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F Sultan

Publications and source records attributed to F Sultan.

At least 19 recordsLinked to original sources

Direct and indirect activation of cortical neurons by electrical microstimulation.

Electrical microstimulation has been used to elucidate cortical function. This review discusses neuronal excitability and effective current spread estimated by using three different methods: 1) single-cell recording, 2) behavioral methods, and 3) functional magnetic resonance imaging (fMRI). The excitability properties of the stimulated elements in neocortex obtained using these methods were found to be comparable. These properties suggested that microstimulation activates the most excitable elements in cortex, that is, by and large the fibers of the pyramidal cells. Effective current spread within neocortex was found to be greater when measured with fMRI compared with measures based on single-cell recording or behavioral methods. The spread of activity based on behavioral methods is in close agreement with the spread based on the direct activation of neurons (as opposed to those activated synaptically). We argue that the greater activation with imaging is attributed to transynaptic spread, which includes subthreshold activation of sites connected to the site of stimulation. The definition of effective current spread therefore depends on the neural event being measured.

Animals↗

Lurcher mice exhibit potentiation of GABA(A)-receptor-mediated conductance in cerebellar nuclei neurons in close temporal relationship to Purkinje cell death.

In heterozygous Lurcher mice (Lc/+), the Purkinje cells (PCs) degenerate almost totally during postnatal development. On the other hand, their projection target, the deep cerebellar nuclei (DCN), shows few signs of degeneration and seems to play an important role in maintaining a residual cerebellar function in Lc/+. We asked whether the DCN in Lc/+ develop cellular adaptations allowing them to cope with the loss of GABAergic PC input. Using whole-cell patch-clamp recordings, we measured inhibitory postsynaptic currents from DCN of Lc/+ and wild-type mice (WT). In experiments on phenotypically striking Lc/+ studied well after the onset of the PC degeneration, we found enlarged average synaptic conductances (g(syn)) compared with WT. We next investigated postnatal mice before and after the onset of PC death. In younger animals </= postnatal day (p) 13, no difference was found in g(syn) between the two groups. At p14, g(syn) in Lc/+ showed an increase, while those in WT stayed on the level found in younger animals. A peak-scaled nonstationary fluctuation analysis suggests that an increase in the average number of channels open at peak is the basis for the change in g(syn). The changes in g(syn), suitable to increase the efficacy of GABAergic transmission, occur in close temporal relationship to PC death and, thus, may reflect a functional adaptation to the loss of the DCN's main GABAergic afferents.

Animals↗

IgM quantification in the cerebrospinal fluid of sleeping sickness patients by a latex card agglutination test.

An increased IgM concentration in cerebrospinal fluid (CSF), occurring as a consequence of massive intrathecal IgM synthesis, is a marker of interest for diagnosis of the meningo-encephalitic stage in human African trypanosomiasis. However, in current practice, IgM in CSF is not determined because of the lack of a simple and robust test that is applicable in African rural regions where the disease prevails. We describe the development of a sensitive semiquantitative card agglutination test, LATEX/IgM, for IgM quantification in CSF. The test is simple and fast and the lyophilized reagent remains stable even at 45 degrees C. CSF end-titres obtained with LATEX/IgM parallel the IgM concentrations determined by nephelometry and enzyme-linked immunosorbent assay. Detection of intrathecal IgM synthesis is the most sensitive marker for CNS involvement in sleeping sickness. At a cut-off value of >or= 8, the sensitivity and specificity of LATEX/IgM for intrathecal IgM synthesis are 89.4 and 92.7%. As a consequence, patients with LATEX/IgM end-titres >or= 8 are likely to have intrathecal IgM synthesis, thus central nervous system involvement and therefore should be treated accordingly. Further studies should concentrate on the relationship between the LATEX/IgM end-titres, presence of intrathecal IgM synthesis and occurrence of treatment failures in patients treated with pentamidine.

Animals↗

Distribution of mossy fibre rosettes in the cerebellum of cat and mice: evidence for a parasagittal organization at the single fibre level.

Mossy fibres are the main afferent input to the granular layer of the cerebellar cortex. In this study, the spatial distribution of the mossy fibres' presynaptic enlargements - the so-called rosettes - were analysed on the single fibre level. Data obtained from the cerebella of cat and mice were compared to look for species differences, and the cerebella of the adult and young mice were also compared to look for developmental changes. The results show that there is a spatial anisotropy in all mossy fibres studied, with neighbouring rosettes being about three times further away from each other along the parasagittal axis and closer to each other in the mediolateral direction. Furthermore, these results suggest that this anisotropy is established at an early developmental stage. The anisotropic orientation of mossy fibres at the single fibre level supports the hypothesis of a timing mechanism in cerebellar function.

Age Factors↗

Two types of neurons in the rat cerebellar nuclei as distinguished by membrane potentials and intracellular fillings.

Classically, three classes of neurons in the cerebellar nuclei (CN), defined by different projection targets and content of transmitters, have been distinguished. However, evidence for different types of neurons based on different intrinsic properties is lacking. The present study reports two types of neurons defined mainly by their intrinsic properties, as determined by whole-cell patch recordings. The majority of cells (type I, n = 63) showed cyclic burst firing whereas a small subset (type II, n = 7) did not. Burst firing was used to distinguish the two types of neurons because, as it turned out, pharmacological interference could not be used to convert the non-bursting cells to bursting ones. Some of the membrane potentials exclusively present in type I neurons, such as sodium and calcium plateau potentials, low-threshold calcium spikes, and a slow calcium-dependent afterhyperpolarization, were found to contribute to the generation of burst firing. Other membrane potentials of type I neurons were not obviously related to the generation of bursts. These were 1) the lower amplitude and width of the action potential during spontaneous activity, 2) a sequence of afterhyperpolarization-afterdepolarization-afterhyperpolarization following each spike, and 3) the high spontaneous firing rate. In contrast, type II neurons lacked slow plateau potentials and low threshold spikes. Their action potentials showed higher amplitude and width and were followed by a single deep afterhyperpolarization. Furthermore, they showed a lower firing rate at rest. In both types of neurons, a delayed inward rectification was present. Neurons filled with neurobiotin revealed that the sizes of the somata and dendritic fields of type I neurons comprised the whole range known from Golgi studies, whereas those of the few type II neurons recovered were found to be in the lowest range. In view of their size and scarcity, we propose that type II neurons may correspond to CN interneurons.

Action Potentials↗

Exploring a critical parameter of timing in the mouse cerebellar microcircuitry: the parallel fiber diameter.

Since the conduction velocity of the parallel fibers is a critical parameter for a theory of timing in the cerebellar cortex, we set out to quantify the diameter of these axons on an ultrastructural level. The overall mean of the fiber diameter was 0.18 microm. Our results confirm that the parallel fibers of the upper molecular layer are significantly thinner than those of the lower layers. Nevertheless, the difference of about 0.02 microm determined by this study is surprisingly small. In addition, the distribution of the fiber diameters of the upper layers differed slightly, but significantly from a normal distribution, partly on account of a positive skew and a positive kurtosis excess. In summary, the results show that there are fewer differences between the parallel fibers of different levels of the molecular layer than previously assumed and that these differences do not contradict a theory of timing in the cerebellar cortex.

Animals↗

Quantitative Golgi study of the rat cerebellar molecular layer interneurons using principal component analysis.

In this study, we applied for the first time a multivariate analysis to describe the anatomy of cerebellar molecular layer interneurons. Forty variables extending over a variety of morphological features (geometrical, topological, and metrical) were obtained from a three-dimensional reconstruction of 26 rat rapid Golgi-stained neurons. The subsequent principal component analysis showed that the first principal component was strongly correlated with variables related to the depth of each cell's soma in the molecular layer. The second principal component was strongly correlated with parameters describing axonal morphology. Finally, an analysis of the distribution of these anatomical features suggested that these cells cannot be classified into distinct groups but, instead, represent one continuously varying population. Thus, the classical division of molecular layer neurons into deep basket cells and superficial stellate cells is not supported by our analysis. These results have important implications for the development of the cerebellar cortex as well as for the expected patterns of Purkinje cell activity following activation of the granule cell layer.

Animals↗

Mucosal immunogenicity of a holotoxin-like molecule containing the serine-rich Entamoeba histolytica protein (SREHP) fused to the A2 domain of cholera toxin.

One strategy for the induction of mucosal immune responses by oral immunization is to administer the antigen in conjunction with cholera toxin. Cholera toxin consists of one A polypeptide (CTA) which is noncovalently linked to five B subunits (CTB) via the A2 portion of the A subunit (CTA2). Coupling of antigens to the nontoxic B subunit of cholera toxin may improve the immunogenicity of antigens by targeting them to GM1 ganglioside on M cells and intestinal epithelial cells. Here, we describe the construction of a translational fusion protein containing the serine-rich Entamoeba histolytica protein (SREHP), a protective amebic antigen, fused to a maltose binding protein (MBP) and to CTA2. When coexpressed in Escherichia coli with the CTB gene, these proteins assembled into a holotoxin-like chimera containing MBP-SREHP-CTA2 and CTB. This holotoxin-like chimera (SREHP-H) inhibited the binding of cholera toxin to GM1 ganglioside. Oral vaccination of mice with SREHP-H induced mucosal immunoglobulin A (IgA) and serum IgG antiamebic antibodies and low levels of mucosal anti-CTB antibodies. Our studies confirm that the genetic coupling of antigens to CTA2 and their coexpression in E. coli can produce holotoxin-like molecules that are mucosally immunogenic without the requirement for supplemental cholera toxin, and they establish the SREHP-H protein as a candidate for evaluation as a vaccine to prevent amebiasis.

Animals↗

Twenty-nine day study of stability for six different parenteral nutrition mixtures.

: BACKGROUND: The aim of the study was to assess the particle size stability of six parenteral nutrition regimens, fitted to various pathologies, and used by the University Hospital of Limoges. The mixtures contained glucose (30 or 50%), amino acids (Hyperamine(R)25), and either long-chain triglycerides (20% Intralipide(R)) or a combination of medium and long-chain triglycerides (20% Médialipide(R)). The regimens were not supplemented. RESULTS: The visual examinations, particle size analysis and physico-chemical tests, carried out during a long storage period, did not reveal any significant evolution of the lipid emulsions. All the tested formulae were stable for 28 days at 4 degrees C plus 24 h at room temperature. CONCLUSIONS: It was concluded that the choice of lipid emulsions depends, for these formulae, on the metabolic and clinical needs of the treated patients.

Journal Article↗

The detection and generation of sequences as a key to cerebellar function: experiments and theory.

Starting from macroscopic and microscopic facts of cerebellar histology, we propose a new functional interpretation that may elucidate the role of the cerebellum in movement control. The idea is that the cerebellum is a large collection of individual lines (Eccles's "beams": Eccles et al. 1967a) that respond specifically to certain sequences of events in the input and in turn produce sequences of signals in the output. We believe that the sequence-in/sequence-out mode of operation is as typical for the cerebellar cortex as the transformation of sets into sets of active neurons is typical for the cerebral cortex, and that both the histological differences between the two and their reciprocal functional interactions become understandable in the light of this dichotomy. The response of Purkinje cells to sequences of stimuli in the mossy fiber system was shown experimentally by Heck on surviving slices of rat and guinea pig cerebellum. Sequential activation of a row of eleven stimulating electrodes in the granular layer, imitating a "movement" of the stimuli along the folium, produces a powerful volley in the parallel fibers that strongly excites Purkinje cells, as evidenced by intracellular recording. The volley, or "tidal wave," has maximal amplitude when the stimulus moves toward the recording site at the speed of conduction in parallel fibers, and much smaller amplitudes for lower or higher "velocities." The succession of stimuli has no effect when they "move" in the opposite direction. Synchronous activation of the stimulus electrodes also had hardly any effect. We believe that the sequences of mossy fiber activation that normally produce this effect in the intact cerebellum are a combination of motor planning relayed to the cerebellum by the cerebral cortex, and information about ongoing movement, reaching the cerebellum from the spinal cord. The output elicited by the specific sequence to which a "beam" is tuned may well be a succession of well timed inhibitory volleys "sculpting" the motor sequences so as to adapt them to the complicated requirements of the physics of a multijointed system.

Animals↗

Characterization and quantification of apolipoprotein E in the genetically hypercholesterolemic rat (RICO).

The levels of apolipoprotein E (apo E) in serum and in isolated lipoprotein fractions from genetically hypercholesterolemic rats (RICO) and their normocholesterolemic controls (SW), were evaluated by immunoblotting, and their polymorphism was analyzed by isoelectrofocusing. The present results confirm previous findings from a qualitative SDS-PAGE analysis. When measured by immunoblotting, total apo E increased by 35% in the RICO rat plasma. In the different lipoprotein fractions, apo E in RICO rat increased in low density lipoproteins; LDL1, LDL2 (apo E rich HDL1) and high density lipoproteins (HDL2, HDL3). Only in the chylomicron fraction did apo E decrease. The two-dimensional electrophoretic method demonstrated that four isoproteins designated E-1, E-2, E-3 and E-4 are present at a pI range from 5.36 to 5.56 in RICO rat as well as in control SW rat.

Animals↗

Effect of dietary cholesterol on activity and mRNA levels of hepatic lipase in rat.

Female lean Zucker rats were fed for four weeks with either a control diet or the same diet enriched with 2% (w/w) cholesterol and cholic acid (0.5%, w/w). This treatment resulted in a 6-fold increase in plasma total cholesterol. A 30% decrease was observed in plasma post-heparin HL activity, in contrast with lipoprotein lipase, which was unmodified in the cholesterol/cholate-fed rats. HL activity measured in liver homogenate from these rats was also decreased (-30%, p < 0.05), as was its protein mass, quantified by immunoblot analysis (-57%, (p < 0.01), whereas HL mRNA levels were 3-fold lower in the cholesterol/cholate-fed rats. We conclude that the cholesterol/cholate-enriched diet decreases the HL gene expression by acting at the transcriptional level and/or by affecting HL mRNA stability, or both.

Animals↗

Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient.

Mycobacterium chelonae (formerly known as M. chelonae subspecies chelonae) is a rapidly growing mycobacterium that can cause disseminated infections, especially in immunocompromised hosts. The bacterium is typically resistant to antimicrobial agents; less than 20% of M. chelonae isolates are susceptible to trimethoprim-sulfamethoxazole, doxycycline, erythromycin, or ciprofloxacin. Findings in a recent study suggested that clarithromycin may be the drug of choice for the treatment of cutaneous (disseminated) disease due to M. chelonae. We describe a 60-year-old heart transplant patient with disseminated M. chelonae infection for whom monotherapy with clarithromycin failed because of the rapid development of resistance to the drug.

Anti-Bacterial Agents↗

Correspondence.

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Comment↗

Shapes and sizes of different mammalian cerebella. A study in quantitative comparative neuroanatomy.

The shape of the cerebellar cortex in fourteen mammalian species and one bird was studied by careful dissection, counts of the numbers of folia, and measurement of their length. All mammalian cerebella conformed to the same general plan, with an anterior region where folia are continuous between right and left, and three separate posterior appendages. There were, however, considerable differences between species, both in the relative length of the posterior appendages and in the relative abundance of folia on the midline compared to the lateral portions. In order to discover general laws referring to the width and length of the cerebellar cortex in their relation to body weight, cerebellar weight, and area of cerebellar cortex, an allometric analysis was performed. By plotting the values for the various species on log-log diagrams, the following statements can be inferred: 1. The weight of the cerebellar cortex is proportionate to the body weight to the power of 0.72, well comparable to the classical proportionality between brain weight and body weight to the power of 2/3 (Jerison 1973). 2. Cerebellar area and cerebellar weight are proportionate in larger animals, but in the smaller species the thickness of the cerebellar cortex varies and therefore a different dependence is valid. 3. The width of the cerebellar cortex increases with body size in the smaller species but tends to remain constant in the larger ones. 4. The longest anterior-posterior extension in our collection was measured in the bovine cerebellum. 5. The position of man in our collection of species is particular in several ways. The width of the human cerebellum is far greater than allometric relations established for the other species would suggest. Also, the vermal length of man falls short of the allometric rule established for the other species.

Animals↗

[Role of hepatic lipase in the catabolism of chylomicron remnants in the rat].

Before being taken up by the liver, chylomicrons are hydrolyzed successively by two lipases. The first one is the lipoprotein lipase which hydrolyzes mainly chylomicron triacylglycerols and gives rise to remnant particles. The latters will be further hydrolyzed by the hepatic lipase which exerts mainly a phospholipase A1-like activity on these particles. Chylomicrons as well as remnants, incubated with hepatic lipase in vitro, lose up to 47% of their phospholipids while triacylglycerols are less or even not hydrolyzed at all. A decrease in phosphatidylcholine (-30% and -34%) and an increase in lysophosphatidylcholine (+260% and +316%) are the main modifications measured in chylomicrons and in their remnants respectively, after hepatic lipase action. From several date (Borensztajn's work and ours), it arises that phospholipolysis of chylomicrons and of chylomicron remnants, is the obligatory metabolic step before these particles are taken up and degraded by the liver.

Animals↗