[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.

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.

Int6 regulates both proteasomal degradation and translation initiation and is critical for proper formation of acini by human mammary epithelium.

INT6/EIF3E has been implicated in breast tumorigenesis, but its functional activities remain poorly defined. We found that, repressing INT6 expression induced transformed properties in normal human mammary epithelium (MCF10A); in contrast, Int6 silencing induced apoptosis in HeLa cells. As in fission yeast, Int6 in human cells was required for assembly of active proteasomes. A reverse-phase protein array screen identified SRC3/AIB1 as one oncoprotein the level and stability of which increased when Int6 was silenced in MCF10A cells. Our data further show that Int6 binds SRC3 and its ubiquitin ligase Fbw7, thus perhaps mediating the interaction between SRC3-Fbw7 and proteasomes. Consistent with this, Int6 silencing did not increase SRC3 levels in HeLa cells, which have low Fbw7 levels. It is surprising that, however, polyubiquitylated proteins do not accumulate or may even decrease in Int6-silenced cells that contain defective proteasomes. Considering that decreased ubiquitin might explain this observation and that Int6 might control ubiquitin levels in its role as a subunit of eIF3 (eukaryote translation initiation factor 3), we found that silencing Int6 reduced monoubiquitin protein levels, which correlated with a shift of ubiquitin mRNAs from larger polysomes to non-translating ribosomes. In contrast, levels of many housekeeping proteins did not change. This apparent reduction in the translation of ubiquitin genes correlated with a modest reduction in protein synthesis rate and formation of large polysomes. To further determine whether Int6 can selectively control translation, we analyzed translation of different 5'-untranslated region reporters and found that indeed, loss of Int6 had differential effects on these reporters. Together the data suggest that Int6 depletion blocks ubiquitin-dependent proteolysis by decreasing both ubiquitin levels and the assembly of functional proteasome machinery, leading to accumulation of oncoproteins, such as SRC3 that can transform mammary epithelium. Our data also raise the possibility that Int6 can further fine-tune protein levels by selectively controlling translation of specific mRNAs.

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.

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.

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.

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.

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.

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.

Yin6, a fission yeast Int6 homolog, complexes with Moe1 and plays a role in chromosome segregation.

The INT6 gene has been implicated in human breast cancer formation, but its function is unknown. We isolated an Int6 homolog from fission yeast, Yin6, by its binding to a conserved protein in the Ras pathway, Moe1. Yin6 and Moe1 converge on the same protein complex to promote microtubule instability/disassembly. Yin6 and Moe1 interact cooperatively: when either protein is absent, the other becomes mislocalized with decreased protein levels. Furthermore, whereas full-length human Int6 rescues the phenotypes of the yin6-null (yin6Delta) mutant cells and binds human Moe1, truncated Int6 proteins found in tumors do not. Importantly, yin6Delta alone impairs chromosome segregation weakly, but yin6Delta together with ras1Delta causes severe chromosome missegregation. These data support a model in which INT6 mutations in humans either alone or together with additional mutations, such as a RAS mutation, may contribute to tumorigenesis by altering genome stability.

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.

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.

Planning for an annual episodic mass gathering: emergency department and clinic utilization in Yellowstone.

OBJECTIVE: Planning and providing emergency and primary care for a large transient population of visitors and employees in a national park can be problematic. Furthermore, planning for emergency and primary health care needs of visitors and itinerant workers in a wilderness area national park has not been well documented. A study was performed to analyze emergency and primary health care utilization in a national park. METHODS: Data was gathered from all patients presenting to Lake Hospital Emergency Department in Yellowstone in 1995, and a retrospective chart review was performed. RESULTS: Two distinct populations with different health care needs were identified. CONCLUSION: Utilization analysis revealed differences between conventional mass gatherings and the mass gatherings in Yellowstone. Because of the unique conditions and populations found in a wilderness area, conventional mass gathering emergency medical service models may not be an appropriate model for planning health care in a national park. Analysis of utilization data can help plan resources for emergency and primary health care for a park population.

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.

Moe1, a conserved protein in Schizosaccharomyces pombe, interacts with a Ras effector, Scd1, to affect proper spindle formation.

In fission yeast, Scd1/Ral1 is a putative guanine nucleotide exchange factor for Cdc42sp and also acts as a Ras1 effector necessary for the regulation of cytoskeleton organization. In this study, we have characterized a protein, Moe1, that binds directly to Scd1. A moe1 null (Delta) mutant exhibits numerous phenotypes indicative of abnormal microtubule functioning, including an abnormality in the spindle. moe1Delta mutants are resistant to microtubule destabilizing agents; moreover, moe1Delta rescued the growth defects of tubulin mutants containing unstable microtubules. These results suggest that Moe1 induces instability in microtubules. Biochemical and subcellular localization studies suggest that Moe1 and Scd1 colocalize in the nucleus. Furthermore, loss of function in Scd1 or Ras1 also induced abnormality in the spindle and is synthetically lethal with moe1Delta producing cells that lack a detectable spindle. These data demonstrate that Moe1 is a component of the Ras1 pathway necessary for proper spindle formation in the nucleus. Human and nematode Moe1 both can substitute for yeast Moe1, indicating that the function of Moe1 in spindle formation has been conserved substantially during evolution.

Social problem-solving deficits and hopelessness, depression, and suicidal risk in college students and psychiatric inpatients.

The Social Problem-Solving Inventory-Revised was used to examine the relations between problem-solving abilities and hopelessness, depression, and suicidal risk in three different samples: undergraduate college students, general psychiatric inpatients, and suicidal psychiatric inpatients. A similar pattern of results was found in both college students and psychiatric patients: a negative problem orientation was most highly correlated with all three criterion variables, followed by either a positive problem orientation or an avoidance problem-solving style. Rational problem-solving skills emerged as an important predictor variable in the suicidal psychiatric sample. Support was found for a prediction model of suicidal risk that includes problem-solving deficits and hopelessness, with partial support being found for including depression in the model as well.

Hope, problem-solving ability, and coping in a college student population: some implications for theory and practice.

The influence of high versus low hope on problem-solving ability and on coping with stressful academic and interpersonal situations was examined in 211 college students. Consistent with Snyder's (1995) model, high-hope students were found to have greater problem-solving abilities than low-hope students. High-hope students were also found to employ less disengagement strategies than low-hope students for coping with stressful academic situations. No difference was found in the strategies used by high- and low-hope students for coping with stressful interpersonal situations. Separate hierarchical regression analyses indicated that hope was an important predictor of both academic and interpersonal life satisfaction independent of coping activities. Implications of the present findings for both theory and practice are discussed.

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.