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At least 235 records · Page 13Linked to original sources

PubMed2002

Uptake of transforming DNA in Gram-positive bacteria: a view from Streptococcus pneumoniae.

In a working model for the uptake of transforming DNA based on evidence taken from both Bacillus subtilis and Streptococcus pneumoniae, the ComG proteins are proposed to form a structure that provides access for DNA to the ComEA receptor through the peptidoglycan. DNA would then be delivered to the ComEC-ComFA transport complex. A DNA strand would be degraded by a nuclease, while its complement is pulled into the cell by ComFA through an aqueous pore formed by ComEC. The nuclease is known in S. pneumoniae only as EndA. We have examined the processing (i.e. binding, degradation and internalization) of DNA in S. pneumoniae strains lacking candidate uptake proteins. Mutants were generated by transposon insertion in endA, comEA/C, comFA/C, comGA and dprA. Processing of DNA was abolished only in a comGA mutant. As significant binding was measured in comEA mutants, we suggest the existence of two stages in binding: surface attachment (abolished in a comGA mutant) required for and preceding deep binding (by ComEA). Abolition of degradation in comGA and comEA mutants indicated that, despite its membrane location, EndA cannot access donor DNA by itself. We propose that ComEA is required to deliver DNA to EndA. DNA was still bound and degraded in comEC and comFA mutants. We conclude that recruitment of EndA can occur in the absence of ComEC or ComFA and that EndA is active even when the single strands it produces are not pulled into the cell. Finally, inactivation of dprA had no effect on the internalization of DNA, indicating that DprA is required at a later stage in transformation.

Bacterial Proteins↗

PubMed2025

Efficient detection and characterization of targets of natural selection using transfer learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pre-trained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Journal Article↗

PubMed1993

Laboratory evaluation of a low prime closed-circuit cardiopulmonary bypass system.

We have explored the potential advantages of a low prime closed-circuit cardiopulmonary bypass (CPB) system using a non-human primate model. Although manufacturers have reduced priming volumes in individual CPB components, the standard circuit volume remains high because of the tubing diameter and length necessary for gravity drainage. By replacing gravity drainage with the negative pressure generated by a centrifugal pump, we can realize significant tubing volume reduction. Closed-circuit bypass was conducted on 13 baboons ranging from 5-15 kg. The circuit consisted of a centrifugal pump, a hollow fiber oxygenator, and 1/4" arterial and venous tubing. The design of the circuit included the capacity to remove a limited amount of venous air. Circulatory arrest during deep hypothermia with volume displacement into a reservoir was also accomplished with this circuit. The potential benefits of this low prime closed-circuit bypass system include blood conservation and reduction in blood surface area contact. The future safe clinical use of this type of closed-circuit bypass for routine open heart surgery will depend upon the incorporation of a device in the venous line to remove air. This is the greatest threat to patient safety in a closed circuit system and its use for open chest surgery must wait until an efficient venous air elimination device is available.

Blood Transfusion, Autologous↗

PubMed2002

Ephrin-A5 restricts topographically specific arborization in the chick retinotectal projection in vivo.

The retinotectal map is the best characterized model system to study how axons respond to guidance cues during the formation of the nervous system. Recent studies have shown that the critical event in forming this map is topographic-specific axon branching. To elucidate the in vivo role of the repulsive cue ephrin-A5 in this event, we used chromophore-assisted laser inactivation (CALI) to generate acute loss of ephrin-A5 function in localized areas of the posterior tectum of chick embryos in ovo and analyzed the resulting changes of retinal projections during initial outgrowth (E11) and when retinal axons arborize in the deep layers in the tectum (E12). We confirmed that ephrin-A5 functions to restrict initial axon outgrowth at E11. At E12, CALI of ephrin-A5 did not affect the extent of axon outgrowth on the tectal surface but instead caused ectopic arborization posterior to the topographically correct site in deeper layers of the tectum. This shows that ephrin-A5 restricts arborization during this critical process for developing the retinotopic map. CALI provides an approach to inactivate in vivo function in higher vertebrates with high temporal and spatial specificity that may have wide application.

Animals↗

PubMed1976

Vitamin-A-induced mucous metaplasia. An in vitro system for modulating tight and gap junction differentiation.

Stratified squamous epithelia from 14-day chick embryo shank skin contain rare tight-junctional strands and only small gap junctions. Exposure of this tissue to retinoic acid (vitamin-A) (20 U/ml) in organ culture, however, induces mucous metaplasia, accompanied by tight-junction formation and gap-junction growth; untreated specimens continue to keratinize. To investigate sequential stages of junctional assembly and growth, we examined thin sections and freeze-fracture replicas at daily intervals for 3 days. During the metaplastic process, tight junctions assemble in midepidermal and upper regions, beginning on day 1 and becoming maximal on day 3. Two tight-junctional patterns could be tentatively identified as contributing to the emergence of fully formed zonulae occludentes: (a) the formation of individual ridges along the margins of gap junctions; (b) de novo generation of continuous ramifying strands by fusion of short strand segments and linear particulate aggregates near cellular apices. Gap junction enlargement, already maximal at day 1, occurs primarily three to four cell layers deep. Growth appears to occur by annexation of islands of 20-40 8.5-nm particles into larger lattices of islands separated by particle-free aisles. Eventually, a single gap junction may occupy much of the exposed membrane face in freeze-fractured tissue, but during apical migration of the cells such junctions disappear. The vitamin- A chick-skin system is presented as a responsive model for the controlled study of junction assembly.

Animals↗

PubMedDate not supplied

Estimates of the net excitatory currents evoked by visual stimulation of identified neurons in cat visual cortex.

The action potential discharge response of single neurons to both visual stimulation and injections of current were obtained during intracellular recordings in cat visual cortex in order to estimate the net excitatory current arriving at the soma during visual stimulation. Of 45 neurons recorded intracellularly, 19 pyramidal neurons and one basket cell were labelled with horseradish peroxidase. The discharge of all neurons adapted to constant current. For 40 neurons, a single exponential provided a good fit to the adapting discharge (r2 = 0.73 +/- 0.03) for all current intensities. Superficial layer neurons were significantly faster adapting [P < 0.001, mean (+/- SEM) time constant of adaptation = 11.5 +/- 1.3 ms; n = 20] than deep layer neurons (mean time constant of adaptation = 51.4 +/- 6.4 ms; n = 10). The percentage adaptation of the spike frequency, %(peak - adapted rate)/peak, was determined from the fitted exponential. Superficial layer neurons adapted significantly more strongly (P < 0.01, mean = 67 +/- 3%) than deep layer neurons (mean = 51 +/- 5%). The mean firing frequency in response to a current step of 320 ms duration had a linear relationship to the amplitude of the injected current (slope 66 spikes/s/nA; origin zero, mean r2 = 0.94; n = 33). This relationship provided a means of estimating the net peak excitatory current generated by visual stimuli. The estimated mean peak somatic current during the passage of a bar across the receptive field was 1.1 nA and the average current for the duration of the visually evoked discharge was 0.64 nA (n = 17). The transfer response of real and model neurons was obtained by differentiating the discharge response to a step input current and was then used to predict the output of the neuron following an arbitrary input. When these transfer responses were convolved with known input signals in model neurons, the predicted output was close to the simulated response of the model neuron to the same input waveforms. The transfer response was calculated for eight real neurons. Estimates of the net excitatory current arriving at the soma during visual stimulation was obtained by deconvolution. The mean peak somatic current for these neurons was 0.62 nA.

Action Potentials↗

PubMed1991

Neuroblastoma grafts are noninvasively removed within mouse neocortex by selective laser activation of intracellular photolytic chromophore.

Studies of neural cell transplantation would be aided by the ability to damage or destroy, noninvasively and extremely selectively, grafted cells at defined times following their initial implantation. Mechanisms of graft integration and performance could be investigated, also providing insight into natural injury and repair mechanisms. At long wavelengths between 650 and 850 nm, laser energy can penetrate several millimeters of brain tissue without absorption or damage to the unpigmented tissue. However, targeted cells are selectively damaged by illumination at these long wavelengths if they contain latex nanospheres with incorporated cytolytic chromophores (e.g., chlorin e6). Light penetration allows many thousands of cells to be lesioned simultaneously, noninvasively, and deep within a surrounding matrix of other tissue. Such laser-activated damage has been termed laser photolysis (PL). We studied damage to C1300 neuroblastoma (NB) cells grafted into mouse neocortex in vivo by this process of PL. NB cells provided a simple and reproducible model of neural grafting, allowing direct histologic assessment of cellular growth and viability by distinct morphologic and mitotic criteria. Cells were cultured by standard methods, labeled in vitro by brief exposure to nanospheres containing chlorin e6, and grafted to sites within deep layers of mouse neocortex. Mice were exposed to transcranial, fractionated, unfocused pulses of 670-nm-wavelength energy totaling 90-120 J/cm2. We histologically assessed graft growth and cellular viability over a period from 2 d to 4 weeks, measured graft volumes quantitatively during the period of early rapid growth in controls (2 and 7 d), and generated 3-D reconstructions from serial sections to assist in visual analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[Changes in the sleep-wakefulness cycle in experimental Parkinson's syndrome].

It was demonstrated in rat experiments that in modelling the akinetico-rigid parkinsonian syndrome by injecting kainic acid into the caudate nuclei the phases of wakefulness and light slow-wave sleep decreased while the phase of deep slow-wave sleep increased. In the tremorogenic from of the parkinsonian syndrome induced by reserpine the phases of wakefulness and deep slow-wave sleep decreased in the rats while the phases of light slow-wave and paradoxical sleep increased. In destruction of the substantia nigra with kainic acid the phase of paradoxical sleep reduced. The results of the study are discussed from the standpoint of the generator mechanisms of the development of neuropathological syndromes and the mechanisms of the interrelations of parkinsonism and epilepsy.

Animals↗

PubMed1985

Infusion strategies to investigate the pharmacokinetics and pharmacodynamics of hypnotic drugs: etomidate as an example.

Etomidate was administered to six healthy volunteers by microprocessor controlled infusions, to generate three cycles of linearly increasing plasma levels, with an anticipated slope of 0.05 microgram ml-1 min-1. The infusions were stopped when a deep hypnotic state was obtained, as indicated by burst suppressions in the EEG. The infusions were restarted when the volunteers were fully orientated to person, place and time. The mean (+/-SD) doses of etomidate delivered by the first, second and third infusion were 165 +/- 30, 137 +/- 25 and 157 +/- 26 mg, respectively. Certain clinical signs were observed and related to the plasma concentrations of etomidate. Pharmacokinetic analysis was undertaken using an open two-compartment model. The therapeutic window was in a range of plasma concentrations between 0.3 and 1.0 microgram ml-1 of etomidate. Pharmacokinetic analysis gave a volume for the central compartment of 50 +/- 11 litre, an apparent volume of distribution of 252 +/- 51 litre and a total clearance of 1693 +/- 504 ml min-1. Microprocessor controlled infusions can serve as a powerful tool for research in clinical pharmacology. The achievement of linearly increasing plasma levels of etomidate allowed further pharmacokinetic and pharmacodynamic modelling concepts to be realized.

Adult↗

PubMed1997

Reaction of Nitrogen Chelates with the [Rh(2)](4+) Core: Bis-Chelate Products and Demonstration of Reversible, Chelate-Based Reduction Processes.

The preparations and properties are described of a series of [Rh(2)](4+) complexes possessing carboxylates and N-based chelates as ligands. Treatment of Rh(2)(O(2)CR)(4)(MeOH)(2) (R = Me (1), Et (2), Ph (3) or CF(3) (4)) with 2 equiv of 2,2'-bipyridine (bpy) in refluxing MeCN leads to the [Rh(2)(O(2)CR)(2)(bpy)(2)](2+) cation (in complexes 5-9). Reaction of 1 with 1,10-phenanthroline (phen), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bpy), 4,4'-diphenyl-2,2'-bipyridine (Ph(2)bpy), and 4,7-diphenyl-1,10-phenanthroline (Ph(2)phen) leads to the analogous cations of complexes 10-13. Complex 6a, [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](PF(6))(2).2MeCN, crystallizes in monoclinic space group P2(1)/a with the following cell parameters at -172 degrees C: a = 14.433(2) Å, b = 12.810(1) Å, c = 22.78(3) Å, beta = 104.42(3) degrees, Z = 4, and V = 3971.2 Å(3). Complex 9, [Rh(2)(O(2)CCF(3))(4)(bpy)(2)].Me(2)CO, crystallizes in triclinic space group P&onemacr; with the following cell parameters at 20 degrees C: a = 14.260(4) Å, b = 15.375(4) Å, c = 9.709(2) Å, alpha = 105.98(2) degrees, beta = 97.49(2) degrees, gamma = 70.32(2) degrees, Z = 2, and V = 1925.2 Å(3). Both 6a and 9 contain a singly-bonded [Rh(2)](4+) unit with two cis bridging RCO(2)(-) groups and two syn-bpy chelate groups in a near-eclipsed conformation about the Rh-Rh vector. Reaction of [Rh(2)(tpy)(2)(MeCN)(4)](BF(4))(4) (15) (tpy = 2,2':6',2"-terpyridine) with NBu(n)(4)(O(2)CPh) gives [Rh(2)(O(2)CPh)(tpy)(2)(MeCN)(2)](BF(4))(3).MeCN (16). Complex 16 crystallizes in triclinic space group P&onemacr; with the following cell parameters at -168 degrees C: a = 11.684(4) Å, b = 20.373(8) Å, c = 10.451(3) Å, alpha = 93.47(2) degrees, beta = 110.53(1) degrees, gamma = 100.03(2) degrees, Z = 2, and V = 2274.1 Å(3). The cation of 16 consists of a [Rh(2)](4+) unit with a bridging PhCO(2)(-) group and two chelating tpy groups. The solution (1)H NMR properties of complexes 6-13 and 16 show the complexes to retain their solid-state structures on dissolution. The electrochemical properties of 6-13 and 16 were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in MeCN. The bis(bpy) and -(phen) complexes 6-8, 10, and 11 show a reversible, one-electron reduction in the range -0.83 to -0.91 V vs ferrocene and an additional, irreversible reduction and an irreversible oxidation; the Ph(2)bpy (12) and Ph(2)phen (13) complexes show a two-electron reversible reduction at -0.61 to -0.76 and a reversible one-electron oxidation at 0.68-0.89 V. Consideration of the potentials as a function of carboxylate and chelate identity leads to the conclusion that the reductions are ligand (chelate)-based. This is supported by an extended Hückel calculation on the model compound [Rh(2)(O(2)CH)(2)(bpy)(2)(HCN)(2)](2+), which shows the LUMO to be a bpy-based orbital comprising in-phase, sigma overlap of two bpy pi orbitals, one on each of the syn-bpy groups. In contrast, complex 16 shows no reversible reduction processes. Complex 6b, [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](BF(4))(2), in MeCN may be reduced with sodium acenaphthylenide in THF to give deep blue [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](BF(4)) (14) in high yield. The cation of 14 may also be generated by controlled potential electrolysis of 6a in MeCN at -0.99 V and by heating of a solution of 6a or 6b in alcohol.

Journal Article↗

PubMed2003

Haplotyping as perfect phylogeny: a direct approach.

A full haplotype map of the human genome will prove extremely valuable as it will be used in large-scale screens of populations to associate specific haplotypes with specific complex genetic-influenced diseases. A haplotype map project has been announced by NIH. The biological key to that project is the surprising fact that some human genomic DNA can be partitioned into long blocks where genetic recombination has been rare, leading to strikingly fewer distinct haplotypes in the population than previously expected (Helmuth, 2001; Daly et al., 2001; Stephens et al., 2001; Friss et al., 2001). In this paper we explore the algorithmic implications of the no-recombination in long blocks observation, for the problem of inferring haplotypes in populations. This assumption, together with the standard population-genetic assumption of infinite sites, motivates a model of haplotype evolution where the haplotypes in a population are assumed to evolve along a coalescent, which as a rooted tree is a perfect phylogeny. We consider the following algorithmic problem, called the perfect phylogeny haplotyping problem (PPH), which was introduced by Gusfield (2002) - given n genotypes of length m each, does there exist a set of at most 2n haplotypes such that each genotype is generated by a pair of haplotypes from this set, and such that this set can be derived on a perfect phylogeny? The approach taken by Gusfield (2002) to solve this problem reduces it to established, deep results and algorithms from matroid and graph theory. Although that reduction is quite simple and the resulting algorithm nearly optimal in speed, taken as a whole that approach is quite involved, and in particular, challenging to program. Moreover, anyone wishing to fully establish, by reading existing literature, the correctness of the entire algorithm would need to read several deep and difficult papers in graph and matroid theory. However, as stated by Gusfield (2002), many simplifications are possible and the list of "future work" in Gusfield (2002) began with the task of developing a simpler, more direct, yet still efficient algorithm. This paper accomplishes that goal, for both the rooted and unrooted PPH problems. It establishes a simple, easy-to-program, O(nm(2))-time algorithm that determines whether there is a PPH solution for input genotypes and produces a linear-space data structure to represent all of the solutions. The approach allows complete, self-contained proofs. In addition to algorithmic simplicity, the approach here makes the representation of all solutions more intuitive than in Gusfield (2002), and solves another goal from that paper, namely, to prove a nontrivial upper bound on the number of PPH solutions, showing that that number is vastly smaller than the number of haplotype solutions (each solution being a set of n pairs of haplotypes that can generate the genotypes) when the perfect phylogeny requirement is not imposed.

Algorithms↗

PubMed2026

Fast, accurate construction of multiple sequence alignments from protein language embeddings.

Multiple sequence alignment (MSA) is a foundational task in computational biology, underpinning protein structure prediction, evolutionary analysis, and domain annotation. Traditional MSA algorithms rely on pairwise amino acid substitution matrices derived from conserved protein families. While effective for aligning closely related sequences, these scoring schemes struggle in the low-identity "twilight zone." Here, we present a new approach for constructing MSAs leveraging amino acid embeddings generated by protein language models (PLMs), which capture rich evolutionary and contextual information from massive and diverse sequence datasets. We introduce a windowed reciprocal-weighted embedding similarity metric that is surprisingly effective in identifying corresponding amino acids across sequences. Building on this metric, we develop ARIES (Alignment via RecIprocal Embedding Similarity), an algorithm that constructs a PLM-generated template embedding and aligns each sequence to this template via dynamic time warping in order to build a global MSA. Across diverse benchmark datasets, ARIES achieves higher accuracies than existing state-of-the-art approaches, especially in low-identity regimes where traditional methods degrade, while scaling almost linearly with the number of sequences to be aligned. Together, these results provide the first large-scale demonstration of the power of PLMs for accurate and scalable MSA construction across protein families of varying sizes and levels of similarity, highlighting the potential of PLMs to transform comparative sequence analysis.

Deep Learning↗

PubMed2025

CASTER-DTA: Equivariant Graph Neural Networks for Predicting Drug-Target Affinity.

Accurately determining the binding affinity of a ligand with a protein is important for drug design, development, and screening. With the advent of accessible protein structure prediction methods such as AlphaFold, predicted protein 3D structures are readily available; however, methods for predicting binding affinity currently do not take full advantage of 3D protein information. Here, we present CASTER-DTA (Cross-Attention with Structural Target Equivariant Representations for Drug-Target Affinity), which uses an equivariant graph neural network to learn more robust protein representations alongside a standard graph neural network to learn molecular representations to predict drug-target affinity. We augment these representations by incorporating an attention-based mechanism between protein residues and drug atoms to improve interpretability. We show that CASTER-DTA represents a state-of-the-art improvement on multiple benchmarks for predicting drug-target affinity and that it generates novel insights for several related tasks. We then apply CASTER-DTA to create a large resource of the binding affinities of every FDA-approved drug against every protein in the human proteome and make these predictions freely available for download. We also make available a web server for researchers to apply a pretrained CASTER-DTA model for predicting binding affinities between arbitrary proteins and drugs.

deep learning↗

PubMed2002

The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: a model for the secondary evolution of the classic C2h dimer and comparison of four mechanisms.

A mechanism is proposed for the formation in gas phase, during a short time, of the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry structures most likely to be formed in the supersonic jet expansion molecular beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown to be capable of unhinging about the hydrogen-bond pair as an axis, from 0 degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h) structure with its delicate geometry and symmetry. This relaxation mechanism is feasible in the 3-micros interval between the nozzle escape and the first laser pulse interception of the molecular beam. In the second part of the paper four published mechanisms are compared for concerted vs. two-step biprotonic phototransfer for the 7AI dimers. The dependence of the latter two models on H-atom instead of proton-transfer as an intermediate step negates the mechanism in a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron orbital that would be generated. The concerted mechanism for biprotonic phototransfer is reaffirmed by the analysis of the quantum mechanical conditions set on the biprotonic transfer in the photo-excited molecular 7AI pair.

Dimerization↗

PubMed1980

Heating patterns produced by 434 MHz erbotherm UHF 69.

Thermal distributions of 434 MHz Erbotherm H 69 hyperthermia/diathermy generators in tissue-equivalent medium have been investigated. Thermocouples were used to measure temperatures at a set of grid points. Cylindrical and abdominal phantoms were heated and sectioned after heating to measure the temperatures at depth. Results indicate that there is potential for heating deep-seated tumors. The distributions were influenced by the number, shape and geometry of the applicators employed.

Diathermy↗

PubMed1997

The vanishing defibrillator syndrome: incidence, mechanism, and clinical relevance.

Intraperitoneal migration of an abdominally implanted cardioverter defibrillator is a complication not yet fully described. In a consecutive series of 195 patients, migration occurred between 1 and 20 months in 5 (8%) of the 63 patients in whom a subrectus abdomini placement of the generator was chosen. It was unrelated to the patients' clinical characteristics or the defibrillator model. Dysuria and inability to interrogate the device were present in every subject, and the diagnosis was confirmed by the characteristic abdominal x-ray appearance and the findings at the time of surgery. Adhesions involving the omentum, and in one case, the small bowels, were present in three patients and seem to be related to the length of intraabdominal permanence of the generator. Because this complication may be due to specific anatomical characteristics of the aponeurosis of the abdominal muscles, it is likely that its incidence will be unchanged by the use of smaller devices. A close follow-up of the generators implanted deep to the rectus fascia is therefore advisable.

Abdomen↗

PubMed1998

Pain processing traced by magnetoencephalography in the human brain.

The temporal and spatial processing of pain perception in human was traced by magnetoencephalography (MEG). We applied a painful CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated areas using a single equivalent current dipole (ECD) at each time point, and a brain electric source analysis (BESA) as a spatio-temporal multiple source analysis method. The four-source model was found to be the most appropriate; sources 1 and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the stimulation, respectively. Activities in all 4 areas were temporally overlapped. Activity in the primary sensory cortex (SI) contralateral to the stimulated site was not identified. Activity in the cingulate cortex was also not clearly identified. These results are probably due to one or more of the following factors; (1) the cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres interfere with each other. No significant or consistent magnetic fields were recorded after 500 msec following the stimulation, probably due to the complicated spatial and temporal overlapping of activities in multiple areas.

Adult↗

PubMedDate not supplied

Fluconazole therapy for experimental cryptococcosis and candidiasis in the rabbit.

Fluconazole is a second-generation azole compound with broad-spectrum antifungal activity. It has been examined in several animal models emphasizing important clinical sites of infection with common yeast pathogens. The drug has an excellent pharmacokinetic profile for central nervous system, renal, and ocular infections; at these sites fluconazole has been successful in the treatment of infections with Cryptococcus neoformans or Candida albicans. On the basis of the experience in animals, fluconazole should be critically evaluated in the treatment of human mycoses such as cryptococcosis of the central nervous system and renal/ocular candidiasis. This agent represents the new wave of interest in the increasingly troublesome problem of deep-seated fungal infections.

Animals↗