Direct and pairwise area estimation of physical shapes through vision and touch.

On a perceptual task in which a participant estimated areas of five physical rigid shapes, participants could view and touch the shapes, using one of two estimation methods, direct or pairwise. For the direct method, participants held one shape at a time and estimated the area based on a unit square (equal to 1/10 of the actual area). Mean error by participants was 14.4%. In the pairwise method, when participants were simultaneously handed two shapes, their error was 0.3%. Both direct and pairwise errors for vision plus touch of physical stimuli were considerably lower than previous errors made when viewing with an overhead projector screen.

The mechanical performance of ambulation using spring-loaded axillary crutches. A preliminary report.

Crutches with the extension post replaced by a spring-loaded post were compared with standard axillary crutches with respect to stresses developed during the stance phase of locomotion. Seven subjects were tested using both standard and spring-loaded crutches. The crutches were fitted with strain gauges; crutch length and grip location were adjusted for each subject using accepted standards. Subjects ambulated using a three-point "swing-through" gait pattern while strain gauge data were recorded. Spring-loaded axillary crutches had 22% smaller shock waves upon initial contact and 24% smaller peak stresses (P less than 0.05). Subjects reported improved endurance and comfort with the spring-loaded crutch. Although larger trials will be necessary, these initial results show promise in reduction of impact-loading of the upper extremity of patients using axillary crutches.

The alpha 1-antitrypsin gene is expressed in a human intestinal epithelial cell line.

alpha 1-Antitrypsin (alpha 1-AT) is considered a typical plasma protein and a prototype of the serine proteinase inhibitor (serpin) family. It is synthesized in hepatocytes and, to a lesser extent, in macrophages. In this study we show that the alpha 1-AT gene is also expressed in human intestine and in a human colonic epithelial tumor cell line, Caco2. A single 1.6-kilobase alpha 1-AT-specific mRNA is present in jejunum and in Caco2 cells. It is identical in apparent size to that present in human hepatoma HepG2 cells but slightly smaller than that present in human macrophages, cells in which an alternative upstream transcriptional start site is used. Synthesis and secretion of alpha 1-AT in Caco2 cells is similar to that in HepG2 cells. It is synthesized as an approximately 52-kDa precursor polypeptide, converted to its mature, fully glycosylated 55-kDa form intracellularly, and the native protein is secreted with a half-time of 37 min. Functionally active alpha 1-AT is secreted into the basolateral and apical (luminal) fluid in pulse-chase labeling experiments of Caco2 cells cultured in polarized orientation on collagen-coated nitrocellulose membranes. Expression of alpha 1-AT in Caco2 enterocytes is not affected by soluble factors that regulate expression of alpha 1-AT in macrophages and hepatocytes. However, expression of alpha 1-AT increases markedly in Caco2 cells as they differentiate into enteric villous-type cells.

Clonidine and cortical plasticity: possible evidence for noradrenergic involvement.

In order to test the hypothesis that noradrenergic transmission modulates ocular dominance plasticity in kitten visual cortex, we monocularly deprived kittens while administering the alpha-2 adrenergic agonist clonidine (CLON). To avoid bias in testing the hypothesis, we included, with a single blind technique, saline-treated control kittens in the series. First, using high-pressure liquid chromatography, we demonstrated that CLON treatments resulted in an average decline in cerebrospinal fluid levels of the norepinephrine metabolite, 3-methoxy-4-hydroxy phenylethylene glyolol (MHPG) of 44%. Then, single-unit recording in area 17 revealed the expected ocular dominance (OD) shift in monocularly deprived saline controls, but recording failed to find a significant shift in CLON-treated kittens. Our results support the notion that CLON treatment interferes with ocular dominance plasticity by inhibiting noradrenergic transmission in visual cortex. We discuss side effects of CLON, concluding that CLON's sedative effect may contribute to the lack of OD shift.

Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II.

The following order of genes on the short arm of human chromosome 11 (11p) was determined previously: parathyroid hormone (PTH)-the beta-globin gene cluster (HBBC)-HRAS1/insulin. Although it is generally agreed that HRAS1 (formerly termed c-Ha-ras-1) and the insulin gene are close to each other [1-4 centimorgans (cM)], their order on chromosome 11p is still in question. We have now added three other genes, those for catalase, calcitonin, and insulin-like growth factor II (IGF-II), to this map of chromosome 11p by use of restriction site polymorphisms adjacent to these genes in classical linkage analysis. Most importantly, we find no evidence of linkage between the catalase and HBBC loci. In addition, our data indicate that the calcitonin gene is located between the catalase gene and the PTH gene. Our best estimate of the distance between the catalase and calcitonin gene is approximately 16 cM, while that between the calcitonin and PTH genes is approximately equal to 8 cM. In agreement, very loose linkage was found between the catalase and PTH loci (approximately 26 cM). Since the catalase locus has been mapped to 11p13, these data support the view that the PTH, HBBC, HRAS1, and insulin loci are located on the distal short arm of chromosome 11. The IGF-II gene is tightly linked to both the HRAS1 oncogene and the insulin gene since no recombinants were observed between the IGF-II and the HRAS1/insulin loci. Thus, based on our linkage analysis we propose that the most likely gene order for the short arm of chromosome 11 is centromere-catalase-calcitonin-PTH-HBBC-HRAS1/insulin-tel ome re and that the IGF-II gene is very close to both the HRAS1 and the insulin genes.

Effects of luminance and flicker on ocular dominance shift in kitten visual cortex.

We raised monocularly deprived kittens in visual environments with low level illumination that was either steady or flickering. With steady scotopic luminance ocular dominance shifted as it does in normal photopic lighting. In flickering light with an average frequency of 2 Hz there was virtually no ocular dominance shift, while in flickering light averaging 0.1 Hz there was a significant shift. Recordings from the 2 Hz flicker-reared were similar to the dark-reared recordings. The flickering illumination was produced in one case by a high contrast-low brightness TV near the cage, and in another case, by a low voltage incandescent bulb driven by a pseudo-random sequence generator. This circuit delivered either a maximum ON time of 1.7 s or a maximum of 40 s, for the 2 Hz and 0.1 Hz respectively. Both the TV and flickering bulb produced average illumination comparable to the dim (0.01 cd/m2) steady scotopic illumination. We conclude that dim flickering light is not a sufficient stimulus for promoting ocular dominance shift in kittens in the critical period unless the flicker rate approaches 0.1 Hz. Furthermore results from the TV rearing suggest that flicker may be capable of preventing an ocular dominance shift expected from a concurrent steady low light level background.

Two methods of catecholamine depletion in kitten visual cortex yield different effects on plasticity.

As first clearly demonstrated by the experiments of Wiesel and Hubel, the developing visual cortex is exquisitely sensitive to sensory deprivation. Temporary closure of one eye of a kitten during a critical period that extends from 3 weeks to 3 months of age results in a dramatic cortical reorganization such that most neurones, originally binocularly driven, are dominated exclusively by the open eye. Recently, attention has been directed to chemical factors which may influence the degree of plasticity during the critical period. The work of Kasamatsu and pettigrew suggests that cortical catecholamines, especially noradrenaline (NA), are essential for the normal plastic response to visual deprivation. In an effort to clarify the role of NA in visual cortical plasticity, we have monocularly deprived kittens whose cortex had been depleted of catecholamines by the neurotoxin 6-hydroxydopamine (6-OHDA). We used two strategies to deplete cortical NA: the first, pioneered by Kasamatsu el al., utilized osmotic minipumps to deliver 6-OHDA to visual cortex; the second involved systemic neonatal injections of 6-OHDA, a technique which has proved effective in rodents. We found, using high-pressure liquid chromatography (HPLC), that both techniques produced a substantial reduction in the level of cortical NA. However, single unit recording in area 17 revealed that the plastic response to monocular deprivation (MD) was only diminished in the kittens depleted by minipump.

The plastic response to monocular deprivation persists in kitten visual cortex after chronic depletion of norepinephrine.

In order to clarify the role of norepinephrine (NE) in visual cortical plasticity, we monocularly deprived kittens that had received systemic injections of the neurotoxin 6-hydroxydopamine (6-OHDA) shortly after birth. We found, using high pressure liquid chromatography, that this means of drug treatment produces a permanent and substantial reduction in the level of cortical NE as compared with littermate controls. Nonetheless, single unit recording in area 17 of these kittens revealed no difference in the cortical response to monocular deprivation: both drug-treated and control kittens displayed large ocular dominance shifts to the open eye. Because local depletion of NE by intracortical 6-OHDA in kittens can prevent the expected ocular dominance shift after short-term monocular deprivation, we propose that neocortex has the capacity to compensate for chronic depletion of NE in a way which allows for the possibility of plastic changes.

Development of single-neuron responses in kitten's lateral geniculate nucleus.

1. In the lateral geniculate nucleus (LGN) of 18 kittens whose ages ranged from 6 to 40 days, 445 cells were studied. 2. LGN cells of kittens younger than 21 days are characterized by very low maintained rates, long latencies to full-field flash, response fatigue, large receptive field, absence of surround responses and surround inhibition, poor responses to fast-moving stimuli, and low-amplitude responses to flashing spots. 3. Cells were characterized as sustained or transient, and on, off, or on-off by their responses to flashing spots of light, and as X-like of Y-like by their responses to contrast reversal. Prior to 21 days, cells are hard to classify as X or Y. 4. A large proportion of cells in kitten LGN have both on- and off-responses to small and center-sized spots of light. This proportion decreases with development. 5. A small number of cells develop mature receptive-field properties very early (14--20 days). These are cells with X-type responses (linear summation) to contrast reversal and tend to have sustained responses to flashing spots. 6. Y-like cells, with nonlinear summation, develop mature receptive-field properties later than 34 days of age and later than all X-cells. 7. We conclude that there are different developmental patterns for cells of the kitten LGN. These different patterns may be important in determining the visual responses of cortical cells and their degree of susceptibility to environmental modification.

Early development of X-cells in kitten lateral geniculate nucleus.

Lateral geniculate nucleus cells of the kitten were classified as X-cells or Y-cells with a contrast reversal test and their latencies to optic chiasm shock were measured. X-cells with mature latencies were found as early as 21 days. Y-cells did not have adult latencies at 40 days. The early development of some X-cells may be due to differential rates of fiber myelination and synaptic maturation within the lateral geniculate nucleus.

Biases for oriented moving bars in lateral geniculate nucleus neurons of normal and stripe-reared cats.

Visual receptive fields of 42 LGN cells from normal cats and 110 cells from striped cylinder-reared kittens were studied with the aid of a computer controlled optical system. In the normal cats, ten of the 42 cells were weakly biased for orientation of the visual stimulus when tested with bars swept through the receptive field. Of those ten, eight were classified as transient. The orientation preferences of the ten biased units appeared randomly distributed around the clock. Of the LGN cells from the cylinder-reared group, about half of the transient cells had weak biases for orientation; only 7% of the sustained cells had biases. The orientation preferences of the biased LGN cells in the stripe-reared animals were either parallel to or orthogonal to the stripes each animal saw during its time in the conditioning cylinder. In 16 out of 18 of the biased LGN cells it was found that increasing the velocity of the test target reduced or eliminated the bias apparent at the lower velocity. For some LGN cells special techniques, such as inhibition of activated discharge, were needed to reveal orientation biases. The results described here, considered with data from others, suggest a role for the corticofugal projection in modulating the responses of some LGN cells.

A study of inhibitory antagonism in cat visual cortex.

Since there seems to be good evidence that GABA may act as an inhibitory neurotransmitter in the mammalian cortex, we tested the effects of an antagonist of GABA, namely the alkaloid bicuculine, on the response properties of visual cortex neurons, using a computer-controlled stimulus presentation system to assess quantitatively the changes in receptive field organization after the drug. Complex cells were most affected, increasing both evoked and spontaneous activity and losing some of their specificities for stimulus parameters such as orientation and direction. Hyper-complex cells lost their inhibitory flanks, responding equally well to long and short bars after the drug. Simple cells were the least affected, usually becoming somewhat depressed after the drug. Preliminary tests with another inhibitory amino acid antagonist, strychnine, showed that it excited simple cells, indicating that possibly more than one inhibitory transmitter is at work in the cortex. The results are discussed with relation to the synaptic anatomy of the cortex, and it is concluded that a class of stellate cells, using GABA, is a likely candidate for the transmitter of some intracortical inhibition.

Gamma-aminobutyric acid antagonism in visual cortex: different effects on simple, complex, and hypercomplex neurons.

Intravenous bicuculline was used to examine how removing gamma-aminobutyric acid-mediated inhibition affects the visual response properties of single cortical neurons. Simple neurons were depressed and complex neurons showed increase in the vigor and range of responses. Hypercomplex cells were no longer inhibited by elongated stimuli. The results are consistent with present evidence concerning the origin and distribution of inhibitory connections within the cortex.