Neural correlate of the overtraining reversal effect.
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Animals↗
Biomedical subjects
R W Lambert
Publications and source records attributed to R W Lambert.
Antibacterial properties of alafosfalin combined with cephalexin.
The phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) exhibited synergy in vitro and in animal studies against a range of bacterial genera when combined with cephalexin. Alafosfalin also showed synergy with mecillinam and, to a much lesser extent, with ampicillin. Synergy with cephalexin was more pronounced when the bacteria were relatively insensitive to the beta-lactam component. The action of this combination involved both an inhibitory and a bacteriolytic mechanism which was abolished by concurrent treatment with the aminopeptidase inhibitor, bestatin. Regrowth of subpopulation resistant to either component was markedly reduced by the combination. The potential of alafosfalin combined with cephalexin for use in therapy is discussed.
Alanine↗
Sperm head morphology of the plains mouse Pseudomys australis.
Spermatozoa of plains mice were studied by transmission and scanning electron microscopy. The occurrence of a distinct dorsal hook and 2 ventral hooks joined at the base was confirmed. Acrosomal material covered the dorsal hook and appeared to constitute most of the 2 ventral hooks which contained nuclear material only at the base. Incubation in sodium dodecyl sulphate resulted in loss of all the material presumed to be acrosomal.
Animals↗
Early and late acquisition of discriminative neuronal activity during differential conditioning in rabbits: specificity within the laminae of cingulate cortex and the anteroventral thalamus.
Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus was recorded during discriminative conditioning of an avoidance response (locomotion) in rabbits. The results indicated a greater unit response in cingulate cortex to the positive conditional stimulus (CS+; a tone paired with a footshock unconditional stimulus [UCS]) relative to the negative conditional stimulus (CS-; a tone randomly interspersed with the positive stimuli but never paired with the UCS). The majority of neuronal records obtained from the deep laminae (V and VI) of cingulate cortex manifested first neuronal discrimination in the session of first exposure to conditioning. However, the majority of neuronal records of the superficial laminae (I-IV) showed first discrimination at a late stage of training, during the session in which the criterion of behavioral discrimination was met. The late developing discriminative activity of the superficial laminae was coincident with the late developing discriminative activity of the AV thalamus. Once acquired, neuronal discrimination in cortex persisted throughout 600 msec after CS onset, and during six sessions of training (overtraining) beyond criterion. Analysis of individual neuronal records suggested that the persistence during overtraining resulted from replacement of early fading neuronal discriminations by late neuronal discriminations.
Animals↗
Cingulate cortical and anterior thalamic neuronal correlates of reversal learning in rabbits.
Unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training following differential conditioning of a locomotory (wheel rotation) avoidance response. The positive and negative conditional stimuli (CS+ and CS-) were pure tones (1 kHz and 8 kHz), and the unconditional stimulus was footshock (1.5 mA). During the first session, activity appropriate to the original task (i.e., a greater neuronal response to the CS- than to the CS+) occurred in the deep cortical laminae (V and VI), but the superficial laminae (I-IV) manifested the original discrimination in certain records and the reverse discrimination in others. All discriminative effects diminished during subsequent sessions except the short-latency (25-msec) deep laminar original discrimination, which persisted throughout reversal training. Activity of the AV nucleus underwent gradual transition, in parallel with the behavior, from the original to the reverse discrimination. Arousal-producing footshocks given after behavioral reversal educed the original and reverse discriminations in the deep and superficial laminae, respectively. These data are interpreted to indicate the role of cingulate cortex and anterior thalamus for encoding the associative significance of the conditional stimuli.
Animals↗
Phosphonopeptide antibacterial agents related to alafosfalin: design, synthesis, and structure-activity relationships.
Dipeptide variants of alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) with substantial differences in potency and antibacterial spectrum in vitro and in vivo have been synthesized. Certain dipeptides with alternatives to the L-alanyl residue had broader antibacterial spectra; activity against Pseudomonas aeruginosa was included. Some compounds had better in vivo activity than alafosfalin when introduced into infected rodents orally, but for the majority of the more active phosphonodipeptides, parenteral administration was more effective. Certain oligopeptides derived from the more active phosphonodipeptides possessed good in vitro activity against an extended range of organisms; they included Haemophilus influenzae, Streptococcus faecalis, and Streptococcus pneumoniae. The in vivo activity of some of these phosphono-oligopeptides was significantly greater than that of the parent dipeptide and correlated well with the in vitro results. This indicates that phosphono-oligopeptides exert part of their in vivo action directly, in addition to that arising from smaller peptides produced by peptidase cleavage.
Alanine↗
Phosphonopeptides as antibacterial agents: rationale, chemistry, and structure-activity relationships.
Peptide mimetics with C-terminal residues simulating natural amino acids have been designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of various l and d residues of natural amino acids combined with 1-aminoalkyl (and aryl-alkyl-) phosphonic acid residues had the most interesting antibacterial properties when the C-terminal residue was l-1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds has been explained in terms of transport into the bacterial cell and intracellular release of the alanine mimetic, which interferes with the biosynthesis of the peptidoglycan of the bacterial cell wall.
Alanine↗
Phosphonopeptides as antibacterial agents: alaphosphin and related phosphonopeptides.
Alaphosphin, l-alanyl-l-1-aminoethylphosphonic acid, was selected from a range of phosphonopeptides for evaluation in humans on the basis of its antibacterial activity, pharmacokinetics, and stability to intestinal and kidney peptidases. In vitro, the antibacterial action was antagonized by small peptides, resulting in low activity on peptone media. On an antagonist-free medium alaphosphin was bactericidal and rapidly lysed most susceptible gram-negative bacteria, but it was largely bacteriostatic and essentially nonlytic against gram-positive organisms. Its spectrum included most strains normally isolated from urinary tract infections, but potency was greatly reduced by very high inoculum levels and by alkaline pH. Although strains of Proteus and Pseudomonas were less susceptible to alaphosphin than were other common gram-negative bacteria, like other species they formed spheroplasts when exposed under appropriate conditions. Alaphosphin was equally effective against penicillin-susceptible and -resistant strains and showed no cross-resistance with known antibiotics. Good synergy and increased bactericidal activity were demonstrated with combinations of alaphosphin and d-cycloserine or beta-lactam antibiotics.
Alanine↗
Phosphonopeptides as antibacterial agents: mechanism of action of alaphosphin.
The novel antibacterial peptide mimetic alaphosphin (l-alanyl-l-1-aminoethylphosphonic acid) selectively inhibited peptidoglycan biosynthesis in both gram-negative and gram-positive bacteria. It induced accumulation of uridine diphosphate-N-acetyl-muramyl-tripeptide in gram-positive organisms and significantly reduced the intracellular pool levels of d-alanine. Alaphosphin was actively transported into bacterial cells by stereospecific peptide permeases and was subsequently hydrolyzed by intracellular aminopeptidases to yield l-1-aminoethylphosphonic acid. This alanine mimetic rapidly accumulated inside susceptible cells to yield a concentration which was 100- to 1,000-fold in excess of that of the precursor peptide in the surrounding medium. In the case of susceptible gram-negative organisms, it was shown that 1-aminoethylphosphonic acid was incorporated into a metabolite which was tentatively identified as uridine diphosphate-N-acetylmuramyl-aminoethylphosphonate. The primary intracellular target site of 1-aminoethylphosphonic acid was alanine racemase (EC 5.1.1.1), which was reversibly and competitively inhibited in the gram-negative organisms Escherichia coli and Pseudomonas aeruginosa and irreversibly inhibited in a time-dependent manner in the gram-positive organisms Staphylococcus aureus and Streptococcus faecalis. A secondary target site could be uridine diphosphate-N-acetylmuramyl-l-alanine synthetase [EC 6.3.2.8(b)]. The mechanism of action of alaphosphin may be regarded as involving at least three stages: (i) active transport by peptide permeases; (ii) intracellular peptidase cleavage; and (iii) action of l-1-aminoethylphosphonate on alanine racemase.
Alanine↗
Phosphonopeptides, a new class of synthetic antibacterial agents.
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Alanine↗
A predictive model for visual recovery following retinal detachment surgery.
By multiple regression analysis we have identified 26 out of 200 observations which significantly affect the visual acuity following retinal detachment surgery. In addition, we have developed a highly significant mathematical model, which is able to predict in rather broad ranges of visual acuity to approximately 67% accuracy. There is still a large percentage of patients for whom we cannot account for the variability in final vision, a problem requiring future investigation. Potentially important factors which were not analyzed in this study include duration of macular detachment, afferent pupil defect, drainage of subretinal fluid, extent of the scleral-buckling procedure, and postoperative follow-up longer than six months. While most of the variables are fixed and cannot be alterd, such as age, senile cataract, and refractive error, improved knowledge of influential factors may allow us to manipulate some of them and provide mechanisms for improving results in recovery or maintenance of macular function after retinal detachment surgery.
Adult↗
Claudication caused by compression of the cauda equina.
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Aged↗
The action of novel chloramphenicol analogues on prokaryotic and eukaryotic systems.
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Aminoacylation↗
Neuropeptides and Langerhans cells.
The immune system and nervous system are intimately related. In addition to neuroendocrine mechanisms, neuropeptides have a variety of effects on immune cells and are responsible at least in part for neurogenic inflammation. The presence of neuropeptides in the skin has been well documented. The influence of neuropeptides on Langerhans cells is the focus of this paper. The physical presence and effects of calcitonin gene-related peptide on Langerhans cells is emphasized. Discussion also includes the putative inflammatory and immunologic roles of vasoactive intestinal peptide, substance P, neurotensin, neuropeptide Y, and somatostatin in the skin.
Animals↗
Comparison of two microkeratome systems.
BACKGROUND: Microkeratomes are currently used for keratomiluesis in situ (automated lamellar keratoplasty) for myopia and hyperopia and for laser in situ keratomileusis (LASIK). Visual and refractive complications have been reported with these refractive surgical procedures. We compared two microkeratomes in their ability to resect corneal lamellae to gain insight into possible mechanism(s) of refractive and visual complications following lamellar refractive procedures. METHODS: Using an eyebank eye model, we performed automated lamellar keratoplasty to theoretically correct 10.00 diopters (D) of myopia using the Automated Corneal Shaper, manufactured by Chiron, Inc. and the MicroPrecision microkeratome, manufactured by Eye Technology, Inc. Diameters before (wet) and after fixation, thicknesses of excised tissue, and scanning electron microscopy were measured in a masked evaluation to compare instruments. Ultrasonic corneal pachymetry and a mechanical tissue compression gauge were also used to assess thickness of excised tissue. RESULTS: The Chiron automated corneal shaper created blade chatter marks at the edges of all excisions, smaller than anticipated excision diameters, and a wide range of tissue thicknesses. In contrast, the MicroPrecision microkeratome created smoother resections of all tissues without creating blade marks; tissue diameters and thicknesses were closer to the intended dimensions compared to the Chiron automated corneal shaper. CONCLUSION: Different microkeratomes create different morphologic features as they excise corneal tissue. Differences in instrument design, mechanics of the tissue excision and blade oscillation, and instrument traverse combined with surgical skill influence the configuration of lamellar keratotomies.
Aged↗