Interaction of a Motor Response, and Reaction Time and Time Estimation Tasks, on Heart Rate and Skin Conductance

The influence of motor responding and typical psychophysiological tasks on heart rate was tested by manipulating motor requirements of reaction time (RT) and time estimation (TE) tasks. Thirty-four volunteers were assigned randomly to four groups. Two groups squeezed a hand dynamometer at the start of a trial and the other two groups squeezed at the finish of the trial. The force of the squeeze was also manipulated: either 3 kg (3) or 7 kg (7). The four groups were Start 3, Start 7, Finish 3, and Finish 7. All subjects participated in the TE and RT tasks. The dependent variables were measurements of forearm flexor muscle tension, heart rate and skin conductance. It was found that the manipulations of when and with what force a person squeezed the dynamometer resulted in reliable group differences in muscle tension. The magnitude of acceleratory components of the triphasic (acceleration-deceleration-acceleration) cardiac response was amplified by tension. The magnitude of the deceleratory component seemed to depend on both muscle tension and stimulus processing. Except for the magnitude of the response-bound deceleration, RT and TE produced very similar heart rate responses, and skin conductance did not differ among groups. The data were interpreted as providing evidence that motor response acts as an amplifier for the phasic HR produced by common psychological paradigms.     

Genome-wide examination of myoblast cell cycle withdrawal during differentiation.

Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21(WAF1/Cip1) increased and alpha-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing approximately 10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation.     

Total lymphocyte count of 1200 is not a sensitive predictor of CD4 lymphocyte count among patients with HIV disease in Kampala, Uganda

Introduction

Total Lymphocyte Count (TLC) has been found to be an inexpensive and useful marker for staging disease, predicting progression to AIDS and death and monitoring response to ART. However, the correlation between TLC and CD4 has not been consistent. Access to HAART is expanding in Kampala, Uganda, yet there are no published data evaluating the utility of TLC as inexpensive surrogate marker of CD4 cell count to help guide therapeutic decisions.

Objective

To evaluate clinical illnesses and total lymphocyte count (TLC) as surrogate markers of the CD4 cell count in HIV infected persons being considered for ART.

Methods

A total of 131 patients were enrolled and evaluated by clinical assessment, TLC and CD4 count. Clinical illnesses and TLC dichotomized at various cut-point values were used to determine the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for the diagnosis of CD4 count <200 cells/mm³ among 100 participants fulfilling criteria for WHO clinical stage 2 and 3.

Results

A strong correlation was observed between TLC and CD4 (r = 0.73, p<0.0001). For all clinical syndromes, except pulmonary tuberculosis, the positive predictive values (PPV) for a CD4 count <200 cells/mm³ were high (>80%) but the negative predictive values (NPV) were low. Using the WHO recommended TLC cut-off of 1200 cells/mm³ to diagnose a CD4 less than 200 cells/mm³, the PPV was 100%, and the NPV was 32%.

Conclusion

Our data showed a good correlation between TLC and CD4 cell count. However, the WHO recommended TLC cutoff of 1200 did not identify the majority of WHO stage 2 and 3 patients with CD4 counts less than 200 cells/mm³. A more rational use of TLC counts is to treat all patients with WHO stage 2 and 3 who have a TLC <1200 and to limit CD4 counts to patients who are symptomatic but have TLC of >1200.     

The initial phase of exercise hyperpnoea in humans is depressed during a cognitive task

Increased wakefulness is known to suppress the initial ventilatory response to passive movement and the steady-state ventilatory response to exercise. However, the effect of increased wakefulness upon the integrated ventilatory response at the onset of exercise is not known. We hypothesized that increasing wakefulness via a cognitive task would attenuate the initial ventilatory response to exercise, and so we examined the response to active leg extensions under two conditions: with and without concurrently solving a puzzle. At rest before exercise, subjects demonstrated greater minute ventilation while solving a puzzle (mean +/- S.E.M., 12.38 +/- 0.55 versus 10.12 +/- 0.51 l min(-1), P < 0.001), due to a higher mean breathing frequency (mean +/- S.E.M., 17.1 +/- 0.93 versus 13.6 +/- 0.59 breaths min(-1), P < 0.001). At the start of exercise, subjects did not increase their ventilation significantly while solving the puzzle (P = 0.170), but did by a mean +/-s.e.m. of 6.16 +/- 1.12 l min(-1) (P < 0.001) when not puzzle solving. The ventilation achieved at the start of exercise in absolute terms was also lower while solving the puzzle (14.6 +/- 1.1 versus 16.3 +/- 1.3 l min(-1), P = 0.047). Despite differences in the rapid ventilatory response to exercise between conditions, the steady-state responses were not different. We conclude that the performance of a cognitive task decreases the initial phase of exercise hyperpnoea, and suggest that this might occur because of either a competitive interaction between drives to breathe or a behavioural distraction from the 'task' of exercise.     

Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions

CD16+ monocytes represent 5-10% of circulating monocytes in healthy individuals and are dramatically expanded in several pathological conditions including AIDS and HIV-1-associated dementia (HAD). CD16+ monocytes constitutively produce high levels of pro-inflammatory cytokines and neurotoxic factors that may contribute to the pathogenesis of these disorders. Monocyte recruitment into the central nervous system (CNS) and other peripheral tissues in response to locally produced chemokines is a critical event in immune surveillance and inflammation and involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we investigate the ability of CD16+ monocytes to undergo transendothelial migration (TEM) under constitutive and inflammatory conditions. CD16+ monocytes underwent TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular endothelial (BMVEC) cell monolayers in response to soluble fractalkine (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) induced high and low expression of membrane-bound FKN on HUVEC and BMVEC, respectively, together with expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC remained negative. Both CD16- and CD16+ monocyte subsets adhered to TNF/IFN-gamma-stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16- monocytes across TNF/IFN-gamma-stimulated HUVEC, whereas soluble FKN failed to induce TEM of CD16+ monocytes across stimulated HUVEC. These results demonstrate that stimulation with TNF and IFN-gamma triggers expression of membrane-bound FKN on both HUVEC and BMVEC, but prevents TEM of CD16+ monocytes in response to soluble FKN. Thus, pro-inflammatory CD16+ monocytes may contribute to the pathogenesis of HAD and other inflammatory CNS diseases by affecting the integrity of the blood-brain barrier as a consequence of their massive accumulation onto inflamed brain vascular endothelial cells expressing FKN and other adhesion molecules.     

Brain regions and their dynamics in prospective memory retrieval: a MEG study.

We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.     

Modulation of activity in medial frontal and motor cortices during error observation

We used measures of the human event-related brain potential (ERP) to investigate the neural mechanisms underlying error processing during action observation. Participants took part in two conditions, a task execution condition and a task observation condition. We found that activity in both the medial frontal cortex and the motor cortices, as measured via the error-related negativity and the lateralized readiness potential, respectively, was modulated by the correctness of observed behavior. These data suggest that similar neural mechanisms are involved in monitoring one's own actions and the actions of others.     

Spectral electroencephalographic correlates of iron status: Tired blood revisited

For some time, clinical reports have described impairment of affective and cognitive functions in iron deficient persons. Recent studies suggest that both brain biochemistry and cognitive performance capacity may be disrupted by inadequate intake of dietary iron, but the relationship of the possible neurophysiological effects to psychological ones is unclear. To examine the relationship of iron status to simultaneous measures of cortical activation and cognitive performance, 8 channels of electroencephalographic (EEG) data were recorded during a resting period and during the performance of several cognitive tasks in two groups of men. The EEG data were spectrally analyzed, and measures of total power and frequency of peak power in each of several bands of the power spectrum for each channel were used as predictors in multiple regression analyses with serum iron and serum ferritin as alternative criteria. Measures of power in the delta frequency in the resting period appeared relevant to iron status in both groups, perhaps indicating alertness or arousal level. Consistently in these regressions, the asymmetry of the EEG appeared relevant to iron and ferritin. These findings suggest that the combination of EEG and performance measures may help characterize the neuropsychological effects of trace element nutrition.     

Cytokine induction of heat shock protein in human granulosa-luteal cells

The infiltration of leukocytes is a characteristic feature ofluteolysis in humans. Leukocytes are known to generate physiologicalinducers of cell stress such as cytokines which have been implicatedas mediators of functional luteal regression. In cells exposedto stress, a response characterized by an increase in heat shockprotein (HSP) synthesis occurs. Recently, the induction of HSP-70in rat luteal cells has been shown to inhibit luteinizing hormone(LH) and cAMP-sensitive progesterone production, possibly byinterfering with the translocation of cholesterol to the mitochondrialcytochrome P450_SCC. We therefore investigated whether HSP-70is induced in human granulosa-luteal cells and its relationshipto steroidogenesis. [³⁵S]Methionine labelling showed an increasein a 70 kDa protein after heat treatment which was demonstratedto be HSP-70 by Western analysis using monoclonal antibodiesagainst the constitutive and inducible forms of HSP-70. Inductionof HSP-70 in human granulosa-luteal cells was also seen withinterferon (IFN) (10 ng/ml), tumour necrosis factor (TNF)-     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.