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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 1,153 records · Page 64Linked to original sources

Inhibition and excitation of the nociceptive flexion reflex by conditioning stimulation of a peripheral nerve in the cat.

A previous study in our laboratory showed a long-lasting, naloxone-reversible inhibition of the flexion reflex after prolonged repetitive stimulation of a peripheral nerve in the spinal cat. The present study employed a special pattern of conditioning stimulation for a shorter period (200 s) to determine the time course of the inhibition and the afferent fibers responsible for the inhibition. We stimulated the common peroneal nerve in 10 decerebrated and spinalized cats to elicit the flexion reflex, which we recorded as single-unit activity from filaments of the L7 ventral root. The C fiber-evoked late component of the flexion reflex was compared before, during, and after conditioning electrical stimulation applied to the tibial nerve. Stimulating the tibial nerve at an intensity that excited only A alpha beta fibers produced weak inhibition of the flexion reflex; increasing intensity above the threshold for A delta fibers produced much greater inhibition. Inhibition began during the first 10 s of conditioning stimulation and was maximum at about 100 s. Stimulation at a suprathreshold intensity for C fibers, however, produced an initial transient excitation, lasting 10 to 20 s, followed by inhibition. Intravenous injection of naloxone (0.05 mg/kg) produced no observable changes in this inhibition and excitation. These results suggest that conditioning stimulation of a peripheral nerve inhibits the flexion reflex. This inhibition has a short latency; the afferent fibers seem to be A delta fibers. In addition, input from afferent C fibers may trigger a mechanism that produces facilitation of the reflex. The differences in recovery time course and in sensitivity to naloxone suggest that two different mechanisms may be responsible for the fast-onset inhibition and the previously observed long-lasting inhibition produced after prolonged conditioning stimulation.

Animals↗

Spinal entry route for ventral root afferent fibers in the cat.

Twelve anesthetized and paralyzed cats were used to study the spinal entry routes of ventral root afferent fibers. In all animals, the spinal cord was transected at two different levels, L5 and S2. The L5 through S2 dorsal roots were cut bilaterally, making spinal cord segments L5-S2 neurally isolated from the body except for the L5-S2 ventral roots. From this preparation, a powerful excitation of the discharge rate of motor neurons and dorsal horn cells within the isolated spinal segments was observed after intraarterial injection of bradykinin (50 micrograms in 0.5 ml saline). This excitation of the spinal neurons can be considered the most convincing evidence of the potential physiologic role of the ventral root afferent fibers entering the spinal cord directly through the ventral root, because the apparent route of neuronal input from the periphery is through the ventral roots. However, additional control experiments conducted in the present study showed that the excitation persisted even after cutting all ventral roots within the isolated spinal segments, indicating that excitation was not mediated by the ventral roots. Furthermore, direct application of bradykinin on the dorsal surface of the spinal cord also increased the motoneuronal discharge rate, suggesting that excitation of spinal neurons produced by intraarterial injection of bradykinin is due to a direct action of bradykinin on the spinal cord. Thus, we provided an alternate explanation for the most convincing evidence indicating that physiologically important ventral root afferent fibers enter the spinal cord directly through the ventral root. Based on existing experimental evidence, it is likely that the majority of physiologically active ventral root afferent fibers travel distally toward the dorsal root ganglion and then enter the spinal cord through the dorsal root.

Action Potentials↗

Blood pressure response evoked by ventral root afferent fibres in the cat.

Systemic arterial blood pressure changes in response to stimulation of the distal stump of the cut spinal ventral root were investigated in anaesthetized, vagotomized, and carotid sinus-denervated cats. Low intensity electrical stimulation (less than 20 T, where T is threshold intensity) of the ventral root caused a rise in blood pressure. This elevation was abolished by paralysing the muscles with gallamine. This pressor response has been reported previously, and it is likely to be evoked by afferents excited by the contracting muscle. High intensity electrical stimulation (500 T) of the ventral root caused a second and marked pressor response. This was not affected by muscular paralysis or by cutting the sciatic nerve, but it was abolished by cutting the dorsal root. Threshold intensity for the second component of the pressor response was within the same range as the intensity needed for activation of C fibres in the ventral root, ranging between 200 T and 300 T. This response was graded with increasing stimulus intensity, and it showed both spatial and temporal summation. From the above results, we conclude that non-myelinated fibres in feline spinal ventral root course distally to the dorsal root ganglion and then enter the spinal cord via the dorsal root. Activation of these fibres results in a marked elevation of the systemic arterial blood pressure as in other somato-sympathetic reflexes induced by peripheral C fibre activation.

Action Potentials↗

Response characteristics of neurons in the ventral posterior lateral nucleus of the monkey thalamus.

The activity of 132 neurons in the caudal part of the ventral posterior lateral nucleus (VPLc) of the thalamus was recorded from 23 anesthetized monkeys. All single thalamic units that could be excited by electrical search stimuli applied to the contralateral sciatic nerve were investigated. Responses of these cells to mechanical, thermal, and electrical stimuli applied in the periphery indicated that at least half of the sampled cells were nociceptive. Based on responses to graded mechanical stimuli applied to the periphery, 110 of the sampled cells that received a predominant input from cutaneous receptive fields were classified. There were 56 low-threshold, 39 wide dynamic range, and 15 high-threshold cells. The same neurons were also classified into five mechanical types based on a cluster analysis: types 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. The fact that about half the population of cells belonged to either the wide dynamic or the high threshold group (or mechanical types 3-5) suggested that a large population of VPLc neurons respond to mechanical nociceptive stimuli either exclusively or preferentially. Responses of 63 thalamic neurons were tested to noxious heat pulses applied to their cutaneous receptive fields with a contact thermostimulator. Of these, 47 cells were excited, whereas only 16 cells did not respond. The peripheral nerve that innervated the receptive field of each of 82 thalamic neurons was stimulated with graded strengths to activate A fibers only or both A and C fibers. All tested cells responded to peripheral A fiber volleys. In addition, 42 of these cells responded to peripheral C fiber volleys. The C fiber responses could be either short lasting (a few hundreds of milliseconds) or long lasting (up to several seconds). The recording sites of 80 cells were reconstructed. Of these, 78 were in the VPLc nucleus and the remaining two were in the reticular nucleus of the thalamus. No obvious relationship between the response characteristics and the locations of the cells within the VPLc nucleus was found. Sampled thalamic units had a variety of sources of input from the periphery, including both cutaneous and/or deep tissue receptive fields. The majority of the cells, however, had exclusively cutaneous receptive fields. The sizes of the cutaneous receptive fields were often very small, so that nearly half (41%) of the receptive fields of cells sampled occupied an area of skin smaller than half the foot.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

The long-latency component of cerebral evoked potentials in anesthetized cats.

A late component of the cortical evoked potential elicited by somatosensory afferent input was studied in cats anesthetized with alpha-chloralose. Cortical evoked potentials were recorded from the somatosensory-motor cortex during stimulation of the sural nerve with graded intensities. The stimulus intensity was adjusted to activate A alpha beta fibers only, then both A alpha beta and A delta fibers, and both A and C fibers, as judged by afferent volleys monitored from the sural nerve proximal to the stimulating site. In addition to early components reported previously, a very late component was identified at a latency of 400 to 600 msec following stimulation of the sural nerve with intensities above threshold for A delta fibers. A further increase in stimulation intensity to include activation of C fibers did not reveal any more components. This late component was depressed by a systemic intravenous injection of morphine (2 mg/kg), and intravenous naloxone (0.1 mg/kg) reversed the effect of morphine. The late component of the evoked potential could also be recorded from subcortical tissue after decortication of the sensorimotor cortex. From these results, it appears that a very late component of the cortical evoked potential can be recorded from cats anesthetized with alpha-chloralose. The late component is evoked by activation of peripheral A delta fibers. Furthermore, its morphine sensitivity suggests that this component may be elicited by nociceptive afferent fibers. If further investigations prove this, the late component, which is analogous to human long-latency potentials, could be used in an experimental model for pain research.

Animals↗

Actions of opioids on primate spinothalamic tract neurons.

The effects of iontophoretically applied opiates were tested on 24 spinothalamic tract cells in 12 anesthetized monkeys. The drugs used were chosen because of their agonist actions on different classes of opiate receptors (mu, morphine; kappa, dynorphin; delta, methionine enkephalinamide; sigma, N-allylnormetazocine or SKF 10047 and phencyclidine). The actions of the opiate drugs were generally inhibitory, although excitatory or mixed effects were sometimes seen, especially with morphine and dynorphin. Drug effects could change, depending on the position of the iontophoretic electrode array or on the current employed. Naloxone sometimes antagonized the action of the opiate drugs used, but naloxone did not seem to be a drug suited for iontophoretic application. A number of explanations are discussed to explain the variable actions of the opiate drugs.

Animals↗

A cloned T cell line that selectively augments antibody responses of phosphorylcholine-specific B cells bearing the T15 idiotype.

Helper T (Th) cells have shown to be heterogeneous both in their function and in their specificity. Several studies have demonstrated that there exist Th cells which do not appear to be specific for antigen:Ia complexes (not H-2 restricted) but interact with the target B cell via recognition of immunoglobulin idiotypic determinants. In analyzing anti-phosphorylcholine (PC) responses, such idiotype-specific Th cells are characterized by 1) their ability to increase responses to phosphorylcholine by augmenting selectively the activation of T15-idiotype-bearing PC-specific B cells, 2) their ability to bind specifically to T15-bearing immunoglobulin and 3) the dependence of their maturation on circulating T15 idiotype rather than Ia. Our aim is to explore further the relationship between Ia-specific and T15-specific Th cells. These studies describe the first step in comparing specificity and function of idiotype-specific Th cells to other known Th cells by the cloning of a T15-specific Lyl T cell (ThId) with properties consistent with those described for uncloned populations. The cloned ThId cells generated do not activate B cells to secrete antibody but augment anti-PC plaque forming cell (PFC) responses induced by Ia-restricted Th cells. This augmentation is seen only in the T15-bearing PFC responses even though non-T15-bearing B cells are equally accessible, and it is seen only in PC responses and not responses to TNP under identical culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of caffeine on mitomycin C induced mutagenesis.

Caffeine significantly repressed MMC induced reversion of Salmonella typhimurium strain TA92 from his- to his+. The addition of MMC (0.5 micrograms/ml) to broth cultures resulted in a slightly decreased growth rate, as measured turbidimetrically, along with a linear decline in CFU of 1 log cycle in 7 h. The addition of caffeine (0.33 mg/ml) plus MMC (0.5 micrograms/ml) resulted in cessation of growth and a decrease in culture turbidity after two generations of growth which was accompanied by a linear decline in CFU of four log cycles in 7 h. The repression of MMC induced mutagenesis by caffeine is therefore most probably due to interference with an error-prone repair process which results in the destruction of cells with damaged DNA.

Caffeine↗

Flexion reflex elicited by ventral root afferents in the cat.

To investigate the physiological role of ventral root afferent fibers, the ventral root was stimulated in spinal cats in an attempt to elicit the flexion reflex, a common nociceptive spinal reflex. The flexion reflex was elicited by stimulating the distal stump of the cut L7 or S1 ventral root and recorded from the proximal stump of the cut S1 ventral root. In 12 of the 14 cats studied, the flexion reflex was recorded as a compound action potential. The finding was confirmed by recording single-unit activity from 5 units in two cats. These results suggest that the ventral root afferent fibers exert a variety of physiological effects that include eliciting such spinal reflexes as the flexion reflex. The responsible fibers in the ventral root travel distally towards the dorsal root ganglion to enter the spinal cord through the dorsal root.

Action Potentials↗

Electrophysiological evidence for the presence of fibers in continuity between dorsal and ventral roots in the cat.

Action potentials were recorded from the L7 or S1 dorsal root of the cat following stimulation of the peripheral end of the cut ventral root of the same segment. Conversely, action potentials were also recorded from the ventral root while stimulating the peripheral end of the cut dorsal root. Based on the conduction velocities of 52 single fibers, one-third were A delta-fibers and the remaining two-thirds belonged to the C-fiber category. These results suggest that there are both A- and C-fibers in continuity between the dorsal and the ventral root.

Animals↗

Distinct functional phenotypes of cloned Ia-restricted helper T cells.

Analysis of activation of phosphorylcholine (PC)-specific B cells by a large number of different cloned, self Ia-specific helper T cell (Th) clones has permitted the classification of such T cells into four distinct functional types. Types 1 and 2 induce B cells to secrete anti-PC antibody in an antigen-specific, Ia-restricted fashion. Type 3 cells induce antigen-specific, Ia-restricted B cell proliferation, but do not lead to specific antibody formation, and have been shown previously to have suppressor functions. Type 4 cells are autoreactive, and induce antigen-independent B cell activation and antibody secretion. The distinction between type 1 and type 2 Th clones was analyzed in detail. In bulk cultures, type 1 cloned lines generate an idiotypically heterogeneous anti-PC antibody response, whereas type 2 cloned lines induce a larger response that is dominated by the T15 idiotype. In limiting-dilution analyses, type 2 cells induce fourfold more T15+, PC-specific precursor B cells than do type 1 cells, and in addition, induce larger burst sizes for T15+, PC-specific B cells. Type 4 clones can also be subdivided into cells that are type 1-like, and cells that are type 2-like. These differences in functional phenotype are seen over a broad range of antigen and cell doses. Detailed analysis of the behavior of these distinct functional types of Th should allow a better understanding of the functional properties of mixed populations of antigen-primed, Ia-restricted Th cells.

Animals↗

Rapid, high-yield purification of cell surface membrane using colloidal magnetite coated with polyvinylamine: sedimentation versus magnetic isolation.

A new technique for the magnetic isolation of external plasma membrane from Dictyostelium discoideum is described and compared to a previously published procedure employing sedimentation of silica-coated plasma membrane. The magnetic isolation technique involves coating intact cells with a polyvinylamine-magnetite colloid and overcoating with polyacrylate to form a dense pellicle. The magnetite pellicle totally coated the cells and was not internalized. Coated cells were lysed and membrane fragments retrieved from the cell homogenate using a diverging field electromagnet. The membrane obtained in such a manner was analyzed for marker enzyme activity and cell surface label. The plasma membrane was obtained in high yield (42%) with an average purification of 8-fold. The polyvinylamine-magnetite pellicle shielded the external plasma membrane face to proteolysis by papain and pronase. It also acted as a barrier to alpha-methylmannoside in concanavalin A-carbohydrate competition studies.

Binding Sites↗

Use of cost prediction simulation models for CON affordability review.

The relationship between capital costs and operating costs is being viewed as one of the driving forces behind the rampant inflation in health care costs. A cost prediction simulation model has been developed that can set affordability criteria readily implemented by CON review agencies.

Capital Expenditures↗

Effect of lectins on the activity of brush border membrane-bound enzymes of rat small intestine.

Highly purified microvillus membrane vesicles isolated from rat small intestine were enriched in sucrase, maltase, and aminopeptidase activities. Approximately 90-95% of each enzyme was released from the membrane fraction by treatment with detergent (Triton X-100) and sonication. Using untreated and solubilized preparations, the effect of lectin binding on the activity of each of the three enzymes was measured. It was observed that wheat germ agglutinin (WGA) and phytohemagglutinin (PHA) dramatically enhanced the activity of membrane-bound maltase but had much less effect on the detergent solubilized enzyme. Under the same conditions aminopeptidase activity was inhibited by WGA and PHA while sucrase activity was not affected. These alterations in enzyme activity occurred at lectin concentrations that also precipitated each solubilized enzyme from solution. Inhibitory sugars prevented the alterations in enzyme activity suggesting that the effect is due to the binding of lectin to specific carbohydrate structures. Enhancement of membrane-bound maltase activity by WGA and PHA was shown to be temperature dependent indicating that the lipid environment of the microvillus membrane may play a role in mediating the lectin effect. A kinetic analysis of the changes in maltase activity induced by these two lectins was due solely to an increase in Vmax. Two other lectins used in this study (concanavalin A and Ricinus communis agglutinin) did not readily precipitate the enzymes in question or alter their activity. These results show that binding of lectins to brush border membranes can induce variable changes in the activity of several membrane associated hydrolases, and suggest that similar changes may occur in vivo in the presence of dietary lectin.

Aminopeptidases↗