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J L Feldman

Publications and source records attributed to J L Feldman.

107 records · Page 6Linked to original sources

Interactions between brainstem respiratory neurons.

Interactions between brainstem respiratory neurons underlie respiratory rhythmogenesis. Several techniques to study these interactions are discussed. Cross-correlation analysis of the firing patterns of pairs of respiratory neurons revealed a high probability of interaction and/or shared inputs between neurons that are immediate neighbors, and the lack and ubiquitous connections between neurons located in different regions. Neuroanatomical studies demonstrated a previously unobserved brainstem projection to the ventrolateral nucleus of tractus solitarius, an important brainstem respiratory-related structure, from a small cluster of neurons in the contralateral ventrolateral medulla several millimeters rostral to the obex; subsequent recordings have shown these neurons to have expiratory firing patterns. Modeling studies suggested that neurons hypothesized to produce inspiratory phase termination should begin firing late in the inspiratory phase and should be excited by lung inflation. Subsequent extracellular recordings have shown that neurons with these properties constitute a significant fraction of neurons in the region of te ventrolateral nucleus of tractus solitarius. The results of these studies indicate that rhythmogenesis results from highly specific interactions between limited subpopulations of respiratory neurons.

Animals↗

Properties of inspiratory termination by superior laryngeal and vagal stimulation.

Electrical stimulation of two respiratory afferent nerves, the vagus and the internal branch of the superior laryngeal, was used to terminate inspiration. The short latency responses of phrenic motoneurones to these stimuli were studied to determine if inspiratory termination was preceded by a characteristic phrenic motoneurone discharge pattern, reflecting changes in brainstem inspiratory neurone discharge and inspiratory terminating mechanisms. Stimulus trains of sufficient intensity delivered to the superior laryngeal nerve terminated inspiration within 50 ms and were preceded by a stereotyped pattern of phrenic motoneurone discharge. This consisted of a short latency (disynaptic), predominantly contralateral excitation in response to the first shock of the train, followed by a marked and long lasting inhibition. In contrast, vagal stimulation typically terminated inspiration hundreds of milliseconds after the onset of the stimulus train and was not preceded by a stereotyped pattern of phrenic motoneurone responses to single shocks. Transient short latency responses were obtained but were extremely small, requiring considerable excitation followed by a moderate bilateral depression of activity. Inspiration could be terminated with or without the presence of these short latency responses. These results indicate that superior laryngeal and vagal (presumably pulmonary stretch receptor) afferents have different projections to brainstem inspiratory neurones and may exert their effects on inspiratory duration through different, but as yet undefined, neural mechanisms.

Action Potentials↗

Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay.

A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa.

Adult↗

Interaction of pulmonary afferents and pneumotaxic center in control of respiratory pattern in cats.

The interaction between the pulmonary afferents (PA) and the pneumotaxic center (PC) in control of respiratory pattern was studied in lightly anesthetized paralyzed cats before and after bivagotomy or lesions of the PC using inflations controlled by the onset or cessation of phrenic nerve discharge, i.e., cycle-triggered inflations. This interaction was also studied using electrical stimulation of the central stumps of cut vagi. Introduction of a delay between inspiratory onset and the commencement of an inflation at constant flow and duration resulted in increases of the durations of inspiration (T1) and expiration (TE) and amplitude of the integrated phrenic nerve discharge (A). The lung volume at inspiratory cutoff, i.e., the volume threshold, increased markedly as T1 increased. There were linear relationships between T1 and TE and between T1 and A. At constant alveolar CO2 and tidal volume, the quantitative effects of delay were dependent on the rate of inflation; i.e., when the flow increased, the volume threshold for a given T1 decreased. Bilateral vagotomy abolished the effects of delay and flow. PC lesions, which resulted in apneusis when the cycle-triggered inflations were stopped, produced the following changes compared to the delay effects seen in intact cats: a) the volume threshold for zero delay doubled and its rate of decrease with increased T1 was significantly smaller, and b) the change in TE for a given change in T1 was reduced markedly. Introduction of a delay between inspiratory onset and the start of electrical stimulation of the afferent vagi resulted in effects similar to those seen for delays in cycle-triggered inflations. The T1-TE relationship remained linear when the stimulus trains ended with inspiratory cessation. These results suggest that: a) the inspiratory cutoff mechanism is responsive to the rate, as well as the level, of lung inflation; b) all of the lung volume information affecting inspiratory cutoff in paralyzed cats is carried via the vagi; c) an intact PC is necessary for the generation of a normal time dependence of the volume threshold for inspiratory cutoff; d) the PC plays an important role in matching TE to T1 when the latter changes. For inflations and vagal stimulations applied during expiration, with introduction of a delay between inspiratory cessation and the start of cycle-triggered inflation or vagal stimulation, the results indicated that the expiratory cutoff mechanism has an irrevocable phase of 300-450 ms.

Animals↗

Multiple putative neuromessenger inputs to the phrenic nucleus in rat.

Immunohistochemical reactions for 12 putative neuromessengers combined with retrograde labeling of phrenic motoneurons identified seven neuromessengers (5-hydroxytryptamine, substance P, thyrotropin-releasing hormone, methionine enkephalin, cholecystokinin, galanin, neuropeptide Y) located within terminal varicosities in the phrenic nucleus. The degree of terminal labeling in the phrenic nucleus varied depending on the peptide. Substance P, thyrotropin-releasing hormone and methionine enkephalin were each tested for colocalization with 5-hydroxytryptamine within terminal varicosities in the phrenic nucleus, and the coincidence of double-labeling varied for each peptide. These results indicate that phrenic motoneurons are subject to modulation by many peptide neuromessengers that may alter their responsiveness to primary excitatory and inhibitory inputs.

Animals↗

Parvalbumin in respiratory neurons of the ventrolateral medulla of the adult rat.

A column of parvalbumin immunoreactive neurons is closely associated with the location of respiratory neurons in the ventrolateral medulla of the rat. The majority (66%) of bulbospinal neurons in the medullary ventral respiratory column (VRC) that were retrogradely labeled by tracer injections in the phrenic nucleus were also positive for parvalbumin. In contrast, only 18.8% of VRC neurons retrogradely labeled after a tracer injection in the VRC, also expressed parvalbumin. The average cross-sectional area of VRC neurons retrogradely labeled after VRC injections was 193.8 microm2 +/- 6.6 SE. These were significantly smaller than VRC parvalbumin neurons (271.9 microm2 +/- 12.3 SE). Parvalbumin neurons were found in the Bötzinger Complex, the rostral ventral respiratory group (VRG), and the caudal VRG, areas which all contribute to the bulbospinal projection. In contrast, parvalbumin neurons were sparse or absent in the preBötzinger Complex and in the vicinity of the retrotrapezoid nucleus, areas that have few bulbospinal projections. Parvalbumin was rarely colocalized within Neurokinin-1 receptor positive (NK1R) VRC neurons, which are found in the preBötzinger complex and in the anteroventral part of the rostral VRG. Parvalbumin neurons in the Bötzinger Complex and rostral VRG help define the rostrocaudal extent of these regions. The absence of parvalbumin neurons from the intervening preBötzinger complex also helps establish the boundaries of this region. Regional boundaries described in this manner are in good agreement with earlier physiological and anatomical studies. Taken together, the distributions of parvalbumin, NK1R and bulbospinal neurons suggest that the rostral VRG may be subdivided into distinct, anterodorsal, anteroventral, and posterior subdivisions.

Animals↗