Biomedical subjects

T C Freeman

Publications and source records attributed to T C Freeman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Perceived head-centric speed is affected by both extra-retinal and retinal errors.

When we make a smooth eye movement to track a moving object, the visual system must take the eye's movement into account in order to estimate the object's velocity relative to the head. This can be done by using extra-retinal signals to estimate eye velocity and then subtracting expected from observed retinal motion. Two familiar illusions of perceived velocity--the Filehne illusion and Aubert-Fleischl phenomenon--are thought to be the consequence of the extra-retinal signal underestimating eye velocity. These explanations assume that retinal motion is encoded accurately, which is questionable because perceived retinal speed is strongly affected by several stimulus properties. We develop and test a model of head-centric velocity perception that incorporates errors in estimating eye velocity and in retinal-motion sensing. The model predicts that the magnitude and direction of the Filehne illusion and Aubert-Fleischl phenomenon depend on spatial frequency and this prediction is confirmed experimentally.

Head↗

PubMed1998

Different mechanisms underlie three inhibitory phenomena in cat area 17.

Recently, it has been proposed that all suppressive phenomena observed in the primary visual cortex (V1) are mediated by a single mechanism, involving inhibition by pools of neurons, which, between them, represent a wide range of stimulus specificities. The strength of such inhibition would depend on the stimulus that produces it (particularly its contrast) rather than on the firing rate of the inhibited cell. We tested this hypothesis by measuring contrast-response functions (CRFs) of neurons in cat V1 for stimulation of the classical receptive field of the dominant eye with an optimal grating alone, and in the presence of inhibition caused by (1) a superimposed orthogonal grating (cross-orientation inhibition); (2) a surrounding iso-oriented grating (surround inhibition); and (3) an orthogonal grating in the other eye (interocular suppression). We fitted hyperbolic ratio functions and found that the effect of cross-orientation inhibition was best described as a rightward shift of the CRF ('contrast-gain control'), while surround inhibition and interocular suppression were primarily characterised as downward shifts of the CRF ('response-gain control'). However, the latter also showed a component of contrast-gain control. The two modes of suppression were differently distributed between the layers of cortex. Response-gain control prevailed in layer 4, whereas cells in layers 2/3, 5 and 6 mainly showed contrast-gain control. As in human observers, surround gratings caused suppression when the central grating was of high contrast, but in over a third of the cells tested, enhanced responses for low-contrast central stimuli, hence actually decreasing threshold contrast.

Action Potentials↗

PubMed1998

Depth information and perceived self-motion during simulated gaze rotations.

When presented with random-dot displays with little depth information, observers cannot determine their direction of self-motion accurately in the presence of rotational flow without appropriate extra-retinal information (Royden CS et al. Vis Res 1994;34:3197-214.). On theoretical grounds, one might expect improved performance when depth information is added to the display (van den Berg AV and Brenner E. Nature 1994;371:700-2). We examined this possibility by having observers indicate perceived self-motion paths when the amount of depth information was varied. When stereoscopic cues and a variety of monocular depth cues were added, observers still misperceived the depicted self-motion when the rotational flow in the display was not accompanied by an appropriate extra-retinal, eye-velocity signal. Specifically, they perceived curved self-motion paths with the curvature in the direction of the simulated eye rotation. The distance to the response marker was crucial to the objective measurement of this misperception. When the marker distance was small, the observers' settings were reasonably accurate despite the misperception of the depicted self-motion. When the marker distance was large, the settings exhibited the errors reported previously by Royden CS et al. Vis Res 1994;34-3197-3214. The path judgement errors observers make during simulated gaze rotations appear to be the result of misattributing path-independent rotation to self-motion along a circular path with path-dependent rotation. An analysis of the information an observer could use to avoid such errors reveals that the addition of depth information is of little use.

Cues↗

PubMed1998

Human pancreatic secretory trypsin inhibitor. Distribution, actions and possible role in mucosal integrity and repair.

Pancreatic secretory trypsin inhibitor is a potent protease inhibitor which was originally identified in the pancreas. It has subsequently been shown to be present in mucus-secreting cells throughout the gastrointestinal tract and also in the kidney, lung and breast. Its major roles are likely to be to prevent premature activation of pancreatic proteases and to decrease the rate of mucus digestion by luminal proteases within the stomach and colon. In addition, PSTI increases the proliferation of a variety of cell lines and stimulates cell migration, possibly acting via the EGF receptor. These findings suggest that PSTI may also be involved in both the early and late phases of the healing response following injury. Further studies including the production of transgenic overexpression and knockout models should help elucidate the physiological function of this peptide.

Animals↗

PubMed1997

Expression of the dystrophin-related protein 2 (Drp2) transcript in the mouse.

We have recently characterised a new member of the dystrophin gene family, DRP2, and its murine counterpart, Drp2, which encode dystrophin-related protein 2 (DRP2). DRP2 is predicted to resemble certain short C-terminal isoforms of dystrophin and dystrophin-related protein 1 (DRP1 or utrophin). We describe here a comprehensive survey of Drp2 expression in the mouse by RT-PCR, and compare the expression profile of Drp2 with that of the related genes Dmd, Drp1 and Dag1 that encode all the known isoforms of dystrophin, DRP1/utrophin and a component of the dystrophin-associated protein complex, dystroglycan, respectively. Drp2 was shown to be expressed throughout the central nervous system (CNS) and in several peripheral tissues including the eye, kidney, teeth, oesophagus, colon, epididymis and ovary. The expression of Drp2 in the CNS was then further defined by in situ hybridization. Overall, the pattern of Drp2 expression corresponds to a subset of the brain regions known to express Dag1, and shows substantial overlap with regions that express various isoforms of dystrophin (particularly in the cerebral cortex, hippocampus and cerebellum). These data define the distribution of Drp2 expression in the mouse, and raise the possibility that in the CNS it may be an important component in neuronal dystrophin-associated complexes.

Animals↗

PubMed1997

Conduction and synaptic transmission in the optic nerve and the superior colliculus during development of the retinocollicular projection in the wallaby (Macropus eugenii).

When do the developing connections between mammalian retinal ganglion cells and the superior colliculus become functional? Evoked potentials elicited by optic nerve stimulation in the pouch young of the wallaby were used to answer the question. Up to 42 days after birth, the evoked potentials in the colliculus appeared to be generated by axon conduction. Synaptic activity was first recorded from the rostral colliculus at 45 days, and was found to be progressively more caudal, spreading to cover the colliculus, by 65 days. From the earliest indication of synaptic activity until eye opening at 140 days, current source density (CSD) analysis consistently showed the same basic pattern: an initial deep sink from synaptic activity of fast (Y type) fibres, and a more superficial longer-latency sink from slower (W type) fibres. All features became more clearly delineated with age. The indirect retinocorticocollicular connection appeared between 134 days and 146 days. The ability of optic nerve fibres to sustain action potentials precedes their formation of functional synapses with collicular neurons, which happens abruptly at three months before eye opening. CSD analysis showed that the relationship between the conduction velocity of optic nerve fibres and their depth of termination is evident from the first signs of synapse formation.

Animals↗

PubMed1997

Perceived location of bars and edges in one-dimensional images: computational models and human vision.

Observers used a cursor to mark the location and polarity of all the bar and edge features seen in compound (f + 3f) gratings of moderate frequency and contrast. They almost always reported six bars and six edges per cycle of the fundamental frequency (f = 0.4 c/deg, contrast 32%), for all phases of the third harmonic (3f = 1.2 c/deg, contrast 10.7%). This general pattern of features was predicted by the positions of peaks and troughs in the outputs of even and odd filters applied to the stimulus waveform, but not by peaks of "local energy" since there were only two energy peaks per cycle. We considered a family of filters whose amplitude spectrum has slope p on a log-log plot. The best-fitting filter slope was determined for bars (even filter) and edges (odd filter) in conjunction with a classification rule in which all peaks and troughs in the response profile are counted as features. If bars were seen at luminance peaks, and edges seen at gradient peaks (zero-crossings in the second derivative) we should have found p = 0 for bars and p = 1 for edges. In fact, for both bars and edges the best-fitting slope was about p = 0.5. For edges, this is consistent with the use of a smoothed (Gaussian) derivative operator. The filters form a quadrature pair, as in the energy model, but features are not constrained to lie at energy peaks. A compressive transducer preceding the filters improved the goodness-of-fit for predicted edge locations, but did not affect the estimate of filter slopes, nor the goodness-of-fit for bar locations. In an experiment with single blurred edges we confirmed that the perceived location of edges is shifted towards the darker side of the edge in direct proportion to the contrast of the edge. This was well predicted by adding a compressive transducer to the filter model.

Contrast Sensitivity↗

PubMed1997

Co-ordinate regulation of the cystic fibrosis and multidrug resistance genes in cystic fibrosis knockout mice.

The cystic fibrosis (Cftr and multidrug resistance (Mdr1) genes encode structurally similar proteins which are members of the ABC transporter superfamily. These genes exhibit complementary patterns of expression in vivo, suggesting that the regulation of their expression may be co-ordinated. We have tested this hypothesis in vivo by examining Cftr and Mdr1 expression in cystic fibrosis knockout transgenic mice (Cftr(tm1CAM)). Cftr mRNA expression in Cftr(tm1CAM)/Cftr(tm1CAM) mice was 4-fold reduced in the intestine, as compared with littermate wild-type mice. All other Cftr(tm1CAM)/Cftr(tm1CAM) mouse tissues examined showed similar reductions in Cftr expression. In contrast, we observed a 4-fold increase in Mdr1 mRNA expression in the intestines of neonatal and 3- to 4-week-old Cftr(tm1CAM)/Cftr(tm1CAM) mice, as compared with age-matched +/+ mice, and an intermediate level of Mdr1 mRNA in heterozygous Cftr(tm1CAM) mice. In 10-week-old, Cftr(tm1CAM)/Cftr(tm1CAM) mice and in contrast to the younger mice, Mdr1 mRNA expression was reduced, by 3-fold. The expression of two control genes, Pgk-1 and Mdr2, was similar in all genotypes, suggesting that the changes in Mdr1 mRNA levels observed in the Cftr(tm1CAM)/Cftr(tm1CAM) mice are specific to the loss of Cftr expression and/or function. These data provide further evidence supporting the hypothesis that the regulation Cftr and Mdr1 expression is co-ordinated in vivo, and that this co-ordinate regulation is influenced by temporal factors.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1996

On the relationship between deformation and perceived surface slant.

A compelling impression of surface slant is produced by random dot displays depicting deformation and translation alone. A simple model of slant estimation based upon deformation is shown to capture quantitatively both the perceived slant in this situation and the distortion in perceived slant produced when constant deformation is added to random dot displays depicting moving slanted surfaces. The results confirm that deformation provides a simple account of perceived slant.

Humans↗

PubMed1996

Sub-pixel accuracy: psychophysical validation of an algorithm for fine positioning and movement of dots on visual displays.

Many visual experiments call for visual displays in which dots are plotted with very fine positional accuracy. Spatial hyperacuities and motion displacement thresholds can be as low as 5 sec arc. On computer graphics displays small angular displacements of a pixel can be obtained only with long viewing distances which impose a small field of view. To overcome this problem, we describe a method for positioning the centroid of a quadrel (a 2 x 2 block of pixels) with very high accuracy, equivalent to 0.4% of a pixel width. This enables dot displays to be plotted with high positional accuracy at short viewing distances with larger fields of view. We show psychophysically that hyperacuities can be measured with sub-pixel accuracy in quadrel displays. Motion displacement thresholds of 16 sec arc were measured in multiple-dot and single-dot displays even though the pixel spacing was 1.2 min arc. Quadrel displays may be especially useful in studies of optic flow and structure-from-motion which demand a fairly large field of view along with fine positional accuracy.

Algorithms↗

PubMed1996

Characterization of DRP2, a novel human dystrophin homologue.

The currently recognised dystrophin protein family comprises the archetype, dystrophin, its close relative, utrophin or dystrophin-related protein (DRP), and a distantly related protein known as the 87K tyrosine kinase substrate. During the course of a phylogenetic study of sequences encoding the characteristic C-terminal domains of dystrophin-related proteins, we identified an unexpected novel class of vertebrate dystrophin-related sequences. We term this class dystrophin-related protein 2 (DRP2), and suggest that utrophin/DRP be renamed DRP1 to simplify future nomenclature. DRP2 is a relatively small protein, encoded in man by a 45 kb gene localized to Xq22. It is expressed principally in the brain and spinal cord, and is similar in overall structure to the Dp116 dystrophin isoform. The discovery of a novel relative of dystrophin substantially broadens the scope for study of this interesting group of proteins and their associated glycoprotein complexes.

Amino Acid Sequence↗

PubMed1996

Tissue distribution of adenosine receptor mRNAs in the rat.

1. A degree of ambiguity and uncertainty exists concerning the distribution of mRNAs encoding the four cloned adenosine receptors. In order to consolidate and extent current understanding in this area, the expression of the adenosine receptors has been examined in the rat by use of in situ hybridisation and the reverse transcription-polymerase chain reaction (RT-PCR). 2. In accordance with earlier studies, in situ hybridisation revealed that the adenosine A1 receptor was widely expressed in the brain, whereas A2A receptor mRNA was restricted to the striatum, nucleus accumbens and olfactory tubercle. In addition, A1 receptor mRNA was detected in large striatal cholinergic interneurones, 26% of these neurones were also found to express the A2A receptor gene. Central levels of mRNAs encoding adenosine A2B and A3 receptors were, however, below the detection limits of in situ hybridisation. 3. The more sensitive technique of RT-PCR was then employed to investigate the distribution of adenosine receptor mRNAs in the central nervous system (CNS) and a wide range of peripheral tissues. As a result, many novel sites of adenosine receptor gene expression were identified. A1 receptor expression has now been found in the heart, aorta, liver, kidney, eye and bladder. These observations are largely consistent with previous functional data. A2A receptor mRNA was detected in all brain regions tested, demonstrating that expression of this receptor is not restricted to the basal ganglia. In the periphery A2A receptor mRNA was also found to be more widely distributed than generally recognised. The ubiquitous distribution of the A2B receptor is shown for the first time, A2B mRNA was detected at various levels in all rat tissues studied. Expression of the gene encoding the adenosine A3 receptor was also found to be widespread in the rat, message detected throughout the CNS and in many peripheral tissues. This pattern of expression is similar to that observed in man and sheep, which had previously been perceived to possess distinct patterns of A3 receptor gene expression in comparison to the rat. 4. In summary, this work has comprehensively studied the expression of all the cloned adenosine receptors in the rat, and in so doing, resolves some of the uncertainty over where these receptors might act to control physiological processes mediated by adenosine.

Animals↗

PubMed1996

Soybean lectin stimulates pancreatic exocrine secretion via CCK-A receptors in rats.

Rats fed raw soy flour (RSF) show pancreatic growth due to excessive cholecystokinin (CCK) release. Soybean trypsin inhibitors are implicated, but rats fed soybean lectin also showed pancreatic growth. Therefore, we studied the effect of soybean lectin on pancreatic protein secretion in anesthetized rats. Intraduodenal administration of 30 mg of RSF stimulated a 1-h integrated rise in pancreatic protein output of 2.2 +/- 1.1 mg/h (mean +/- SE) in rats with bile pancreatic (BP) juice returned to the duodenum. Selective removal of the lectin by affinity to N-acetyl-D-galactosamineagarose abolished the response (-0.1 +/- 0.2 mg/h). Adding back the 84 micrograms of lectin restored the output of 2.2 +/- 0.9 mg/h. With BP juice returned to the duodenum, 84 micrograms of lectin required the added presence of protein and protease inhibitors to have this effect. However, when BP juice was not returned, 84 micrograms of lectin given alone produced a pancreatic response of 3.2 +/- 1.3 mg/h. Plasma CCK concentrations rose significantly from 6.6 +/- 1.9 to 14.3 +/- 2.9 pmol/l, and the pancreatic response was abolished by CCK-A receptor blockade (0.0 +/- 0.1 mg/h). We conclude that soybean lectin plays a major role in the acute stimulation of pancreatic protein secretion by RSF. The lectin releases CCK and the effect is mediated by CCK-A receptors.

Animals↗

PubMed1995

Interocular suppression in cat striate cortex is not orientation selective.

For the majority of neurones in cat striate cortex, the response to an optimal stimulus presented to one eye is suppressed when a stimulus of substantially different orientation is presented to the other eye. In order to determine the true orientational tuning of the underlying inhibitory interactions in the absence of binocular facilitation for matched stimuli, we tested how the response of such cells to an optimal grating in one eye is affected by gratings in the other eye of spatial frequencies too high or low to elicit an excitatory response through either eye: the vast majority of cells displayed suppression that was essentially independent of orientation. Our results indicate that interocular inhibition derives from cells representing all orientations, but is swamped by interocular facilitation for stimuli matched in orientation and spatial frequency.

Animals↗

PubMed1995

Distribution of mRNA encoding the inwardly rectifying K+ channel, BIR1 in rat tissues.

The distribution of mRNA encoding the inwardly rectifying K+ channel, BIR1 [1] was investigated in rat tissues, and a comparison made with the expression of related genes rcKATP and GIRK1 using the reverse transcription-polymerase chain reaction (RT-PCR). This showed BIR1 to be expressed in all areas of the brain examined, in the eye but not in any other peripheral tissue. This pattern was distinct from rcKATP and GIRK1. Additional in situ hybridisation studies of the central expression of BIR1 demonstrated high levels of BIR1 mRNA in the hippocampus, dentate gyrus, taenia tecta and cerebellum and at lower levels in the cortex, habenular nucleus, olfactory bulb, primary olfactory cortex, thalamus, pontine nucleus and amygdaloid nucleus.

Animals↗

PubMed1995

H+/di-tripeptide transporter (PepT1) expression in the rabbit intestine.

In order to examine the intestinal expression of the recently cloned H+/di-tripeptide transporter (PepT1), oligonucleotide probes were synthesized and their specificity confirmed by Northern blot analysis of rabbit jejunal RNA. In situ hybridization studies, using these probes, show that PepT1 is expressed all along the small intestine and at a very much reduced level in the colon. In contrast, PepT1 mRNA was not detected in the stomach, sacculus rotundus or caecum. Microscopic examination of tissue sections showed PepT1 expression to be restricted to intestinal epithelium with no detectable expression in the lamina propria, muscularis mucosae, muscularis or serosa. The accumulation of PepT1 mRNA along the crypt-villus axis was also investigated. In all regions of the small intestine (in duodenum, jejunum and ileum), PepT1 mRNA was undetectable in deeper epithelial cells of the crypts. Expression was first detectable at or near the crypt-villus junction, the amount of PepT1 mRNA increasing rapidly in the lower villus to a maximum approximately 100-200 microns from this point. Along the length of the small intestine PepT1 mRNA was most abundant in duodenal and jejunal enterocytes, with lower levels in the ileal epithelium. PepT1 expression is greatly depressed in the follicle-associated epithelium of the Peyer's patch relative to both interfollicular and adjacent "normal" villi. These data are discussed in the context of the known physiological role of PepT1 in the gastrointestinal tract.

Animals↗

PubMed1995

Speed gradients and the perception of surface slant: analysis is two-dimensional not one-dimensional.

Motion parallax provides cues to the three-dimensional layout of a viewed scene and, in particular, to surface tilt and slant. For example, as a textured surface, inclined around a horizontal axis, translates horizontally relative to an observer's view point, then, in the absence of head and eye movements, the observer's retinal flow will contain a one-dimensional (1D) vertical speed gradient. The direction of this gradient indicates the direction of surface tilt, and its magnitude and sign can be used in calculating the magnitude and sign of the surface slant. Alternatively, the same retinal flow contains a 1D translating component, plus a two-dimensional (2D) component of rotation (curl), and a 2D component of deformation (def). On this view, the direction of surface tilt is related to the orientation of def and the magnitude and sign of the surface slant is related to the magnitude and sign of def. We used computer generated random dot patterns as stimuli to determine whether the human visual system employs a 1D analysis (i.e. 1D speed gradients) or a 2D analysis (i.e. deformation) of surface slant from motion parallax. Using a matching technique we found compelling impressions of slant when we vector summed a translation field with (i) vertical shear, horizontal shear or deformation (made from vertical and horizontal shear), but not rotation; and (ii) vertical compression, horizontal compression or deformation (made from vertical and horizontal compression), but much less so for expansion. In both cases, the first three conditions contain def, but the fourth does not, and the last three conditions contain 1D speed gradients orthogonal to the perceived axis of inclination, but the first one does not. Therefore, the results from the first and fourth conditions distinguish between the two processing strategies. They support the idea that surface slant is coded by combining both horizontal and vertical speed gradients in a way similar to the 2D differential invariant def and oppose the view that surface slant is encoded by a 1D analysis of motion in a direction orthogonal to the perceived axis of inclination. In a further experiment, we found essentially no effect of reducing the field size from 18 to 9 deg.

Cues↗

PubMed1995

Parallel patterns of cell-specific gene expression during enterocyte differentiation and maturation in the small intestine of the rabbit.

Enterocytes are the major epithelial cell type of the small intestine. Their capacity to secret, absorb and digest specific ions and nutrients is dependent on their position along the length of the small intestine as well as their stage of development as they migrate and differentiate along the crypt-villus axis. In order to further understand the molecular processes that regulate enterocyte differentiation and function, this study has compared the levels of six mRNA species produced by genes expressed in rabbit enterocytes; specifically, the multidrug resistance (MDR1) gene encoding the 170-kDa P-glycoprotein, CaBP 9k, which encodes a putative intracellular calcium buffer, calbindin, LPH, APN, and AP which encode the brush-border hydrolases lactase-phlorizin hydrolase, aminopeptidase N and alkaline phosphatase, respectively, and SGLT1, encoding the brush border Na(+)-glucose cotransporter. The level of each mRNA species has been mapped along the small intestine using quantitative in situ hybridisation. This has revealed characteristic regional variations in the abundance of each of the mRNAs, supporting the opinion that there is a strong genetic component to the maintenance of gradients in epithelial function along the length of the small intestine. Analysis of the cellular accumulation of mRNA during enterocyte migration along the crypt-villus axis, over gut-associated lymphoid tissue, and at epithelial boundaries, has, by contrast, established a clear correlation in the expression of these genes. These data illustrate the dynamics of enterocyte gene expression, thereby providing an insight into the molecular mechanisms which co-ordinate the events of cell transformation that underlie functional differences between the epithelial populations of the small intestine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗