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J A Kemp

Publications and source records attributed to J A Kemp.

At least 127 records · Page 7Linked to original sources

Lithium ions increase action potential duration of mammalian neurons.

During Lucifer Yellow staining of mammalian neurons, intracellular recording revealed a prolongation of the action potential that is probably the result of leakage of lithium ions into the intracellular fluid. In experiments on dorsal root ganglion neurons intracellular iontophoresis of lithium ions also broadened the action potential. Cadmium, a calcium channel blocker, shortens the lithium-evoked wide actions potentials. The present experiments do not reveal whether lithium directly enhances inward calcium current, or whether a block of outward rectification allows calcium currents to increase the action potential duration.

Action Potentials↗

Cholinergic modulation of the functional organization of the cat visual cortex.

The cortex receives a cholinergic input which is considered to be involved in mediating the effects of arousal. The experiments reported here have examined the nature of the cholinergic influence on the neuronal organization of the cat visual cortex. Out of 83 cells studied, 92% exhibited a modification in their visual response properties during the iontophoretic application of ACh. These comprised 61% in which responses were facilitated and 31% in which responses were depressed. The facilitatory effects were associated with a striking increase in stimulus specific responses without any concomitant loss in the selectivity. This comment applied equally to orientation and direction selectivity. It is argued that the facilitatory action of ACh on stimulus specific responses is consistent with a modulation of potassium conductance and most probably the conductance associated with a voltage dependent channel. We found no evidence to support the view that the facilitatory action involved disinhibition; the action of bicuculline, which blocks inhibitory influences in the visual cortex, was quite distinct to that of ACh. The facilitatory and depressive effects of ACh did not show any correlation with the simple-complex classification of cells or any other obvious parameter of receptive field organization, but there was a correlation with cortical lamination. Cells facilitated by ACh were found in all cortical laminae, but those depressed by ACh were found in laminae III and IV.

Acetylcholine↗

The distribution of putative neurotransmitters in the lateral geniculate nucleus of the rat.

Immunocytochemical techniques were used to examine the distribution of several putative peptidergic and aminergic neurotransmitters within the various subdivisions of the rat lateral geniculate nucleus (LG). Neuronal cell bodies, immunoreactive for enkephalin and neuropeptide Y and neuronal fibers immunoreactive for enkephalin, neuropeptide Y, substance P, vasoactive intestinal polypeptide and 5-HT were each localized within distinct subdivisions of the LG. These results suggest that the anatomical and functional differences of LG neurons are also reflected by differences in the transmitters which they utilize.

Animals↗

The cholinergic influence on the function of the cat dorsal lateral geniculate nucleus (dLGN).

The functional influence of the cholinergic input to cat dLGN has been examined by assessing the action of iontophoretically applied acetylcholine (ACh) on the visual responses of cells in layers A and A1. Iontophoretically applied pulses of ACh exerted a strong excitatory action on all 113 cells studied within these layers. In the presence of a sustained application of ACh, the excitatory responses to an optimal stimulus such as a spot of light located within the receptive field centre were greatly facilitated, but at the same time stimulus-specific inhibitory influences were also enhanced. The action of ACh on the stimulus-specific inhibitory influences had the consequence that the responses to non-optimal stimuli were not facilitated to the same extent as those to optimal stimuli and in some cases even diminished. The stimulus-specific inhibitory effects seen in the presence of ACh were very powerful and frequently resulted in complete suppression of the elevated background discharge. We suggest that the ACh directly excites both the relay cells and the Golgi type II inhibitory interneurones within the dLGN. The facilitation of the stimulus-specific inhibition may follow from a direct action on the presynaptic dendrites of the Golgi type II cells which arborize within the dendritic field of the relay cell. Supplementary observations on cells in the perigeniculate nucleus confirm previous findings showing that ACh has an inhibitory effect on these cells. We suggest a tripartite action for the cholinergic influence on the dLGN, involving direct facilitation of relay cells, enhancement of stimulus-specific inhibition via the Golgi type II cells, and disinhibition of the non-specific inhibitory influence form the perigeniculate nucleus.

Acetylcholine↗

The influence of GABAergic inhibitory processes on the receptive field structure of X and Y cells in cat dorsal lateral geniculate nucleus (dLGN).

Visually elicited inhibitory processes, underlying the receptive field structure of cells in layers A and A1 of the cat dorsal lateral geniculate nucleus (dLGN), have been examined by a combination of visual neurophysiological and iontophoretic techniques. Discrete visual stimulation of both centre and surround mechanisms, produced a powerful suppression of the elevated background discharge levels induced by iontophoretic application of an excitatory amino acid. These observations are consistent with the activation of a postsynaptic inhibitory input, a view supported by the fact that the suppressive effects were blocked by iontophoretic application of bicuculline, an antagonist of GABA, a putative inhibitory transmitter in the dLGN. These inhibitory effects were always elicited by the opposite phase of a flashed stimulus to that eliciting responses associated with the receptive field region. That is 'on' inhibitory effects were elicited from 'off' excitatory regions and 'off' inhibitory effects from 'on' excitatory regions. Plotting the responses of dLGN cells to flashed stimuli of increasing diameter, before and during iontophoretic application of bicuculline, revealed a marked reduction of the surround antagonism of centre response in the presence of the drug. During bicuculline application, surround antagonism of centre responses was at a level associated with that seen in retinal ganglion cells. Annular stimuli of internal and external diameter selected to be just outside the centre-surround border, insofar as they gave pure surround responses, were observed in the presence of bicuculline to elicit strong centre responses, as well as surround responses. These observations indicate that GABAergic inhibitory processes generate the enhanced centre-surround antagonism associated with dLGN cells and serve to increase the contrast between the two sets of mechanisms at the centre-surround border. The present conclusions apply equally to 'X' and 'Y' cells.

Animals↗

Ovarian rhabdomyosarcoma presenting as leukemia. Case report.

A condition of pure ovarian rhabdomyosarcoma in a 16-year-old female is described. The tumor presented with a leukemia-like picture, with extensive peripheral blood and bone marrow involvement which led to an initial diagnosis of acute lymphoblastic leukemia. The diagnosis was achieved at autopsy and was supported by ultrastructural findings of Z-band-like material and alternating thin and thick filaments.

Adolescent↗

Further studies on the action of 5-hydroxytryptamine in the dorsal lateral geniculate nucleus of the cat.

The possibility that 5-HT has a presynaptic inhibitory influence on the optic nerve input to the LGNd has been examined. We have compared the effect of iontophoretic application of 5-HT on the excitatory responses of LGNd neurons to visual stimulation and iontophoretic pulses of ACh and DLH. In contrast to previous studies the results suggest that 5-HT has only postsynaptic depressant effects and we found no evidence for a selective inhibition of the optic nerve input. It is proposed that the difference between the present result and those previously reported may reflect the method of stimulation of the optic nerve input. The weaker excitatory responses produced with electrical stimulation and diffuse light flashes of the earlier studies may be more susceptible to the postsynaptic depressant actions of 5-HT than the powerful visually evoked responses of the present study. Our data are only consistent with a postsynaptic depressant role for 5-HT in the LGNd.

Acetylcholine↗

The nature of the excitatory transmitter mediating X and Y cell inputs to the cat dorsal lateral geniculate nucleus.

1. In experiments examining the possibility that an excitatory amino acid may be an optic nerve transmitter in mammals, excitatory amino acid antagonists have been ionophoretically applied to cells in layers A and A(1) of the cat dorsal lateral geniculate nucleus and their effect on the excitatory response to visual stimulation of the receptive field centre has been assessed.2. The antagonists used were D-alpha-aminoadipate (D-alpha-AA), DL-alpha-epsilon-diaminopimelic acid (DAP), 1-hydroxy-3-amino-2-pyrrolidone (HA-966) and L-glutamate diethyl ester (GDEE). The antagonist effects on the visual response were compared with their effect on similar magnitude responses evoked by ionophoretic pulses of selected agonists and a control excitant, generally acetylcholine.3. Both D-alpha-AA and HA-966 would selectively block or depress the visual response with respect to the response to the control excitant. At the stage the visual input was blocked, responses to the agonists N-methyl-D-aspartate (NMDA), DL-homocysteic acid (DLH) and glutamate were also greatly reduced or blocked. At dose levels below those causing a significant reduction in the visual response, D-alpha-AA and HA-966 would selectively depress responses to NMDA and DLH with respect to the response to glutamate.4. GDEE was relatively ineffective in blocking either agonist responses or the visual response and only produced a significant reduction in either at dose levels that caused a similar depression in the response to acetylcholine. DAP would block responses to DLH but produced no significant effect on the visual response or the responses to glutamate and acetylcholine.5. The cholinergic antagonists atropine and dihydro-beta-erythroidine (DHbetaE) blocked responses to acetylcholine without significantly reducing either visual driving or the response to DLH.6. The effects were the same for X and Y cells in the dorsal lateral geniculate nucleus (dLGN). There was also no distinctions between ;on' and ;off' centre types of each of the two groups.7. The significance of these results is discussed. It is argued that they reintroduce the possibility that either L-aspartate, L-glutamate or a similar substance may be the transmitter mediating the optic nerve input to the cat dLGN.

2-Aminoadipic Acid↗

Comparative efficacies of ceftriaxone, moxalactam, and ampicillin in experimental Salmonella typhimurium infection.

The activities of ceftriaxone, moxalactam, and ampicillin against Salmonella typhimurium LT-2 were compared in culture media at pH 5, 6, 7 and 8 and in mice inoculated intraperitoneally. The minimal inhibitory concentrations for strain LT-2 in Mueller-Hinton broth were 0.03 microgram of ceftriaxone per ml, 0.08 microgram of moxalactam per ml, and 0.4 microgram of ampicillin per ml. A comparison of minimal inhibitory concentrations in buffered broth at pH 5 with those in media at higher pH values showed that ceftriaxone was more acid stable than the other antibiotics. Groups of CF-1 female mice inoculated intraperitoneally with 3 X 10(4) colony-forming units received saline or each drug in fourfold decremental doses by the subcutaneous route every 8 h for 3 days, beginning at 24 h after challenge. The mean log 10 colony-forming units of S. typhimurium per spleen at the end of treatment and the mortality rates at 21 days after inoculation were measured for each treatment group. The mean log 10 colony-forming units per spleen was significantly reduced from that of the saline control by dosages of greater than or equal to 0.06 mg of ceftriaxone per kg, 64 mg of moxalactam per kg, or greater than or equal to 16 mg of ampicillin per kg (P less than 0.05). Mortality rates of infected mice were significantly reduced by dosages of greater than or equal to 1 mg of ceftriaxone per kg or greater than or equal to 64 mg of ampicillin per kg (P less than 0.05), whereas moxalactam in dosages as high as 16 mg/kg did not significantly reduce mortality rate. These results demonstrate the superiority of ceftriaxone to the other tested antibiotics on a weight basis in this model of experimental Salmonella infection.

Ampicillin↗

Recovery and function of human fetal pancreas frozen to -196 C.

Human fetal pancreases were dissected into 1- to 2- mm3 fragments and frozen to -196 C using a modification of procedures previously used successfully for cryopreservation of the rat fetal pancreas. Freeze-recovered pancreatic pieces were able to incorporate radioactive amino acids into proteins. When placed into organ culture, nonfrozen control and freeze-recovered pancreas tissue secreted radioimmoassayable insulin in response to glucose plus theophylline, but not to glucose alone. Freeze-killed pancreatic pieces were totally inactive functionally. With respect to those parameters tested, freeze-recovered pancreas tissues were equivalent to nonfrozen tissue.

Cell Survival↗

A re-evaluation of the mechanisms underlying simple cell orientation selectivity.

Following from evidence supporting GABA as a putative inhibitory transmitter in the visual cortex, we have iontophoretically applied the GABA antagonist N-methyl bicuculline (Nmb) to simple cells in order to block the inhibitory inputs acting on them. We found that under these conditions previously sharply-tuned simple cells responded equally to all orientations. Moreover receptive field dimensions, judged by the response to stimuli at the optimal and orthogonal orientations, equated best with that expected from a single dLGN cell input. It seems thus, that asymmetries in the excitatory input are not a significant factor in the generation of simple cell orientation selectivity. The asymmetry underlying orientation selectivity rather originates from the operation of an intracortical inhibitory mechanism.

Animals↗

Inhibitory interactions contributing to the ocular dominance of monocularly dominated cells in the normal cat striate cortex.

Experiments have been carried out to ascertain whether intracortical inhibitory processes influence the ocular dominance of monocularly dominated cells in the primary visual cortex of the normal cat. The GABA antagonist bicuculline has been iontophoretically applied to the cells studied to produce a localised block of inhibitory mechanisms acting on them. The ocular dominance of these cells was tested before, during, and after bicuculline application. In a sample of 42 cells studied, approximately 50% (19) showed a significant change in ocular dominance during bicuculline application. Some exclusively monocular cells became equally driven by either eye during bicuculline application. All the effects were reversible. Receptive field properties revealed in the non-dominant eye were not identical to those in the dominant eye. Evidence is presented to suggest that for some of the cells there is a selective GABA-mediated inhibitory process suppressing the non-dominant eye input. The possible implications of these data are discussed.

Animals↗

Relationship of antibody to outcome in neonatal herpes simplex virus infections.

Neutralizing antibody titers to herpes simplex virus type 1 (HSV-1) and HSV-2 were measured at birth in normal infants and uninfected infants of mothers with genital HSV infections during pregnancy and at the onset of infection in 5 infants with mild infections and 11 infants with severe infections. Thirty-eight percent of premature and 29% of term infants had neutralization titers of <1:5. High titers ([unk]1:40) were found in 55% of infants of mothers with primary infections during pregnancy and in 76% of infants of mothers with recurrent infections. The mean titers to HSV-1 and -2 in 5 infected infants with mild infections were 1:56 and 1:65 at the time of onset of infection, whereas the mean titers in 11 infants with severe infections were 1:11 and 1:12. Six natally exposed infants who remained asymptomatic were also studied and had a mean titer to HSV-1 of 1:85 and to HSV-2 of 1:69. Therefore, infants with high titers of transplacentally derived antibody had a more favorable outcome than infants with lower titers. Ninety-five percent of the infants of mothers with recurrent infections had a Rawls index of more than 85, suggesting that the antibody response was to HSV-2. However, low levels of antibody with this type specificity failed to protect four infants from infection with HSV-2. Augmentation of the neutralization titer to HSV-2 by the amount of complement present in cord serum was less than twofold. The study suggests that the quantity of antibody derived transplacentally affects the outcome of infection after natal exposure to herpes simplex virus. Complete neutralization of virus by antibody may occur in some infants, and prolongation of the incubation period and modification of the infection may occur in others.

Age Factors↗

Cryopreservation of human fetal pancreas.

To determine the optimal conditions for successful cryopreservation of the human fetal pancreas, techniques developed for the rat organ were modified. The parameters studied were the conditions of exposure to the cryopreservation agent dimethyl sulfoxide (dmso), the rate of cooling and thawing, and the effect of in vitro culture. A total of 33 pancreases, obtained after fetal death due to prostaglandin-induced abortion, was studied. Survival of the pancreas is based on incorporation of 3H-amino acids into protein by pancreas pieces (2 mm3) during a 4-h incubation compared with nonfrozen control pieces from the same pancreas. Toxicity of DMSO at 37 degrees C was found to be severe after a 4-h exposure. Varying the effects of temperature, time of exposure, and concentrations of DMSO on survival after freeze-thaw revealed that 1.5 M DMSO for 1 h at room temperature was optimal. The cooling rate was 0.22 degrees C/min and thawing was at room temperature. Since these conditions resulted in only 50% survival, a period of culture before exposure to DMSO was added. The optimal duration of culture was 12--16 h. Using this method with addition of culture for 24 h after thawing, survival has varied from 70 to 120% of control. If a functional test for growth and insulin production by the frozen-thawed pancreas is positive, permanent shortage of the human fetal pancreas will be possible.

Amino Acids↗

Reversal of diabetes in rats using fetal pancreases stored at -196 C.

Fetal rat pancreases frozen to and stored at -196 C were used for transplantation into streptozotocin-induced diabetic syngeneic adult recipients. Transplantation was carried out either directly after thawing from -196 C, or after a 21-day growth period in a syngeneic, normoglycemic adult carrier. All transplants were placed under the kidney capsule. A single, frozen fetal rudiment was sufficient to restore blood glucose, urine volume, and urine glucose to normal, provided it had first been grown for 21 days in a normal carrier. It vitro perfusion studies showed that fetal pancreases stored at -196 C were equivalent to fresh rudiments in their responses to a glucose stimulus.

Animals↗