[Pain in patients with paraplegia]. / Schmerzen bei Patienten mit Querschnittlähmung.

Chronic pain is one of the most reported health problems in patients suffering from spinal cord injuries and is described by the patients as one of the most burdensome sequelae of paraplegia. Various types of pain, such as nociceptive, neuropathic and other types of pain can occur. In addition, multiple pathophysiological mechanisms based on the biopsychosocial pain model play a role in the origins of the pain. These aspects necessitate a multimodal pain management approach in this patient group. This article presents an overview of the occurrence, importance and pathophysiology of chronic pain following spinal cord injury as well as diagnostic and therapeutic approaches.

Water-assisted CO(2) laser ablated glass and modified thermal bonding for capillary-driven bio-fluidic application.

The glass-based microfluidic chip has widely been applied to the lab-on-a-chip for clotting tests. Here, we have demonstrated a capillary driven flow chip using the water-assisted CO(2) laser ablation for crackless fluidic channels and holes as well as the modified low-temperature glass bonding with assistance of adhesive polymer film at 300 degrees Celsius. Effect of water depth on the laser ablation of glass quality was investigated. The surface hydrophilic property of glass and polymer film was measured by static contact angle method for hydrophilicity examination in comparison with the conventional polydimethylsiloxane (PDMS) material. Both low-viscosity deionized water and high-viscosity whole blood were used for testing the capillary-driving flow behavior. The preliminary coagulation testing in the Y-channel chip was also performed using whole blood and CaCl(2) solution. The water-assisted CO(2) laser processing can cool down glass during ablation for less temperature gradient to eliminate the crack. The modified glass bonding can simplify the conventional complex fabrication procedure of glass chips, such as high-temperature bonding, long consuming time and high cost. Moreover, the developed fluidic glass chip has the merit of hydrophilic behavior conquering the problem of traditional hydrophobic recovery of polymer fluidic chips and shows the ability to drive high-viscosity bio-fluids.

Signaling in the yeast pheromone response pathway: specific and high-affinity interaction of the mitogen-activated protein (MAP) kinases Kss1 and Fus3 with the upstream MAP kinase kinase Ste7.

Kss1 and Fus3 are mitogen-activated protein kinases (MAPKs or ERKs), and Ste7 is their activating MAPK/ERK kinase (MEK), in the pheromone response pathway of Saccharomyces cerevisiae. To investigate the potential role of specific interactions between these enzymes during signaling, their ability to associate with each other was examined both in solution and in vivo. When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins. These complexes were specific because neither Hog1 nor Mpk1 (two other yeast MAPKs), nor mammalian Erk2, was able to associate detectably with Ste7. Neither the kinase catalytic core of Ste7 nor the phosphoacceptor regions of Ste7 and Kss1 were necessary for complex formation. Ste7-Kss1 (and Ste7-Fus3) complexes were present in yeast cell extracts and were undiminished in extracts prepared from a ste5delta-ste11delta double mutant strain. In Ste7-Kss1 (or Ste7-Fus3) complexes isolated from naive or pheromone-treated cells, Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner; dissociation of the high-affinity complex was shown to be required for either phosphorylation event. Deletions of Ste7 in the region required for its stable association with Kss1 and Fus3 in vitro significantly decreased (but did not eliminate) signaling in vivo. These findings suggest that the high-affinity and active site-independent binding observed in vitro facilitates signal transduction in vivo and suggest further that MEK-MAPK interactions may utilize a double-selection mechanism to ensure fidelity in signal transmission and to insulate one signaling pathway from another.

A conserved interaction between Moe1 and Mal3 is important for proper spindle formation in Schizosaccharomyces pombe.

Moe1 is a conserved fission yeast protein that negatively affects microtubule stability/assembly. We conducted a two-hybrid screen to search for Moe1-binding proteins and isolated Mal3, a homologue of human EB1. We show that Moe1 and Mal3 expressed in bacteria form a complex and that Moe1 and Mal3 expressed in fission yeast cosediment with microtubules. Deletion of either moe1 or mal3 does not result in lethality; however, deletion of both moe1 and mal3 leads to cell death in the cold. The resulting cells appear to die of chromosome missegregation, which correlates with the presence of abnormal spindles. We investigated the cause for the formation of monopolar spindles and found that only one of the two spindle pole bodies (SPBs) contains gamma-tubulin, although both SPBs appear to be equal in size and properly inserted in the nuclear membrane. Moreover, the moe1 mal3 double null mutant in the cold contains abnormally short and abundant interphase microtubule bundles. These data suggest that Moe1 and Mal3 play a role in maintaining proper microtubule dynamics/integrity and distribution of gamma-tubulin to the SPBs during mitosis. Finally, we show that human Moe1 and EB1 can each rescue the phenotype of the moe1 mal3 double null mutant and form a complex, suggesting that these proteins are part of a well-conserved mechanism for regulating spindle functioning.

Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West.

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

Fission yeast Ras1 effector Scd1 interacts with the spindle and affects its proper formation.

Ras1 GTPase is the Schizosaccharomyces pombe homolog of the mammalian Ha-Ras proto-oncoprotein. Ras1 interacts with Scd1 (aka Ral1), a presumptive guanine nucleotide exchange factor for Cdc42sp, to control organization of the cytoskeleton. In this study, we demonstrated that the scd1 deletion (scd1Delta) induced hypersensitivity to microtubule destabilizing drugs and instability of the minichromosome. Overexpression of scd1 induced formation of abnormal spindles and chromosome missegregation. The scd1 deletion worsened the defects of spindle formation in tubulin mutants; by contrast, it did not induce lethality in mutants defective in the spindle pole bodies. These genetic data suggest that Scd1 can interact with tubulin with substantial specificity to affect proper spindle formation and chromosome segregation. Subcellular localization data further illustrated that a GFP-Scd1 fusion protein can associate with the spindle. Finally, we showed that unlike ras1Delta and scd1Delta, byr2Delta (affecting the Ras1 effector for mating) is not synthetically lethal with the tubulin mutations. These data collectively suggest that the Ras1 pathway can impinge upon microtubules through Scd1, but not Byr2, to affect proper spindle formation and chromosome segregation.

Motor patterns and propulsion in the rat intestine in vivo recorded by spatio-temporal maps.

We have used spatio-temporal maps derived from video images to investigate propagated contractions of the rat small intestine in vivo. The abdomen, including an exteriorized segment of jejunum, was housed in a humid chamber with a viewing window. Video records were converted to spatio-temporal maps of jejunal diameter changes. Intraluminal pressure and fluid outflow were measured. Contractions occupied 3.8 +/- 0.2 cm of intestine and propagated anally at 3.1 +/- 0.2 mm s(-1) when baseline pressure was 4 mmHg. Contractions at any one point lasted 8.7 +/- 0.6 s. Contractions often occurred in clusters; within cluster frequencies were 2.28 +/- 0.04 min(-1). Pressure waves, with amplitudes greater than about 9 mmHg, expelled fluid when the baseline pressure was 4 mmHg. In the presence of L-NAME, circular muscle contractions occurred at a high frequency, but they were not propagated. We conclude that video recording methods give good spatio-temporal resolution of intestinal movement when applied in vivo. They reveal neurally-mediated propulsive contractions, similar to those previously recorded from intestinal segments in vitro. The propagated contractions had speeds of propagation that were slower and frequencies of occurrence that were less than speeds and frequencies of slow waves in the rat small intestine.

Cultural variations in optimistic and pessimistic bias: do Easterners really expect the worst and Westerners really expect the best when predicting future life events?

The authors compared levels of optimistic and pessimistic bias in the prediction of positive and negative life events between European Americans and Japanese. Study 1 showed that European Americans compared with Japanese were more likely to predict positive events to occur to self than to others. The opposite pattern emerged in the prediction of negative events. Study 2 replicated these cultural differences. Furthermore, positive associations emerged between predictions and occurrence of life events 2 months later for both European Americans and Japanese. Across both studies, results of within-groups analyses indicated that both groups expected negative events to be more likely to occur to others than to self (optimistic bias). In addition, Japanese expected positive events to be more likely to occur to others than to self (pessimistic bias). However, European Americans failed to show the expected optimistic bias for positive events.

Effects of reduced-fat diets consumed ad libitum on intake of nutrients, particularly antioxidant vitamins.

OBJECTIVES: To determine whether a reduced-fat diet consumed ad libitum can achieve the recommended intakes of other macronutrients, fiber, and cholesterol and whether such a diet affects intake of other important micronutrients such as fat-soluble vitamins. DESIGN: Twelve-month, randomized, controlled trial of a reduced-fat, ad libitum diet vs usual diet. SUBJECTS: One hundred ten adults older than 40 years with glucose intolerance (2-hour blood glucose concentration = 7.0 to 11.0 mmol/L) who were selected from a previous workforce survey. INTERVENTION: Monthly small-group meetings aimed at identifying sources of dietary fat and ways to reduce fat consumption. MAIN OUTCOME MEASURES: Nutrient intakes derived from 3-day food diaries at the beginning and end of the study. Blood levels of retinol, alpha-tocopherol, and beta carotene at the end of the study. STATISTICAL ANALYSES PERFORMED: Unpaired t tests for determining changes in nutrient intake and antioxidant vitamin concentrations. Separate analyses were conducted with users of mineral and vitamin supplements and people who changed smoking status to reduce potential confounding. RESULTS: Fat intake decreased from 35% to 26% of energy in the reduced-fat diet group compared with a 2% decrease in the control group (P < .0001). Total energy intake also decreased in the 2 groups (-362 vs -59 kcal/day, P < .02). Those changes were reflected in a 3.1 +/- 4.7 kg (mean +/- standard deviation) weight loss in the intervention group compared with a 0.4 +/- 3.0 kg weight gain in the control group (P < .0001). There were no differences between groups in the changes in micronutrient intakes, except for an energy-adjusted increase in beta carotene intake in the reduced-fat diet group. Serum retinol and alpha-tocopherol concentrations were not different between the groups, but the reduced-fat diet group had higher beta carotene concentrations (P = .009). APPLICATIONS: A reduced-fat, ad libitum diet can be prescribed to improve overall macronutrient intake and achieve modest weight loss without sacrificing micronutrient intakes.

Optimism, pessimism, and positive and negative affectivity in middle-aged adults: a test of a cognitive-affective model of psychological adjustment.

This study attempted to address limitations in the understanding of optimism and pessimism among middle-aged adults. Specifically, a model of affectivity as a mediator of the link between outcome expectancies and psychological adjustment (life satisfaction and depressive symptoms) was presented and examined in a sample of 237 middle-aged adults. Consistent with a mediation model, results of path analyses indicated that optimism and pessimism (particularly the former) had significant direct and indirect links (by means of positive and negative affectivity) with depressive symptoms and life satisfaction. These results add to the small but growing literature identifying optimism and pessimism as important concomitants of psychological adjustment in more mature adults.

Relations between problem orientation and optimism, pessimism, and trait affectivity: a construct validation study.

This study investigated the construct validity of the Positive and Negative Problem Orientation scales of the Social Problem-Solving Inventory-Revised (SPSI-R) by examining the relations between these scales and measures of optimism, pessimism, and trait affectivity. Consistent with expectations based on social problem-solving theory, positive problem orientation was found to have a relatively large amount of variance in common with optimism and positive affectivity, and negative problem orientation was found to share a large amount of variance with pessimism and negative affectivity, but not enough to be considered redundant in either case. Positive problem orientation was found to add significant incremental validity to the prediction of adaptive problem-engagement coping even after partialing out the variance associated with optimism and positive affectivity. In addition, negative problem orientation was found to add unique variance to the prediction of psychological distress even after controlling for pessimism and negative affectivity.

Use of gene gun for genetic immunotherapy : in vitro and in vivo methods.

A major thrust in the application of gene transfer technology for cancer therapy has been the modulation of the immune response. There has been a veritable explosion of information regarding the components of the immune response that are required to generate a meaningful cellular response to tumorassociated antigens (TAAs) capable of eliciting rejection of established tumor. Many of the preclinical and clinical immunogenetic studies have focused on melanoma. Historically, melanoma has been an immunoresponsive tumor for which several melanoma TAAs have been identified.

Lymphocytes and urine in ceroid lipofuscinosis.

Pathognomonic ultrastructural inclusions were found in the lymphocytes of 16 patients with neuronal ceroid lipofuscinosis (Batten's disease) and in the urine of three of four of such patients. These inclusions remained type specific for each patient and were identical with deposits in nerve cells and other body tissues. They persisted in lymphocytes in short-term tissue culture, but disappeared with stimulation by phytohemagglutinin. Siblings had identical inclusions. None were present in heterozygotes. Examination of lymphocytes in the peripheral blood cells is an easy method to use in the diagnosis of ceroid lipofuscinosis, but it cannot be used to detect carriers.

The Multidimensional Dream Inventory: preliminary evidence for validity and reliability.

The present study focused on the development of the Multidimensional Dream Inventory, an individual difference measure of dimensions of dreams. Items were administered to 151 college students. Consistent with expectations, results of an exploratory factor analysis of intercorrelations among items indicated a four-factor solution was appropriate. As a result, four dream-relevant scales were constructed, viz, Dream Importance, Dream Vividness, Dream Usefulness, and Dream Recall. In addition, these scales showed good internal consistency for research. Implications and uses for the Multidimensional Dream Inventory were discussed.

What makes dreams positive or negative: relations to fundamental dimensions of positive and negative mood.

The present study examined the general emotional content of dreams reported by individuals who typically experience "positive" versus "negative" dreams. Self-reports of the 153 participants indicated that positive versus negative dreamers (ns = 42 and 24, respectively) generally experienced more positive emotions, e.g., joviality, self-assurance, and fewer negative emotions, e.g., fear, sadness. No differences were found in the self-reports of the participants in the experience of surprise, guilt, fatigue, and shyness between the groups, hence, positive and negative dreams do not appear to reflect simply more positive and fewer negative emotions, respectively.

Locus of control and the fundamental dimensions of moods.

The present study examined the association between locus of control and positive and negative moods in 253 college students. Using the PANAS-X, designed by Watson and Clark, individuals scoring high on internal locus of control also scored higher across different dimensions of positive mood. Conversely, individuals scoring high on external locus of control had higher scores across different dimensions of negative mood.

Preliminary study of health value as a moderator of the link between age and life satisfaction.

In the present study of the influence of health value as a potential moderator of age and life satisfaction. 157 undergraduate students (M = 20.8 yr.) completed a battery in which they provided demographic information and completed a number of different self report measures, including the Satisfaction With Life Scale and the Health Value Scale. A 2 (younger vs older) x 2 (high vs low health value) analysis of variance with life satisfaction as the dependent variable showed a significant man effect for health value and a significant interaction between age and health value but no man effect for age. These findings support health value as a moderator of the relation between age and psychological well-being. Implications for research and practice are discussed.

How the value of health moderates the link between age and depressive symptoms: further evidence.

To extend earlier findings, this pilot study explored the role of self-reported value of health as a moderator between age and scores on the Beck Depression Inventory. 157 undergraduate students completed the Health Value Scale and the Beck inventory. There was no significant main effect for age with scores on the Beck inventory; however, scores on the Health Value Scale and their interaction with age were significant contributors to scores on the Beck Depression Inventory. These results are consistent with earlier findings. Implications for research and development are discussed.

CHMP6 and VPS4A mediate the recycling of Ras to the plasma membrane to promote growth factor signaling.

While Ras is well-known to function on the plasma membrane (PM) to mediate growth factor signaling, increasing evidence suggests that Ras has complex roles in the cytoplasm. To uncover these roles, we screened a cDNA library and isolated H-Ras-binding proteins that also influence Ras functions. Many isolated proteins regulate trafficking involving endosomes; CHMP6/VPS20 and VPS4A, which interact with ESCRT-III (Endosomal Sorting Complex Required for Transport-III), were chosen for further study. We showed that the binding is direct and occurs in endosomes. Furthermore, the binding is most efficient when H-Ras has a functional effector-binding loop, and is GTP-bound and ubiquitylated. CHMP6 and VPS4A also bound to N-Ras but not K-Ras. Repressing CHMP6 and VPS4A blocked Ras-induced transformation, which correlated with inefficient Ras localization to the PM as measured by cell fractionation and photobleaching. Moreover, silencing CHMP6 and VPS4A also blocked epidermal growth factor receptor (EGFR) recycling. These data suggest that Ras interacts with key ESCRT-III components to promote recycling of itself and EGFR back to the PM to create a positive feedback loop to enhance growth factor signaling.