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Identity and regulation of ion transport mechanisms in the corneal endothelium.

Corneal transparency is dependent on regulation of the hydration of the corneal stroma. Water is driven into the cornea across the epithelial and endothelial cell layers by the stromal swelling pressure. This fluid leak into the cornea is counterbalanced by the corneal fluid pump, which is predominantly attributed to the ion and fluid transport capacity of the endothelial cell layer. Primary and secondary active transport mechanisms are responsible for generating a net ion flux from the stromal to anterior chamber side of the endothelium; however, the identity and location of all the components of this transport system are not known. The endothelial fluid pump is dependent on the presence of Cl(-) and HCO(3)(-), and can be slowed by carbonic anhydrase inhibitors. A number of anion transport mechanisms have been identified and characterized in the endothelium, including basolateral Na(+)/2HCO(3)(-) cotransport, Na(+)/K(+)/2Cl(-) cotransport, Cl(-)/HCO(3)(-) exchange, and apical anion channels permeable to both Cl(-) and HCO(3)(-). Furthermore, there is evidence for a carbonic anhydrase mediated CO(2)-diffusive mode of apical HCO(3)(-) flux. These findings are incorporated into a new model of transendothelial anion transport, which suggests that there are a number of alternate pathways for anion transport. There have been few studies on activation of signal transduction pathways that could stimulate endothelial fluid transport. Interestingly, recent studies show that multiple autocrine signaling pathways are in place that could be upregulated during physical stimulation and may be responsible for maintaining basal levels of fluid secretion.

Adenylyl Cyclases↗

[Effect of the method of feeding on the physical development of infants born with symptoms of intrauterine dystrophy].

In the Clinical Department of Metabolic Studies of the National Research Institute of Mother and Child the attempt was made to stimulate physical development of S-F-D infants through introducing modifications in standard feeding in order to make up for the deficits of foetal age. In the years 1970-1975, 118 infants were under observation: 44 out of this group, in the Clinical Department, 70 in the Outpatient Clinic of Infant Nutrition disorders, 4 were observed both in the Clinical Department and in the Outpatient Clinic. The control group of 40 S-F-D- infants was observed in the Child Outpatient Department of Wola Borough of Warsaw. Foetal age of S-F-D infants underwent anthropometric measurements, psychological and neurological examinations. Investigations of haematological and biochemical indices were also carried out. Physical development of children in 4 (S,G,H,C) dietary groups was observed and compared with the control group. Initial diet differed from the standard diet, used at the National Research Institute of Mothers and Child, by excluding gluten and by replacing saccharose with glucose. In other diets (G, H and C) milk formulas with different quantitative and qualitative protein and fat content were enriched with unsaturated fatty acids. Longitudinal analysis included 61 infants from single pregnancies which were put on regular and sufficiently long (5-12 months) diet. Evaluation of physical development was based on the analysis of mean values, increments and rate of growth of body--length, body weight, arm, scapular and abdominal skin-fold thickness. These data are presented in Tables I-IX, variate curves of individual features in Figures 1-9. Somewhat higher developmental indices were observed in the group of infants fed enriched formulas with unsaturated fatty acids. Growth rate of skin-fold thickness in group S, was extremely intensive all the first year through and decreasing physiological tendencies were not observed in 4th trimester of life.

Age Factors↗

Sleep deprivation in the rat by the disk-over-water method.

Chronic sleep deprivation may be required to reveal the most serious physiological consequences of sleep loss, but it usually requires strong stimulation which can obscure the interpretation of effects. The disk-over-water method permits chronic sleep deprivation of rats with gentle physical stimulation that can be equally applied to yoked control rats. A series of studies with this method has revealed little or no pathology in the control rats. The deprived rats show a reliable syndrome that includes temperature changes (which vary with the sleep stages that are lost); heat seeking behavior; increased food intake; weight loss; increased metabolic rate; increased plasma norepinephrine; decreased plasma thyroxine; an increased triiodothyronine-thyroxine ratio; and an increase of an enzyme which mediates thermogenesis by brown adipose tissue. The temperature changes are attributable to excessive heat loss and an elevated thermoregulatory setpoint, both of which increase thermoregulatory load, and the other changes are interpretable as responses to this increased load. This pattern indicates that sleep serves a thermoregulatory function in the rat. The sleep deprived rats also show stereotypic ulcerative and hyperkeratotic lesions localized to the tail and plantar surfaces of the paws, and they die within a matter of weeks; the mediation of these changes is unresolved.

Animals↗

Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues.

Vascular endothelial-cadherin (VE-cadherin) plays a key role in angiogenesis and in vascular permeability. The regulation of its biological activity may be a central mechanism in normal or pathological angiogenesis. VE-cadherin has been shown to be phosphorylated on tyrosine in vitro under various conditions, including stimulation by VEGF. In the present study, we addressed the question of the existence of a tyrosine phosphorylated form of VE-cadherin in vivo, in correlation with the quiescent versus angiogenic state of adult tissues. Phosphorylated VE-cadherin was detected in mouse lung, uterus, and ovary but not in other tissues unless mice were injected with peroxovanadate to block protein phosphatases. Remarkably, VE-cadherin tyrosine phosphorylation was dramatically increased in uterus and ovary, and not in other organs, during PMSG/hCG-induced angiogenesis. In parallel, we observed an increased association of VE-cadherin with Flk1 (VEGF receptor 2) during hormonal angiogenesis. Additionally, Src kinase was constitutively associated with VE-cadherin in both quiescent and angiogenic tissues and increased phosphorylation of VE-cadherin-associated Src was detected in uterus and ovary after hormonal treatment. Src-VE-cadherin association was detected in cultured endothelial cells, independent of VE-cadherin phosphorylation state and Src activation level. In this model, Src inhibition impaired VEGF-induced VE-cadherin phosphorylation, indicating that VE-cadherin phosphorylation was dependent on Src activation. We conclude that VE-cadherin is a substrate for tyrosine kinases in vivo and that its phosphorylation, together with that of associated Src, is increased by angiogenic stimulation. Physical association between Flk1, Src, and VE-cadherin may thus provide an efficient mechanism for amplification and perpetuation of VEGF-stimulated angiogenic processes.

Animals↗

Uncoupling of omnivore-mediated positive and negative effects on periphyton mats.

The riverine grass shrimp (Palaemonetes paludosus) and eastern mosquitofish (Gambusia holbrooki) consume periphyton and small invertebrates, potentially affecting periphyton through negative effects (i.e., consumption) and/or positive effects such as nutrient regeneration, physical stimulation, and trophic cascades. We performed field experiments in the Everglades in which omnivores and periphyton were maintained in cages, with a fraction of the periphyton held in omnivore-exclusion bags that allowed passage of nutrients but prevented its consumption or physical disturbance. In some instances, periphyton growth rate increased with increasing omnivore biomass. Omnivores probably stimulated periphyton growth through nutrient regeneration, possibly subsidizing periphyton with nutrients derived from ingested animal prey. The net balance of omnivore-mediated negative and positive effects varied among experiments because of seasonal and spatial differences in periphyton characteristics. Consumption of periphyton mats might have been reduced by the arrangement of palatable algae (green algae and diatoms) within a matrix of unpalatable ones (CaCO(3)-encrusting filamentous cyanobacteria). In a laboratory feeding experiment, mosquitofish consumed more green algae and diatoms in treatments with disrupted mat structure than in those with intact mats. No difference in diet was observed for shrimp. Our study underscores the complexity of consumer-periphyton interactions in which periphyton edibility affects herbivory and consumers influence periphyton through multiple routes that cannot be fully appreciated in experiments that only investigate net effects.

Animals↗

Peripheral bone mineral density and different intensities of physical activity in children 6-8 years old: the Copenhagen School Child Intervention study.

This study aimed to evaluate the association between objectively measured habitual physical activity and calcaneal and forearm bone mineral density (BMD, g/cm(2)), one mechanically more loaded and one less loaded skeletal region, in children aged 6-8 years. BMD was measured in 297 boys and 265 girls by peripheral dual-energy X-ray absorptiometry in the forearm and calcaneus. An accelerometer registered the level of physical activity during 4 days (2 weekdays and the weekend). Weight, height, and skinfold thickness were measured. In order to establish thresholds (count . min(-1)) for bone-stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more daily physical activity and spent 14.6-19.0% more time in vigorous physical activity (all P < 0.05) compared to the girls. In contrast, the girls had 3.8% higher calcaneal BMC (P < 0.01) and 2.5% higher calcaneal BMD (P < 0.05) than the boys. Both calcaneal and forearm BMD were significantly related to total time of daily physical activity as well as with intense physical activity above all the chosen cut-off points (all P < 0.05). The beta value for mean count . min(-1) physical activity was significantly lower than that for all the chosen cut-off points of vigorous activity both for calcaneal and distal forearm BMD. This study suggests that both habitual daily physical activity and amount of vigorous physical activity in children aged 6-8 years are associated with appendicular BMD.

Absorptiometry, Photon↗

'Real-motion' cells in the primary visual cortex of macaque monkeys.

Extracellular recordings were carried out in the primary visual cortex of behaving macaque monkeys. Neurons were activated by moving a visual stimulus across their receptive fields during periods of steady fixation and by moving their receptive fields (by visual tracking) across a motionless visual stimulus, taking care that the velocities of stimulus and eye movements were the same. The total cell population (108 neurons) ws divided into 3 groups according to the cell sensitivity to visual stimulus orientation (non-oriented cell and oriented cells) and to the presence or absence of antagonistic areas in in the receptive fields (oriented cells with antagonistic areas). All the non-oriented cells (n = 14) showed almost the same response to visual stimulation both during steady fixation and during visual tracking. Out of a total number of 86 oriented cells, 77 turned out to be activated by the visual stimulation both during fixation and tracking. Eight oriented cells gave a very weak response or no response at all to visual stimulation during smooth pursuit eye movements and one neuron of the same group showed a greater response during visual tracking than during fixation. Six out of 8 oriented cells with antagonistic areas showed almost the same response to the two types of visual stimulation, while the remaining two neurons showed very weak responses during smooth pursuit eye movements. Our results show that a small percentage (about 10%) of striate neurons in macaque monkeys gave very different responses to the same physical stimulation at retinal level, according to the presence or absence of slow eye movements (smooth pursuit eye movements). The activity of these neurons seems to be related to the real movement of something in the visual world, in spite of the retinal image movement per se.

Animals↗

[Application of group psychology of animals into pharmacological studies. 12. Specificities of actions of psychotropic drugs on emotional and exploratory behaviors of a single mouse or groups of 2 or 3 animals].

The exploratory movement recorder of Tokyo University of Education type was utilized to assess the exploratory motor activity of groups of 1, 2 and 3 mice of the dd-strain. As the animals were observed during 15 min periods to move spontaneously, psychotropic drugs were administered and the specific actions of these agents were determined. Each drug was given i.p. in a dose which proved non-effective in a single mouse. Observations were as follows: The ratio of exploratory motor activity of each pair of mice as compared to a single mouse was not always different from that of control animals. When a 3rd mouse was added to the pair, the motor activity either increased or decreased considerably. The rate of increase in motor activity was calculated 45 min after caffeine, pentetrazol, ephedrine and DL-amphetamine and was found to be less than in the control animals. After administration of chlordiazepoxide, diazepam, imipramine, chlorpromaxine or mescaline, the rate of increase in motor activity was considerably greater than in the controls. With dimorphoramine or hexobarbital, the rate was much the same as control. After beta-oxy gamma-aminobutyric acid, the rate was slightly increased and with diphenhydramine the rate was slightly less than control. Thus the exploratory motor activity of 3 mice as compared to that of 2, decreased considerably after administration of psychotropic stimulants, while after psychotropic depressants, an even greater increase was observed. We have already reported on the mutual relation of mice in fighting episodes and E1-mice convulsions. Those relations were, however, responses elicited by the physical stimulation. In contrast, the mutual relation in this paper is more of a natural nature. In view of observations in this paper, it is considered that CNS stimulants increase the mutual, emotional, checking behavior in groups of 3 animals while CNS depressants decrease the checking behavior. Such behavior is one example of the emotional conduct when a 3rd party is added to a 2 member group.

Animals↗

Effect of total sleep deprivation on 5'-deiodinase activity of rat brown adipose tissue.

Prolonged sleep deprivation of the rat produces a progressive increase in energy expenditure and an eventual decrease in body temperature, which suggests a profound derangement in thermoregulation. Because increased thermogenic activity in brown adipose tissue (BAT) is a likely mechanism mediating the observed increase in energy expenditure, we focused our attention on the effect of total sleep deprivation on BAT type II 5'-deiodinase (5'D-II), since its activation indicates BAT stimulation and is essential for full BAT thermogenic response. Five euthyroid rats were subjected to total (92%) sleep deprivation (euD-rats). Sharing the sleep deprivation apparatus, yoked control rats (euC-rats) received the same degree of physical stimulation as the D-rats, but were only partially (25%) sleep deprived. Additional cage controls (euCC-rats) were housed in the same room. Since during sleep deprivation the animals undergo a reduction in plasma T4 concentration and inability to maintain body temperature heralds death, an identical study was performed in five trios of hyperthyroid rats (hyperD-, hyperC-, and hyper CC-rats) given daily ip injections of 15 micrograms T4/100 g BW, 10 days before and throughout the deprivation period. Experiments were carried out at an ambient temperature of 29 C, close to thermoneutrality for rats. Sleep deprivation in hyperD-rats was maintained until death seemed imminent (9-14 days), and in euD-rats for 12-15 days. Sleep deprivation induced a significant increase in BAT 5'D-II activity in both hyperD- and euD-rats compared with that in euCC-rats (P less than 0.01). BAT 5'D-II in euC-rats was also significantly higher than that in euCC-rats (P less than 0.05), probably because they were partially sleep deprived. BAT 5'D-II activity in hyperD-rats was increased compared to that in both hyperC- and hyperCC-rats (P less than 0.05), in which the activity was slightly but not significantly lower than that in euCC-rats. No significant differences were observed in liver and kidney type I 5'-D (5'D-I) and in pituitary 5'D-II among euD-rats, euC-rats, and euCC-rats. As expected, the hyperthyroid groups (hyperD-rats, hyperC-rats, and hyperCC-rats) had significantly higher kidney 5'D-I and lower pituitary 5'D-II than the euCC-rats. Liver 5'D-I was also significantly increased in the hyperC-rats and hyperCC-rats, but not in the hyperD-rats. These observations indicate that total sleep deprivation is associated with a marked increase in BAT 5'D-II activity in both euthyroid and hyperthyroid rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization↗

Sound emission from cochlear filters and foveae--does the auditory sense organ make sense?

Sense organs filter relevant information from a broad background of physical interactions and discard possible perceptual input that has not proven useful during the course of biological evolution. Sense organs not only limit the access to physical reality, under certain conditions they have a life of their own and produce responses even in the absence of physical stimulation. As a perfect example, the inner ear, the cochlea, in addition to detecting incoming sound waves, it also is capable of producing sound energy. Such "active" processes, however, seem to be necessary to push detection thresholds close to physical limits. The price that has to be paid are "cochlear artifacts" like otoacoustic emissions. In the following, measurement of sound that is emitted by the ear will be introduced as a noninvasive means to assess cochlear function and to help to unravel the mechanical interaction between sensory cells and supporting structures that ultimately leads to sensitive and sharply tuned auditory perception. One focus will be on the cochlea of echo-locating bats that use audition as the main window of perception to their environment and therefore have highest demands on cochlear performance.

Animals↗

Immunoglobulin and secretory component regulation in the rat uterus at the time of decidualization.

To determine the effect of decidualization on uterine immunoglobulins (Igs), we measured the levels of IgG, IgA, and secretory component (SC) after induction of artificial decidual cell reactions (DCR) in hormonally primed ovariectomized rats. When progesterone-treated (2.5 mg/day, 3 days) rats received an intraluminal instillation of oil or a needle scratch stimulation in one uterine horn, the stimulated horn had an increase in wet weight and cytoplasmic protein relative to the contralateral horn. Under these conditions, IgG levels increased 10-fold in the lumen of the stimulated horn. This response was selective for IgG, because induction of DCR had no effect on accumulation of IgA or SC in the stimulated horn. The progesterone-induced accumulation of IgG after DCR was further enhanced by estradiol. The addition of a small amount of estradiol (0.2 microgram) on day 3 of a 4-day progesterone pretreatment resulted in further increases in both the wet weight of the stimulated horn and the concentration of IgG in the lumen. The amount of IgG in the lumen of the stimulated horn was 5-fold greater than that in the stimulated horn after progesterone alone. Levels of IgA and SC, however, remained unchanged with this treatment. These results indicate that movement of IgG into the uterine lumen occurs as a part of the DCR and that both an appropriate endocrine balance and physical stimulation are essential for maximal IgG accumulation. Further, they suggest that IgG may play a central role in early pregnancy, which results in the successful implantation of the blastocysts.

Animals↗

Conscious sedation in a specialty hospital.

1. The patient under i.v. conscious sedation retains the ability to independently maintain a patent airway and respond appropriately to verbal commands and physical stimulation. He or she also has a depressed level of consciousness, and decreased pain and anxiety. 2. For a nurse to administer conscious sedation, conscious sedation policies, procedures and protocols must be in place within the institution. 3. Patients receiving conscious sedation must be monitored for physical changes in blood pressure, cardiac rate and rhythm, oxygen saturation, skin condition, pain, emotional status, and cognitive ability.

Procedural Sedation↗

Spinal inhibition of phrenic motoneurones by stimulation of afferents from leg muscle in the cat: blockade by strychnine.

1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in paralysed high (C1) spinal cats whose phrenic nerve activity was evoked by activation of the intercostal-to-phrenic reflex. End-tidal PCO2 was maintained at a constant level by means of a servo-controlled ventilator. 2. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve uniformly caused inhibition of phrenic activity evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued, and there was a post-stimulus augmentation of phrenic activity. 3. Pre-treatment with subconvulsive doses of strychnine, an antagonist of the neurotransmitter glycine, partially or completely blocked the inhibitory effects on phrenic activity of muscle-afferent stimulation. The blockade was reversible with time. 4. Pre-treatment with a subconvulsive dose of bicuculline, an antagonist of the neurotransmitter gamma-aminobutyric acid (GABA), had no effect on the inhibitory mechanism. 5. We conclude that glycine is an important transmitter of the inhibition of phrenic motoneurones induced by muscle-afferent stimulation, but that GABA is not involved in this inhibitory mechanism.

Action Potentials↗

[A case of radiculitis induced by spinal cord electrical stimulation by a percutaneously inserted needle].

Spinal cord electrical stimulation was performed by a percutaneously inserted needle for causalgia of the right upper limb. The end of electrode was positioned along a line extending down the 5th vertebral body in the vicinity of the right 6th cervical nerve root, after which it was permanently implanted following confirmation of desensitizing effects. Although the patient later returned to normal life without requiring any ancillary medication, beginning after a period of roughly six months, the pain suddenly began to increase when stimulated. When stimulated by extracting the electrode 1 cm under fluoroscopic guide, the irritation was relieved somewhat. As radiculitis of 6th cervical nerve was suspected, selective radicular block of 6th cervical nerve was performed. After selective radicular block, the patient's complaint diminished. Based on the above findings, we consider that the physical stimulation caused by the electrode in contact with the nerve root brought about inflammation of the 6th cervical nerve root. This patient was then treated by removing the causative stimulation and selective radicular block of affected nerve, the details of which are reported.

Electric Stimulation Therapy↗

Transcranial magnetic stimulation differentially affects speed and direction judgments.

This study was conducted to determine whether humans' judgments about the speed and direction of moving stimuli was differentially affected by transcranial magnetic stimulation (TMS). Subjects viewed two successively presented moving stimuli that differed from each other both in speed and direction of motion. Single-pulse TMS was applied either medially (approximately 2 cm above the inion) or laterally (approximately 5 cm lateral to and 4 cm above the inion), while subjects judged the speed and direction differences. The physical stimulation (visual and TMS) was identical on the two tasks, as was discriminability (d') when TMS was not applied. We found significant criterion (beta) shifts on the speed discrimination task at both stimulation sites. Specifically, on TMS trials the proportion of "slower" judgments increased significantly, consistent with subjective reports that stimuli often appeared to slow when TMS was applied. The subjective reports indicated no corresponding change in perceived direction. We also found that speed discriminability was impaired significantly more than direction discriminability, but only when TMS was applied medially. Indeed, after controlling for TMS-related changes in reaction time, speed discriminability was impaired significantly, while direction discriminability remained largely intact. This dissociation suggests that the sensory response constraining speed discrimination is at least partially independent from the sensory response constraining direction discrimination. Combined with previous psychophysical data, the present data suggest a double dissociation between speed and direction discrimination in humans.

Adult↗

Compartmentalized autocrine signaling to cystic fibrosis transmembrane conductance regulator at the apical membrane of airway epithelial cells.

Physical stimulation of airway surfaces evokes liquid secretion, but the events that mediate this vital protective function are not understood. When cystic fibrosis transmembrane conductance regulator (CFTR) channel activity was used as a functional readout, we found signaling elements compartmentalized at both extracellular and intracellular surfaces of the apical cell membrane that activate apical Cl(-) conductance in Calu-3 cells. At the outer surface, ATP was released by physical stimuli, locally converted to adenosine, and sensed by A(2B) adenosine receptors. These receptors couple to G proteins, adenylyl cyclase, and protein kinase A, at the intracellular face of the apical membrane to activate colocalized CFTR. Thus, airways have evolved highly efficient mechanisms to "flush" noxious stimuli from airway surfaces by selective activation of apical membrane signal transduction and effector systems.

Adenosine↗

Response of gerbera jamesonii acrocarpous callus stimulated by mechanical vibration.

Applying different mechanical vibrations, 2-3 Hz frequency, to stimulate the gerbera jamesonii acrocarpous callus, we found that it increases the growth rate and the content of soluble protein but decreases the fluidity of cell membranes. When the frequency was greater than 4 Hz, the effect was contrary to that of 2-3 Hz. In this paper, we also prove the double effects in the plant callus growth and explore the mechanism of the double effects in physical stimulation.

Journal Article↗

Independent trafficking of Ig-alpha/Ig-beta and mu-heavy chain is facilitated by dissociation of the B cell antigen receptor complex.

The BCR relays extracellular signals and internalizes Ag for processing and presentation. We have previously demonstrated that ligation of the BCR destabilizes Ig-alpha/Ig-beta (Ig-alphabeta) from mu-H chain (mum). In this study we report that receptor destabilization represents a physical separation of mum from Ig-alphabeta. Sucrose gradient fractionation localized Ig-alphabeta to G(M1)-containing lipid microdomains in the absence of mum. Confocal and electron microscopy studies revealed the colocalization of unsheathed mum with clathrin-coated vesicles. Furthermore, mum failed to associate with clathrin-coated vesicles when receptor destabilization was inhibited, suggesting that unsheathing of mum is required for clathrin-mediated endocytosis. In summary, we found that Ag stimulation physically separates Ig-alphabeta from mum, facilitating concomitant signal transduction and Ag delivery to the endocytic compartment.

Animals↗