Prediction of vertebral failure loads from spinal and femoral dual-energy X-ray absorptiometry, and calcaneal ultrasound: an in situ analysis with intact soft tissues

The anatomic and physiological bases for nociception are present even in very preterm neonates. Neonates show the same behavioral, endocrine, and metabolic responses to noxious stimuli as older subjects. Preterm infants appear to be more sensitive to painful stimuli and have heightened responses to successive stimuli. Infants receiving intensive care are subjected to frequent stressful procedures and also chronic noxious influences related to the environment of care. Inflammatory conditions such as necrotizing enterocolitis may also cause pain. Untreated pain in babies is associated with increased major morbidity and mortality. Nonpharmacological interventions, including environmental modification and comforting during procedures reduce stress. Intravenous opiates are the mainstay of pharmacological analgesia. A pure sedative agent can provide physiological stability in settings in which there are less acutely painful stimuli or when there are adverse effects from, or tolerance to, opiates. Local anesthesia of skin and mucous membranes is helpful for invasive procedures. Antipyretic analgesics such as acetaminophen have a role in inflammatory pain.     

Measuring female mating preferences

Interest in the evolution of female mating preferences has increased greatly in recent years, and numerous hypotheses have been proposed to explain how mating preferences evolve. Despite this interest, little is known about how selection acts on mating preferences in natural populations. One reason for this lack of information may be that experimental designs commonly used for testing female preferences make it difficult to quantify the preferences of individual females. Most commonly used designs share three features: they examine the preferences of populations of females, they test female responses when they are presented simultaneously with two stimuli, and they infer information on female preferences by observing female choices between alternative stimuli. Population-level choice tests, in which each female is tested only once with a set of stimuli, do not evaluate within-female variation in preference, which is necessary to document between-female variation in preference. Two-stimulus designs test only for directional preferences if female responses are tested with only a single pair of stimuli. In addition, dichotomous scoring of female responses makes detection of between-female variation in preference difficult. Simultaneous stimulus presentations can confound female preference and female sampling behaviour. An alternative method to assess female preferences is to measure repeatedly the preference functions of individual females using a single-stimulus design. The shape of a female's preference function indicates how a female's mating response varies with male trait value, and repeated measures of individual preference functions allow measurement of within- and between-female variation in preferences. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

Relation between signal detectability theory and the traditional procedures for measuring sensory thresholds: Estimating d' from results given by the method of constant simuli.

The theory of signal detectability assumes that the central effect of a stimulus varies because of physical and neural noise; consequently, the detection of a signal requires a central statistical decision procedure. Similar assumptions have been made by psychophysicists to explain the results of traditional threshold measurement procedures. The interrelations between signal detectability and threshold measures are discussed in relation to psychophysical statistical decision theory, and it is shown that (a) the false positive rate should be related to the Crozier ratio C = ΔΙ/?ΔΙ, and (b) it should be possible to use responses given in the method of constant stimuli to predict the value of d' that will be assigned to a given stimulus by a signal detectability procedure. Evidence supporting both predictions is reported, and the relation between threshold measures and "personality tests" is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reconsidering formative measurement.

The relationship between observable responses and the latent constructs they are purported to measure has received considerable attention recently, with particular focus on what has become known as formative measurement. This alternative to reflective measurement in the area of theory-testing research is examined in the context of the potential for interpretational confounding and a construct's ability to function as a point variable within a larger model. Although these issues have been addressed in the traditional reflective measurement context, the authors suggest that they are particularly relevant in evaluating formative measurement models. On the basis of this analysis, the authors conclude that formative measurement is not an equally attractive alternative to reflective measurement and that whenever possible, in developing new measures or choosing among alternative existing measures, researchers should opt for reflective measurement. In addition, the authors provide guidelines for researchers dealing with existing formative measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.     

Assessing the social validity of behavioral interventions: A review of treatment acceptability measures.

Increased attention to the construct of social validity in school psychology research and practice has resulted in a focus on treatment acceptability, the extent to which interventions are considered appropriate, effective, and fair. Questionnaires represent the typical measurement approach to treatment acceptability. This article reviews treatment acceptability measures and practices that have been developed and used to assess the social validity of behavioral interventions. A comparative framework was developed and applied to provide a systematic critique of 9 treatment acceptability measures along such dimensions as content and purpose of the instrument, psychometric properties, scoring procedures and interpretation, and use of the measure in research in practice. No one instrument was selected to be the most comprehensive and it is argued that treatment acceptability assessment practices need to move beyond the traditional questionnaire format. Alternatives to rating scales are presented and directions for future research regarding the measurement of treatment acceptability are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Cognitive reappraisal of negative affect: Converging evidence from EMG and self-report.

Prior psychophysiological studies of cognitive reappraisal have generally focused on the down-regulation of negative affect, and have demonstrated either changes in self-reports of affective experience, or changes in facial electromyography, but not both. Unfortunately, when taken separately, these measures are vulnerable to different sources of bias, and alternative explanations might account for changes in these indicators of negative affect. What is needed is a study that (a) obtains measures of self-reported affect together with facial electromyography, and (b) examines the use of reappraisal to regulate externally and internally generated affective responses. In the present study, participants up- or down-regulated negative affect in the context of both negative and neutral pictures. Up-regulation led to greater self reports of negative affect, as well as greater corrugator and startle responses to both negative and neutral stimuli. Down-regulation led to lesser reports of negative affect, and lesser corrugator responses to negative and neutral stimuli. These results extend prior research by (a) showing simultaneous effects on multiple measures of affect, and (b) demonstrating that cognitive reappraisal may be used both to regulate responses to negative stimuli and to manufacture a negative response to neutral stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin

Pain differs from other sensations in many respects. Primary pain-sensitive neurons respond to a wide variety of noxious stimuli, in contrast to the relatively specific responses characteristic of other sensory systems, and the response is often observed to sensitize on repeated presentation of a painful stimulus, while adaptation is typically observed in other sensory systems. In most cases the cellular mechanisms of transduction and sensitization in response to painful stimuli are not understood. We report here that application of pulses of noxious heat to a subpopulation of isolated primary sensory neurons rapidly activates an inward current. The ion channel activated by heat discriminates poorly among alkali cations. Calcium ions both carry current and partially suppress the current carried by other ions. The current is markedly increased by bradykinin, a potent algogenic nonapeptide that is known to be released in vivo by tissue damage. Phosphatase inhibitors prolong the sensitization caused by bradykinin, and a similar sensitization is caused by activators of protein kinase C. We conclude that bradykinin sensitizes the response to heat by activating protein kinase C.     

Fear conditioning in panic disorder: Enhanced resistance to extinction.

Enhanced conditionability has been proposed as a crucial factor in the etiology and maintenance of panic disorder (PD). To test this assumption, the authors of the current study examined the acquisition and extinction of conditioned responses to aversive stimuli in PD. Thirty-nine PD patients and 33 healthy control participants took part in a differential aversive conditioning experiment. A highly annoying but not painful electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures were used as either the paired conditioned stimulus (CS+) or the unpaired conditioned stimulus (CS-). Results indicate that PD patients do not show larger conditioned responses during acquisition than control participants. However, in contrast to control participants, PD patients exhibited larger skin conductance responses to CS+ stimuli during extinction and maintained a more negative evaluation of them, as indicated by valence ratings obtained several times throughout the experiment. This suggests that PD patients show enhanced conditionability with respect to extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical evaluation of heparin concentration and activated clotting time monitoring (HEPCON HMS) system

The strength of neural response to sensory stimuli is often estimated by measurement of the amplitude of gross neural potentials. These gross potentials reflect the summed activity of a population of neurons. The amplitude of these potentials is dependent upon the synchrony of the contributing neural responses. We compared the variability of the peak-to-peak amplitude of the auditory nerve compound action potential (CAP) with that of the area under the peaks. The area under the peaks was significantly less variable than the amplitude for responses to low frequency stimuli. Responses to other stimuli showed differences in the same direction, but these were not significant. We conclude that the area under these peaks is a more precise measure of neural response than measurement of waveform amplitude at least for responses to low frequency stimuli.     

Newborn mice develop balanced Th1/Th2 primary effector responses in vivo but are biased to Th2 secondary responses

Newborn mice are impaired in their abilities to mount protective immune responses. For decades, it was generally held that the poor responses of newborns were largely due to the developmentally immature state of the T cells. In vitro studies showing that neonatal T cells were deficient in Th1 cytokine production, proliferation, and secondary responsiveness strongly supported this idea. Recently, several studies have challenged this view; animals exposed to Ag as neonates were shown to have mature Th1 responses in adulthood. However, it is not clear whether the mature immune responses were actually mounted by T cells generated after the neonatal stage. We have reexamined this issue by analyzing the capabilities of neonatal lymph node T cells to develop into Ag-specific effector cells during the actual neonatal period. Our results demonstrate that the capacity to develop a balanced Th1/Th2 primary effector response is fully mature within the first week of life. However, while neonatal and adult primary cytokine profiles were very similar, Th2 secondary responses predominated in animals first immunized as newborns. Moreover, we have observed other differences between adults and neonatal responses, including 1) the kinetics of cytokine production and responsiveness to adjuvant during the primary response, and 2) the contribution of spleen and lymph node to secondary responses. We propose that these differences reflect developmental regulation of effector cell function that has important consequences to neonatal immune function.     

Lens induced aniso-accommodation

Despite the evidence for consensual accommodation in response to consensual accommodative stimuli, only a few studies have investigated the binocular accommodative response to unequal (aniso) accommodative stimuli. Past studies investigating an unequal binocular accommodative response (aniso-accommodation) to aniso-accommodative stimuli have been limited by viewing conditions and measurement technique making the results, which were equivocal, difficult to interpret. This investigation addressed these limitations by the following design parameters: (1) monocular dichoptic blur cuese were provided in the binocular stimulus target to provide subjects feedback on their aniso-accommodative response and to alert the investigator of a monocular blur suppression response; (2) a training period was provided; (3) in the subjective method, each eye's stigma was positioned near the dichoptic letter viewed by the other eye. By this method, a true aniso-accommodative response could be differentiated from successive consensual responses; (4) a large range of aniso-accommodative stimuli was used, 0.50-3.0 D, presented in incremental steps of 0.5 D, allowing measurement of an average 0.75 D aniso-accommodative response for the highest (3.0 D) aniso-accommodative stimulus; (5) aniso-accommodation was measured as a function of viewing distance. For four of seven subjects, the gain of the aniso-accommodative response was significantly greater at near than at far viewing distances; (6) aniso-accommodation was confirmed objectively with measures of the response to steady state and step aniso-accommodative stimuli, using a binocular SRI Dual Purkinje Eye Tracker Optometer System. The aniso-accommodative response to step stimuli showed a very long latency period (about 11 s) and a response time of 4.5 s. A potential benefit of aniso-accommodation would be to overcome small amounts of uncorrected anisometropic refractive error. This would preserve fine stereo acuity which is impaired by unequal intraocular image contrast. Aniso-accommodation also may provide an appropriate efferent feedback signal for each eye's unique refractive error which could be used to guide developmental isometropization (attainment of equal refractive error in the two eyes.).     

Aversion techniques in behavior therapy: Some theoretical and metatheoretical considerations.

Notes that certain cues may be singularly appropriate as functional conditional stimuli for certain response systems, raising into question the trend in the aversion conditioning literature away from chemically produced aversion and toward fear produced by painful electric shock. Although this shift from the chemical to the electrical is being made on sound functional grounds, the physiological research on appropriateness of cues suggests that, contrary to prevalent assumptions in behavior therapy, one must consider most carefully the topographical nature of stimuli and responses. At the metatheoretical level, the argument that behavior modification as a field be concerned with areas of psychology outside of learning and conditioning is presented. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Congenital thrombophilia

Previous functional imaging studies have demonstrated a number of discrete brain structures that increase activity with noxious stimulation. Of the commonly identified central structures, only the anterior cingulate cortex shows a consistent response during the experience of pain. The insula and thalamus demonstrate reasonable consistency while all other regions, including the lentiform nucleus, somatosensory cortex and prefrontal cortex, are active in no more than half the current studies. The reason for such discrepancy is likely to be due in part to methodological variability and in part to individual variability. One aspect of the methodology which is likely to contribute is the stimulus intensity. Studies vary considerably regarding the intensity of the noxious and non-noxious stimuli delivered. This is likely to produce varying activation of central structures coding for the intensity, affective and cognitive components of pain. Using twelve healthy volunteers and positron emission tomography (PET), the regional cerebral blood flow (rCBF) responses to four intensities of stimulation were recorded. The stimulation was delivered by a CO2 laser and was described subjectively as either warm (not painful), pain threshold just painful), mildly painful or moderately painful. The following group subtractions were made to examine the changing cerebral responses as the stimulus intensity increased: (1) just painful - warm; (2) mild pain - warm; and (3) moderate pain - warm. In addition, rCBF changes were correlated with the subjective stimulus ratings. The results for comparison '1' indicated activity in the contralateral prefrontal (area 10/46/44), bilateral inferior parietal (area 40) and ipsilateral premotor cortices (area 6), possibly reflecting initial orientation and plans for movement. The latter comparisons and correlation analysis indicated a wide range of active regions including bilateral prefrontal, inferior parietal and premotor cortices and thalamic responses, contralateral hippocampus, insula and primary somatosensory cortex and ipsilateral perigenual cingulate cortex (area 24) and medial frontal cortex (area 32). Decreased rCBF was observed in the amygdala region. These responses were interpreted with respect to their contribution to the multidimensional aspects of pain including fear avoidance, affect, sensation and motivation or motor initiation. It is suggested that future studies examine the precise roles of each particular region during the central processing of pain.     

The pupillary light response: assessment of function mediated by intracranial retinal transplants

We have adapted a pupillometry measurement system to test the functional efficacy of retinae previously transplanted over the midbrain of neonatal rats in mediating a pupillary light reflex in the host eye. This has permitted us to examine factors influencing various parameters of the response, and to study transplant-mediated responses in comparison with responses mediated by way of the normal consensual pathway. Despite the unusual location of these transplanted retinae and the absence of supportive tissues normally associated with retinae in situ, it is clear that pupilloconstriction in the host eye can be elicited by transplant illumination. Under the optimal conditions here defined, response parameters for individual animals were stable with repeated testing over extended periods. When considered as individual cases, response amplitude, constriction rate and response latency were intensity dependent, although responses elicited by transplant illumination were less sensitive than normal, typically by 2-3 log units. Large-amplitude transplant-mediated pupillary responses could, however, be elicited repeatedly throughout long trains of stimuli, unlike normal responses, which rapidly failed to recover to baseline under similar test conditions. Finally, even though some cellular elements of the visual cycle are absent in transplanted retinae, pupilloconstriction in the host eye could be elicited repeatedly by transplant illumination as long as two years after transplantation took place. These observations indicate the applicability of this preparation as an assay for the effects of experimental manipulations on information processing and response plasticity in the visual system, and as a tool for examining, in general, the necessary conditions for optimal function of grafts that work by synthesizing and relaying neural signals.     

Responses of cutaneous A-fiber nociceptors to noxious cold

Responses of cutaneous nociceptors to natural stimuli, particularly mechanical and heat stimuli, have been well documented. Although nociceptors are excited by noxious cold stimuli, there have been few studies of their stimulus-response functions for cold stimuli over a wide range of stimulus temperatures. Furthermore, the proportion of nociceptors excited by noxious cold is not clear. In the present study, we examined responses of mechanosensitive A delta-nociceptors and low-threshold mechanoreceptors to a wide range of cold stimuli that included stimulus temperatures <0 degrees C. Electrophysiological recordings were made from single primary afferent fibers in the saphenous nerves of anesthetized rats. Cutaneous sensory receptors were classed according to their conduction velocity and subgrouped functionally according to their responses evoked by mechanical, heat, and cold stimuli (0 degrees C). Responses evoked by a wide range of cold stimulus intensities that included stimuli considered innocuous and noxious (painful) were then assessed. Stimuli of 20 to -20 degrees C were delivered to the receptive field via a 1-cm2 contact thermode from a base temperature of 32 degrees C. Stimuli were applied in descending order of 2 degrees C decrements. Stimulus ramp rate was 5 degrees C/s, and stimulus temperatures were applied for a duration of 10 s. A total of 90 A fibers was studied, of which 61 were nociceptors and had conduction velocity in the A delta-range (2-30 m/s). Nociceptors were classed initially as mechanical, mechanoheat, and mechanocold nociceptors. The remaining 29 fibers were low-threshold mechanoreceptors with conduction velocity in the A delta- or A beta-range (>30 m/s). These were subgrouped according to their adaptive properties as slowly or rapidly adapting, and according to whether they were excited by hair movement (hair follicle afferent fibers). All nociceptors were excited by noxious cold. Only 30% of nociceptors were considered sensitive to cold on initial classification with the use of a cold stimulus of 0 degrees C. However, all nociceptors were excited by stimulus intensities <0 degreesC. Response thresholds for cold ranged from 14 to -18 degrees C (-4.6 +/- 1.07 degrees C, mean +/- SE). The total number of impulses, discharge rate, and peak discharge increased monotonically as intensity of cold stimuli increased. Power functions were used to determine the rate at which the number of impulses increased as stimulus intensity increased. The slopes of power funcions ranged from 0.12 to 2.28 (mean 1.07 +/- 0.13). Most mechanoreceptors were not excited by cold stimuli. The only types of mechanoreceptors that responded reliably to cold stimuli were the slowly adapting mechanoreceptors. Responses usually occurred during the temperature ramp when the skin temperature was decreasing. There was no evidence that mechanoreceptors encoded the intensity of cold stimuli at intensities above or below 0 degrees C, because evoked responses did not increase with intensity of cold stimuli. It is concluded that the proportion of cutaneous A delta-nociceptors excited by noxious cold stimuli has been underestimated in previous studies. All nociceptors were excited by stimulus temperatures <0 degrees C and encoded the intensity of cold stimuli. It is therefore likely that cutaneous A delta-nociceptors contribute to the sensation of cold pain, particularly pain produced by stimulus temperatures <0 degrees C.     

Kappa-opioids produce significantly greater analgesia in women than in men

Sex differences in human responses to nociceptive stimuli and painful pathological conditions have generally indicated that women report higher pain levels or exhibit less tolerance than men for given stimulus intensities (reviewed in ref. 1 and 2). However, studies have not evaluated sex differences in analgesic responses. We recently reported that the opioid agonist-antagonist pentazocine, which acts predominantly at kappa-receptors, produced significantly better postoperative analgesia in females than in males in patients who underwent surgery for the removal of their third molars (wisdom teeth). In the current study, we evaluated the hypothesis that this sex difference is a characteristic of kappa-opioid agonism. In order to determine whether there are sex differences associated with kappa-opioid agonism, the analgesic efficacy of two other predominantly kappa-opioid analgesics, nalbuphine and butorphanol; was compared in males and females who underwent surgery for the removal of third molar teeth. We found that both nalbuphine and butorphanol produced significantly greater analgesia in females as compared with males. Considering our earlier findings, we conclude that kappa-opioid analgesia is greater in females than in males, probably reflecting a difference in kappa-opioid-activated endogenous pain modulating circuits.     

Relationship between pain sensitivity and resting arterial blood pressure in patients with painful temporomandibular disorders

OBJECTIVE: Patients experiencing temporomandibular disorders (TMD) show greater sensitivity to painful stimuli than age- and gender-matched control subjects. This enhanced pain sensitivity may result, at least in part, from an alteration in pain regulatory systems that are influenced by resting arterial blood pressure. In this study, we examined the relationship between resting systolic blood pressure and pain perception in 64 female TMD and 23 age-matched pain-free female subjects. METHOD: Resting arterial blood pressure and measures of thermal and ischemic pain threshold and tolerance were determined for each participant. Subjective ratings of thermal pain evoked by suprathreshold noxious thermal stimuli (45-49 degrees C) using a magnitude matching procedure were also obtained for both groups. RESULTS: TMD patients had lower thermal and ischemic pain thresholds and tolerances than pain-free subjects (ps < .05). Both groups provided equivalent intensity ratings to suprathreshold noxious thermal stimuli. A median split of each group based on resting systolic blood pressure revealed an influence of blood pressure on both thermal and ischemic pain perception for the Pain-Free group. The Pain-Free high resting blood pressure subgroup had higher thermal pain tolerances, higher ischemic pain thresholds, and provided lower magnitude estimates of the intensity of graded heat pulses compared with the Pain-Free low blood pressure subgroup. A trend toward a significant effect of blood pressure level on ischemic pain tolerance was also observed for the Pain-Free group. In contrast to the Pain-Free group, blood pressure level did not influence ischemic or thermal pain perception for TMD patients. Similar to the lack of effect of resting blood pressure on experimental pain perception in TMD patients, resting blood pressure was not related to measures of clinical orofacial pain in TMD patients. CONCLUSIONS: These findings confirm our previous findings that TMD patients are more sensitive to noxious stimuli and suggest that painful TMD may result, at least in part, from an impairment in central pain regulatory systems that are influenced by resting arterial blood pressure.     

Long-latency responses of brain noradrenergic neurons to noxious stimuli are preferentially attenuated by intravenous morphine

The nucleus locus coeruleus (LC) has been strongly implicated in the processing of noxious stimuli. Consistent with this, previous studies have shown that spontaneous LC discharge is depressed by morphine. However, effects of morphine on evoked responses of LC neurons to noxious stimuli have not been systematically examined. We reported recently that responses to footshock stimuli in rat locus coeruleus neurons consist of an early (A-fiber mediated) component and a previously undescribed late (C-fiber mediated) component. In the present study, we administered analgesic doses of morphine (0.1, 0.5, or 1.0 mg/kg, i.v.) to determine the effect on A- and C-fiber components of footshock responses in LC neurons. Doses of 0.5 and 1.0 mg/kg significantly attenuated the C-fiber mediated response of LC neurons without affecting the A-fiber response component. Spontaneous LC discharge was reduced by administration of all doses of morphine. Both depressive effects of morphine were abolished by intravenous administration of naloxone. In contrast, local microinfusion of naloxone into the LC abolished the morphine-induced decrease of spontaneous discharge but did not prevent the depression of the C-fiber mediated footshock response by morphine. This indicates that the site of action for morphine's attenuation of the late LC response to footshock stimulation is outside of the LC. The results are consistent with the hypothesis that the late (C-fiber-mediated) footshock responses in locus coeruleus are involved in the processing of noxious stimuli and may contribute to anti-nociceptive mechanisms.     

Immature B cells from neonatal mice show a selective inability to up-regulate MHC class II expression in response to antigen receptor ligation

Immature and mature B cells show phenotypic and functional differences. Thus immature B cells are functionally unresponsive to stimuli including ligation of slg and CD38 which induce proliferation in mature B cells. Furthermore, immature B cells have been widely shown to be hypersensitive to tolerance induction. To investigate the reasons for this differential responsiveness we have compared the ability of mature and immature B cells to show receptor-induced tyrosine phosphorylation of cellular substrates, a receptor-proximal response and MHC hyperexpression, which occurs later. Mature and neonatal B cells displayed a similar pattern of slg-induced tyrosine phosphorylation and their responses had similar kinetics. Importantly, cross-linking of slg on immature B cells induced tyrosine phosphorylation of substrates with mol. wt corresponding to the chains of the lg alpha beta dimer, which plays a critical role in B cell signalling. Immunofluorescence analysis showed that immature B cells constitutively express lower levels of MHC class II than their mature counterparts, consistent with previous studies. Here we report for the first time that immature B cells fail to hyperexpress class II after slg ligation, although this response is induced by other stimuli. These observations suggest that the ability to up-regulate class II is developmentally regulated in the B cell lineage. Moreover, the selective failure of slg-induced class II hyperexpression shown by immature B cells may not allow effective T-B cell collaboration and contribute to tolerance induction.