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Biomedical subjects

H Meiri

Publications and source records attributed to H Meiri.

At least 19 recordsLinked to original sources
PubMed2007

First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia.

OBJECTIVE: To evaluate whether measurement of maternal serum placental protein-13 (PP-13) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks of gestation alone or in combination with second-trimester uterine artery pulsitility measured by Doppler velocimetry is useful in predicting those women who will develop pre-eclampsia METHODS: This was a nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum. Samples were collected as part of a first-trimester prenatal chromosomal anomaly screening program and were routinely tested for PAPP-A. PP-13 was tested using an enzyme linked immunosorbent assay (ELISA) by an examiner who was blinded to pregnancy outcome. All patients also underwent uterine artery Doppler flow velocimetry to measure the mean pulsatility index (PI) at 22-24 weeks' gestation. RESULTS: There were 446 controls and 44 cases with early pre-eclampsia where delivery was induced prior to 35 weeks. In addition there were a further 44 cases with pre-eclampsia in which delivery was not induced before term. Median PP-13 levels for controls, all cases and early pre-eclampsia cases were 176.9, 121.9 and 111.7 pg/mL, with multiples of the median (MoMs) of 1.00, 0.69 and 0.63, respectively (P < 0.001). PAPP-A MoMs were 1.00, 0.89 (P = 0.076) and 0.89 (P = 0.042) and mean PIs were 1.0, 1.6 (P < 0.001) and 1.7 (P < 0.001) for controls, all cases and early cases, respectively. Receiver-operating characteristics (ROC) curve analysis for either all cases or early cases vs. controls yielded areas under the curve for PP-13, PAPP-A and PI respectively of 0.68 (95% CI, 0.61-0.74; P < 0.001), 0.56 (95% CI, 0.49-0.63; P = 0.076) and 0.79 (95% CI, 0.72-0.87; P < 0.001) for all cases and 0.71 (95% CI, 0.63-0.79; P < 0.001), 0.59 (95% CI, 0.51-0.68; P = 0.076) and 0.86 (95% CI, 0.77-0.94; P < 0.001) for early cases. At a specificity set to 0.80 the sensitivities were 0.50, 0.23 and 0.76 for PP-13, PAPP-A and PI in the early cases and 0.44, 0.24 and 0.73 in all cases. Combining PP-13 and PI using logistic regression analysis yielded an area under the curve of 0.84 (95% CI, 0.78-0.90; P < 0.001) and a sensitivity of 0.74 in all cases, and 0.90 (95% CI, 0.84-0.96; P < 0.001) and a sensitivity of 0.79 for early cases. PAPP-A with PI gave an area under the curve of 0.82 (95% CI, 0.76-0.90; P < 0.001) and a sensitivity of 0.76 in all cases. Combining PAPP-A with PP-13 and PI did not add significantly to the sensitivity. CONCLUSION: First-trimester PP-13 levels may be useful in predicting pre-eclampsia and early pre-eclampsia, and the accuracy of the method increases when coupled with second-trimester Doppler PI measurement. First-trimester PAPP-A provides some prediction for pre-eclamspia when combined with PI but does not add to the prediction of early pre-eclampsia when PP-13 and PI are used together. Further studies are required to establish the real value of PP-13 in first-trimester screening for pre-eclampsia.

Adult↗
PubMed2006

A novel approach to first-trimester screening for early pre-eclampsia combining serum PP-13 and Doppler ultrasound.

OBJECTIVE: To investigate the value of maternal serum placental protein 13 (PP-13) measurement and uterine artery Doppler during first-trimester screening in the prediction of early pre-eclampsia. METHODS: This was a nested case-control prospective study of pregnancies at 11 + 0 to 13 + 6 weeks of gestation. The pulsatility index (PI) of blood flow in the uterine arteries and the maternal serum concentration of PP-13 were measured in 10 women who went on to develop pre-eclampsia that necessitated delivery before 34 weeks, and in 423 unaffected women. Results were expressed as multiples of the gestation-specific median in controls (MoM). A logistic regression model was used to predict detection and false-positive rates. RESULTS: In the cases that developed pre-eclampsia requiring delivery before 34 weeks, compared with the unaffected pregnancies, the median uterine artery PI was higher (1.43 MoM) and the median serum PP-13 level was lower (0.07 MoM; P < 0.001, Wilcoxon rank sum test for both). Modeling predicted that for a 90% detection rate of pre-eclampsia requiring delivery before 34 weeks, the false-positive rate of screening by PP-13 was 12%, by uterine artery PI was 31% and by a combination of the two methods was 9%. A policy of contingency screening, whereby all women are screened by maternal serum PP-13 and only the 14% at highest risk are then screened by Doppler, achieved a detection rate of 90% with an overall false-positive rate of 6%. CONCLUSION: Effective screening for pre-eclampsia requiring delivery before 34 weeks can potentially be provided by assessment of a combination of maternal serum PP-13 and uterine artery Doppler in the first trimester of pregnancy.

Adult↗
PubMed2004

Placental protein 13 (PP-13): effects on cultured trophoblasts, and its detection in human body fluids in normal and pathological pregnancies.

Placental tissue protein 13 (PP-13), one of the 56 known placental proteins identified till today, was purified from placentas obtained from women at delivery, and used to evoke antibodies against it. The purified PP-13 was lysed to peptides, which were sequenced, leading to the full-length cDNA sequencing and its expression in Escherichia coli. Sequence analysis in databases showed homology to the galectin family. Of the various antibody preparations developed, a pair of monoclonal antibodies (MAbs) coupled to the recombinant PP-13 (PP-13-R) was used for the immunodetection of PP-13 in pregnant women's serum with the solid-phase ELISA format. With a dynamic range of 25-500 pg/mL with no background in non-pregnant women's serum and men's serum, the ELISA test was suitable for the detection of PP-13 in the 1st, 2nd, and 3rd trimesters. PP-13 levels slowly increase during pregnancy. In the 1st trimester, lower than normal PP-13 levels were found in fetal growth restriction (IUGR), preeclampsia (PE), and particularly in early PE (<34 weeks of gestation). In the 2nd and 3rd trimesters, higher than normal concentrations were found in PE, IUGR and in preterm delivery (PTD). Application of PP-13 to cultured trophoblasts elicited depolarization carried by calcium ions, followed by liberation of linoleic and arachidonic acids from the trophoblast membrane, and a subsequent elevation of prostacyclin and thromboxane. These effects were negligible when PP-13 derived from the placentas of patients with IUGR, PE or PTD was used. The results are discussed in view of the potential utilization of PP-13 for early serum screening to assess the risk to develop placental insufficiency, coupled to a differential analysis of the various pathologies by analyzing cultured trophoblasts.

Amino Acid Sequence↗
PubMed2000

Rhythmic opening and closing of vesicles during constitutive exo- and endocytosis in chromaffin cells.

Constitutive exo- and endocytic events are expected to increase and diminish the cell surface area in small spontaneous steps. Indeed, cell-attached patch-clamp measurements in resting chromaffin cells revealed spontaneous upward and downward steps in the electrical capacitance of the plasma membrane. The most frequent step size indicated cell surface changes of <0.04 microm(2), corresponding to vesicles of <110 nm diameter. Often downward steps followed upward steps within seconds, and vice versa, as if vesicles transiently opened and closed their lumen to the external space. Transient openings and closings sometimes alternated rhythmically for tens of seconds. The kinase inhibitor staurosporine dramatically increased the occurrence of such rhythmic episodes by making vesicle closure incomplete and by inhibiting fission. Staurosporine also promoted transient closures of large endocytic vesicles possibly representing remnants of secretory granules. We suggest that staurosporine blocks a late step in the endocytosis of both small and large vesicles, and that endocytosis involves a reaction cascade that can act as a chemical oscillator.

Animals↗
PubMed1996

[The management selection of renal angiomyolipoma].

BACKGROUND: Nephron-sparing surgery is ideal in the treatment of renal angiomyolipoma (AML). But, in fact, occasional cases are found in post-ruptured AML and/or in bilateral multiple AMLs, that is seen in tuberous sclerosis. And we cannot perform nephron sparing surgery so easily. We proposed the treatment selection in such complicated AML. METHODS: We experienced 10 cases (12 kidneys) for about ten years, and studied our treatment selection and prognosis on each cases retrospectively. RESULTS: Of the 5 kidneys with AML less than 4 cm in diameter, 4 have not encountered with rupture. Of the 7 kidneys with AML more than 4 cm in diameter, 4 kidneys had rupture. Of the 3 kidneys unruptured AML more than 4 cm in diameter, 2 kidneys were treated by enucleation and we performed preventive embolization for rupture in residual one kidney. The patients was suffered from tuberculosis sclerosis, and she had bilateral multiple AMLs. Of the 4 kidneys with ruptured AML, 2 kidneys were treated by enucleation, and the other 2 kidneys were entirely resected. We succeeded enucleation in 2 of 4 kidneys with ruptured complicated AML. In those cases, we did long term watching after rupture and in-situ perfusion technique at the operation. CONCLUSIONS: Active treatment of AML, that is more than 4 cm in diameter, might be recommended. Because most of those will be ruptured. The ideal treatment, nephron-sparing surgery is difficult in complicated situation, such as after rupture and bilateral multiple AMLs. In our opinion, the point of success of nephron-sparing surgery might be long term watching after rupture and in-situ perfusion technique at the operation.

Adult↗
PubMed1995

The difference in shape of spontaneous and uniquantal evoked synaptic potentials in frog muscle.

1. Spontaneous and stimulation-induced uniquantal synaptic activity at the frog cutaneous pectoris muscle, treated with neostigmine, was recorded by focal extracellular microelectrodes. A monoexponential curve was fitted to the decay of each synaptic response. 2. A highly significant positive relationship was found between the amplitude and the decay time constant of spontaneous extracellular miniature endplate potentials (MEPPs(o)), whereas the relationship displayed by evoked uniquantal extracellular endplate potentials (EPPs(o)) was only slightly greater than zero. 3. The difference did not stem from changes in the muscle membrane conductance or from inclusion of outstanding MEPPs(o) formed as a result of the block of acetylcholinesterase. 4. The dependence of the rise time on the amplitude was also stronger in MEPPs(o) than in EPPs(o). 5. In the absence of neostigmine, MEPPs(o) exhibited a positive correlation between decay time constant and amplitude, while EPPs(o) did not show such a correlation. 6. In view of previously published models of transmitter release, it is suggested that spontaneous secretion of quanta occurs both within and outside the active zones facing postsynaptic areas of variable receptor density.

Acetylcholinesterase↗
PubMed1994

Resonant behavior and frequency preferences of thalamic neurons.

1. We studied the voltage responses of thalamocortical neurons to a periodic current input of variable frequency, in slices of mediodorsal thalamus (guinea pig). The ratio of the Fourier transform of the voltage response to the Fourier transform of the oscillatory current input was used to calculate the frequency response of the neurons at different resting and imposed membrane potentials. 2. Most neurons displayed a resonant hump in the frequency response curve. A narrow band of low-frequency (2-4 Hz) resonance occurred near the resting level [-66 +/- 8 mV (SD)] and at imposed membrane potentials in a range of -60 to -80 mV. An additional wide band (12-26 Hz) of peak resonant frequencies was observed at depolarized levels. 3. The low-frequency resonance was insensitive to tetrodotoxin (TTX) application in concentrations (0.5-1 microM) that blocked a depolarization activated inward rectifier and Na(+)-dependent action potentials. TTX, however, eliminated the wide-band resonant hump centered at 12-26 Hz that we observed at depolarized membrane potentials. 4. Application of Ni2+ (0.5-1 mM) reversibly blocked all slow spikes and greatly reduced the low-frequency resonant humps, without changing the resting potential. Octanol in concentrations of 50 microM had similar effects. 5. Application of Cs+ (3-5 mM), a blocker of the hyperpolarization activated inward rectifier, produced a 5- to 10-mV depolarization and completely blocked the rectification. Cs+ did not alter the low-frequency resonant hump or its dependence on membrane voltage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Involvement of different S4 parts in the voltage dependency of Na channel gating.

Three synthetic peptides corresponding to parts of S4 of the first repeat of eel electroplax sodium channel were synthesized. The basic peptide was C1+ which corresponds to amino acids 210-223 (eel channel numbering) and two subfractions: an external fraction, C1+ex (amino acid 210-217); and an internal part, C1+in (amino acid 218-221). Peptide C1+ includes four of the charged amino acids of this domain; peptide C1+ex includes three of the charged amino acids and is closer to the external membrane surface (according to channel models) than peptide C1+in which includes the fourth charged amino acid alone. Antibodies generated in rabbits against these peptides were shown to be site specific. Using the whole-cell patch-clamp technique, we found that in rat dorsal root ganglion (DRG) cells, the antibodies against C1+in but not against C1+ex had an effect on the gating parameters. They shifted the Na-channel inactivation curve towards hyperpolarization and decreased the slope of the Na-channel activation curve. These results demonstrate that during the conformational changes associated with channel gating, the fourth charged amino acid of S4 must be accessible to antibodies given to the external solution. Furthermore, they indicate a specific involvement of S4 in the voltage dependency of the gating processes.

Amino Acid Sequence↗
PubMed1992

Depolarization exposes the voltage sensor of the sodium channels to the extracellular region.

Two domains of Na channels were mapped with site-specific antibodies raised in rabbit against synthetic peptides corresponding to a part of the voltage sensor of internal repeat 1-C1+ (amino acids 210-223) and to a region designated dipole (amino acids 1690-1699) of eel electroplax sodium channels. The antibodies bind to their respective domains in both purified and membrane-bound channels and immunoprecipitate the channels from eel electroplax and rat brain synaptosomes. Anti-C1+ depresses the action potential of rat sciatic nerve in a concentration-dependent way. It binds to the external side of rat brain synaptosomal vesicle, and its binding is potentiated by depolarization. Anti-dipole binds to the inner side of the vesicle, and the binding is inhibited by depolarization.

Action Potentials↗
PubMed1992

Aluminium modifies the electrical response of neuroblastoma cells to a short hypertonic pulse.

The effect of aluminium (50-100 micrograms/ml) on the electrical response of N1E-115 neuroblastoma cells to a short hypertonic pulse was examined using conventional electrophysiological techniques and computer assisted analysis. Application of a small dose of hypertonic solution in the vicinity of the cell evoked depolarization of the membrane potential and a biphasic change in input resistance: an initial increase followed by a profound decrease. Upon washout of the hypertonic stimulus, repolarization of membrane potential and complete recovery of the input resistance were observed. In the presence of aluminium application of hypertonic solution had a reversible effect which showed a prolonged duration of the response without a change in its amplitude. It is suggested that the retardation in recovery from hypertonically induced shock may be due to rigidification of the plasma membrane in the presence of aluminium. Possible implications to human diseases associated with accumulation of aluminium in brain tissue are discussed.

Aluminum↗
PubMed1991

Postsynaptic effects of DMSO at the frog neuromuscular junction.

Postsynaptic effects of dimethylsulfoxide (DMSO) were studied at the frog cutaneous pectoris neuromuscular junction using electrophysiological techniques and computer assisted analysis. It was found that the average amplitude of extracellularly recorded miniature end-plate potentials (meppse) as well as the time constant of their monoexponential decay (tau) were both elevated in the presence of DMSO. In spite of increased scatter of individual values, amplitude and tau of meppse highly correlated with each other. These results imply that DMSO partially blocked the activity of acetylcholine esterase in addition to its already known presynaptic action of acetylcholine release enhancement. Inhibitory action of DMSO on activity of isolated acetylcholine esterase was previously demonstrated by biochemical methods.

Animals↗
PubMed1991

Protein phosphatase inhibitor okadaic acid enhances transmitter release at neuromuscular junctions.

To test the hypothesis that continual phosphorylation and dephosphorylation of protein components of nerve terminals might be important determinants of synaptic efficacy, the effect of okadaic acid, a potent natural inhibitor of two serine threonine protein phosphatases (phosphatase 1 and phosphatase 2A), was examined on synaptic transmission at frog (cholinergic) and lobster (glutamatergic and GABAergic) neuromuscular junctions. At frog junctions, the addition of 1 microM okadaic acid to the extracellular fluid caused almost a doubling of the amplitude of the end-plate potential. The effect of okadaic acid was reversible. Quantal analysis showed that the augmenting effect was presynaptic, resulting from an increase in the number of quanta of transmitter released by a nerve impulse. Where was no significant change in the amplitude of spontaneously liberated miniature end-plate potentials, but their frequency of release increased in parallel with the increase in amplitude of the nerve-evoked synaptic potential. Similar studies with lobster neuromuscular junctions showed increases in the size of both excitatory and inhibitory synaptic responses that were similar in magnitude to the effects seen in the frog junctions. No significant changes in membrane potential or in input resistance accompanied the increased response size. These results suggest that transmitter release at a variety of junctions using different transmitters is constantly modulated by phosphorylation and dephosphorylation of important protein components within nerve terminals.

Animals↗
PubMed1991

Effects of aluminium on electrical and mechanical properties of frog atrial muscle.

1. The effects of aluminium on membrane ionic currents were studied in single cardiac myocytes. Most of the work was done on frog atrial cells, but some experiments were also carried out on single cells isolated from rabbit ventricles and atria. 2. The effects of aluminium on the force of contraction of frog atrial trabeculae were also investigated. 3. Aluminium was prepared from AlCl3 as a stock 0.5 M solution which has a pH of 3.5. Before each experiment, this solution was added to the control solution, to give a final concentration of 20-100 micrograms ml-1 aluminium (0.75-3.75 mM AlCl3). The solutions were brought to a pH of 7.4 or 7.6. at which they consist of a mixture of amorphous aluminium hydroxides and a very small amount of soluble ionic aluminium complexes: free aluminium cations (less than 10 pM), aluminohydroxide anions (less than 8 microM). The addition of this suspension reduced the peak inward calcium currents in single rabbit atrial and ventricular cells and in frog atrial cells. In the latter, the peak current was reduced (at + 10 mV) to 45% of control (mean of 9 cells). This effect was reversible upon washout, and was obtained at all membrane potentials, with no shift of the calcium current voltage relationship along the voltage axis. 4. Aluminium also reduced the time-dependent potassium current IK. This reduction was observed at all membrane potentials. For example, at + 10 mV, the mean reduction of IK (n = 9) was to 69% of the control amplitude. This effect, which was very difficult to reverse, was not due to IK rundown. The fully activated current-voltage relationships (obtained by standard 'tail' analysis) showed that the effect of aluminium was due mainly to a decrease in conductance and not to a shift in the activation range of IK. The mean voltage of half activation was shifted by 8 mV in the depolarizing direction (n = 5). 5. The background potassium current IK1 was also slightly but consistently changed in a complex fashion, with an outward shift at membrane potentials positive to -60 mV. For example, at a membrane potential of -40mV, the mean shift was by 22 + 4pA. At more negative potentials, there was an inward shift in the current amplitudes. For example, for steps to -I00 mV the current elicited was larger (more inward) by 53 pA (mean value, n = 10). The reversal potential was slightly shifted (<10 mV) in the hyperpolarizing direction. 6. The force of contraction of frog atrial trabeculae was altered by aluminium in a complex manner, which showed marked seasonal variation. During most of the year, 50-100,ug ml-1 aluminium caused a biphasic change, with an early small and consistent decrease, followed by a large increase in twitch amplitude. For a short period corresponding to the (local) winter months the sensitivity to aluminium was greatly enhanced. Aluminium lOOupgml-1 totally abolished contraction (n = 5), while a lower concentration (20,ug ml- 1) produced a sustained reduction in the force of contraction. Similar biphasic and seasonal responses have been reported to be induced by lanthanum. 7. The biphasic changes in twitch amplitude were independent of the transmembrane sodium gradient. Aluminium produced the same effects when 90% of the extracellular sodium was replaced by lithium. Caffeine (5 mM) attenuated or even inverted the positive inotropic effect of aluminium. These results imply that aluminium alters the release of calcium from intracellular, caffeine-sensitive stores. This could be effected either by augmenting the amount released during each activation, and/or by increasing the loading of stores prior to release.

Aluminum↗
PubMed1990

Colchicine prevents recovery of nerve conduction at chronic demyelination.

A colchicine cuff was applied to rat sciatic nerve proximal to a demyelinating region produced by a focal injection of lysophosphatidylcholine (LPC). The colchicine cuff prevented the recovery of function normally seen within 6-8 days after LPC-induced demyelination. Colchicine blocked the delivery of sodium channels to the demyelinated region and induced their accumulation proximal to the cuff. The dual effect of colchicine in blocking both the recovery of impulse propagation through the demyelinated region and the delivery of sodium channels suggests a central role for fast axonal transport of sodium channels in the recovery of function at demyelination.

Action Potentials↗
PubMed1990

Vasopressin produces long-lasting increase in transmitter release.

Arginine-vasopressin has a widespread distribution in the nervous system, and has been implicated in cellular and behavioral functions. Its effect on the neuromuscular synapse reveals that it produces long-lasting augmentation in synaptic transmission due to an increase in spontaneous and nerve stimulation evoked quantal transmitter release. No significant postsynaptic effect was detected.

Action Potentials↗
PubMed1990

Structural and developmental differences between three types of Na channels in dorsal root ganglion cells of newborn rats.

The changes in Na current during development were studied in the dorsal root ganglion (DRG) cells using the whole-cell patch-clamp technique. Cells obtained from rats 1-3 and 5-8 days after birth were cultured and their Na currents were compared. On top of the two types of Na currents reported in these cells (fast-FA current and slow-S current) a new fast current was found (FN). The main characteristics of the three currents are: (i) The voltages of activation are -37, -36 and -23 mV for the FN, FA and S currents, respectively. (ii) The activation and inactivation kinetics of FN and FA currents are about five times faster than those of the S current. (iii) The voltages at which inactivation reaches 50% are -139, -75 and -23 mV for the FN, FA and S currents, respectively. The kinetics and voltage-dependent parameters of the three currents and their density do not change during the first eight days after birth. However, their relative frequency in the cells changes. In the 1-3 day-old rats the percent of cells with S, FA, and mixed S + FN currents is 22, 18, and 60% of the cells, respectively. In the 5-8 day-old, the percent of cells with S, FA, and FN + S is 10, 66 and 22%. The relative increase in the frequency of cells with FA current during development can contribute to the ease of action potential generation compared with cells with FN currents, which are almost completely inactivated under physiological conditions. The predominance of FA cells also results in a significant decrease in the relative frequency of cells with the high-threshold, slow current. Antibodies directed against a part of the S4 region of internal repeat I of the sodium channel (C1+, amino acids 210-223, eel channel numbering) were found to shift the voltage dependence of FA current inactivation (but not of FN or S currents) to more negative potentials. The effect was found only when the antibodies were applied externally. The results suggest that FN, FA and S types of Na currents are generated by channels, which are different in the topography of the C1+ region in the membrane.

Action Potentials↗