Search PubMed⌕ Search

Biomedical subjects

Y Talmon

Publications and source records attributed to Y Talmon.

At least 37 records · Page 2Linked to original sources

Vesicle-to-Micelle Transformation in Systems Containing Dimeric Surfactants

The vesicle-to-micelle transformation has been investigated thus far in lipid + surfactant systems where the vesicle-forming lipid is chemically very different from the micelle-forming surfactant. The dimeric surfactants, alkanediyl-alpha, omega-bis(dimethyldodecylammonium bromide), are known to form vesicles when the alkanediyl spacer is long enough (for instance, spacer = eicosanediyl, referred to as 12-20-12) and spheroidal micelles for shorter spacers (spacer = decanediyl, referred to as 12-10-12). These surfactants together with the conventional surfactant dodecyltrimethylammonium bromide (DTAB) permitted us to study the transformation of the 12-20-12 vesicles into micelles on addition of the chemically similar micelle-forming DTAB and 12-10-12. Spectrophotometry (light absorbance measurements), video-enhanced light microscopy, and transmission electron microscopy at cryogenic temperatures (cryo-TEM) were used to study the transformation at different scales of aggregate size. Electrical conductivity, which probes the system at the atomic scale (free counterions), was also used. Absorbance measurements showed the transformation to occur between 1.8 and 2.8 wt% added surfactant at a constant 12-20-12 concentration of 1.4 wt%. Light microscopy showed the progressive solubilization of the larger vesicles. Cryo-TEM showed that the initial effect of DTAB addition was to reduce the size of the vesicles, whereas 12-10-12 addition resulted in the formation of multilamellar vesicles. Further additions of either surfactant reduced the size of the vesicles, then brought about the formation of spheroidal micelles until complete solubilization of the vesicles. The giant threadlike micelles seen in previous studies of vesicle-to-micelle transformation in lipid/surfactant systems were never observed with the systems investigated. The conductivity results also revealed differences in behavior on additions of DTAB and 12-10-12.

Journal Article↗

On the structure of aggregated kappa-carrageenan helices. A study by cryo-TEM, optical rotation and viscometry.

Cryo-transmission electron microscopy (cryo-TEM), viscometry and optical rotation have been used to study the microstructure of dilute solutions of helical kappa-carrageenan under varied electrolyte composition (0.1 M of NaI, CsI and mixtures of the two salts). Microfibers (300-400 nm in length) were observed above a critical cesium content, while below that no microstructure was seen in the micrographs. A drastic increase in the specific viscosity and an onset of thermal hysteresis in the optical rotation above the same critical cesium content provide clear evidence of aggregate formation. This leads to the conclusion that the observed microfibers are aggregates consisting of several helices. At high proportions of cesium, further aggregation of the microfibers was observed by cryo-TEM.

Biopolymers↗

[Clozapine for resistant schizophrenia and characteristics of those responding].

Clozapine (Leponex) is an atypical antipsychotic drug which is effective in the treatment of resistant schizophrenia. The most severe side-effect is agranulocytosis, which occurs in 12%. 50 patients with resistant schizophrenia were screened retrospectively in order to characterize features which might help predict good response to the drug. The drug was more effective in young patients with recent onset of illness and short total duration of hospitalization.

Adolescent↗

Cholesterol precipitation from cholesterol-supersaturated bile models.

Bile-model systems containing cholesterol (CH), phosphatidylcholine (PC) and sodium cholate (NaC) at concentrations similar to those found in supersaturated human gall bladder bile ([CH]/[PC] = 0.60 +/- 0.01; CH saturation index, CSI = 1.58 +/- 0.03) were prepared by mixing PC-CH vesicles with NaC micellar solutions. Following mixing, the dispersion became transparent and gave rise to high resolution 1H-NMR spectra typical of mixed micellar systems. Cryo-transmission electron micrographs of specimens vitrified at that stage support the conclusion that the vesicles had become completely micellized. Following micellization, the metastable (cholesterol-supersaturated) bile-models spontaneously underwent a series of reorganizational steps: first, cholesterol-rich vesicles with a [CH]/[PC] ratio of 1.57 +/- 0.69 were formed, in co-existence with a mixed micellar system with [CH]/[PC] = 0.43 +/- 0.01 and CSI = 1.12 +/- 0.03. The resultant cholesterol-rich vesicles subsequently aggregated and cholesterol crystals of varying sizes and shapes appeared within the aggregates: needle-like structures were first observed, followed by clusters of those crystals and of helical crystals. Eventually, typical plate-like cholesterol crystals appeared, at which time some of the PC returned to the non-particulate (isotropic) phase. Consequently, the system contained cholesterol crystals coexisting with mixed micelles, whose composition was close to the limit of saturation (CSI = 1.08). These findings confirm the sequence of events preceding the appearance of cholesterol crystals, as previously proposed in our less detailed studies ((1990) Hepatology 12, 149S) and support the relevance of the morphologically similar results of Konikoff et al. ((1992) J. Clin. Invest. 90, 1155) obtained in a very dilute supersaturated bile-model.

Bile↗

Structures of nanoparticles prepared from oil-in-water emulsions.

Hydrophobic substances were dissolved in an organic solvent and emulsified with an aqueous solution at very high shear. Droplets of very small sizes (50-100 nm) were obtained by using surfactants which were combinations of lecithins and bile salts. After emulsification, the organic solvent was removed by evaporation, yielding stable dispersions of solid particles. The sizes, shapes, and structures of the particles were examined through quasi-elastic light scattering, small-angle neutron scattering and cryotransmission electron microscopy. Cholesterol acetate particles stabilized by lecithin and bile salts were found to be platelets of 10-20 nm thickness and 80 nm diameter. Cholesteryl acetate particles stabilized with POE-(20)-sorbitan monolaurate were dense spherical globules of diameter 100 nm. Particles with a composition similar to the endogenously occurring, lipoprotein, LDL, were large spherical globules studded with small vesicles. The subsequent evolution of the cholesteryl acetate dispersion upon aging was examined. There was no transfer of cholesteryl acetate between particles nor to large crystals. However, some aggregation of the particles was observed when the volume fraction of the particles in the aqueous dispersion exceeded 0.05. Thus, the structure of the nanoparticles obtained through deswelling of emulsion droplets changes according to the nature of the emulsifiers and to the composition of the hydrophobic substances which they contain.

Bile Acids and Salts↗

[Retrograde ejaculation as a side-effect of clozapine].

3 chronic paranoid schizophrenic men, aged 29, 30 and 37 years, respectively, developed retrograde ejaculation, a rare side-effect of clozapine. It disappeared after the dose was lowered in 1 of the patients and after stopping the drug in the other 2. On rechallenging with the drug, retrograde ejaculation recurred.

Adult↗

Direct visualization of lipid aggregates in native human bile by light- and cryo-transmission electron-microscopy.

The evolution of microstructures present in human gallbladder and hepatic bile was observed simultaneously by video-enhanced light microscopy (VELM) and transmission electron microscopy of vitrified specimens (cryo-TEM), as a function of time after withdrawal from patients. Fresh centrifuged gallbladder bile samples contained small (6 nm) spherical micelles in coexistence with vesicles (40 nm). Out of the seven bile samples investigated four contained, in addition, two types of elongated aggregates that have not been previously described. Uncentrifuged gallbladder bile also contained a mixture of ribbon- and plate-like crystals seen by VELM, but not by cryo-TEM. In aged (3-6-week-old) gallbladder bile samples VELM also revealed spiral and helical crystal structures. No such crystals were present in hepatic bile samples, although microcrystals, not observable by VELM were seen by cryo-TEM in addition to micelles and vesicles. The similarity of these observations to those observed in bile models lends strong support for the validity of the model systems. Furthermore, the presence of microcrystals in hepatic bile samples, apparently devoid of crystals by light microscopy, indicates that under certain conditions the common criterion of 'nucleation time' (NT), based on light microscopy, does not represent the real time of nucleation. In the human bile samples investigated in this study the dissociation between NT and the time of observation of microcrystals was seen in hepatic but not in gallbladder bile samples. Hence, crystal growth may be rate limiting only in dilute biles.

Bile↗

The mechanism of lamellar-to-inverted hexagonal phase transitions: a study using temperature-jump cryo-electron microscopy.

The lamellar/inverted hexagonal (L alpha/HII) phase transition can be very fast, despite the drastic change in the topology of the lipid/water interfaces. The first structures to form in this transition may be similar to those that mediate membrane fusion in many lipid systems. To study the transition mechanism and other dynamic phenomena in membrane dispersions, we constructed an apparatus to rapidly trigger the transition and then vitrify the specimens to preserve the structure of transient intermediates. The apparatus applies millisecond-long temperature jumps of variable size to aqueous dispersions of lipids on electron microscope grids at times 9-16 ms before specimen vitrification. The vitrified specimens are then examined by cryo-transmission electron microscopy. Dispersions of egg phosphatidylethanolamine completed the transition within 9 ms when superheated by 20 K. Similar transition times have been observed in dioleoylphosphatidylethanolamine via time-resolved x-ray diffraction. N-monomethylated dioleoylphosphatidylethanolamine dispersions superheated to lesser extent exhibited slower transitions and more complex morphology. The structure of the first intermediates to form in the transition process could not be determined, probably because the intermediates are labile on the time scale of sample cooling and vitrification (< 1 ms) and because of the poor contrast developed by some of these small structures. However, the results are more compatible with a transition mechanism based on "stalk" intermediates than a mechanism involving inverted micellar intermediates. Temperature-jump cryo-transmission electron microscopy should be useful in studying dynamic phenomena in biomembranes, large protein complexes, and other colloidal dispersions. It should be especially helpful in studying the mechanism of protein-induced membrane fusion.

Biophysical Phenomena↗

A new diagnostic approach to congenital stridor using a laryngeal mask airway and rigid endoscope.

Neonates with symptoms of stridor from birth, present a difficult diagnostic problem. We have demonstrated that by the use of a laryngeal mask airway in an anaesthetized baby breathing spontaneously, we are able to reach a diagnosis. This is accomplished by the introduction of a rigid fibre-optic endoscope through a Portex swivel connector and visualizing the glottis and larynx.

Anesthesia, General↗

[A case of self-circumcision].

A 29-year-old bachelor had immigrated from Uzbekistan to Israel 2 years before to improve his economic situation. He began drinking at the age of 20, and increased to 1-1.5 bottles of vodka a day. He was unable to keep a job more than a few months. When called up for limited military service, he thought that the army might be a solution for his employment problem. However, he felt that he would not be able to integrate into the army, and later into Israeli society, unless he was circumcised. The Ministry of Religion deferred his request for a religious circumcision because they did not consider him Jewish. Since he could not afford to pay for the operation, he read up on the procedure, drank a bottle of vodka as premedication, and tried to circumcise himself with a razor blade. Since he was unable to control bleeding, he applied to the hospital emergency room half an hour later, where the circumcision was completed and sutured. The psychiatric diagnosis was an unspecified personality disorder with psychopathic but not psychotic features.

Adult↗

[Mediagenic psychoses].

Disturbances of psychotic intensity resulting from external trauma at times of crisis and tension have been described in the literature, particularly in combat reactions, including the Saddam syndrome. Acute psychoses as reactions to mystical-religious fervor have also been described. We describe 2 clusters of patients admitted with an acute, delusional, psychotic picture against the background of the Vanunu treason trial and later the strong messianic expectations aroused among the followers of the Rebbe of Lubavitch. Both of these events received extensive coverage in the Israeli press and electronic telecommunication media. The emergence of the mental disturbances and the content of the psychoses were linked to the particularly strident and dramatic media coverage of these 2 events. The impact of the reports of wide-spread messianic fantasies in the contemporary news bulletins on those with preexisting premorbid sensitivity was sufficient to trigger the psychoses. The delusional content was topical, and not that of the traditional psychotic delusions such as that of being Napoleon. This emphasizes that not only an authentic major external trauma such as a war is capable of triggering psychosis, but also emotionladen, stressful news items, frequently repeated in the media (such as reports of espionage or messianic fervor), may have similar effects.

Acute Disease↗

Re-emergence of meningococcal carriage on three-year follow-up of a kibbutz population after whole-community chemoprophylaxis.

A long-term study was conducted to determine the rate of re-emergence of throat carriage of meningococci in a semi-closed kibbutz community after the administration of chemoprophylaxis to all its members. Serotype B:4 was selected as marker organism since it was isolated from a fatal case and was the most frequently occurring strain (80%) among serogroup B isolates, which themselves comprised 54% of all meningococci. The carriage rate among Israeli residents (volunteer workers were analyzed separately) before treatment was 6.6% (49/748) overall, with 4.3% group B strains. Three weeks after treatment, in most cases with rifampicin (whereby three persistently positive persons were retreated with minocycline), no meningococci were recovered. Six months later, 1.9% of a population sample aged < or = 30 years were positive, while before treatment and one and three years later, 9.4%, 8.6% and 4.6% respectively were positive in this age group. Serotype B:4 comprised 81.3% of group B strains before prophylaxis, 5.3% after one year, and 28.6% after three years, thus possibly re-establishing itself as the single dominant serotype. The marked suppression of carriage after mass chemoprophylaxis appeared to last at least six months, with the meningococcal population being re-established within a year.

Adolescent↗

A temperature-jump device for time-resolved cryo-transmission electron microscopy.

We describe a temperature-jump device that permits time-resolved studies of thin cryo-transmission electron microscopy specimens. The specimen is rapidly heated to induce a change in microstructure just prior to cryo-fixation. The apparatus consists of a xenon arc lamp equipped with a shutter controlled by timing circuitry, used in conjunction with an environmental specimen preparation chamber. The specimen is heated by exposure to focused light from the lamp, and then plunged into cryogen. Using a thermocouple constructed from an electron microscope grid, we show that temperature jumps of 30-60 K are achieved with exposure times of 150-450 milliseconds. Micrographs of dimyristoyl phosphatidylcholine (DMPC) vesicles and n-docosane films, subjected to these exposures, show that the specimens are still at least 20-30 K above their initial temperature when they contact the cryogen. This method could be applied to a variety of biological and chemical systems which undergo structural changes activated by a rise in temperature.

Dimyristoylphosphatidylcholine↗

["Saddam syndrome:" acute psychotic reactions during the Gulf War--renewal of concept of brief reactive psychosis].

6 patients came to our psychiatric emergency room during the first 2 weeks of the Gulf War presenting the clinical picture of acute delusional paranoid psychosis (4 women and 2 men between the ages of 30-77). 4 were without previously known psychopathology, while the other 2 were known to have had some nonpsychotic cognitive impairment. The first 4 recovered completely within a short time while the other 2 continued to have psychopathological symptoms. We discuss psychogenic or reactive psychosis, and the concept of reactivation when cumulative trauma exceed the individual's personal threshold, as may occur during a war. Different phenomenological syndromes may follow.

Acute Disease↗

[Combined tricyclic antidepressants and ritalin in elderly depressives].

Psychostimulants, including ritalin (methylphenidate), were used as antidepressives in the '50s but were then replaced by tricyclics and MAO inhibitors. Treatment of depression with psychostimulants is still controversial. Several anecdotal reports in the past decade approved the use of tricyclic antidepressants (TCA) together with methylphenidate in apathetic and withdrawal states in medically ill and in elderly patients. Ritalin elevates mood by releasing catecholamines and blocking their re-uptake, and also increases serum TCA levels. 5 men and 5 women between the ages of 65 and 79 were diagnosed as suffering from major depressive disorders, either single or recurrent, based on the Revised Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). They had been treated with TCA for up to several months with no response. Following addition of methylphenidate, 5-15 mg/d for 2 weeks, 4 men and 3 women improved rapidly, 2 of them within 24 hours.

Aged↗

Physico-chemical characterization of Intralipid emulsions.

Fat emulsions containing soy triacylglycerols (100-300 g/l) and egg-yolk phospholipids (12 g/l) are often used for intravenous feeding. Previous studies have shown that these emulsions contain chylomicron-like emulsion particles of diameters of 300-400 nm and excess phospholipids aggregated as vesicles (liposomes), which remain in the infranatant upon floatation of the emulsion particles by ultracentrifugation. This work is devoted to the characterization of the commercial lipid emulsions commonly denoted Intralipids, with special emphasis on the presently ill-defined liposomes. The lipid particles composing commercial lipid emulsions (10%, 20% and 30% Intralipids, Kabivitrum Nutrition) were characterized by the combined use of physical and chemical methods. Each of the emulsions was fractionated by ultracentrifugation in saline into a 'cream' layer which floats to the top of the dispersion upon ultracentrifugation and a relatively transparent infranatant. The cream layer contains large emulsion particles of diameters ranging from 300 to 400 nm, in agreement with theoretical considerations based on their chemical composition as determined by chemical analysis. The infranatants contain about 1 g/l triacylglycerols in addition to phospholipids (from 7.2 g/l in 10% Intralipid to 2.4 g/l in 30% Intralipid) in the form of smaller particles of 70-100 nm diameter. Cryo-transmission electron microscopy shows that the infranatants contain vesicles (mostly unilamellar) at the side of residual small emulsion particles. This conclusion is also consistent with the distribution of phospholipids between outer and inner lamellae, as determined by 31P-NMR.

Fat Emulsions, Intravenous↗

Time-resolved cryotransmission electron microscopy.

We describe a new technique, time-resolved cryotransmission electron microscopy (TRC-TEM), that can be used to study changes in microstructure occurring during dynamic processes such as phase transitions and chemical reactions. The sample is prepared on an electron microscope grid maintained at a fixed temperature in a controlled atmosphere. The dynamic process is induced on the grid by a change in pH, salt, or reactant concentration by rapid mixing with appropriate solutions. Alternatively, induction is by rapid change of specimen temperature, or by controlled evaporation of a volatile component. We call such procedures on-the-grid processing. The dynamic process is permitted to run for a defined time and then the thin-film specimen is thermally fixed by plunging into liquid ethane at its freezing point, producing a cryotransmission electron microscopy specimen. By repeating this procedure with varying delays between induction and sample fixation, we can observe transient microstructures. We demonstrate the use of TRC-TEM to study the intermediate structures that form during the transitions between L alpha, III, and HII liquid crystalline phases in phospholipid systems. We also identify several other possible applications of the technique.

Cryopreservation↗

Intermediates in membrane fusion and bilayer/nonbilayer phase transitions imaged by time-resolved cryo-transmission electron microscopy.

Bilayer-to-nonbilayer phase transitions in phospholipids occur by means of poorly characterized intermediates. Many have proposed that membrane fusion can also occur by formation of these intermediates. Structures for such intermediates were proposed in a recent theory of these transition mechanisms. Using time-resolved cryo-transmission electron Microscopy (TRC-TEM), we have directly visualized the evolution of inverted phase micro-structure in liposomal aggregates. We have identified one of the proposed intermediates, termed an interlamellar attachment (ILA), which has the structure and dimensions predicted by the theory. We show that ILAs are likely to be the structure corresponding to "lipidic particles" observed by freeze-fracture electron microscopy. ILAs appear to assemble the inverted cubic (III) phase by formation of an ILA lattice, as previously proposed. ILAs are also observed to mediate membrane fusion in the same systems, on the same time scale, and under nearly the same conditions in which membrane fusion was observed by fluorescence methods in earlier studies. These earlier studies indicated a linkage between a membrane fusion mechanism and III phase formation. Our micrographs suggest that the same intermediate structure mediates both of those processes.

Lipid Bilayers↗