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Expression of a variant of CD28 on a subpopulation of human NK cells: implications for B7-mediated stimulation of NK cells.

The ability of NK cells to kill tumor cells is controlled by a balance between activating and inhibitory signals transduced by distinct receptors. In murine tumor models, the costimulatory molecule B7.1 not only acts as a positive trigger for NK-mediated cytotoxicity but can also overcome negative signaling transduced by MHC class I molecules. In this study, we have evaluated the potential of human B7.1-CD28 interaction as an activating trigger for human blood NK cells. Using multiparameter flow cytometric analysis and a panel of different CD28 mAbs, we show that human peripheral blood NK cells (defined by CD56+, CD16+, and CD3- surface expression) express the CD28 costimulatory receptor, with its detection totally dependent on the mAb used. In addition, the level of CD28 varies among individuals and on different NK cell lines, irrespective of CD28 steady-state mRNA levels. By performing Ab binding studies on T cells, our data strongly suggest that binding of two of the anti-CD28 Abs (clones 9.3 and CD28.2) is to a different epitope to that recognized by clones L293 and YTH913.12, which is perhaps modified in the CD28 molecule expressed by the NK cells. We also show that B7.1 enhances the NK-mediated lysis of NK-sensitive but not of NK-resistant tumor cells and that this increased lysis is dependent on CD28-B7 interactions as shown by the ability of Abs to block this lysis. Coculture of the B7.1-positive NK-sensitive cells also led to the activation of the NK cells, as determined by the expression of CD69, CD25, and HLA class II.

Adult↗

The activity reaction core and plasticity of metabolic networks.

Understanding the system-level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches, such as constraint-based flux-balance analysis, have proved highly successful in analyzing the capabilities of cellular metabolism, including its capacity to predict deletion phenotypes, the ability to calculate the relative flux values of metabolic reactions, and the capability to identify properties of optimal growth states. Here, we use flux-balance analysis to thoroughly assess the activity of Escherichia coli, Helicobacter pylori, and Saccharomyces cerevisiae metabolism in 30,000 diverse simulated environments. We identify a set of metabolic reactions forming a connected metabolic core that carry non-zero fluxes under all growth conditions, and whose flux variations are highly correlated. Furthermore, we find that the enzymes catalyzing the core reactions display a considerably higher fraction of phenotypic essentiality and evolutionary conservation than those catalyzing noncore reactions. Cellular metabolism is characterized by a large number of species-specific conditionally active reactions organized around an evolutionary conserved, but always active, metabolic core. Finally, we find that most current antibiotics interfering with bacterial metabolism target the core enzymes, indicating that our findings may have important implications for antimicrobial drug-target discovery.

Escherichia coli↗

The role of the kidney in the maintenance of water balance.

This chapter shows how the mammalian kidney is able to regulate the excretion of water independently from that of solutes. For this function, which derives from several evolutionary steps among vertebrates, it takes advantage of the diluting ability of the thick ascending limb to produce osmotic energy which is then used to concentrate solutes in the urine. This concentration is permitted by a highly sophisticated architecture of nephrons and vessels in the renal medulla, combined with special permeability characteristics of the different nephron segments and specific hormonal regulation. Two different types of loops of Henle and several well-insulated vascular compartments contribute to this process. The major nitrogenous waste product, urea, is concentrated by an indirect process involving a transfer of osmotic energy from the outer to the inner medulla. As known for several decades, concentrating function is primarily regulated by the effect of antidiuretic hormone (ADH) on water permeability of the collecting duct. However, as discovered more recently, it is also largely dependent upon the effect of the same hormone on urea permeability in the terminal collecting duct. In addition, recent investigations have revealed a much more complex hormonal regulation of the concentrating process than previously thought. ADH itself acts on many other structures in the kidney, and many other hormones and mediators, the secretion of which is not thought to be influenced by the water status, do affect urine concentration either directly or by their interaction with ADH. Rodents display a wide spectrum of morphological and functional renal adaptations improving water conservation. Their study has brought a better understanding of the significant steps and anatomical structures that contribute to the concentrating process. Finally, it is also apparent that the capacity to concentrate urine is influenced in individual animals of a given species by the availability of water, by specific feeding patterns, and by the protein content of the diet.

Animals↗

The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.

The purpose of the present experiment was to examine the effectiveness of a modified rotarod test in detecting motor deficits following mild and moderate central fluid percussion brain injury. In addition, this investigation compared the performance of the rotarod task with two other commonly used measures of motor function after brain injury (beam-balance and beam-walking latencies). Rats were either injured with a mild (n = 14) or moderate (n = 8) level of fluid percussion injury or were surgically prepared but not injured (n = 8). All rats were assessed on all tasks for 5 days following their respective treatments. Results revealed that both the mild and moderate injury levels produced significant deficits in the ability of the animals to perform the rotarod task. Performance on the beam-balance and beam-walking tasks were not significantly impaired at the mild injury level. It was only at the moderate injury level that the beam-balance and beam-walking tasks detected deficits in motor performance. This result demonstrated that the rotarod task was a sensitive index of injury-induced motor dysfunction following even mild fluid percussion injury. A power analysis of the three tasks indicated that statistically significant group differences could be obtained with the rotarod task with much smaller sample sizes than with the beam-balance and beam-walking tasks. Performance on the rotarod, beam-walk, and beam-balance tasks were compared and evaluated by a multivariate stepdown analysis (multiple analysis of variance followed by univariate analyses of covariance). This analysis indicated that the rotarod task measures aspects of motor impairment that are not assessed by either the beam-balance or beam-walking latency. These findings suggest that compared to the beam-balance and beam-walking tasks, the rotarod task is a more sensitive and efficient index for assessing motor impairment produced by brain injury.

Animals↗

Involvement of type I corticosteroid receptor in the effects of ovariectomy on energy balance.

The effects of the glucocorticoid receptor antagonist, RU-38486 (RU-486), and the mineralocorticoid receptor (MR) antagonist, RU-28318, on energy balance were investigated in a 2 [surgery: ovariectomy (OVX) and sham operation] x 3 (corticosteroid antagonist: placebo, RU-28318, RU-486) experimental design. Rats were treated for 28 days. Food intake and body weight were monitored throughout the treatment period. At the end of the treatment, rats were killed and their carcasses were analyzed for energy and nitrogen contents. Energy content was determined by adiabatic bomb calorimetry, whereas nitrogen was determined in 250-to 300-mg samples of dehydrated carcasses, with the use of the Kjeldahl procedure. The energy as protein was subtracted from total carcass energy to determine energy as fat. The gains in energy, fat, and protein were calculated by subtracting the values obtained at the end of the treatment period from initial values estimated from the body weights measured at the beginning of the experiment. A significant interaction effect of surgery and corticosteroid antagonist was observed on body energy gain, energetic efficiency, and fat gain. Whereas body energy gain, energetic efficiency, and fat gain were larger in OVX rats than in sham-operated animals treated with either placebo or RU-486, they were comparable in OVX and sham-operated rats treated with RU-28318. Surgery, but not corticosteroid antagonist, had a significant effect on digestible energy intake, energy expenditure, and protein gain. All these variables were higher in OVX rats than in sham-operated animals. Surgery also affected corticosterone levels and adrenal weight. Both of these variables were lower in OVX rats than in sham-operated animals. By demonstrating the ability of RU-28318 to attenuate the effects of OVX on energy balance, the present study provides evidence that MR occupation by corticosteroids facilitates the OVX-induced changes in energy balance.

Animals↗

The subfornical organ's neural connections and their role in water balance.

The subfornical organ (SFO) has projections to specific sets of nuclei within the preoptic area and hypothalamus which enable it to influence behavioral and physiological controls of water balance. It projects to the nuclei of the anteroventral third ventricular area, to vasopressinergic (heavily) and oxytocinergic (moderately) magnocellular neurons of the supraoptic and paraventricular nucleus. It also projects to the parvocellular areas of the paraventricular nucleus which project to the median eminence and to all the motor nuclei of the autonomic nervous system. In addition the SFO projects to regions of the lateral preoptic area, lateral hypothalamus and the dorsal perifornical region. Cutting the efferent projections from the SFO causes disturbances in behavioral and physiological controls of water balance. There is moderate polyuria and a concentrating defect in urine osmolality. The rats do not drink to intravenous angiotensin II but retain their ability to drink to angiotensin II given intracerebroventricularly. They appear to drink normally to overnight water deprivation but remain in negative water balance because of excessive urinary water loss during the deprivation period.

Animals↗

Effects of balance training on hemiplegic stroke patients.

BACKGROUND: The purpose of this study was to evaluate the delayed effects of balance training program on hemiplegic stroke patients. METHODS: A total of 41 ambulatory hemiplegic stroke patients were recruited into this study and randomly assigned into two groups, the control group and trained group. Visual feedback balance training with the SMART Balance Master was used in the trained group. Bruunstrom staging of affected limb scores and Functional Independent Measure (FIM) scores of each patient were recorded. Quantitative balance function was evaluated using the SMART Balance Master. Data were collected before training and 6 months after completing the training program. RESULTS: Significant improvements in dynamic balance function measurements were found for patients in the trained group at 6 months after completing the training program. The ability of self-care and sphincter control also improved for patients in the trained group. On the other hand, no significant differences were found in static balance functions between the trained group and control group at 6 months of follow up. The locomotion and mobility scoring of FIM also revealed no differences between the groups. CONCLUSION: Dynamic balance function of patients in the visual feedback training group had significant improvements when compared with the control group. Activities of daily living (ADL) function in self-care also had significant improvements at 6 months of follow up in the trained group. The results showed that balance training was beneficial for patients after hemiplegic stroke.

Adult↗

Balance and fear of falling in Parkinson's disease.

To assess internal consistency and validity of measures of balance (Berg balance scale, BBS), postural changes (postural changes scale, PCS) and fear of falling (fear of fall measure, FFM) in 70 ambulant Parkinson's disease (PD) persons, these instruments were matched with performance-based balance and mobility tests, and other clinical, functional and quality of life PD-specific measures. The BBS, PCS and FFM showed a good internal consistency, moderate to good inter-correlation, and a significant correlation with measures of both disability (UPDRS-ADL, Schwab and England scale) and--to a lesser extent--impairment/severity of symptoms (UPDRS-ME, Hoehn and Yahr Scale). Tandem Romberg, Single-Limb Stance, Functional Reach, and the Timed Up & Go test correlated slightly better with BBS than with PCS and FFM. This study shows that problems of balance and postural control in PD patients result from complex interactions between motor impairment, functional abilities and fear of falling.

Accidental Falls↗

Sensory reweighting with translational visual stimuli in young and elderly adults: the role of state-dependent noise.

The properties of sensory reweighting for control of human upright stance have primarily been investigated through experimental techniques such as sinusoidal driving of postural sway. However, other forms of visual inputs that are commonly encountered, such as translation, may produce different adaptive responses. We directly compared sinusoidal and translatory inputs at stimulus parameters that made stimulus velocity comparable with each type of stimulus. Young healthy individuals were compared with healthy elderly and elderly designated as "fall-prone" to investigate whether the hypothesized basis for poor balance control in the "fall-prone" elderly is related to their ability to reweight sensory inputs appropriately. Standing subjects were presented with visual displays which moved in the medial-lateral direction either by (1) oscillating at different amplitudes or (2) simultaneously oscillating and translating at different speeds. All three subject groups showed that increasing the amplitude of the oscillations led to a decrease in gain. Increasing translation speed led to decreases in gain only at speeds above 1 cm/s. This suggests that the nervous system is processing more than just stimulus velocity to determine the postural response. A model implementing "state-dependent noise", in which visual stimulus noise increases with relative speed, was developed to account for the difference between translation and oscillation. The weak group effects question the common view that the fall-prone elderly are deficient in sensory reweighting. One explanation for the apparent discrepancy is that the slow, small-amplitude visual stimuli used in this study probe the asymptotic dynamics of the postural response. If given enough time, even the fall-prone elderly are able to adapt to a new sensory environment appropriately. However, the asymptotic adaptive response may not be functional in terms of preventing falls.

Adaptation, Physiological↗

[Direct and indirect effects of mineral water Naftusia and its components on the sodium-potassium pump of the small-intestinal epithelium in rats].

Experiments on rats have shown that intragastric single introduction of mineral water Naftusia to animals in a dose of 1.5% of the body weight of animals induces sodium accumulation in the small intestine epithelium, that is a result of Na(+)-, K(+)-pump inhibition by fatty acids of this water. Naftusia absorption induces appearance of inhibitors of Na(+)-, K(+)-ATPase enzymic system in blood serum of rats. Artificial salt Naftusia analog (ASNA) has induced contrary changes in the water-electrolytic balance and activated Na(+)-, K(+)-ATPase. Blood serum of ASNA-loaded rats acquired ability to activate Na(+)-, K(+)-pump of epitheliocytes in intact rats.

Animals↗

Daily living abilities and work abilities of people with Parkinson's disease.

A questionaire survey was conducted on 60 items of daily living abilities linked to 13 basic work abilities such as memory, learning, planning, muscular power and concentration etc. covering a total of 133 subjects with Parkinson's disease. Results of the survey were as follows: 1. Daily living abilities and work abilities decreased in accordance with Yahr's stages and the degree of daily living abilities. 2. Daily living abilities provided clues for aging and prognosis of the Parkinson's disease. 3. "Cope well with heat and coldness", "Being confident in the strength of legs and loins" and "Keep balance in the train" were difficult to do from the early stages of the onset. 4. Audio-visual ability, memory and judgement were well maintained despite the severity of the disease. 5. All subjects showed poor endurance, while learning, planning and manual dexterity showed higher performance in those under 59.

Journal Article↗

Effects of growth hormone on steroid-induced increase in ability of urea synthesis and urea enzyme mRNA levels.

Growth hormone (GH) reduces the catabolic side effects of steroid treatment due to its effects on tissue protein synthesis/degradation. Little attention is focused on hepatic amino acid degradation and urea synthesis. Five groups of rats were given 1) placebo, 2) prednisolone, 3) placebo, pair fed to the steroid group, 4) GH, and 5) prednisolone and GH. After 7 days, the in vivo capacity of urea N synthesis (CUNS) was determined by saturating alanine infusion, in parallel with measurements of liver mRNA levels of urea cycle enzymes, N contents of organs, N balance, and hormones. Prednisolone increased CUNS (micromol . min-1 . 100 g-1, mean +/- SE) from 9.1 +/- 1.0 (pair-fed controls) to 13.2 +/- 0.8 (P < 0.05), decreased basal blood alpha-amino N concentration from 4.2 +/- 0.5 to 3.1 +/- 0.3 mmol/l (P < 0.05), increased mRNA levels of the rate- and flux-limiting urea cycle enzymes by 20 and 65%, respectively (P < 0. 05), and decreased muscle N contents and N balance. In contrast, GH decreased CUNS from 6.1 +/- 0.9 (free-fed controls) to 4.2 +/- 0.5 (P < 0.05), decreased basal blood alpha-amino N concentration from 3. 8 +/- 0.3 to 3.2 +/- 0.2, decreased mRNA levels of the rate- and flux-limiting urea cycle enzymes to 60 and 40%, respectively (P < 0. 05), and increased organ N contents and N balance. Coadministration of GH abolished all steroid effects. We found that prednisolone increases the ability of amino N conversion into urea N and urea cycle gene expression. GH had the opposite effects and counteracted the N-wasting side effects of prednisolone.

Animals↗

Effect of ibuprofen and indomethacin on the O2 supply/consumption balance in ischemic rabbit myocardium.

The purpose of this study was to determine if differences in the cardioprotective abilities of ibuprofen and indomethacin were due to their differing abilities to alter the O2 supply/consumption ratio in the ischemic myocardium. Experiments were done on 21 anesthetized open-chest rabbits. Regional flow (using radioactive microspheres), O2 extraction, O2 consumption, and O2 supply/consumption ratio were determined 1 hr after occlusion of the left anterior descending coronary artery in controls and animals given iv 10 mg/kg ibuprofen or iv 3 mg/kg indomethacin. Myocardial blood flow was depressed in the occluded region compared to the nonoccluded region after occlusion for all treatments. O2 extraction in the occluded region was elevated compared to the nonoccluded region for all treatments after occlusion. No differences in O2 consumption were noted between any treatment within the occluded or nonoccluded regions. The O2 supply/consumption ratio was lower in the occluded region compared to the nonoccluded region for all treatments. No differences in this ratio were noted between any treatment. Thus, the effects of indomethacin or ibuprofen on ischemia are not related to acute changes in myocardial O2 supply/consumption balance.

Animals↗

Involvement of anteroventral third ventricular AMPA/kainate receptors in both hyperosmotic and hypovolemic AVP secretion in conscious rats.

The area of the brain called the anteroventral third ventricular region (AV3V) includes three different subtypes of glutamate receptor, as well as neural circuits controlling fluid balance and cardiovascular and neuroendocrine functions. Although our previous data indicate the ability of AV3V N-methyl-d-aspartate (NMDA) and metabotropic receptors to provoke vasopressin (AVP)-releasing, pressor and hyperglycemic responses, the roles of non-NMDA receptors selective for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate have not been elucidated to date. To address this question, the effects of intracerebral infusion with FWD or NBQX (specific agonist and antagonist for non-NMDA receptors, respectively) on plasma AVP, glucose, osmolality, electrolytes and cardiovascular parameters were examined in conscious rats in the absence or presence of an osmotic or volemic stimulus. When applied topically to AV3V structures such as the median preoptic nucleus, FWD augmented plasma AVP, osmolality, glucose and arterial pressure in a dose-associated fashion. All responses of the variables were abolished by pre-administering NBQX, which exerted no conspicuous effect on any variable except arterial pressure. It was revealed that NBQX administration in AV3V structures such as the median preoptic nucleus and the periventricular nucleus inhibited the rise of plasma AVP in response to intravenous infusion with hypertonic saline or removal of systemic blood through the femoral artery. Elevation of plasma osmolality and sodium evoked by osmotic load, and elevation of plasma osmolality, glucose and angiotensin II and decrease of arterial pressure caused by bleeding, were not significantly affected by NBQX treatment. These results suggest that AV3V non-NMDA receptors, as well as NMDA receptors, may elicit AVP-releasing, pressor and hyperglycemic actions when stimulated in the basal state, and may facilitate AVP secretion under both hyperosmotic and hypovolemic conditions, without contributing to cardiovascular, blood glucose or other responses.

Animals↗

Adaptation for water balance in the partial gastrointestinal tract of summer flounder.

Marine teleosts continually drink and absorb water across the intestine to prevent dehydration. Surprisingly, summer flounder that are missing most of their intestine, due to necrotizing enteritis, maintain osmotic homeostasis. Here, we tested the hypothesis that this remnant gastrointestinal tract undergoes compensatory adaptation for fluid uptake. Flounder (Paralicthys dentatus) with a partial gastrointestinal tract had an emaciated liver. Moisture content of muscle however was similar to healthy cohorts with an intact gastrointestinal tract, indicative of an undisturbed osmoregulatory status. Mass-specific rates of fluid uptake across all segments of the partial gastrointestinal tract were less than or similar to rates in corresponding segments from intact flounder. In contrast, weights (percent of body mass) were doubled in stomach and partial intestine of the remnant gastrointestinal tract. Consequently, total capacity for fluid uptake (microL h(-1) g body mass(-1)) was similar for both groups. The functional capacity of the remnant gastrointestinal tract was therefore of a magnitude sufficient to maintain osmoregulatory ability, further evidencing a critical role of the intestine in salt and water balance of marine teleosts.

Acclimatization↗

Maximal and explosive force production capacity and balance performance in men of different ages.

A group of 32 healthy men (M) divided into three different age groups, i.e. M20 years [mean 21 (SD 1); n = 12], M40 [mean 40 (SD 2); n = 10] and M70 [mean 71 (SD 5); n = 10] volunteered as subjects for examination of maximal and explosive force production of leg extensor muscles in both isometric and dynamic actions (squat jump, SJ and counter movement jump, CMJ, and standing long-jump, SLJ). The balance test was performed on a force platform in both isometric and dynamic actions. Maximal bilateral isometric force value in M70 was lower (P < 0.001) than in M40 and as much as 46% lower (P < 0.001) than that recorded in M20 (P < 0.001). The maximal rate of force development (RFD) on the force-time curve was in M70 lower (P < 0.001) than in M40 and as much as 64% lower than in M20. The heights in SJ and CMJ and the distance in SLJ in M70 were lower (P < 0.001) than in M40 and M20 (P < 0.001). In response to modifications of the visual surroundings the older subjects were 24%-47% (P < 0.05 and P < 0.001) slower in their response time in reaching the lit centre (TT) and remained 20%-34% (P < 0.001) less time inside the centre (TC) from the overall time of lighting than M40 and M20, respectively. In both older groups the individual values of isometric RFD correlated significantly (P < 0.05) with the individual balance values of TT and TC. The present results would suggest that the capacity for explosive force production declines drastically with increasing age, even more than maximal muscle strength. Aging may also lead to impaired balance with a decrease in event detection and speed of postural adjustments. The decreased ability to develop force rapidly in older people seems to be associated with a lower capacity for neuromuscular response in controlling postural sway.

Adult↗