Biomedical subjects

I Jacobson

Publications and source records attributed to I Jacobson.

At least 37 records · Page 2Linked to original sources

PubMed1994

Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve.

Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients) either 3 to 5 h or 22 to 26 h before surgery. Serum samples were taken from all patients at 0, 1, 3 to 5, 7 to 9, and 22 to 26 h after dosing; an additional serum sample was obtained at 48 h from patients who received sparfloxacin. A single sample of brain tissue was taken from all patients; a sample of cerebrospinal fluid (CSF) uncontaminated with blood was obtained from five patients. Serum and brain tissue samples were assayed by high-pressure liquid chromatography. Drug concentrations in brain tissue exceeded those in CSF by 1.8- to 19.4-fold. Kinetic modeling suggested that peak sparfloxacin concentrations in brain tissue may have occurred later than 3 to 5 h and that actual peak concentrations may therefore have been higher (up to 10 micrograms/g of tissue). The activities of ciprofloxacin and sparfloxacin as antagonists of the gamma-aminobutyric acid antagonist (GABAA) receptor were measured with the rat vagus nerve preparation. The 50% inhibitory concentration (IC50) of ciprofloxacin was 250 microM (95.25 micrograms/ml), but in the presence of biphenyl acetic acid (BPAA), the IC50 of ciprofloxacin was only 0.6 microM (0.23 microgram/ml). In contrast, the IC50 of sparfloxacin alone or in the presence of BPAA was > 300 microM (> 100 micrograms/ml). We conclude that the concentrations of ciprofloxacin and sparfloxacin in brain tissue may exceed serum drug concentrations and cannot be predicted from the concentrations in CSF. Sparfloxacin does not have any activity as a GABA antagonist, either alone or in the presence of BPAA, at the concentrations which are likely to be reached in human brain tissue.

Animals↗

PubMed1993

Gamma-L-glutamyl-L-glutamate is an endogenous dipeptide in the rat olfactory bulb which activates N-methyl-D-aspartate receptors.

The concentration of gamma-L-glutamyl-L-glutamate (gamma-glu-glu), a potent displacer of excitatory amino acid receptor binding, and other structurally related dipeptides were determined in extracts of the rat olfactory bulb by a novel liquid chromatographic method. Whole-cell patch clamp recordings of currents from freshly isolated neurons showed that gamma-glu-glu produced inward currents at negative holding potentials, provided microM concentrations of glycine were added and no Mg(2+)-ions were present, indicating activation of N-methyl-D-aspartate receptors. Consistently, geometry optimization of gamma-glu-glu using molecular mechanics calculations, suggested a bent conformer with structural features supporting this view.

Animals↗

PubMed1993

Beware the clunking neck: a report of two cases.

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Adolescent↗

PubMed1992

Idiopathic epidural lipomatosis as a cause of pain and neurological symptoms attributed initially to radiation damage.

Epidural lipomatosis is a rare condition in which overgrowth of extradural fat can lead to back pain, spinal cord compression and radiculopathy. A 51-year-old man developed back pain and reduced mobility following a standard course of radiotherapy for a Stage I seminoma. His symptoms and radiological appearances were initially attributed to radiation fibrosis. Further investigations and operative intervention revealed epidural lipomatosis. The excess lipomatous tissue was removed with complete resolution of his symptoms.

Back Pain↗

PubMed1992

Enhanced calcium uptake by CA1 pyramidal cell dendrites in the postischemic phase despite subnormal evoked field potentials: excitatory amino acid receptor dependency and relationship to neuronal damage.

After 6-12 h of recovery from transient cerebral ischemia, the pyramidal cells of the hippocampal CA1 region take up excessive amounts of calcium upon electrical stimulation, which has been suggested to be important for the development of delayed neuronal death. The aim of this study was to further characterize this enhanced calcium uptake with respect to time-course of development, relationship to neuronal damage, and amplitude of evoked field potentials as well as the dependency on N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Adult Wistar rats were used and calcium-sensitive microelectrodes were placed in the stratum radiatum of the CA1 hippocampus for recording of the extracellular calcium concentration ([Ca2+]ec) during 20 min of ischemia and for 6 h of reflow. High-frequency stimulation of the perforant pathway elicited burst firing in CA1 and a transient decrease in [Ca2+]ec which reflects neuronal uptake. Shifts in [Ca2+]ec could not be evoked 0-1 h after ischemia. However, from 1-2 h burst firing could be evoked and the accompanying shift in [Ca2+]ec increased thereafter in amplitude with prolonged reflow, exceeded preischemic levels after 4 h, and reached 250 +/- 116% (mean +/- SD) of control after 6 h of reflow (p less than 0.05). The extracellular reference potential shift during electrical stimulation and the amplitude of evoked field potentials were still subnormal after 6 h [85 +/- 25% and 83 +/- 25%, respectively (mean +/- SD)]. There was a significant correlation between the degree of stimulated calcium uptake at 6 h postischemia and the extent of CA1 damage evaluated 7 days after the ischemic insult (r = 0.849; p less than 0.001). The shifts in [Ca2+]ec were reduced by the NMDA antagonist MK-801 (0.5-2 mg/kg, i.v.) to approximately 50% of the initial level during both control and postischemic conditions (p less than 0.01). The non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[F]quinoxaline (NBQX) (42 +/- 13 mg/kg, i.p.; mean +/- SD) decreased the amplitude of the evoked field potentials (to 30 +/- 28% of control, p less than 0.05) and completely abolished the evoked shifts in [Ca2+]ec. In conclusion, the uptake of calcium into CA1 pyramidal cells during electrical stimulation was enhanced already 4 h after ischemia in spite of the fact that other measures of excitability were subnormal. This calcium uptake correlated to the extent of CA1 pyramidal cell damage and was dependent on both NMDA and non-NMDA receptor activation.

Analysis of Variance↗

PubMed1992

The mechanism by which procaine inhibits catecholamine secretion from bovine chromaffin cells.

1. We have investigated the action of procaine on stimulus-secretion coupling in bovine adrenal chromaffin cells. 2. Procaine inhibited the catecholamine secretion evoked by 500 microM carbachol (CCh) with an IC50 of 35 microM and the associated calcium influx (IC50 60 microM). It inhibited the catecholamine secretion evoked by depolarization with high potassium by less than 20% even at the highest concentrations tested (3.2 mM). 3. The secretion evoked by CCh was associated with an increase in sodium influx. This evoked influx was also inhibited by procaine (IC50 80 microM). 4. This selective action of procaine on the CCh-evoked catecholamine secretion was investigated further by patch-clamp techniques. 5. In agreement with the ion flux studies, procaine inhibited the inward current evoked by CCh. Procaine also altered the spectral characteristics of the noise associated with the agonist-induced current by adding an additional high frequency component. The amplitude of this component showed an e-fold increase for a 55 mV membrane hyperpolarization. 6. Data from cell-attached patches showed that increasing concentrations of procaine produced a progressive fall in the mean channel open time and an increase in mean blocked time. This combination led to a decrease in mean burst length. In addition, Popen was reduced by 50 microM procaine. These changes in channel conducting time were sufficient to account for the reduction in inward current. A limited study of the action of procaine on nicotinic channels in outside-out patches gave similar results. 7. The data were considered in relation to various schemes of anaesthetic-channel interactions. The data did not fit the sequential blocking model or the extended channel block model but could be fitted to a modified sequential blocking model in which the rate constant for channel reopening after block was itself subject to modulation by the anaesthetic and the blocked channel could close without passing through the open state.

Animals↗

PubMed1991

Effects of pentobarbitone on the properties of nicotinic channels of chromaffin cells.

We have used the whole cell patch clamp technique to investigate the action of pentobarbitone on the nicotinic channels of bovine chromaffin cells. Application of agonists induced an inward current associated with a large increase in current noise. The noise could be fitted by Lorentzian functions with time constants of 17 +/- 2 ms for 10 microM acetylcholine and 10 +/- 1 ms for 10 microM carbachol. The single channel conductance estimated from the current variance was about 25 pS in each case. Pentobarbitone decreased the time constants in a concentration-dependent fashion, but the unit conductances were unaffected. Single channel events were recorded in chromaffin cells held under voltage clamp. Pentobarbitone did not reduce the amplitude of channel openings or the probability of channel opening but reduced the mean channel open time. This reduction was sufficient to account for the decrease in inward current produced by pentobarbitone.

Acetylcholine↗

PubMed1991

Microdialysis sampling of the neuronal environment in basic and clinical research.

Microdialysis is a technique for sampling extracellular fluid (ECF) which has been employed in brain research for about 10 years, and is now in experimental and clinical use in a number of biomedical disciplines. We report on microdialysis of neuroactive amino acids in the central nervous system (CNS) and discuss some technical problems of microdialysis, such as tissue reactions, calibration and the difficulties involved, as well as strategies for determination of the true extracellular concentration of various compounds. Possible mechanisms of nerve cell death in ischaemia and hypoglycaemia are among the factors that have been elucidated using data obtained by microdialysis. The neuronal environment overflows with excitatory amino acids both in brain ischaemia and in hypoglycaemia.

Animals↗

PubMed1991

Changes in extracellular amino acids and spontaneous neuronal activity during ischemia and extended reflow in the CA1 of the rat hippocampus.

This study addresses the possible involvement of an agonist-induced postischemic hyperactivity in the delayed neuronal death of the CA1 hippocampus in the rat. In two sets of experiments, dialytrodes were implanted into the CA1 either acutely or chronically (24 h of recovery). During 20 min of cerebral ischemia (four-vessel occlusion model) and 8 h of reflow, we followed extracellular amino acids and multiple-unit activity. Multiple-unit activity ceased within 20 sec of ischemia and remained zero during the ischemic insult and for the following 1 h of reflow. During ischemia, extracellular aspartate, glutamate, taurine, and gamma-aminobutyric acid increased in both acute and chronic experiments (seven- to 26-fold). Multiple-unit activity recovered to preischemic levels following 4-6 h of reflow. In the group with dialytrodes implanted acutely, the continuous increase in multiple-unit activity reached 110% of basal at 8 h of reflow. In the group with dialytrodes implanted chronically, multiple-unit activity recovered faster and reached 140% of control at 8 h, paralleled by an increase in extracellular aspartate (5.5-fold) and glutamate (twofold). In conclusion, the postischemic increase of excitatory amino acids and the recovery of the neuronal activity may stress the CA1 pyramidal cells, which could be detrimental in combination with, e.g., postsynaptic impairments.

Action Potentials↗

PubMed1991

Extracellular acidic sulfur-containing amino acids and gamma-glutamyl peptides in global ischemia: postischemic recovery of neuronal activity is paralleled by a tetrodotoxin-sensitive increase in cysteine sulfinate in the CA1 of the rat hippocampus.

An excessive activation of the excitatory amino acid system has been proposed as one possible mediator of the ischemia-induced delayed death of CA1 pyramidal cells in the hippocampus. Using dialytrodes in the CA1 of the rat, we have investigated multiple-unit activity and extracellular changes in acidic sulfur-containing amino acids and gamma-glutamyl peptides during ischemia (20-min, four-vessel occlusion) and during 8 h of reflow. Multiple-unit activity was abolished during ischemia and for the following 1 h, but then recovered, gradually reaching preischemic levels after 8 h of reflow. Extracellular cysteate, cysteine sulfinate, and gamma-glutamyltaurine increased (1.5- to threefold) during ischemia, and extracellular glutathione and gamma-glutamylaspartate plus gamma-glutamylglutamine increased during early reflow (two- to threefold). The recovery of neuronal activity at 4-8 h was paralleled by an increase in extracellular cysteine sulfinate (2.5-fold at 8 h of reflow). Perfusion with 10 microM tetrodotoxin at 8 h of reflow abolished the multiple-unit activity and reduced extracellular cysteine sulfinate. Considering the glutamate-like properties of cysteine sulfinate, the observed postischemic increase may be involved in the development of the delayed neuronal death.

Acids↗

PubMed1990

Ketamine and MK801 attenuate paired pulse inhibition in the olfactory bulb of the rat.

We have investigated the effects of the phencyclidine like-compounds ketamine and MK801 on the evoked field potentials of rat olfactory bulb. Low doses of ketamine (3-6 mg/kg) blocked the inhibition of mitral cells by granule cells evoked by stimulation of lateral olfactory tract fibres or by stimulation of olfactory nerve. This blockade was not accompanied by a decrease in granule cell excitation as revealed by field potential recording. MK801 had a similar effect on the inhibition of mitral cells evoked by stimulation of the lateral olfactory tract. As ketamine does not influence the inhibitory action of GABA (Anis et al. 1983) these results suggest that both ketamine and MK801 block inhibition by an action on intrinsic excitatory feed-back circuits in the olfactory bulb.

Action Potentials↗

PubMed1989

DNA content of rectal scrapings from individuals at low and high risk for the development of colorectal cancer. A feasibility study.

Scrapings of superficial rectal mucosa were collected from 31 patients with colorectal carcinoma, 66 patients with sporadic adenoma, and 53 control subjects with no personal or family history of colorectal cancer. The DNA ploidy level and proliferative patterns of each specimen were analyzed by flow cytometry (FCM). A GMS index, calculated as the ratio of G2 + M:S, was found to be significantly lower in control subjects than in any of the high-risk groups studied. Aneuploidy was more prevalent in rectal scrapings from cancer patients and adenoma patients than in those from control subjects. Aneuploid cell populations were detected in apparently normal rectal scrapings from two control subjects. Some high-risk individuals (i.e., cancer patients and patients with adenomas and a family history of cancer) exhibited higher proportions of tetraploid (designated G2/M) cells and a higher G2/M:S phase ratio than control subjects. The results accumulated thus far show that the rectal scraping procedure is safe and easy to perform. Our limited findings give hope that the DNA content analysis of cells obtained by rectal scraping may eventually prove useful in mass screening for colorectal cancer risk. However, definitive evaluation will require further refinement and elaboration of analytic technique and testing on more patients at various levels of predetermined risk.

Adenoma↗

PubMed1989

CNV abnormalities following closed head injury.

Event-related potentials (ERPs) were recorded in a GO/NO-GO reaction time task from 20 closed head injury patients, at least 6 months postinjury, and from 20 controls. In this task the pitch of an initial tone (Sl) indicated whether or not a response was required to a second tone (S2) occurring 1.5 s later. In the control group both the early, frontal-maximum, and the later vertex-maximum, components of the contingent negative variation (CNV) were larger on GO than NO-GO trials. In the patients, the early frontal CNV wave did not differentiate GO and NO-GO trials, and the late CNV showed a smaller separation between these trial types than did the late CNV of the control group. These CNV abnormalities may reflect impairments in selectively orienting to salient stimuli, and in differential response preparation. Such impairments might in turn reflect the damage to the frontal lobes and/or their connections that commonly occurs as a result of closed head injury.

Acoustic Stimulation↗

PubMed1988

On the epileptogenic effects of kainic acid and dihydrokainic acid in the dentate gyrus of the rat.

The in vivo effects of the acidic amino receptor agonist, kainic acid and the inhibitors of the uptake of glutamate, dihydrokainic acid and threo-3-hydroxyaspartate, on spontaneous activity and perforant path evoked field potentials were examined in the dentate gyrus of the rat. The effect of these compounds on extracellular levels of endogenous amino acids in the hippocampus was assessed simultaneously using in vivo microdialysis. Kainic acid (10-100 microM) and dihydrokainic acid (1-10 mM) both evoked epileptiform activity and an apparent loss of recurrent inhibition (as assessed using the paired-pulse technique). Extracellular increases in taurine, alanine and phosphoethanolamine were noted following administration of kainate (100 microM) and dihydrokainate (1-10 mM). An increase in extracellular glutamate and aspartate was also noted in rats treated with dihydrokainate (100 microM-10 mM). In contrast, threo-3-hydroxyaspartate did not induce epileptiform activity, suggesting that the epileptogenic effects of dihydrokainate and kainate are not mediated by inhibition of uptake. The effect of the N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovalerate on these responses was studied. This compound attenuated the epileptiform activity and reversed the apparent loss of recurrent inhibition in response to both kainic acid and dihydrokainic acid. These data suggest that activation of N-methyl-D-aspartate receptors underlies the epileptogenic effects of both compounds, and the possible mechanisms which might be involved in this response are discussed.

Amino Acids↗

PubMed1988

Bimanual co-ordination in callosal agenesis and partial commissurotomy.

Studies [Preilowski, B.F.B. in Cerebral Localization, pp. 116-131, Springer, Berlin, 1975; Reynolds, D.M. and Jeeves, M.A. Neuropsychologia 12, 287-290, 1974] of bilateral motor coordination in commissurotomy patients pointed to the importance of direct interhemispheric integration for the fine regulation of the lower motor system within each hemisphere. When external visual feedback was withdrawn in the performance of a bimanual tracking task, partial commissurotomy patients, in whom the anterior portions of the callosum were cut, deviated significantly when drawing lines which required asymmetrical input from the two hands. The task devised by Preilowski was given to two adult acallosals, an 11 yr old acallosal boy, and an 11 yr old girl in whom the centre one-third of the corpus callosum had been sectioned. The acallosals performed in a manner similar to Preilowski's partial commissurotomy patients. The results were interpreted as confirming the interhemispheric integrative function of the corpus callosum. It is argued that they constitute further evidence for the existence of hemispheric dominance for motor control in acallosals. The partial commissurotomy patient did not differ in performance from normals. Her results were consistent with the view that it is the anterior parts of the callosum which are crucial for the interhemispheric integration of the lower motor system in each hemisphere.

Adult↗

PubMed1988

Calcium uptake evoked by electrical stimulation is enhanced postischemically and precedes delayed neuronal death in CA1 of rat hippocampus: involvement of N-methyl-D-aspartate receptors.

Extracellular calcium concentration changes in the CA1 of the hippocampus during burst activity were measured during postischemic reflow, and the involvement of N-methyl-D-aspartate (NMDA) receptors was evaluated. In adult Wistar rats global ischemia was induced by four-vessel occlusion for 20 min. After 6 h of postischemic reflow, the animals were halothane-anesthetized and reintubated. A double-barrelled calcium-sensitive microelectrode was advanced through stratum oriens, pyramidale, and radiatum in 50-micron steps. At each step the perforant pathway was stimulated (15 Hz, 30 s), and changes in extracellular calcium concentration were recorded. High-frequency stimulation elicited burst firing and transient decreases in extracellular calcium concentration, which are interpreted as neuronal calcium uptake. In control hippocampus, the extracellular calcium decreases were maximal in the stratum pyramidale. Six to eight hours after ischemia, a threefold enhancement of extracellular calcium decreases was found in the dendritic layers of the CA1. The NMDA-receptor antagonist ketamine (15-30 mg/kg intraperitoneally) reduced these electrically evoked calcium decreases. Seven days after ischemia, there was a 60-90% loss of pyramidal cells in the CA1. In conclusion, the cellular calcium uptake, possibly through NMDA receptors evoked by neuronal activity, is enhanced during early postischemia and precedes delayed neuronal death.

Animals↗

PubMed1988

Event related potentials from closed head injury patients in an auditory "oddball" task: evidence of dysfunction in stimulus categorisation.

Event-related potentials (ERPs) were recorded from 19 closed head injury (CHI) patients, at least 6 months after injury, and an equal number of control subjects, during a task requiring the covert counting of rare auditory "target" stimuli against a background of frequent "non-targets". In both groups, ERPs to targets contained enhanced frontal N2 and parietal P3 components. N2 was larger in amplitude in the CHI patients than in the controls, and its peak latency was delayed. P3 amplitude was smaller in the patients, but its latency was not significantly different from that of the control group. The delay in N2 latency is interpreted as evidence of an increase in the time needed to achieve stimulus categorisation in CHI patients. The larger N2s in this group are thought to reflect the additional cognitive effort required after CHI to cope with the task. The negative findings with respect to P3 latency suggest that this may be a less sensitive measure of information-processing efficiency in this task than the latency of N2.

Adult↗

PubMed1987

Analysis of amino acids: neurochemical application.

For high sensitivity analysis of neuroactive amino acids, liquid chromatography employing precolumn derivatisation with o-phthalaldehyde (OPA) is suitable for several reasons. The OPA reagent is non-fluorescent per se, the reaction occurs rapidly in alkaline aqueous solutions and forms highly fluorescent derivatives with primary amines.

Amino Acids↗