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Biomedical subjects

S Carlson

Publications and source records attributed to S Carlson.

At least 109 records · Page 6Linked to original sources

Gyrate atrophy of the choroid and retina: ERG of the neural retina and the pigment epithelium.

The function of the neural retina and the pigment epithelium in 10 patients with gyrate atrophy was examined by the conventional alternating current electroretinogram and by direct current electroretinography to study the c-wave. The a- and b-wave responses were subnormal in all patients and the ERG was undetectable in patients with an advanced stage of the disease. The c-wave was recordable by the DC ERG from three patients with a less advanced stage of the disease. In one patient the c-wave could be recorded only from the other eye but the a- and b-wave responses were recordable in both his eyes.

Adolescent↗

Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia.

Glucose alters absorptive cell tight junction structure and, as deduced from an impedance analysis model, diminishes tight junction resistance in the small intestine (J.R. Pappenheimer, J. Membr. Biol. 100: 137-148, 1987; and J.L. Madara and J.R. Pappenheimer, J. Membr. Biol. 100: 149-164, 1987). Here we provide further evidence in support of this hypothesis using the conventional approach of analysis of mucosal sheets mounted in Ussing chambers. This approach offers advantages for investigating underlying mechanisms, including the effects of ions and inhibitors on the regulation of intercellular junctions by glucose. We show that phlorizin blocks a resistance decrease elicited by glucose and demonstrate that substitution of choline for sodium also prevents the response. The dilatations in absorptive cell tight junctions that accompany this glucose-elicited response are similarly prevented by phlorizin exposure or sodium substitution. The effects of phlorizin on junctional permeability can also be demonstrated in vivo. Phlorizin reduces the transjunctional flux of creatinine in glucose-perfused intestines of anesthetized animals, even when account is taken of the reduction of fluid absorption caused by phlorizin. Last, in vivo perfusion studies suggest that although, at 25 mM luminal glucose, virtually all glucose absorption is transcellular, at a luminal glucose concentration of 125 mM approximately 30% of glucose absorption occurs paracellularly because of solvent drag across tight junctions of altered permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

C. difficile toxin A increases intestinal permeability and induces Cl- secretion.

Mucosal sheets of guinea pig ileum mounted in Ussing chambers were used to determine effects of highly purified Clostridium difficile toxin A on intestinal structure and barrier function in the absence of recruited neutrophils and blood flow. With the use of standard electrophysiological and morphological techniques, our results indicate that 5 micrograms/ml mucosal toxin A induces substantial alteration in epithelial permeability and in structure of absorptive cells. Transepithelial fluxes of mannitol (3.6 A) and inulin (11.5 A) increased 20-80 min after toxin A exposure (63 +/- 13 vs. 149 +/- 14 and 2.33 +/- 0.43 vs. 7.03 +/- 1.0 nmol.cm-2.h-1 for mannitol and inulin; controls vs. toxin exposed, respectively, both P less than 0.01). Toxin A exposure diminished short-circuit current (153 +/- 8 vs. 77 +/- 6 microA/cm2 for control and toxin exposed, respectively, P less than 0.001), decreased transepithelial electrical resistance (61.6 +/- 3 vs. 50.1 +/- 3.9 omega.cm2 for control and toxin exposed, respectively, P less than 0.05), increased passive permeation of Na+ (19.1 +/- 0.9 vs. 27.4 +/- 0.9 mumol.cm-2.h-1 for control and toxin exposed, respectively), and induced a Cl- secretory response (net flux 3.65 +/- 3.0 vs. -4.62 +/- 2.6 mumol.cm-2.h-1, for control and toxin exposed, respectively, P less than 0.05) over the 2-h experimental time course. Toxin A-induced structural alterations of villus tip absorptive cells were strikingly similar to those induced by the actin-binding agent cytochalasin D. Specifically, cells displayed constricted subjunctional zones, flared microvillus brush borders, condensation of microfilaments in the zone of the perijunctional actomyosin ring, and breakdown of intercellular tight junctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Visually guided behavior of monkeys after early binocular visual deprivation.

Four infant monkeys were binocularly deprived of vision through their first year of life. After the end of the deprivation their visually guided behavior was followed for one year. Behavioral tests were performed to assess their visual functions. The performance of the deprived monkeys was compared with the performance of three normally sighted monkeys. The following functions were tested: the monkey's ability to detect a moving light spot, to track a moving object, to grasp an object, to chatter the teeth in response to a threatening face, to pick pellets from a board, to respond to a sudden visual threat and to move about in a wide space. The visually deprived monkeys remained severely visually handicapped. They were able to detect a moving light spot in a darkened room and to recognize the movement of large objects. However, they continued bumping into objects and used tactile exploration when moving about in a wide space. They never learned to respond to a threatening face, which for a normal monkey is part of the normal behavioral repertoires. The persistently poor visually guided behavior of these monkeys is in agreement with the electrophysiological findings in the posterior parietal association cortex of these monkeys; early visual deprivation permanently reduces the number of visually responsive cell groups in this association area.

Animals↗

Comparison of tactile discrimination ability of visually deprived and normal monkeys.

The tactile discrimination ability of visually deprived and normal monkeys was tested to study whether loss of vision would improve the utilization of the tactual sense. Three normally sighted monkeys and three monkeys that had been deprived of vision during the first year of their life were trained in two tactile discrimination tasks by using a reward system in which the animals received a raisin or half a peanut under a correctly chosen wooden block. Discrimination was based on the gradual roughness or size of various blocks. When the monkeys had learned the tasks to the criterion, discrimination thresholds were determined. All monkeys improved their performance in both tasks with time, but no statistically significant differences between the performance of the two groups of monkeys were obtained. These results suggest that although the representation of the tactual sense in the cortical association areas has been shown to increase as a result of visual deprivation during the early sensitive period of life, increased representation does not improve the tactual discrimination ability of simple tactual stimuli.

Animals↗

Villus contraction aids repair of intestinal epithelium after injury.

A highly reproducible in vitro model of intestinal epithelial injury in guinea pig ileum was used to study the structural and functional events that accompany rapid epithelial repair. This model is characterized by denudation of the villus tip followed by rapid restitution of the epithelial barrier. Using standard electrophysiological and quantitative morphometric techniques, we found that immediately after injury the number of cells lost exceeded the number of empty cell positions on the denuded basement membrane by 100%. Concurrently, cytoplasmic processes of subepithelial myofibroblasts contained condensations of microfilaments that were not apparent in controls. Additionally, villus height was diminished immediately after injury, and progressively decreased during the restitution period. In tissues that were depleted of ATP using the uncoupler dinitrophenol and in tissues functionally denervated by tetrodotoxin, villus shortening after injury was significantly reduced. Denervation also retarded functionally and structurally defined reestablishment of epithelial barrier function. These data suggest that intestinal epithelial repair is aided by energy-dependent, neurally mediated villus contraction. We speculate that the subepithelial network of myofibroblasts is responsible for this process, which effectively minimizes the denuded surface area to be reepithelialized.

2,4-Dinitrophenol↗

Reversible middle cerebral artery occlusion without craniectomy in rats.

To develop a simple, relatively noninvasive small-animal model of reversible regional cerebral ischemia, we tested various methods of inducing infarction in the territory of the right middle cerebral artery (MCA) by extracranial vascular occlusion in rats. In preliminary studies, 60 rats were anesthetized with ketamine and different combinations of vessels were occluded; blood pressure and arterial blood gases were monitored. Neurologic deficit, mortality rate, gross pathology, and in some instances, electroencephalogram and histochemical staining results were evaluated in all surviving rats. The principal procedure consisted of introducing a 4-0 nylon intraluminal suture into the cervical internal carotid artery (ICA) and advancing it intracranially to block blood flow into the MCA; collateral blood flow was reduced by interrupting all branches of the external carotid artery (ECA) and all extracranial branches of the ICA. In some groups of rats, bilateral vertebral or contralateral carotid artery occlusion was also performed. India ink perfusion studies in 20 rats documented blockage of MCA blood flow in 14 rats subjected to permanent occlusion and the restoration of blood flow to the MCA territory in six rats after withdrawal of the suture from the ICA. The best method of MCA occlusion was then selected for further confirmatory studies, including histologic examination, in five additional groups of rats anesthetized with halothane. Seven of eight rats that underwent permanent occlusion of the MCA had resolving moderately severe neurologic deficits (Grade 2 of 4) and unilateral infarcts averaging 37.6 +/- 5.5% of the coronal sectional area at 72 hours after the onset of occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rapid barrier restitution in an in vitro model of intestinal epithelial injury.

Mild forms of intestinal epithelial injury commonly occur in many disease states. In order to study how such epithelial "wounds" heal, we have developed a highly reproducible in vitro model of intestinal epithelial injury. Guinea pig ileal mucosal sheets were mounted in Ussing chambers and the mucosal surfaces were exposed to 0.06% Triton-X 100 for 5 minutes. This resulted in denudation of the epithelium at the tips of 86% of villi. As a result of this injury, resistance to passive ion flow decreased significantly (56.5 +/- 1.3 versus 38.4 +/- 2.3 ohm.cm2 for control and injury, respectively, p less than 0.01), as did transepithelial potential difference (-11.9 +/- 0.7 versus -4.3 +/- 0.4 mV for control versus injury respectively, p less than 0.01). In parallel, transepithelial fluxes of the extracellular space markers mannitol and inulin increased 3- to 5-fold immediately after injury. Two hours after injury, villus tips were again confluently covered by columnar absorptive cells, a time course of healing too fast to be accounted for by enhanced cell proliferation. Analysis of the structural events occurring during recovery showed that absorptive cells shouldering the foci of denudation rapidly changed shape after injury: they became flattened and sent cell projections over the denuded basement membrane. By 60 minutes after injury, cells from opposite shoulders of the denudation abutted, thus resealing the defect. Paralleling these structural changes, transepithelial resistance, potential difference, and mannitol and inulin fluxes returned toward control values. These data show that focal epithelial discontinuities in the small intestine may be rapidly resealed. Such reparative processes may substantially limit the deleterious physiologic impact of superficial forms of intestinal injury.

Animals↗

Astrology.

As a divinatory practice, astrology is without equal in both its colorful history and modern day popularity. Astrology has grown, over thousands of years, into a huge and ornate superstructure that lacks a central design. Although astrology has been dimly veiled by its occult mystique for centuries, the light of modern day inquiry has shown its substance to be mostly illusionary and revealed its foundation to be the shakiest possible: that of self-justification and anecdotal evidence. Despite the many claims of its practitioners and followers, extensive investigation has revealed astrology to be a great teetering monument to human gullibility.

Astrology↗

Effect of naloxone on tooth pulp-evoked jaw-opening reflex in the barbiturate-anaesthetized cat.

The threshold of the tooth pulp-evoked jaw-opening reflex was uninfluenced by administration of 0.5 or 5.0 mg kg-1, i.v. naloxone, a specific opioid antagonist, in the barbiturate-anaesthetized cat. Furthermore, facilitatory or inhibitory interactions between two successive tooth pulp-evoked jaw reflex responses were not influenced by naloxone. It is concluded that naloxone-sensitive opioid receptor-mediated mechanisms do not contribute to the modulation of tooth pulp-evoked reflexes by conditioning dental stimuli. Also they do not exert a tonic inhibition on the sensory or motor part of the tooth pulp-driven reflexes. Experiments performed for comparison showed that the non-nociceptive polysynaptic reflex discharge in the flexo-motor neurons of the limb was not influenced by naloxone either.

Animals↗

Functional coupling of tight junctions and microfilaments in T84 monolayers.

The actin-binding agent cytochalasin D (CD) in intact intestinal epithelium appears to elicit segmentation and contraction of a perijunctional ring of actomyosin and, consequently, to diminish tight junction resistance. We determined if an intestinal epithelial model composed of T84 cells also displayed such a perijunctional cytoskeletal specialization and, if so, whether exposure to CD also affected the tight junction barrier. We find T84 cells display a prominent perijunctional microfilament ring that is actin rich. CD elicits large decreases in transepithelial resistance due specifically to perturbed tight junction permeability as determined with dual Na+-mannitol flux analysis. Transepithelial mannitol and insulin fluxes also increase after CD exposure, but these molecules remain differentially restricted in accordance with their sizes, indicating that gross disruption of the monolayer has not occurred. Structurally, CD elicits segmentation and condensation of the perijunctional ring into actin-rich plaques. These features have similarity to those seen in native intestinal epithelia. This system may represent a simple model for studies of cytoskeletal-tight junction relationships.

Actin Cytoskeleton↗

Response characteristics of tooth pulp-driven postsynaptic neurons in the spinal trigeminal subnucleus interpolaris of the cat: comparison with primary afferent fiber, subnucleus caudalis, reflex, and sensory responses.

Tooth pulp-evoked single neuron responses were recorded in the spinal trigeminal subnucleus interpolaris of the cat. The thresholds to monopolar electric pulses of varying duration (0.2-20 ms) were determined using a constant current stimulator. The thresholds were comparable with those of primary afferent A-fibers, although the most sensitive primary afferent fibers have lower thresholds. The thresholds and latencies showed that none of the interpolaris neurons received their input solely from intradental C-fibers. The most sensitive subnucleus interpolaris neurons had lower thresholds than the respective subnucleus caudalis neurons studied in our previous work. The thresholds and strength-duration curves of the most sensitive interpolaris neurons and of the tooth pulp-elicited jaw-opening reflex are nearly similar, although the jaw reflex can be elicited at an intensity which is slightly lower than that needed to activate the most sensitive interpolaris neurons of the present sample. The most sensitive interpolaris neurons were activated at current intensities that were below the intensity needed to produce liminal dental pain in man, and the strength-duration curves of these neurons were flatter than the curve depicting liminal dental pain sensation in man. The relationship between stimulus intensity and response magnitude could be well described by power functions, the median exponent of which was 1.251. A conditioning stimulation of the tooth pulp at low intensity produced a short (less than 25 ms) enhancement of the response to the following test stimulus, whereas a high intensity conditioning stimulus produced a longer (greater than 40 ms) suppression of the response to the following stimulus. The threshold of 33% of the neurons was elevated during a noxious tail pinch, and this elevation was not reversed by naloxone, an opioid antagonist. The results indicate that in the trigeminal subnucleus interpolaris there are tooth pulp-driven neurons with an input from intradental A-fibers and that a considerable temporal summation of impulses from primary afferent fibers is needed to activate most of them. Human dental pain thresholds cannot be explained by the liminal response properties of the most sensitive interpolaris neurons, but they may be important in the mediation of near-threshold reflex events. It is possible, however, that the high-threshold interpolaris neurons may have a role in the mediation of sensory responses.

Afferent Pathways↗

Tooth pulp-evoked activity in the spinal trigeminal nucleus caudalis of cat: comparison to primary afferent fiber, reflex, and sensory responses.

Tooth pulp-evoked single-neuron responses were recorded in the spinal trigeminal nucleus caudalis of the cat. The thresholds to monopolar electric pulses of various durations (0.2 to 20 ms) were determined using a constant current stimulator. With stimulus pulse durations of 10 to 20 ms, the thresholds were comparable with those of primary afferent A-fibers, although the most sensitive primary afferent fibers had lower thresholds. Primary afferent C-fibers had higher thresholds than the postsynaptic neurons studied. The threshold for the tooth pulp-elicited jaw-opening response was obtained at a lower stimulus intensity than the liminal response in most postsynaptic neurons of this study. The threshold rise of the postsynaptic trigeminal neurons with decreasing stimulus pulse duration (from 5 to 0.2 ms) was much steeper than that of primary afferent A-fibers or jaw-opening response. The strength-duration curves for tooth pulp-elicited pain sensations in man resemble those of spinal trigeminal neurons. Sixty-two percent of the units had a threshold elevation during a noxious pinch of the tail. The results indicate that the activation of postsynaptic trigeminal neurons requires a considerable temporal summation of primary afferent impulses. The jaw reflex thresholds cannot be explained by the properties of the neurons in the subnucleus caudalis of the trigeminal tract. The results support the concept that dental pain is based on the activation of spinal trigeminal nucleus caudalis neurons receiving their input from intradental A-fibers.

Animals↗

Late effects of early binocular visual deprivation on the function of Brodmann's area 7 of monkeys (Macaca arctoides).

It has been shown earlier that binocular visual deprivation during the early sensitive period of life reduces the representation of visual functions in the posterior parietal association cortex of monkeys, in Brodmann's area 7 (Exp. Brain Res., 42 (1981) 1-8). Moreover, the representation of somatic functions increases suggesting that competitive mechanisms between the inputs from different modalities function during the early sensitive period of life in area 7. The aim of the present study was to find out whether further reorganization of functions takes place in the posterior parietal association cortex if monkeys that have experienced binocular visual deprivation through the first year of their life, are allowed to recover from the deprivation for a longer period of time. Four monkeys were deprived of binocular vision after the birth by lid closure for 12 months. Transdural extracellular multiunit recordings were performed in Brodmann's area 7 at the end of the deprivation period after the opening of the eyes. A second set of recordings was conducted in area 7 after a recovery period of 12 months from the deprivation. The results of the recordings at the end of the deprivation period confirmed the already known deprivation effect: there was a reduction in visually responsive neurons, an increase in the representation of somatosensory and somatomotor functions as well as an increase in the amount of cell groups that were 'only spontaneously active'. The recordings performed after the recovery period showed that the representation of visual functions had remained low. However, the amount of 'only spontaneously active' neurons had decreased and the amount of cell groups responding to the monkey's own explorative movements of the hand had further increased. The results indicate that visual deprivation during the early critical period of life results in a profound and persistent reduction of visual functions in area 7. However, activity-dependent competition between inputs from different modalities continue, resulting in the domination of somatosensory and somatomotor functions over visual functions in area 7. The results also suggest that neurons which during the visual deprivation are left without active input from the visual system, gradually become integrated into other functionally active neuronal networks increasing the representation of somatic functions in this cortical area.

Action Potentials↗

Structural analysis of a human intestinal epithelial cell line.

Confluent monolayers of epithelial cell lines of intestinal derivation may serve as useful models for studies of intestinal epithelial structure and function. Cells of the T84 line appear to be a useful model for studies of Cl- secretion. We now define the fine structure of this cell line, the structural events that occur during monolayer formation, and the influence of plastic versus collagen substrates and permeable versus impermeable substrates on the structural development of these monolayers. When plated on collagen-coated filters at confluency, T84 cells cover the filter surface and lay down basement membrane-like material within 18 h. Such "monolayers" multifocally display areas with many cell layers alternating with areas composed of a single layer of cells. During this stage of development cell polarization is minimal, ultrastructural discontinuities exist that impart low transepithelial resistance, and morphologic features reminiscent of stratified intestinal epithelium during fetal development are present. Within 5 days of plating on collagen-coated filters, true monolayers form. These monolayers have high transepithelial resistance and consist of highly polarized columnar cells with structural similarity to intestinal crypt cells. Cells plated on a plastic substrate are also capable of rapidly producing basement membrane-like material but, unlike those plated on collagen-coated filters, under these conditions the rapid initial spreading of cells over the substrate surface does not occur. As a result, at 5 days monolayers plated on plastic are less uniform than those plated on collagen-coated filters, exhibit areas in which unpolarized flattened cells abound, and multifocally leak macromolecules. Studies using collagen-coated filters made impermeant with glass backing suggest that the enhancing effect of this substrate on monolayer structural development is not simply due to the greater access that basolateral membranes have to nutrient media when grown on permeable supports. This study defines the structure and structural development of this useful model epithelium, and demonstrates the importance of substrate selection.

Carcinoma↗