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Biomedical subjects

R H Carpenter

Publications and source records attributed to R H Carpenter.

At least 19 recordsLinked to original sources

Neural computation of log likelihood in control of saccadic eye movements.

The latency between the appearance of a visual target and the start of the saccadic eye movement made to look at it varies from trial to trial to an extent that is inexplicable in terms of ordinary 'physiological' processes such as synaptic delays and conduction velocities. An alternative interpretation is that it represents the time needed to decide whether a target is in fact present: decision processes are necessarily stochastic, because they depend on extracting information from noisy sensory signals. In one such model, the presence of a target causes a signal in a decision unit to rise linearly at a rate r from its initial value s0 until it reaches a fixed threshold theta, when a saccade is initiated. One can regard this decision signal as a neural estimate of the log likelihood of the hypothesis that the target is present, the threshold being the significance criterion or likelihood level at which the target is presumed to be present. Experiments manipulating the prior probability of the target's appearing confirm this notion: the latency distribution then changes in the way expected if s0 simply reflects the prior log likelihood of the stimulus.

Humans

Saccadic eye movements while reading music.

Subjects' eye movements were measured whilst they read and performed lines of music consisting of rhythmic information only, in conventional musical notation. The relationship between the spatial pattern of the notes displayed and of the fixations made in reading them is stochastic, and similar to that in ordinary reading, but with a tendency to fixate salient details of the notation such as notes and barlines rather than the spaces in between. Shorter notes are less likely to be fixated than longer ones, and this is determined by their performance length rather than their visual appearance. Despite the timing constraints imposed by the music, the time of execution of individual saccades appears to be entirely unrelated to the time of the execution of elements of the performance itself. However, as the tempo of performance of a given piece of music is increased, the average time between saccades decreases but their mean amplitude increases. These observations suggest a new model of the oculomotor and perceptual processes involved, in which an central, iconic representation of the fixated image is internally scanned and interpreted to a given criterion of accuracy, the scan ending when this criterion cannot be reached, and this end-point determining the position of the next fixation. It is proposed that the fullness of the buffer between the perceptual and motor processes determines the strictness of the criterion which is adopted, and hence the amplitude and timing of the eye movements.

Fixation, Ocular

"Express" smooth pursuit.

For the majority of human smooth pursuit eye movements made to a horizontal ramp target of unpredictable direction, the reciprocal of the latency appears to have a Gaussian distribution of the same general form as for saccades to step targets, but with smaller median. There are more latencies shorter than some 100 msec than would be expected from such a distribution: they form a distinct population ("express smooth pursuit responses") whose distribution is similar to that of express saccades. They still occur in the absence of a cue, when the target is unpredictable.

Adult

Subchronic oral administration of acemannan in the rat and dog.

Acemannan is the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed O-acetyl groups, with a mannose monomer/acetyl ratio of approximately 1:1. This complex polysaccharide is extracted from Aloe vera (barbadensis Miller); the technical material contains approximately 78% acemannan. Technical grade acemannan was administered po to rats for 14 d at 5% of the diet and for 6 mo at up to 2,000 mg/kg/d, and to beagle dogs for 90 d at up to 1,500 mg/kg/d without significant effect on any parameter measured in either species.

Administration, Oral

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.

Animals

In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir.

The antiviral effects of selected combinations between acemannan (ACE-M), a long-chained, polydispersed, beta-(1,4)-acetylated mannan, were tested in combination with azidothymidine (AZT) and acyclovir (ACY) in vitro. The rationale for such combinations was based on the antiviral and immunomodulatory properties exhibited by ACE-M. In addition, the observed antiviral effects of ACE-M against human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses appear to be related to modification of the glycosylation of viral glycoproteins. Therefore, the inhibitory effect of ACE-M does not overlap with that of AZT or ACY. The studies presented herein show that ACE-M combined with suboptimal noncytotoxic concentrations of AZT or ACY act synergistically to inhibit the replication of HIV-1 and herpes simplex virus type 1 (HSV-1), respectively. The median effect method was not applicable for analysis because the test compounds show mutually nonexclusive drug effects. For a meaningful evaluation and interpretation of the effects of drug combinations, the biological significance of combinations must be considered, that is, the protective effect of the combination, the noncytotoxicity of the combination, the mechanism(s) of action of the individual compounds comprising the combination, and so forth. With respect to effects on U1 cells latently infected with HIV-1, treatment with combinations of AZT and ACE-M does not potentiate virus replication.

Acyclovir

Inhibition of AIDS virus replication by acemannan in vitro.

Acemannan (ACE-M), a beta-(1,4)-linked acetylated mannan, was evaluated for in vitro activity against human immunodeficiency virus type 1 (HIV-1). Castanospermine (CAS), deoxymannojirimycin (DMN), swainsonine (SWS), azidothymidine (AZT), and dideoxythymidine (DDC) were tested in parallel as control compounds. In vitro antiviral efficacy of ACE-M was evaluated in a variety of cell lines including human peripheral mononuclear, CEM-SS1 and MT-2(2) cells. The virus strain, number of infectious units per cell, and target cell line were important factors in determining the degree of inhibition of viral cytopathic effect in the presence of ACE-M and other control compounds tested. Maximum inhibitory effect was observed in CEM-SS cells infected with the RFII strain of HIV-1. This inhibitory effect was determined to be concentration-dependent. Assay design included primary screening to measure cell viabilities of infected target cells in the presence and absence of test compounds. When tested on HIV-1/RFII-infected CEM-SS cells, the 50% inhibitory effect of CAS (IC50 = 28), an inhibitor of alpha-glucosidase I, was determined to be similar to that observed for ACE-M (IC50 = 45). However, DMN and SWS, inhibitors of mannosidase I and II, tested in parallel to CAS and ACE-M, exhibited no IC50 values. Antiviral potential of ACE-M as an inhibitor of syncytia formation was also explored using CEM-SS cells. Suppression of syncytia formation was observed at an ACE-M concentration of 31.25 micrograms/ml, and complete inhibition was observed at 62.5 micrograms/ml. In addition, HIV-1 RNA levels were studied to establish the antiviral potential of ACE-M in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents

The biological activities of mannans and related complex carbohydrates.

Complex polymers containing mannose (mannans) possess significant biological activity when administered to mammals. When given orally, they inhibit cholesterol absorption and induce hypocholesterolemia. If administered by other routes, they bind to mannose-binding proteins and induce macrophage activation and interleukin-1 release, inhibit viral replication, stimulate bone marrow activity, promote wound healing and inhibit tumor growth. This range of activities makes the mannans, potentially important biological-response modifiers and therapeutic agents.

Animals

Automated and manual quantitative assays of choriogonadotropin in serum compared.

We found the analytical performance of a rapid, automated assay of human choriogonadotropin (hCG) in serum, the Stratus hCG Fluorometric Enzyme Immunoassay, superior to a widely used manual assay for hCG (Hybritech Tandem-E hCG). The two assays were comparable in sensitivity; recovery; cross reactivity with lutropin, follitropin, and thyrotropin; and freedom from interference from hemoglobin and bilirubin. Patient-correlation studies indicated good quantitative agreement [Stratus hCG = (1.08 X Tandem hCG) - 4.3 int. units/L]. However, intra- and interassay precision was substantially better with the Stratus hCG assay, and this may allow earlier confirmation of pregnancy.

Antibodies, Monoclonal

Synchronized breeding of cycling ewes to produce fetuses of known gestational age.

A treatment regime involving a subcutaneous ear implant containing 3 mg of 17 alpha-acetoxy-11 beta-methyl-19-nor-preg-4-ene-3,20,dione (norgestomet) accompanied by an intramuscular injection of 1.5 mg norgestomet and 0.5 mg estradiol valerate proved effective for synchronizing estrus in the cycling ewe. Pregnancy rates were equivalent to those of control ewes mated concurrently. Sixty-two percent of all treated ewes became pregnant at the synchronized estrus. The initiation of the treatment regime was scheduled to allow delivery of fetuses of a specified age on the date requested by the investigator.

Animals

Contour-like phosphenes from electrical stimulation of the human eye: some new observations.

1. The contour-like phosphenes that may be seen with electrical stimulation of the human eye are described.2. It is found that a moving edge is particularly effective in generating these patterns.3. The relation between the velocity of the edge, the frequency of the current and the resultant spatial frequency of the lines is as if one line were generated at the edge for every cycle of the current.4. The frequency-dependence of the phase-shift between phosphene and current is such as would be expected if the light was delayed by some 30 msec relative to the current at the site of interaction.5. Evidence is brought forward suggesting that this phenomenon is the result not of interference-like processes, but of coupling interactions of the retinal neurones, dividing the population into domains responding in opposite phase to the electrical stimulation.

Accommodation, Ocular

Electrical stimulation of the human eye in different adaptational states.

1. Experiments are described in which the phosphene produced by passing alternating current of frequency 100 Hz through the eye is matched with a patch of light having the same apparent size.2. Matches of this type have been made against different background light intensities, and at various times after a strong retinal bleach.3. To match the phosphene under particular conditions of this type, it is found that the patch must be set some 1.5 log td brighter than its own threshold under the same conditions. Exceptions to this rule occur with very bright backgrounds, or very soon after bleaching.4. The increment threshold for a small spot of light on the phosphene in the dark is some 0.5 log td higher than for the same spot on a patch of light matched in appearance to the phosphene under the same conditions.5. The process linking electrical stimulation of the eye to firing of fibres in the optic nerve is deduced to be substantially unaffected by the state of adaptation of the eye, save perhaps in the exceptional conditions described in (3).6. It is therefore argued that this phosphene is the result of stimulation both of the retinal visual pathways lying central to the variable-gain element commonly accepted to explain the facts of dark adaptation, and also of the input to this element that is supposed to alter its gain.

Adaptation, Ocular