to the factor found in bone conditioned medium. Many other biologically active factors have also been extracted from bone cells or demineralized bone by different laboratories. Their actions on bone cells range from chemotactic to mitogenic. These recently discovered bone factors emphasize that there is important regulation of bone metabolism at the local level.
The nudibranch mollusk Hermissenda crassicornis' normal attraction to light can be suppressed by repeated pairings of light with rotation. The present study examines the effects of extinction procedures on this simple form of associative learning. Presentation of non-reinforced light steps following associative conditioning resulted in an attenuation of phototaxic suppression, evident at both short- and long-term retention intervals. The absence of habituation of phototaxic behavior, coupled with the failure to demonstrate spontaneous recovery of extinguished conditioned suppression, indicates that extinction of associative conditioning in Hermissenda depends little upon non-associative learning processes. Electrophysiological evidence indicates that the Type B photoreceptors, which have been causally implicated in the acquisition and retention of associative learning, play an important role in mediating extinction as well. Enhanced input resistances and light responses of B cells, which are produced by associative training, are absent for animals subsequently exposed to light unaccompanied by rotation. In terms of both behavioral and electrophysiological measures, extinction appears to result primarily from a reversal of the original acquisition process.
Two-microelectrode voltage clamp studies were performed on the somata of Hermissenda Type B photoreceptors that had been isolated by axotomy from all synaptic interaction as well as any impulse-generating (i.e., active) membrane. In the presence of 2-10 mM 4-aminopyridine (4-AP) and 100 mM tetraethylammonium ion (TEA), which eliminated two previously described voltage-dependent potassium currents (IA and the delayed rectifier), a voltage-dependent outward current was apparent in the steady state responses to command voltage steps more positive than -40 mV (absolute). This current increased with increasing external Ca++. The magnitude of the outward current decreased and an inward current became apparent following EGTA injection. Substitution of external Ba++ for Ca++ also made the inward current more apparent. This inward current, which was almost eliminated after being exposed for approximately 5 min to a solution in which external Ca++ was replaced with Cd++, was maximally activated at approximately 0 mV. Elevation of external potassium allowed the calcium (ICa++) and calcium-dependent K+ (IC) currents to be substantially separated. Command pulses to 0 mV elicited maximal ICa++ but no IC because no K+ currents flowed at their new reversal potential (0 mV) in 300 mM K+. At a holding potential of -60 mV, which was now more negative than the potassium equilibrium potential, EK+, in 300 mM K+, IC appeared as an inward tail current after positive command steps. The voltage dependence of ICa++ was demonstrated with positive steps in 100 mM Ba++, 4-AP, and TEA. Other data indicated that in 10 mM Ca++, IC underwent pronounced and prolonged inactivation whereas ICa++ did not. When the photoreceptor was stimulated with a light step (with the membrane potential held at -60 mV), there was also a prolonged inactivation of IC. In elevated external Ca++, ICa++ also showed similar inactivation. These data suggest that IC may undergo prolonged inactivation due to a direct effect of elevated intracellular Ca++, as was previously shown for a voltage-dependent potassium current, IA. These results are discussed in relation to the production of training-induced changes of membrane currents on retention days of associative learning.
This report is a preliminary description of the cloning, DNA sequence determination, and expression of the protein A gene from Staphylococcus aureus in Escherichia coli and yeast recombinant host systems. The deduced amino acid sequences of the Fc-binding domains agree well with a previously published peptide analysis. The deduced amino acid sequence of the cell wall anchorage domain reveals 11 short repeating units (designated S repeats). The S repeat consensus sequence is the octapeptide Lys-Pro-Gly-Lys-glu-Asp-Gly-Asn. The potential for the use of genetic engineering to enhance the therapeutic utility of the protein A molecule is also discussed.
Single type B photoreceptors in intact, restrained Hermissenda were impaled with a microelectrode and exposed to either paired or unpaired presentations of light and depolarizing current to simulate natural stimulus effects during conditioning with light and rotation. Paired, but not unpaired, stimulus presentations produced cumulative depolarization and increased input resistance in type B cells. These membrane changes are similar to those observed after pairings of light and rotation are administered to either intact animals or isolated nervous systems or when light is paired with electrical stimulation of the vestibular system in isolated nervous systems. One and two days after treatment, pairing- and light-specific suppression of phototactic behavior was observed in recovered animals. These findings indicate that the membrane changes of type B cells produced by pairing light with current injections cause acquisition of the learned behavior.
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Blot hybridization studies revealed that the deletion which characterizes the DNA from the B95-8 strain of Epstein-Barr virus was not present in the virus from which the B95-8 strain was derived (883L). The deletion event must have occurred during establishment of the B95-8 cell line or very soon afterward, since the deletion was present in Epstein-Barr virus DNA from a cell line established with B95-8 virus soon after it became available. The presence of the deletion correlates with decreased expression of the gp220 viral envelope glycoprotein.
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