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PubMed1985

Peripheral influences on the central pattern-rhythm generator for tongue movements in the rat.

Rhythmic activity in the tongue and other oral muscles was evoked by mechanical stimulation of the hard palate in ketamine-anaesthetized rats. The relation between neural discharges of single hypoglossal motoneurones and activity in the masseter and anterior digastric muscle, and stimulus parameters was analysed. By varying the stimulus parameters, hypoglossal-motoneurone activity was modulated from phasic reflex activity into rhythmic activity. The tongue and other recorded muscles are likely to be controlled by the same pattern-rhythm generator, when rhythmic activity is induced by palatal stimulation. Exteroceptive oral stimuli can activate the tongue pattern-rhythm generator independently of proprioceptive feedback. Proprioceptive input from oral structures influenced the burst duration of rhythmic hypoglossal motoneurone activity. The cycle duration and the number of discharges/burst, however, was not affected by proprioceptive input. The hypoglossal-motoneurone pool may be influenced by more than one pattern-rhythm generator because the burst characteristics of rhythmically-firing hypoglossal motoneurones depend upon stimulus conditions. These hypoglossal pattern-rhythm generators have possible hierarchic relations because a shift from one burst pattern into another can be evoked by changing stimulus conditions. The pattern-rhythm generators for oral movements may be composed of a neural-pattern generator and a neural-rhythm generator, which can be modulated separately by peripheral inputs.

Action Potentials↗

PubMed2003

Effect of interstimulus interval on attentional modulation of cortical activities in human somatosensory areas.

OBJECTIVE: To investigate the effect of interstimulus interval (ISI) on attentional enhancement of cortical activity in human somatosensory cortices. METHODS: Somatosensory magnetic fields (SEFs) evoked by electrical stimulation of the right median nerve at ISIs of 0.5, 1, 3 and 5 s were recorded in two separate conditions by using whole head type magnetoencephalography. In the attend-condition: subjects directed attention to the stimuli by watching the stimulated body site and mentally counting the stimuli. In the ignore-condition: subjects ignored the stimuli by reading a book. RESULTS: Attention to the tactile stimulation amplified SEFs in contralateral secondary (SIT) at ISIs of 1, 3 and 5 s and in ipsilateral SII at ISI of 5 s. There was no effect of attention on the SEF in primary. The ratios of the equivalent current dipole moments calculated for the attend-condition compared to ignore-condition were 1.49 +/- 0.14 at ISI of 1 s, 1.47 +/- 0.29 at 3 s and 1.34 +/- 0.23 at 5 s in the contralateral SII and 1.40 +/- 0.24 at 5 s in the ipsilateral SII. CONCLUSIONS: Time longer than 0.5 s might be required for active attention genesis and, after it was generated, the cortical activation in the attend condition was proportional to the activity in the ignore condition.

Adult↗

PubMed1975

Habituation of mechanoreceptive interneurons in the crayfish.

The effect of repetition of sensory stimuli was studied on the responses of mechanoreceptive interneurons in the optic tract of the crayfish (Procambarus bouvieri (Ortmann)). The number of spikes recorded from a given unit gradually decreased during a train of stimuli. The decrease showed a negative exponential time course, with a curvature dependent upon the frequency of stimulation, the intensity of stimuli, and the hour of the day. Habituation is selective for the intensity and rate of stimulation, and the particular spot of receptive field stimulated. Locomotor excitation results in a dimminution of the rate of decay. The effect of a single train of stimuli when leading to pronounced habituation may persist for periods longer than 24 hr.

Animals↗

PubMed1999

Are there long-term changes in the basal or evoked Fos expression in the dorsal horn of the spinal cord of the mononeuropathic rat?

The long-term changes in Fos like-immunoreactivity (Fos-LI) in the dorsal horn of the spinal cord following various peripheral nerve lesions remain controversial. This study considers such an approach with chronic constriction injury rats (CCI: loose ligations of the sciatic nerve), at 2 weeks after the surgery, when changes in spontaneous and evoked behaviour were clearly described. All rats used for Fos studies displayed allodynia to mechanical stimulation (decrease of 32% of the vocalization threshold to paw pressure). In CCI rats, which displayed 'spontaneous pain-related behaviour', the number of Fos-LI neurones, in the absence of any intentional stimulation, was very low and comparable with that observed in normal and sham-operated rats (<10 neurones/40 microm section). Thus, in this model, the expression of Fos protein is not a reliable index of spontaneous pain. Surprisingly, despite the fact that in this model numerous anatomical studies described a dramatic loss of large and unmyelinated primary afferent fibers, we were unable to detect changes in the number and distribution of Fos-LI evoked by various modalities of peripheral noxious stimulation (noxious thermal stimuli, noxious mechanical stimuli and carrageenin induced inflammation). For example, the stimulus-response curves for the number of Fos-LI neurones evoked by a series of heat stimuli (40, 45, 48, 52, 55 degrees C) were almost superimposable for CCI, sham-operated and normal rats. In contrast, stroking of the nerve-injured paw induced a significant expression of Fos-LI in the superficial laminae (I-II) of the dorsal horn of CCI rats (19.5 +/- 3/sections, P = 0.027) which was greater than that observed in sham-operated (6.5 +/- 3/sections) or in normal rats (3.5 +/- 2/section). These modifications may reflect mechanical allodynia observed in behavioural studies and could be related to A beta fibers, which are known to be severely affected after the constriction of the nerve. These results suggest that this approach could be useful to study, at the cellular level, in freely moving rats, some pharmacological aspects of neuropathic pain.

Animals↗

PubMed1998

Physiological modulation of jejunal sensitivity in health and in irritable bowel syndrome.

OBJECTIVES: In irritable bowel syndrome (IBS), enhanced sensitivity to distention of the small bowel has been demonstrated. We sought to compare, in healthy subjects and in IBS patients, the effects on jejunal sensitivity and compliance of feeding, nonperceived rectal mechanoreceptor stimulation, and the above two stimuli in combination. METHODS: Eleven female IBS patients (49 +/- 13 yr)--six with predominant constipation (IBS-C), and five with predominant diarrhea (IBS-D)--and seven healthy female controls (39 +/- 13 yr) participated. Jejunal distention was applied during fasting, 30 min after a 400-kcal meal, and also during simultaneous nonperceived rectal stimulation. RESULTS: Jejunal sensitivity was increased after feeding in IBS patients (p = 0.004), specifically in IBS-C patients (p = 0.0001) and in controls (p = 0.02), and was reduced during rectal stimulation in IBS patients (p = 0.0001)--both in IBS-D (p = 0.0001) and in IBS-C (p = 0.03) patients--but not significantly so in controls (p = 0.06). Jejunal sensitivity remained unaltered in both IBS patients and controls during concurrent feeding and rectal stimulation. CONCLUSIONS: Physiological stimuli in different parts of the gut modify the intensity of jejunal perception, and the interaction of such stimuli further modifies enteric sensitivity. Nonperceived rectal stimulation appears to modify the intensity of jejunal perception to a greater extent in IBS than in health.

Adult↗

PubMed1993

Real-time imaging of neurons retrogradely and anterogradely labelled with calcium-sensitive dyes.

Membrane-impermeant calcium indicator dyes were used to retrogradely label dorsal root ganglia, spinal motoneurons and interneurons in the spinal cord of the chick embryo. The dyes were also used to label anterogradely primary afferent axons in the spinal cord and synaptic endings in the ciliary ganglion. Labelled neurons were imaged using digital videomicroscopy. Motoneurons and dorsal root ganglion cells exhibited a frequency-dependent change in fluorescence during antidromic stimulation. Single antidromic stimuli resulted in fluorescence transients that could be resolved in individual cells in real time. In addition, fluorescence changes could be recorded in motoneurons during episodes of bursting generated by rhythmic synaptic inputs from premotor networks. Stimulus-induced fluorescence signals were also detected in axons and synaptic endings labelled anterogradely. Optical signals were largely abolished in the absence of extracellular calcium. The results show that calcium changes can now be measured in identified populations of neurons and presynaptic terminals. The strong dependence of these signals on impulse activity suggests that the technique will be useful for monitoring the activity of identified neuronal populations. The calcium-dependent fluorescence signal probably results from cytosolic dye derived from diffusion which may limit the technique to situations in which the dye can be applied close (< 1 cm) to cell bodies.

Animals↗

PubMed2006

Preservation of functional architecture in visual cortex of cats with experimentally induced hydrocephalus.

We investigated how neural function is preserved or matured in the visual cortex of cats, following the induction of hydrocephalus by kaolin injection. In vivo optical imaging of intrinsic signals in 11-17-week-old hydrocephalic cats revealed orientation maps showing the orderly arrangement of preferred orientations when stimulated by grating stimuli at a low spatial frequency, whereas stimulus-evoked intrinsic signals in response to gratings at a high spatial frequency were often too weak to construct orientation maps. Furthermore, in two of the three hydrocephalic cats, initially deteriorated orientation maps became almost regular maps in the second imaging experiments conducted 8 and 11 weeks, respectively, after the first imaging. This indicates that, despite large structural deformation of the hydrocephalic brain, orientation maps are elaborated sufficiently after the age of 5-6 months, by which time the orientation map formation is usually completed in normal cats. Single unit recording from the decompressed visual cortex revealed that many neurons showed normal orientation selectivity, whereas the binocularity of these neurons was found to be reduced. These results suggested that the deformed visual cortex of hydrocephalic cats exhibits a high plasticity, retaining its functional organization.

Action Potentials↗

PubMed2001

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia.

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.

Acoustic Stimulation↗

PubMed2006

Transcranial magnetic stimulation. A case report and review of the literature.

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. CASE REPORT: A 2-years-old male infant was referred to our department with a history of Epstein-Barr virus (EBV) encephalitis, treated with foscarnet and steroids, for he developed mutism and ataxia and loss of the ability to eat, walk and talk. Brain imaging revealed loss of white matter around ventricles and progressive global brain atrophy, findings consistent with encephalopathy. Serology for antibodies against EBV infection was positive and the diagnosis of acute and prolonged EBV infection was made. There was an improvement of the clinical findings after the application of TMS with proper field characteristics (intensity: 1-7.5 pT, frequency: 8-13 Hz). CONCLUSIONS: Our case illustrates the possibility of therapeutic applications of TMS (in the order of pT) with proper field characteristics to normalize pathologically decreased levels of brain cortex activity. TMS might provide novel insights into the pathophysiology of the neural circuitry, be developed into clinically useful diagnostic and prognostic tests, and have therapeutic uses in various diseases.

Atrophy↗

PubMed2000

Differential temporal coding of the vibratory sense in the hand and foot in man.

OBJECTIVE: We studied the difference in the temporal tuning function of the vibratory senses between the hand and foot in man by using steady-state somatosensory evoked potentials (S-SEPs) to vibratory stimulation. METHODS: Vibratory stimuli were applied to the palm and sole, and the S-SEPs were then recorded in 8 normal subjects. A total of 200 responses were recorded from 4 electrodes including the ipsi-and contralateral somatosensory areas of the hand and foot. The amplitude of the first harmonic component (1F) was obtained by a Fourier analysis. The effect of modulation frequency (17-30 Hz) on the 1F at a stimulus intensity of 0.05 N was studied. RESULTS: The amplitudes of the S-SEPs were the greatest in the contralateral hand and foot areas. The mean 1F amplitudes of the palm S-SEPs as a function of the modulation frequency showed a narrow tuning curve with a peak near 21 Hz while those of the sole demonstrated a broad tuning curve. CONCLUSION: Our results suggest the differential temporal coding of the vibratory sense in the hand and foot areas of the somatosensory cortex in man. This is probably caused by the different characteristics in the receptors situated in the hand and foot.

Adolescent↗

PubMed2000

Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol.

In this study, we have investigated the developmental range over which different stimulus protocols induce long-term depression (LTD). Low-frequency stimulation (LFS; 900 stimuli, 1 Hz) produced LTD in hippocampal slices from rats younger than approximately 40 days old, but not in animals aged between approximately 40 days and 16 weeks. We demonstrate, however, that different stimulus protocols can result in LTD in the adult hippocampus. Whilst one paired-pulse low-frequency stimulus protocol [PP-LFS; 50 ms paired-pulse interval (PPI), 900 pairs of stimuli] produced N-methyl-D-aspartate (NMDA) receptor-independent LTD, another PP-LFS protocol (200 ms PPI; 900 pairs) produced NMDA receptor-dependent LTD. Furthermore, the saturation of NMDA receptor-dependent LTD did not prevent the induction of further NMDA receptor-independent LTD. This lack of occlusion suggests that different mechanisms of expression may underlie each of the above forms of LTD in the adult hippocampus. In contrast to the adult hippocampus, NMDA receptor-dependent LTD was induced by both LFS and PP-LFS (50 ms PPI) in slices from young animals (12-20 days). Although they share a common induction mechanism, LTD induced by PP-LFS may be expressed through other mechanisms in addition to those underlying LFS-induced LTD in the young hippocampus. In conclusion, the results in this study demonstrate that mechanisms of long-term synaptic depression within the hippocampus can alter radically with development of the central nervous system and with the use of different induction protocols.

2-Amino-5-phosphonovalerate↗

PubMed1990

Frequency and space representation in the inferior colliculus of the FM bat, Eptesicus fuscus.

The tonotopic organization and spatial sensitivity of 217 inferior collicular (IC) neurons of Eptesicus fuscus were studied under free field stimulation conditions. Acoustic stimuli were delivered from a loudspeaker placed 21 cm ahead of the bat to determine the best frequency (BF) and minimum threshold (MT) of isolated IC neurons. A BF stimulus was then delivered as the loudspeaker was moved horizontally across the frontal auditory space of the bat to locate the best azimuthal angle (BAZ) at which the neuron had its lowest MT. The stimulus was then raised 3 dB above the lowest MT to determine the horizontal extent of the auditory space within which a sound could elicit responses from the neurons. This was done by moving the loudspeaker laterally at every 5 degrees or 10 degrees until the neuron failed to respond. These measurements also allowed us to redetermine the BAZ at which the neuron fired maximal number of impulses. Electrodes were placed evenly across the whole IC surface and IC neurons were sampled as many as possible within each electrode penetration. Tonotopic organization and spatial sensitivity were examined among all 217 IC neurons as a whole as well as among IC neurons sequentially sampled within individual electrode penetrations. The whole population of 217 IC neurons is organized tonotopically along the dorsoventral axis of the IC. Thus, low frequency neurons are mostly located dorsally and high frequency neurons ventrally with median frequency neurons intervening in between. The BAZ of these 217 IC neurons tend to shift from lateral to medial portions of the contralateral frontal auditory space with increasing BF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1991

Motor potentials evoked in tibialis anterior by single and paired cervical stimuli in man.

Latencies of compound muscle action potentials evoked in lower limb muscles after transcranial stimulation shorten and amplitudes enlarge when the target muscle is contracted. After transcutaneous stimulation of the cervical cord with single electrical stimuli, the latency is not affected by muscle contraction. This is thought to be due to a lack of temporal summation at the spinal motoneurones. Results are different when paired stimuli are used. With contraction most motoneurones respond to the first cervical stimulus while in a relaxed condition they respond to the second. Temporal summation brings motoneurones to their firing threshold. Therefore, cervical double stimulation is more effective than single stimuli. It is however less powerful than cortical stimulation. Paired stimuli are most powerful at an interval of 2 ms similar to the D I-wave interval after cortical stimulation.

Action Potentials↗

PubMed2001

An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat.

1. We have investigated the prediction of a relationship between the magnitude of activity-dependent increases in postsynaptic calcium and both the magnitude and direction of synaptic plastic change in the central nervous system. 2. Activity-dependent increases in calcium were buffered to differing degrees using a range of concentrations of EGTA and the effects on synaptic plasticity were assessed. Activity-dependent synaptic plasticity was induced during whole-cell recording in rat perirhinal cortex in vitro. In control conditions (0.5 mM EGTA) low frequency stimulation (LFS; 200 stimuli) delivered to neurones held at -40 or -70 mV induced long-term depression (LTD) or, at -10 mV, induced long-term potentiation (LTP). 3. The relationship between EGTA concentration (0.2 to 10 mM) and the magnitude of LTD was examined. This relationship described a U-shaped curve, as predicted by models of synaptic plasticity. This provides strong evidence that the magnitude of LTD is determined by the magnitude of the increase in intracellular calcium concentration. 4. LFS paired with depolarisation to -10 mV induced LTD, no change or LTP as activity-dependent postsynaptic calcium levels were allowed to increase progressively by the use of progressively lower concentrations of buffer (10 to 0.2 mM EGTA). 5. We investigated if the lack of plasticity that occurs at the transition between LTD and LTP is due to induction of both of these processes with zero net change, or is due to neither LTD nor LTP being induced. These experiments were possible as LTP but not LTD was blocked by the protein kinase inhibitor staurosporine while LTD but not LTP was blocked by the mGlu receptor antagonist MCPG. At the transition between LTD and LTP, blocking LTP mechanisms did not uncover LTD whilst blocking LTD mechanisms did not uncover LTP. This suggests that the transition between LTD and LTP is due to the lack of induction of both of these processes and also suggests that these two processes are induced independently of one another.

Animals↗

PubMed1990

Interactions between Ca2+ and cAMP messenger system in regulation of airway smooth muscle contraction.

Cholinergic stimuli acting via muscarinic receptors stimulate airway smooth muscle to contract and beta-adrenergic stimuli induce it to relax. Cholinergic agonists stimulate intracellular Ca2+ release and Ca2+ influx, and beta-adrenergic agonists stimulate adenosine 3',5'-cyclic monophosphate (cAMP) production. Since it was found that cAMP alters cholinergic agonist-induced changes in cellular Ca2+ metabolism, it was postulated that cAMP brought about a relaxation of this smooth muscle primarily by altering Ca2+ metabolism. More recently, it has become clear that when cholinergic agonists, as well as histamine and serotonin, act, the hydrolysis of polyphosphoinositols is stimulated, diacylglycerol production is increased, and coordinated changes in Ca2+ metabolism and protein kinase function occur. These agonists also act to inhibit adenylate cyclase activity. Conversely, it has been found that in the absence of agonist activation, cAMP increases Ca2+ influx without stimulating contraction and that in the presence of muscarinic agonists, it acts to inhibit polyphosphoinositide hydrolysis. In addition, cAMP has been shown to alter the state of phosphorylation of a number of cellular proteins, an effect that is independent of any effect on cellular Ca2+ metabolism. Based on these newer data, an expanded model of Ca2(+)-cAMP interactions in the regulation of airway smooth muscle tone is presented. A key feature of this model is the operation of dual, reciprocal inhibitory signals by which the Ca2+ and cAMP messenger systems modulate each other's expression.

Animals↗

PubMed2002

Potential role of medullary raphe-spinal neurons in cutaneous vasoconstriction: an in vivo electrophysiological study.

In rabbits, raphe magnus/pallidus neurons form a link in the CNS pathway regulating changes in cutaneous blood flow elicited by nociceptive stimulation and activation of the central nucleus of the amygdala. To characterize relevant raphe-spinal neurons, we performed extracellular recordings from the rostral medullary raphe nuclei in anesthetized, paralyzed, mechanically ventilated rabbits. All studied neurons were antidromically activated from the dorsolateral funiculus of the spinal cord (C(8)-T(2)). Of 129 studied neurons, 40% were silent. The remaining neurons discharged spontaneously at 0.3-29 Hz. Nociceptive stimulation (lip squeeze with pliers) excited 63 (49%), inhibited 9 (7%), and did not affect 57 (44%) neurons. The same stimulation also elicited falls in ear pinna blood flow. In neurons activated by the stimulation, the increase in discharge preceded the fall in flow. Electrical stimulation of the spinal trigeminal tract excited 61/63 nociception-activated neurons [onset latencies range: 6-75 ms, mean: 28 +/- 3 (SE) ms], inhibited 9/9 nociception-inhibited neurons (onset latencies range: 9-85 ms, mean: 32 +/- 10 ms), and failed to affect 55/57 neurons insensitive to nociceptive stimulation. Neurons insensitive to nociceptive/trigeminal stimulation were also insensitive to nonnociceptive tactile stimulation and to electrical stimulation of the amygdala. They were either silent (32/45) or discharged regularly at low frequencies. They possessed long-duration action potentials (1.26 +/- 0.08 ms) and slow-conducting axons (6.0 +/- 0.5 m/s). These neurons may be serotonergic raphe-spinal cells. They do not appear to be involved in nociceptive-related cutaneous vascular control. Of the 63 neurons sensitive to nociceptive and trigeminal tract stimulation, 35 also responded to tactile stimulation (wide receptive field). These neurons possessed short action potentials (0.80 +/- 0.03 ms) and fast-conducting axons (30.3 +/- 3.1 m/s). In this subpopulation, electrical stimulation of the amygdala activated nearly all neurons tested (10/12), with a mean onset latency of 34 +/- 3 ms. The remaining 28 neurons sensitive to nociceptive and trigeminal stimulation did not respond to tactile stimuli and were mainly unaffected by amygdala stimulation. It may be that fast-conducting raphe-spinal neurons, with wide multimodal receptive fields and with input from the central nucleus of the amygdala, constitute the bulbo-spinal link in the CNS pathway regulating cutaneous blood flow in response to nociceptive and alerting stimuli.

Amygdala↗

PubMed1988

Temperature-dependent interaction between vasoconstrictor and vasodilator mechanisms in human skin.

The putative influence of the thermoregulatory state on skin blood-flow responses to various stimuli was studied in 17 healthy subjects exposed to different ambient temperatures. Skin blood flow was monitored by laser Doppler flowmeters and photoelectrical pulse plethysmographs. Stimuli included painful intraneural electrical stimulation (INS) in the median nerve at the wrist, mental stress, arousal stimuli and deep breaths. Intraneural electrical stimulation and mental stress were accompanied by virtually identical changes in skin blood flow, warm subjects responding with cutaneous vasoconstriction whereas cold subjects responded with vasodilatation. Similar but less pronounced responses were obtained with arousal stimuli and single deep breaths. The data indicate that the thermoregulatory state profoundly influences the extent and direction of various cutaneous vasomotor reflex responses. Furthermore, there were differences between responses in hands and feet, suggesting a spatial organization of vasomotor control.

Adolescent↗

PubMed1982

Immunological characterization of non-Hodgkin's lymphoma: enrichment of neoplastic cells from lymphoid tissues and blood.

Cell suspensions prepared from lymph nodes, spleen or peripheral blood of patients with non-Hodgkin's lymphoma (NHL) often contain a high percentage of residual nonmalignant cellular elements. By E-rosette sedimentation, it was possible to enrich such suspensions from patients with various types of lymphoma for malignant cells. In patients with a B- or non-B/non-T-cell lymphoma, the neoplastic cells were found in the non-T fraction. The capacity to respond to stimulation by various stimuli was then confined to the T-cell fraction, which contained the residual normal T-cells. In patients with T-cell lymphomas, in which the malignant cells had retained the capacity to form E-rosettes, lymphoma cells were found in the T fraction. These cells usually did not respond to mitogenic stimuli. Using this separation method, small proportions of neoplastic cells could be identified in mixed cell populations. Thus, in the blood from nine out of 23 lymphoma patients without abnormalities in routine blood tests, a population of abnormal cells was detected after cell separation. This included a monoclonal B-cell population in the blood of four patients, a questionably monoclonal B-cell population in the blood of two patients and in increased non-B/non-T cell population in the blood of three patients.

B-Lymphocytes↗