Search PubMed⌕ Search

Biomedical subjects

P Jonas

Publications and source records attributed to P Jonas.

At least 73 records · Page 4Linked to original sources

Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices.

1. Currents activated by glutamate receptor (GluR) agonists were recorded from outside-out patches isolated from the soma of visually identified pyramidal neurones of the CA3 and CA1 region of rat hippocampal slices. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), L-glutamate (L-Glu), and kainate (KA) were delivered either by bath application through perfusion of the recording chamber or by rapid application via a piezo-driven two-barrelled fast application system. 2. Bath application of each of the three agonists activated inward currents in all patches (n = 134) at holding potentials of -50 or -60 mV. The current amplitude increased in size between 3 to 30 microM-AMPA and 100 microM to 1 mM-KA. With this slow mode of bath application, the responses showed no apparent desensitization even at saturating concentrations of AMPA (30 microM) and KA (1 mM). 3. The ratio of currents activated by 30 microM-AMPA and 300 microM-KA showed a characteristic difference between CA3 and CA1 neurones. The ratio was 0.242 +/- 0.028 (mean +/- S.E.M., n = 16) for CA3 cell patches and 0.097 +/- 0.012 (n = 8) for CA1 cell patches indicating that GluRs in the two cell populations are different. 4. The steady-state current-voltage relations (I-Vs) for AMPA- and KA-activated currents showed pronounced outward rectification for both cell types (when the main cations are Na+ in the bath and Cs+ in the pipette solution). The current reversed close to 0 mV and the ratio of chord conductances 80 mV on either side of the reversal potential was 2.66 for KA-activated currents in CA3 cell patches and 2.60 in CA1 cell patches. AMPA-activated currents showed a time-dependent increase after steps to positive membrane potentials and a decrease after steps to negative voltages, indicating that a gating process is responsible for outward rectification of the steady-state I-V. 5. The permeability (P) of GluR channels was high for Na+ as compared to Cs+ for both cell types (PNa/PCs = 0.88 and 0.84). The permeability was low for N-methyl-D-glucamine+ (PNMG/PCs < or = 0.03) and Ca2+ (PCa/PCs < or = 0.05). 6. The current noise level increased during application of AMPA or KA. Apparent single-channel conductances obtained from fluctuation analysis were higher for AMPA than for KA, but similar for both cell types. In CA3 cell patches, AMPA activated channels with an apparent chord conductance of 7.2 pS, KA of 3.0 pS conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices.

1. Outside-out patches were isolated from granule cells of dentate gyrus and pyramidal cells of CA3 and CA1 regions of rat hippocampal slices. Patches were exposed briefly to L-glutamate using a piezo-driven double-barrelled application pipette. 2. Applications of glutamate (1 mM) of 1 ms duration activated patch currents which rose and decayed rapidly. The 20-80% rise time of these glutamate receptor (GluR)-mediated currents was usually 0.2-0.6 ms. At -50 mV the peak current varied from 10 to 500 pA in different patches. 3. The peak current-voltage relation for brief pulses of 1 mM glutamate was virtually linear in normal extracellular solution for patches from the three cell types (-100 to 60 mV). 4. The permeability of GluR channels activated at the peak to Ca2+, relative to K+, was less than 0.1 for all three cell types (under bi-ionic conditions with Ca2+ on the extracellular side and K+ on the intracellular side of the membrane). 5. The offset decay time constant of the current following 1 ms pulses of 1 mM glutamate was brief, with mean values of 3.0 +/- 0.8, 2.5 +/- 0.7, and 2.3 +/- 0.7 ms for dentate, CA3 and CA1 cell patches, respectively. Offset time constants were independent of membrane potential and independent of glutamate concentration (200 microM and 1 mM) for the three cell types. 6. Applications of 1 mM glutamate of 100 ms duration showed that glutamate responses desensitized rapidly. The time constants for desensitization were 9.4 +/- 2.7, 11.3 +/- 2.8, and 9.3 +/- 2.8 ms for patches from dentate, CA3 and CA1 cells respectively. Desensitization time constants were only weakly dependent on glutamate concentration (200 microM and 1 mM) for the three cell types. Thus offset time constants are about four times faster than desensitization time constants for both glutamate concentrations. 7. Double pulse application of glutamate indicated that even a 1 ms pulse of 1 mM glutamate causes partial (about 60%) desensitization of GluR channels. The time course of recovery from desensitization was slower in dentate gyrus granule cell patches than in CA3 or CA1 pyramidal cell patches. 8. Desensitization was studied at equilibrium by exposing patches to low glutamate concentrations for at least 15 s before a 1 ms test pulse of 1 mM glutamate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Management of neonatal testicular torsion].

Neonatal testicular torsion is rare, and is distinguished both clinically and anatomically from torsion in the older age group. We describe 2 cases of neonatal torsion treated in different ways, which reflect the current controversy regarding the timing of surgical exploration, the need for orchiectomy, as well as the indications for contralateral orchiopexy. The distinction between prenatal and the postnatal subgroups is emphasized and a policy of treatment is proposed.

Humans↗

Long-term results of simple and radical nephrectomy for renal cell carcinoma.

From 1974 to 1983, simple and radical nephrectomies were performed at the Chaim Sheba Medical Center (Tel Hashomer, Israel) for renal cell carcinoma. The authors reviewed 109 cases that were followed for a period ranging from 5 to 14 years. Simple nephrectomy was performed in 55 patients, and 54 patients underwent radical nephrectomy. The selection of the surgical procedure was based on the surgeon's preference and not on the basis of clinical stage, age, or sex. The surgical results and survival rates were assessed according to the pathologic stage of the tumors. Among patients with Stage I tumor, radical nephrectomy produced better survival rates at 5 and 10 years (P = 0.03); however, when the non-cancer deaths were excluded, the difference in survival was not statistically significant. For Stage I tumors the survival free of disease at 5 years was better for the radical nephrectomy group, but this difference was not statistically significant. No difference was noticed in the local recurrence rate between the two groups. Nephrectomy in patients with Stage IV disease did not alter survival regardless of the type of operation.

Aged↗

Homing receptors reexamined: mouse LECAM-1 (MEL-14 antigen) is involved in lymphocyte migration into gut-associated lymphoid tissue.

Specific recognition molecules ("homing receptors") on lymphocytes are thought to direct selective entry of cells into different organs. The lectin-related cell adhesion molecule LECAM-1 has previously been supposed to mediate lymphocyte entry into peripheral lymph nodes and, partially, mesenteric nodes but not into Peyer's patches. Here we present evidence that in vivo the molecule is also implicated in homing of mouse lymphocytes to Peyer's patches and may have a more general role as homing receptor for high endothelial venules-bearing lymphoid tissue, but not for most non-lymphoid tissue.

Animals↗

ATP-sensitive and Ca-activated K channels in vertebrate axons: novel links between metabolism and excitability.

Two types of metabolically regulated K channels have been identified for the first time in enzymatically demyelinated fibres of amphibian sciatic nerve using the patch-clamp technique. A maxi K channel with a single-channel conductance of 132 pS (105 mM K on both sides of the membrane, 15 degrees C) is activated both by micromolar concentrations of internal Ca and by depolarization. A second type of K channel with a conductance of 44 pS is inhibited by intracellular adenosine 5'-triphosphate (ATP) with a half-maximal inhibitory concentration (IC50) of 35 microM. It is blocked by submicromolar concentrations of external glibenclamide. Both channels are sensitive to external tetraethylammonium chloride (IC50 = 0.2 mM for the maxi K channel and 4.2 mM for the ATP-sensitive channel). They may be part of a complex feedback system regulating axonal excitability under various metabolic conditions.

Action Potentials↗

[Contribution of imaging in the diagnosis and follow-up of brain tumors].

With the use of modern radiological imaging (US, CT-scan, MRI), the most important informations to recognize a tumor remain the morphological features (localization, size, extension, number of lesions...). The precision of these informations is constantly improved (use of contrast medium, various slices angulations...) and in this field, MRI is the most precise examination. Moreover, these less aggressive investigations allow a repeated and more efficient therapeutic follow-up. In contrast with initial expectations, these radiological investigations do not always allow a formal histological characterization of the different tumor types of the central nervous system, even if some intratumoral components are recognized (fat, calcifications, liquids...).

Brain Neoplasms↗

Structure and developmental expression of the D alpha 2 gene encoding a novel nicotinic acetylcholine receptor protein of Drosophila melanogaster.

Nicotinic acetylcholine receptors (nAChRs) represent a heterogeneous group of excitatory neurotransmitter receptors in the insect brain. We have characterized the D alpha 2 gene of Drosophila melanogaster, a new member of the nAChR gene family. The protein coding region is interrupted by six introns. The positions of three of these introns are shared with all other nAChR genes. The deduced D alpha 2 protein shows the structural features of ligand-binding nAChR alpha-subunits. Cytogenetically, the D alpha 2 gene maps at position 96A of the 3rd chromosome, close to the ALS gene which also encodes an alpha-like nAChR subunit. D alpha 2 transcripts are predominantly expressed in late embryos and in fly heads.

Animals↗

A K+ channel in Xenopus nerve fibres selectively blocked by bee and snake toxins: binding and voltage-clamp experiments.

1. The effects of mast cell degranulating peptide (MCDP), a toxin from the honey bee, and of dendrotoxin (DTX), a toxin from the green mamba snake, were studied in voltage-clamp experiments with myelinated nerve fibres of Xenopus. 2. MCDP and DTX blocked part of the K+ current. About 20% of the K+ current, however, was resistant to the toxins even in high concentrations. In Ringer solution half-maximal block was reached with concentrations of 33 nM-MCDP and 11 nM-DTX. In high-K+ solution the potency of both toxins was lower. beta-Bungarotoxin (beta-BuTX), another snake toxin, also blocked part of the K+ current, but was less potent than MCDP and DTX. 3. Tail currents in high-K+ solution were analysed and three K+ current components were separated according to Dubois (1981 b). Both MCDP and DTX selectively blocked a fast deactivating, slowly inactivating K+ current component which steeply activates between E = -60 mV and E = -40 mV (component f1). In concentrations around 100 nM, MCDP and DTX blocked neither the slow K+ current (component s) nor the fast deactivating, rapidly inactivating K+ current which activates between E = -40 mV and E = 20 mV (component f2). Similar results could be derived from K+ outward currents in Ringer solution. In high-K+, IC50 of MCDP for component f1 was 99 nM, whereas it was 7.6 microM for f2. Corresponding values for DTX are 68 nM and 1.8 microM. 4. Binding studies with nerve fibre membranes of Xenopus reveal high-affinity binding sites for 125I-labelled DTX (KD = 22 pM in Ringer solution and 81 pM in high-K+ solution). 125I-labelled DTX can be displaced from its sites completely by unlabelled DTX, toxin I (black mamba toxin), MCDP, and partially by beta-BuTX. 5. Immunocytochemical staining demonstrates that binding sites for DTX are present in nodal and paranodal regions of the axonal membrane. 6. The axonal membrane of motor and sensory nerve fibres is equipped with three types of well-characterized K+ channels and constitutes so far the best preparation to study MCDP- and DTX-sensitive K+ channels with electrophysiological and biochemical methods.

Animals↗

[Massive bone grafts in children (apropos of 10 cases)].

We studied 10 massive - 70 degrees C frozen dried allografts (7 terminal intermediate) in children between the ages of 9 and 16 with malignant tumors (8 primary osteogenic sarcomas and 2 Ewing sarcomas). A good response to chemotherapy was observed. The average follow-up is 2 years (7-36 months). Results showed 4 mechanical complications (2 plate failures, 2 graft fractures) and no deaths. The surgical procedure and postoperative management are discussed and compared to prosthetic reconstruction.

Adolescent↗

[Mesenchymal solid hamartoma of the liver].

The authors describe a mesenchymal hamartoma of the liver without cyst. The diagnosis was radiologically approached by US, CT and US guided cytological puncture. They discuss the radiological aspects of mesenchymal hamartomas of the liver.

Celiac Artery↗

[Developments in the treatment of osteosarcoma since 1979. Report of the statistics at the Centre Léon-Bérard].

Seventy-two patients with a localized osteosarcoma were treated between September 1979 and December 1987 by neoadjuvant chemotherapy, local surgery and post-operative chemotherapy. Chemotherapy regimens varied throughout the years but always comprised high dose methotrexate with leucovorin rescue and adriamycin pre-operatively for children under the age of 15, and ifosfamid and cis platinum in adults. Post-operative chemotherapy for bad responders (greater than 10% of residual malignant cells), was at first an association of adriamycin and cis platinum, and later of holoxan and cis platinum. Surgery changed from amputation to local conservative surgery (graft or prosthesis) which is now the most frequent surgery--61% of the patients are alive and disease-free at 5 years. Good responders to pre-operative chemotherapy have a much better prognosis (81% at 5 years) than bad responders (45%). There is no significant difference according to age or pre-operative chemotherapy regimen.

Adolescent↗

Temperature dependence of gating current in myelinated nerve fibers.

Asymmetrical displacement currents and Na currents of single myelinated nerve fibers of Xenopus laevis were studied in the temperature range from 5 to 24 degrees C. The time constant of the on-response at E = 4 mV, tau on, was strongly temperature dependent, whereas the amount of displaced charge at E = 39 mV, Qon, was only slightly temperature dependent. The mean Q10 for tau on-1 was 2.54, the mean Q10 for Qon was 1.07. The time constant of charge immobilization, tau i, at E = 4 mV varied significantly (alpha = 0.001) with temperature. The mean Q10 for tau i-1 was 2.71 +/- 0.38. The time constants of immobilization of gating charge and of fast inactivation of Na permeability were similar in the temperature range from 6 to 22 degrees C. The Qoff/Qon ratio for E = 4 mV pulses of 0.5 msec duration decreased with increasing temperature. The temperature dependence of the time constant of the off-response could not be described by a single Q10 value, since the Q10 depended on the duration of the test pulse. Increasing temperature shifted Qon (E) curves to more negative potentials by 0.51 mV K-1, but shifted PNa (E) curves and h infinity (E) curves to more positive potentials by 0.43 and 0.57 mV K-1, respectively. h infinity (E = -70 mV) increased monotonously with increasing temperature. The present data indicate that considerable entropy changes may occur when the Na channel molecule passes from closed through open to inactivated states.

Analog-Digital Conversion↗