Replication as a determinant of the intestinal response to rotavirus

Mucosal antibody induction by otherwise identical replication-competent and replication-incompetent rhesus monkey rotaviruses was compared. Although psoralen-inactivated virus induced diarrhea, the magnitude of the intestinal antibody response was severely attenuated compared with that of replicating rotavirus, as determined by assay of mucosal antibody-secreting cells. Rotavirus that was neutralized by monoclonal antibodies (anti-VP4 and -VP7) prior to inoculation was similarly ineffective at induction of specific antibodies in intestinal secretions. In contrast to genetically inactivated virus, antibody-neutralized virus did not induce diarrhea. In this murine model, viral replication is an important determinant of antibody induction. The diarrhea response is blocked by neutralizing antibodies, but the mechanism of action is not exclusively the inhibition of viral replication.     

Neonatal movement response decrement and recovery to sounds as a function of stimulus intensity.

Studied response decrement, novelty response, and dishabituation of body movements to repeated presentations of white noise stimulus (of 66, 76, and 86 db) to 89 2–3 day old Ss in the 1st epoch of active-quiet sleep following a feeding. In Part 1, Ss receiving the 86 db repeating stimulus had greater movement scores compared to Ss receiving the 76 db intensity, who in turn had greater movement scores than those receiving the 66 db intensity. All groups demonstrated movement response decline following repeated stimulation, and, in Part 2, a novelty response was observed when either a 66 or 76 db repeating stimulus was increased to 86 db. A novelty response was not observed when intensity was decreased. Dishabituation was not observed following a novelty response. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apoptosis as a mechanism of neuronal cell death following acute experimental spinal cord injury

The complex biochemical interactions following acute spinal cord injury have undergone considerable investigation recently. Progress has been made in discovering both primary and secondary injury cascades that combine to produce the ultimate neurologic insult. Traditionally, neuronal and supporting cell death following spinal cord injury have focused on necrotic death pathways resulting passively from the actual mechanical tissue damage and inflammatory processes which follow. However, the occurrence of programmed apoptotic cell death which is an actively mediated cellular process may occur following acute spinal cord injury and, if present, may play a role in the ultimate neurologic insult. In this study, we document a chronologically-specific course of apoptotic cell death by the TUNEL assay technique following an acute experimental spinal cord injury in the rat model. In this manner, apoptotic cell death following acute spinal cord injury may play a pivotal role in the secondary injury cascade which produces the ultimate neurologic insult and may allow potential for mediating neuronal survival via anti-apoptotic factors such as the protooncogene Bcl-2.     

Mitochondrial function in rat renal cortex in response to proteinuria and iron

1. Proximal tubular cell dysfunction in chronic glomerular disease (CGD) has been ascribed, in part, to reabsorption of transferrin-iron from tubular fluid and subsequent cytosolic peroxidative injury. To investigate a possible role for altered mitochondrial function in tubular cell injury in CGD, renal cortical mitochondrial respiratory function was examined in rats with adriamycin nephrosis. 2. State 4 (resting) respiration was increased in adriamycin nephrosis in comparison with control (51 +/- 2 vs 43 +/- 2 ng atoms oxygen (O)/min per mg protein, respectively; P < 0.02). 3. Mitochondrial iron concentration was increased in nephrotic rats compared with control (9.52 +/- 0.70 vs 5.97 +/- 0.26 nmol Fe/mg protein, respectively; P < 0.001) and rates of state 3, state 4 and uncoupled respiration and the severity of proteinuria correlated with mitochondrial iron concentration. 4. To further define the relationship between mitochondrial iron accumulation and altered respiratory function, rats were loaded with iron. 5. In comparison with control, acute iron loading of normal rats impaired creatinine clearance (1.48 +/- 0.02 vs 0.40 +/- 0.29 mL/min), increased kidney weight (1.33 +/- 0.07 vs 1.74 +/- 0.14 g) and impaired mitochondrial enzyme activity (e.g. cytochrome oxidase 185.0 +/- 46.6 vs 362.0 +/- 32.8 delta log [cytochrome C]/min per mg protein; P < 0.05), but had no significant effect on rates of mitochondrial respiration or on mitochondrial fragility. 6. Mitochondrial iron concentration was not increased by iron loading, despite a similar increment in cytoplasmic iron to that seen in rats with adriamycin nephrosis. 7. In summary, resting mitochondrial respiration is increased in nephrotic rats in proportion to mitochondrial iron accumulation. Changes in mitochondrial oxygen consumption do not appear to be a primary event in the tubular cell injury of iron loading.     

Peripheral airways as a determinant of ventilatory function in the human lung

We have investigated the morphological differences responsible for the variability in two tests of pulmonary function, maximal expiratory flow rates (MEF) and the frequency dependence of dynamic compliance (CDYN ratio). Functional measurements were obtained from 53 normal and minimally diseased postmortem human lungs. Morphological measurements performed on these same lungs included airway diameter at three levels in the bronchial tree, the amount of bronchial gland mass, and the alveolar surface to volume ratio. Multiple regression analysis suggests that the diameter of the peripheral conduction airways (membranous bronchioles) is the major morphological determinant for both MEF and the CDYN ratio in lungs at any particular age. Age-dependent changes in both functional tests were associated primarily with differences in the alveolar surface to volume ratio. Minimal emphysema and a lesion associated with cigarette smoking, respiratory bronchiolitis, have no demonstrable effect on either MEF or the CDYN ratio. These studies provide further evidence that the peripheral conducting airways are a major determinant of ventilatory function in the normal human lung.     

Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats

Administration of 2-acetylaminofluorene (2-AAF) given before partial hepatectomy (PHx) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. Our objective in this study was to examine the oval cell response and associated alpha-fetoprotein (AFP) gene expression by combining 2-AAF with selective damage of centrilobular regions (carbon tetrachloride [CCl4]) or periportal regions (allyl alcohol [AA]). Centrilobular damage results in a more enhanced oval cell response and AFP gene expression than periportal damage. Conversely, more intense proliferation of intraportal bile duct epithelia was seen with 2-AAF/AA than with 2-AAF/CCl4. The oval cell response and AFP gene expression was ranked as 2-AAF/ CCl4 > or = 2-AAF/PHx > 2-AAF/AA. AFP mRNA expression was also examined in an acute AA and CCl4 injury. We found very little AFP gene expression compared with the 2-AAF/hepatic injury models. To see a true oval cell response, the hepatocytes must be inhibited from proliferating. In addition, the results presented with the 2-AA/AA model suggest that the periportal matrix may be as important as the cells that populate the area.     

Cellular thiols as a determinant of responsiveness to menadione in cardiomyocytes

The role of intracellular thiols in menadione-mediated toxicity was studied in neonatal rat cardiomyocytes. The sensitivity of cardiomyocytes to menadione was greater than that of skeletal muscle cells and 3T3 fibroblasts. Before cell degeneration, menadione induced marked depletion of intracellular thiols and an increase of oxidized glutathione. The sensitivity of these cells to menadione correlated with the level of depletion of intracellular thiols. After incubation of cardiomyocytes with menadione, glutathione reductase activity was inhibited and lipid peroxidation was increased. Both dicumarol (an inhibitor of DT-diaphorase) and diethyldithiocarbamate (an inhibitor of superoxide dismutase) enhanced the capacity of menadione to induce cellular damage and to cause depletion of intracellular glutathione. Decreasing intracellular glutathione by pretreatment of cells with N-ethylmaleimide or buthionine sulphoximine also increased menadione-induced cell degeneration. Preincubation with cysteine or dithiothreitol suppressed the capacity of menadione to damage the cells. Menadione-induced lipid peroxidation was also suppressed by the same treatment. These results show that the oxidative stress induced by menadione in cardiomyocytes results in the depletion of glutathione and protein thiols. Both DT-diaphorase and superoxide dismutase can protect cells from the toxicity of menadione. Cellular thiols are determinants of the responsiveness to menadione.     

Event-related potentials as an index of cognitive function during recovery from severe closed head injury

OBJECTIVE: To evaluate the utility and neuropsychological correlates of serially performed recordings of event-related potentials (ERPs) in patients recovering from a severe closed head injury (CHI). DESIGN: Prospective longitudinal study. SETTING: Brain injury rehabilitation unit based in a national rehabilitation hospital. SUBJECTS: Sixteen patients with severe CHI (significant degree of impaired consciousness greater than 24 hours) subclassified into two severity groups according to initial Glasgow Coma Scale (GCS) score: those with initial GCS score < 9, consistent with a more severe injury; and those with initial GCS score > 8, indicating a less severe injury. METHODS: ERPs were elicited using the standard auditory P300 "oddball" detection paradigm. ERP recordings were carried out three times: 2 months after injury, 1 month later, and 2.5 months or more after the initial study. Parameters analyzed included latencies and amplitudes of the P3, N2, P2, and N1 components of the ERPs. Correlations between changes in these ERP parameters and specific neuropsychological test results were evaluated. RESULTS: Initial P3 latencies in the more severely injured group were significantly longer (P < .05) than those recorded in the less severely injured patients. In subsequent recordings, P3 latency was found to be significantly shorter compared with the initial P3 latency, and the difference in P3 latency between the two patient groups was no longer statistically significant by the time of the third recording. For the group as a whole, P3 latency decreased significantly on each repeated recording. N2 latency was found to be significantly shorter (P < .05) between the first and third recordings. Cognitive performance significantly improved between the first and third recordings. P3 latency shortening was correlated with improvement in neuropsychological test scores for short-term and long-term story recall and for word recall. N2 latency shortening was correlated with improvement in the neuropsychological test scores for word recall only. CONCLUSION: ERP recordings performed in the subacute stage after CHI may assist in evaluating injury severity. Moreover, serially performed recordings of P3 latency may be used as a physiologic index of brain activity that correlates with recovery from CHI.     

Caspases and programmed cell death in the hypersensitive response of plants to pathogens

The hypersensitive response (HR) is induced by certain plant pathogens and involves programmed cell death (PCD) to restrict the spread of pathogens from the infection site [1]. Concurrent with the induction of cell death, the host activates a defense response [2]. The cell death associated with the HR in several plant-pathogen systems has morphological similarities to animal apoptosis [3,4], which suggests that cell death mechanisms in plants and animals may share common components that lead to similar cellular events. Caspases are conserved cysteine proteases that regulate animal PCD [5]; caspase activity or an involvement of caspases in cell death has yet to be reported in plants. In this work, we investigated the participation of caspases in HR cell death. Caspase-specific peptide inhibitors, Ac-YVAD-CMK [6] and Ac-DEVD-CHO [7], could abolish bacteria-induced plant PCD but did not significantly affect the induction of other aspects of HR, such as the expression of defense genes. This result confirmed our previous model that cell death can be uncoupled from defense gene activation during HR [8]. Caspase-like proteolytic activity was detected in tobacco tissues that were developing HR following infection with tobacco mosaic virus (TMV). Our results provide evidence for the presence of caspase-like plant protease(s) that participate in HR cell death.     

Changes in counselor response as a function of experience.

The responses of 67 counselors to 21 widely varying client statements were rated on eight dimensions (dominance, approach–avoidance, focus on affect, immediacy, breadth vs. specificity, meeting client's demands, verbosity, and confrontation). The counselors were divided into three experience levels (beginning students [n?=?24], advanced students [n?=?23], and doctoral level professionals [n?=?20]), and their responses were compared. We hypothesized that student counselors would evidence different amounts of these variables than would the doctoral counselors. This hypothesis was supported on the dimensions of dominance, immediacy, meeting client's demands, verbosity, and confrontation. It was also hypothesized that response flexibility would differ across the experience levels. On the dimensions of dominance, meeting client demands, and confrontation, doctoral counselors were more flexible than were advanced student counselors. The results indicate that students focus on learning and honing the use of certain counseling skills. In the process of doing this, they tend to apply them in a rigid manner. Doctoral counselors appear more able to apply their skills flexibly depending on the situation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Type of punishment as a determinant of resistance to deviation.

Compared the effectiveness of an aversive stimulus, withholding of resources, withdrawal of love, and reasoning, when used alone and when combined with praise, in a standard laboratory punishment paradigm using 120 1st- and 2nd-grade boys and girls as Ss. Resistance to deviation and stability of resistance to deviation were used as the measures of punishment effectiveness. Sex of child, use of praise, and type of punisher were combined in a 2 * 2 * 5 factorial design, with a female as the punitive agent. An aversive stimulus appeared to produce more suppression of deviant behavior, but the effect was not significant for all response measures. The stability of the deviant response pattern varied for each punisher, but the most stable response pattern resulted from the use of an aversive stimulus. Neither use of praise nor sex of child significantly influenced punisher effectiveness. Results are discussed within the framework of anxiety arousal and information content of the punishers, and the practice of grouping various punishers under the categories of sensitization and induction measures is considered. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preference as a function of absolute response durations.

The durations of 2 responses, 2 categories of reinforced nondiscriminated interresponse times, were varied while their relative durations were held approximately constant, with the longer about 2? times longer than the shorter. Three pigeons pecked for food. Reinforcers for the shorter and longer responses were arranged by a concurrent VI, VI schedule. Preference for the shorter response increased when both were lengthened. These results, taken together with previous results for discriminated interresponse times, show that preference for the shorter of 2 responses depends on their absolute durations, whether they are discriminated or not and regardless of autoshaped key pecks that may occur in the discriminated case. Time-allocation-matching was not generally obtained. The results qualitatively agree with an associative learner, a computational processing model derived from a molecular analysis of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Female gender as a determinant of cough threshold to inhaled capsaicin

Chronic, nonproductive cough and cough associated with the use of angiotensin converting enzyme inhibitors, are more frequently observed in females as compared to males. To examine the influence of sex, age, height, weight and pulmonary function on airway cough sensitivity, cough threshold to inhaled capsaicin, an index of the airway cough sensitivity, was measured in 160 nonsmoking, nonatopic healthy subjects. Forty young males (aged 24 +/- 2 yrs) 40 young females (aged 22 +/- 2 yrs) 40 middle-aged males (aged 48 +/- 5 yrs) and 40 middle-aged females (aged 50 +/- 7 yrs) were studied. The cough threshold was defined as the lowest concentration of inhaled capsaicin causing five or more coughs. The cough threshold was 3-5 fold lower in females than in males both in young (p<0.001) and middle-aged (p<0.005) subjects. Cough threshold was weakly but significantly correlated to height, weight, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) when all subjects were considered together but not when each group was considered separately. Multiple regression analysis revealed that sex difference was the significant predictive factor for the cough threshold in either age group. These results confirm that cough sensitivity is heightened in females and suggest that influence of height and pulmonary function on the cough threshold may have resulted from sex difference.