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Biomedical subjects

P Hillman

Publications and source records attributed to P Hillman.

At least 19 recordsLinked to original sources
PubMed1994

Facilitation of the responses to injections of inositol 1,4,5-trisphosphate analogs in Limulus ventral photoreceptors.

Injection of inositol 1,4,5-trisphosphate and its metabolically resistant analogs InsP3S3 and L-chiro-2,3,5-InsP3 into the ventral photoreceptors of Limulus results in the release of calcium from internal stores and in a current flow into the cells. We show here that the dependence of the current response on the amount of analog injected is supralinear. The injections also facilitate the responses to subsequent injections. We analyze the kinetics of the responses either by very slow application of the analogs directly into the lobe that is sensitive to InsP3 and light or by delivering a pulse into the nonsensitive lobe of the cell, in both cases creating a ramp of rising concentration in the sensitive region. Typically, a long latent period was followed by a strong brief inward current. The ratio between the latency and the duration of the response, defined as twice the time from half-amplitude to the peak of the response, reaches values greater than 10. Our analysis shows that this value cannot be attained within realistic models whose only nonlinearity is the cooperative binding of the ligand to its receptor. The observed ratio, however, can be achieved with a positive feedback model. Treatments that lead to partial depletion of calcium stores reversibly increase the latency of the response. We conclude that the mechanisms of the response of Limulus ventral eye to the metabolically resistant analogs of InsP3 probably involves a positive feedback mechanism and that the carrier of the feedback is likely to be Ca2+.

Animals↗
PubMed1992

Response transfer functions of Limulus ventral photoreceptors: interpretation in terms of transduction mechanisms.

In recent years, our knowledge of the biochemical mechanisms underlying the transduction process in photoreceptors has expanded rapidly. However, a full picture of the temporal dynamics of these mechanisms remains elusive. To study the dynamics in the Limulus ventral photoreceptor, we measure its light-evoked transfer function under voltage clamp. Comparison of this transfer function to biochemically realistic theoretical models of transduction provides insights into the photoreceptor dynamics. This comparison supports the suggestion that the low-frequency behaviour of the Limulus photoreceptor, corresponding to light and dark adaptation, is that of a nonlinear negative feedback loop. The main reactions of this loop have time constants between about 1 and 40 s. Such a feedback loop does not account, however, for the high-frequency behaviour of the responses, which implies the existence of a further, fast-acting, mechanism.

Adaptation, Ocular↗
PubMed1992

The amplitudes of unit events in Limulus photoreceptors are modulated from an input that resembles the overall response.

Light adaptation is a gain-control process that endows photoreceptors with large dynamic range. In invertebrates, this process appears to be mediated by a negative feedback that sets the amplitude of the isolated photon responses (bumps) by modulating an enzyme's rate of catalysis. This paper reports measurements of the feedback dynamics of Limulus from the responses to small modulations in light intensity. The responses show a noise that apparently arises from the random arrival of photons. We use a dynamic noise-analysis technique to extract the cell's frequency-response transfer function for bump amplitude. Its ratio to the transfer function for the summed response of the cell has a simple form at low frequencies. This indicates that the origin of the feedback responsible for the adaptation is at a stage temporally close to the final conductance response. Moreover, the form of the transfer function suggests feedback by a chemical agent which is removed by a single enzymatic-like stage at low light intensity and by several such stages in parallel but with a spread of time constants at high intensity.

Adaptation, Ocular↗
PubMed1992

A recombinant-based feline immunodeficiency virus antibody enzyme-linked immunosorbent assay.

We have developed an antibody detection enzyme-linked immunosorbent assay (ELISA) for the identification of animals infected by feline immunodeficiency virus (FIV). The ELISA solid-phase antigen consists of recombinant FIV gag proteins expressed in bacteria. The proteins are purified from bacterial lysates as insoluble inclusion bodies. In the case of bacterially expressed p24gag, it is shown that all of the linear, sequential epitopes presented by viral p24 during infection are retained. Purified preparations can be substituted for solid-phase whole virus in the IDEXX PetChektm immunoassay. The antibody ELISA duplicates the sensitivity and specificity of the whole virus based PetChek plate assay.

Animals↗
PubMed1992

Ventilation system to minimize airborne bacteria, dust, humidity, and ammonia in calf nurseries.

We installed a ventilation system that minimizes airborne bacteria, dust, humidity, and ammonia levels; conserves animal heat during the winter months by precise control of the amount of fresh air admitted to the calf nursery; and prevents cross transfer of airborne pathogens between neighboring calves by providing uniform air distribution throughout the calf nursery. Because of the effectiveness of air filtration and uniform air distribution within the nurseries, respiratory problems of calves were reduced greatly. Airborne dust and bacteria as small as .5 mu were filtered from the air.

Aerosols↗
PubMed1991

Gender differences in apparent motion perception.

Distance disparity is a strong cue to element correspondence in apparent motion. Using a 2-AFC paradigm we have previously shown that shape similarity also plays a role. We now demonstrate a small gender difference in these effects: women are more sensitive to distance disparity, whereas men are more sensitive to differences in shape. Furthermore, in the competing presence of a shape cue, women's sensitivity to distance decreases while men's sensitivity is unaffected. These observations may be related to putative gender differences in the 'form' and 'motion-spatial relations' cortical pathways.

Adult↗
PubMed1990

Time course of perceptual discrimination and single neuron reliability.

The reliability of identification of a visual target increases with time available for inspection of the stimulus. We suggest that the neural basis of this improvement is the existence of a mechanism for integrating a noisy firing rate over some period, leading to a reduction in mean firing rate variance with available processing time. We have determined the experimental time course of the improvement in reliability in a parallel search task where the available inspection time is limited by the presentation of a mask at various times after a brief stimulus. We compare the resulting psychometric functions with the predictions of a model based on Signal Detection Theory. The model is based on the assumption that the reliability of the observer's response is limited by the variability of the responses of individual neurons. The reliability of the discrimination between two stimuli at the neuronal level is then directly related to the ratio of the difference between their integrated mean responses (over many trials) to the response standard deviation. This reliability increases with inspection time. To demonstrate application of the model to electrophysiological data, "neurometric functions" are derived from the firing rates of a monkey V1 cortical neuron. The data were obtained while the animal was active in a discrimination task. The results correspond qualitatively to our observed human psychometric functions.

Animals↗
PubMed1988

Shape similarity and distance disparity as apparent motion correspondence cues.

Apparent motion is perceived when two spots of light are presented successively in different locations. When more than one element is present in each frame, there is a correspondence problem in matching the elements in one frame with those in the other. We report the effects of shape similarity and distance disparity on the correspondence process. Twenty subjects were tested using a 2-AFC design. We found that both shape and distance cues are used by the correspondence process: when distance is the only cue the motion which is usually perceived is that involving the shorter distance; when shape is the only cue the motion involving two elements of the same shape is preferred. We also studied the interaction between the two cues when both were present. Quantitative measures of the relative strengths of these effects and of their interaction are reported. A Signal Detection Theory model is used to analyze these apparent motion correspondence effects.

Cues↗
PubMed1988

Biophysical evidence that light adaptation in Limulus photoreceptors is due to a negative feedback.

The steady-state stimulus-response curve of the Limulus ventral photoreceptor comprises a linear portion followed by a less-than-unity power law dependence, which is maintained over at least 4 decades of intensity. This progressive desensitization corresponds to light adaptation. For flash stimulation of dark-adapted cells, the stimulus-response curve again has an initial linear portion, but this is followed by a region of supralinearity before the curve saturates. In a previous article, we showed that the distribution of time integrals of the single-photon responses is consistent with a model of a single chain of first-order reactions. Starting with such a model, we have looked at relevant elementary nonlinear biochemical mechanisms to determine which of them can modulate the enzymatic amplifications of the chain in such a way as to lead to these behaviors. We assume that each of the two phenomena, adaptation and supralinearity, derives from a single mechanism that acts on a single enzymatic stage. We then conclude that the adaptation must be a cooperative negative feedback, in which an accessory material activated by a late stage of the transduction chain acts cooperatively to inhibit an earlier enzymatic amplification. In Limulus, the number of molecules that cooperate is between 3 and 5. We were not able to discard any of the mechanisms tested for the supralinearity, except to say that they must act at a stage of the chain later than that on which the adaptive material acts. If we assume the conclusions of a previous work which shows that the supralinearity mechanism is active during the steady state, we can also conclude that the supralinearity stage must precede the stage that is the source of the adaptive material.

Adaptation, Physiological↗
PubMed1988

The quantal source of area supralinearity of flash responses in Limulus photoreceptors.

The time integrals of the responses of dark-adapted Limulus ventral photoreceptors to flashes exhibit a supralinear dependence on intensity at intermediate intensities. By decomposing the responses into their elementary single-photon components ("bumps"), we are able to calculate the overall quantum efficiency and to display the time courses of the bump amplitude and rate of appearance. Since the time course of the flash response is not slow compared with that of the bump, it was necessary, in order to carry out the decomposition, to develop a new technique for noise analysis of dynamic signals. This new technique should have wide applications. Our main finding is that the supralinearity of the flash responses corresponds to an increase in bump amplitude, with little change in bump duration or quantum efficiency. The time courses of the bump rate and of the change in bump amplitude are peaked and have widths similar to that of the response itself. The peaks of the time courses of the bump rate and amplitude displayed against the starting times of the bumps do not coincide and occur approximately 80 and approximately 40 ms, respectively, before the peak of the response. The time from the start of a bump to its centroid is approximately 70 ms, which means that the time at which the bump centroid reaches its maximum follows the response peak by 30 ms. These results impose constraints on possible mechanisms for the amplitude enhancement.

Animals↗
PubMed1986

Spatial properties of the prolonged depolarizing afterpotential in barnacle photoreceptors. I. The induction process.

In invertebrate photoreceptors, when the light stimulus results in substantial net transfer of the visual pigment from the rhodopsin (R) to the metarhodopsin (M) state, the ordinary late receptor potential (LRP) is followed by a prolonged depolarizing afterpotential (PDA). The dependence of the amplitude of the PDA on the amount of pigment conversion is strongly supralinear, and the PDA duration also depends on this amount. These observations indicate an interaction among the elements of the PDA induction process and also make possible a test of the range of this interaction. The test consists of a comparison of the PDA after localized pigment conversion, obtained by strong spot illumination, to that after weaker diffuse illumination converting a comparable total amount of pigment. The experiment was performed on the barnacle lateral eye. The effective spot size was measured by the early receptor potential (ERP), in seawater saturated with CO2, which considerably reduced the electrical coupling between the photoreceptors. The ERP was also used to determine whether there is diffusion of R molecules into the illuminated spot. The spot illumination induced a PDA with small amplitude and long duration, while no detectable PDA was induced by the diffuse light. This indicates that the range of the PDA interaction is much smaller than the entire cell. In addition, the ERP results showed that there was no detectable diffusion of R molecules into the illuminated spot area over 30 min. This measurement, with a calculated correction for the microvillar geometry of the photoreceptor, enabled us to put an upper limit on the diffusion coefficient of the pigment molecules in the inact, unfixed barnacle photoreceptor of D less than 6 X 10(-9) cm2 s-1.

Animals↗
PubMed1986

Spatial properties of the prolonged depolarizing afterpotential in barnacle photoreceptors. II. Antagonistic interactions.

In the preceding article, we investigated the spatial properties of the induction of the prolonged depolarizing afterpotential (PDA) by shifting visual pigment from the rhodopsin (R) to the metarhodopsin (M) state in the barnacle photoreceptor. In this work, we have studied the ranges within the cell of the antagonistic effects on the PDA of M-to-R transfer. When this transfer occurs during a PDA, it depresses the PDA; when it precedes PDA induction, it impedes that induction ("anti-PDA"). These ranges were previously shown (by a statistical technique) to be at least a few tens of nanometers within a half-second (D greater than 10(-13) cm2 s-1). We now demonstrate, with local illumination techniques in which a PDA was induced in one side of the cell and PDA depression or anti-PDA was induced in the other side, that both ranges are much smaller than the cell diameter (approximately 100 microns) within 30 s (D less than 10(-6)). We further show, using a less direct but shorter-range technique involving colored polarized light, that the interaction of the PDA with the anti-PDA is restricted to less than approximately 6 microns (D less than 6 X 10(-9)). This figure is quite low and suggests that the interaction may be confined to the pigment molecules, possibly in a complex of the type suggested in the preceding article.

Animals↗
PubMed1985

Statistical test of linearity of photoreceptor transduction process: Limulus passes, others fail.

We present the results of a theoretical analysis of a completely general linear chain model for transduction in photoreceptors from which we have derived a statistical test for the intrinsic linearity of the single-photon transduction process. By linearity we mean comprising first-order chemical reactions only. We show results of our own measurements in Limulus ventral photoreceptors that pass this linearity test, suggesting that the single-photon transduction in Limulus may be a simple chain of first-order biochemical reactions (plus possible diffusional processes). However, we also demonstrate that published data show the existence of strong nonlinearities in the single-photon responses of toad and perhaps also of locust. Such nonlinearities are not difficult to construct from existing biochemical notions (feedback, cooperativity), but all but one [Kramer, L. (1975) Biophys. Struct. Mech. 1,239-257] of the published analytical models of the single-photon process have been linear. The test we have used is the distribution of "areas" (time integrals of conductance changes) of single-photon responses or "bumps." Reasonable molecular linear chain models do not allow distributions very sharply peaked at non-zero values. Such peaked distributions are seen in toad and locust but not in Limulus.

Animals↗
PubMed1982

The contribution of pigment transitions to sensitivity changes in the barnacle photoreceptor and the correlation with the prolonged depolarizing afterpotential.

A conditioning light can cause a decrease (adaptation) or an increase (facilitation) in the sensitivity of barnacle photoreceptors, as measured by the amplitude of the late receptor potential (LRP). We show that a net transfer of visual pigment from the rhodopsin (R) to the metarhodopsin (M) state induces a large facilitation whereas the reverse transfer results in a much smaller facilitation or even an adaptation. These effects were not due to the response to the conditioning light but to the pigment reactions. When the conditioning light did not alter the pigment population (i.e., M leads to M, R leads to R) it was followed by an intermediate degree of facilitation. These conclusions are correct for cells which have relatively low sensitivity. In sensitive cells, all pigment transitions produce adaptation. LRP facilitation and the prolonged depolarizing afterpotential (PDA) show several common characteristics with respect to pigment transitions: 1. Their magnitude increases with the amount of pigment transferred from R to M. 2. Both are depressed by the M leads to R transition. 3. Their production is impeded by the M leads to R transition. 4. The PDA itself is facilitated by the R leads to M transition and this facilitation decays with a time course comparable to that of LRP facilitation. These results suggest that there may be an underlying process common to LRP facilitation and PDA.

Animals↗