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  • 2000-2004  (41)
  • 1995-1999  (735)
  • 1890-1899
  • 1820-1829
  • Human  (776)
  • 1
    ISSN: 1530-0358
    Schlagwort(e): Barostat ; Colon ; Human ; Ileus ; Manometry ; Motility ; Postoperative ; Rectum ; Surgery
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: Colonic motility is crucial for the resolution of postoperative ileus. However, few data are available on postoperative colonic motility and no data on postoperative colonic tone. We aimed to characterize postoperative colonic tone and motility in patients. METHODS: Nineteen patients were investigated with combined barostat and manometry recordings after left colonic surgery. During surgery a combined recording catheter was placed in the colon with two barostat bags and four manometry channels cephalad to the anastomosis. Recordings were performed twice daily from Day 1 to Day 3 after surgery. RESULTS: Manometry showed an increasing colonic motility index, which was a mean (± standard error of the mean) of 37±5 mmHg/minute on Day 1, 87±19 mmHg/minute on Day 2, and 102±13 mmHg/minute on Day 3 (P〈0.05 for Day 1vs. Day 2 and Day 2vs. Day 3). Low barostat bag volumes indicating a high colonic tone were observed on Day 1 after surgery and increased subsequently (barostat bag I was 19±4, 32±6, and 32±6 ml; barostat bag II was 13±1, 19±3, and 22±5 ml on Days 1, 2, and 3, respectively; for both barostat bagsP〈0.05 for Day 1vs. Day 2 but not Day 2vs. Day 3). CONCLUSIONS: Colonic motility increased during the postoperative course. The low barostat bag volumes indicated a high colonic tone postoperatively which would correspond to a contracted rather than to a distended colon. High colonic tone postoperatively may be relevant for pharmacologic treatment of postoperative ileus.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of hepato-biliary-pancreatic surgery 7 (2000), S. 575-579 
    ISSN: 1436-0691
    Schlagwort(e): Key words Precancerous conditions ; Pancreatic duct adenocarcinoma ; Hamster ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Precancerous conditions for ductal adenocarcinoma of the pancreas in hamsters and human beings are discussed. In hamsters, ductal adenocarcinomas induced by nitrosamines are of nonmucin-hypersecreting tubular or papillary tumor types, and genetic alterations resembling these types are found in their human counterparts. Ductal lesions develop step-by-step from hyperplasias to carcinomas, and atypical ductal cell hyperplasias may be precancerous. In humans, ductal lesions, hyperplasias, or dysplasias, with or without mucin hypersecretion, are possible preneoplastic conditions. Genetic or phenotypic markers to determine their likelihood of progressing to pancreatic duct adenocarcinomas are a high priority for future research.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-2307
    Schlagwort(e): Keywords Lung ; Ozone ; Centriacinar ; Human ; Autopsy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Semiquantitative measurements of chronic inflammation of the centriacinar region (proximal acinus of lung) were compared between 20 Miami and 18 Los Angeles residents (ages 11–30 years) for whom smoking histories were available. Mean extent and severity scores of four lung sites were higher for Los Angeles than Miami residents, with effect of city statistically significant for extent (P=0.02). Also, maximum scores for extent and severity by city were significantly greater for Los Angeles residents (P=0.02, each), but not by smoking history. Smokers did have higher scores for mean extent and severity (by lung site and smoking history), but neither this nor inclusion of smoking and city in the model reached significance. With respect to maximum extent and maximum severity scores, a stratified comparison of cities by smoking history showed a trend (not significant) toward higher scores for Los Angeles residents. Mean extent and severity scores for the lower lobe were higher for basilar sections than for apical sections (each P〈0.001). Cumulative data indicate that expanded pathologic studies are essential for efforts to complete a convergence of epidemiological and experimental data implicating exceedences of the Federal ozone standard as a contributor to human lung injury.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Medical electron microscopy 33 (2000), S. 109-114 
    ISSN: 1437-773X
    Schlagwort(e): Key words Ciliogenesis ; Ciliated cell ; Abnormal cilia ; Basal body ; Ultrastructure ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cilia are motile processes extending from the basal bodies, playing important roles in the mucociliary clearance in the respiratory tract and the transport of the ovum from the ovary to the uterus in mammals. Ciliogenesis is divided into four stages: (1) duplication of centrioles; (2) migration of centrioles to the apical cell surface to become basal bodies; (3) elongation of cilia containing the axoneme; and (4) formation of accessory structures of basal bodies. The orderly course of ciliogenesis appears to be disturbed by various internal and external factors and, as a result, various unusual forms of the ciliary apparatus develop in the cell. Inhibition of basal body migration results in development of intracytoplasmic axonemes, cilia within periciliary sheaths, and intracellular ciliated cysts. Swollen cilia and the bulging type of compound cilia are formed during ciliary budding and elongation. This review also discusses the origin, composition, and function of the centriolar precursor structures.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-0533
    Schlagwort(e): Key words Skeletal muscle ; Human ; Differentiation ; Protein kinase C ; Isozymes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The mechanism of skeletal muscle regeneration in vivo can be well modeled in vitro by culturing skeletal muscle cells. In these cultures mononuclear satellite cells fuse to form polynuclear myotubes by proliferation and differentiation. The aim of this study was to determine how the different protein kinase C (PKC) isozymes were expressed during differentiation of human skeletal muscle in vitro. The expressions of desmin, used as a muscle-specific intermediate filament protein marker of differentiation, and of different PKC isozymes were detected by single and double immunohistochemical labeling, and by Western blot analysis. In skeletal muscle cells we could identify five PKC isozymes (PKCα, -γ, -η, -θ and -ζ). The expressions of PKCα and -ζ did not change significantly during differentiation; their levels of expression were high in the early immature cells and remained unchanged in later phases. In contrast, the expression levels of PKCγ and -η increased with differentiation. Furthermore, the cellular localization of PKCγ markedly altered during differentiation, with a perinuclear-nuclear to cytoplasmic translocation. The change in the level of expression of PKCθ during differentiation showed different pattern; its expression was high during the early phases, but a decreased immunostaining was detected in the matured, well-differentiated myotubes. We conclude, therefore, that cultured human skeletal muscle cells possess a characteristic PKC isozyme pattern, and that the different phases of differentiation are accompanied by different expression patterns of the various isozymes. These data suggest the possible functional and differential roles of PKC isozymes in human skeletal muscle differentiation.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 201 (2000), S. 207-215 
    ISSN: 1432-0568
    Schlagwort(e): Keywords Granulosa cells ; Ontogeny ; Ovary ; Rete ovarii ; Cytokeratin ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Cells from the inner and outer granulosa cell layers of the ovarian follicles differ in function, probably because of their different origins from the surface epithelium and from the rete. This suggestion has not so far been thoroughly investigated in the human ovary. We examined fetal ovaries from the early, middle and late gestational periods, ovaries from fertile women, and preovulatory follicular cells obtained from patients under in vitro fertilization therapy (IVF). Indirect immunohistology and immunocytology were used to detect the presence of cytokeratin (CK)-positive epithelial cells. In fetal ovaries from the early gestational period, prominent rete tubules (sometimes with oocytes) appeared to be fused with the sex cords and primordial follicles. Both showed CK-positively, detected with the pan-CK antibody Lu-5. Cytokeratin 19 was clearly expressed in the fusion area. In the fetal and adult ovaries, CK-positive follicular or granulosa cells were noted in the primordial and primary follicles as well as the preovulatory follicles. Cytokeratin was not detected in the granulosa cells of growing follicles, CK-positive and -negative luteal cells were identified in the developing corpus luteum. We conclude for the human ovary: (1) the heterogeneous morphology of granulosa cells may be explained by their twofold origin from the surface epithelium and the rete, (2) the rete tubules appear to be involved in folliculogenesis, (3) the transient absence of CK expression in growing follicles compared to resting and mature follicles or to the developing corpus luteum indicates a particular role of CK-positive cells at the periovulatory period.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Archives of dermatological research 292 (2000), S. 9-15 
    ISSN: 1432-069X
    Schlagwort(e): Key words Epidermal T cells ; Function ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The function of human epidermal T cells (ETC) is unknown. In the present study, dermal T cells (DTC), ETC and keratinocytes were cultured from normal human skin. DTC and ETC lines were expanded in medium containing interleukin 2. The autologous keratinocytes were transfected with a human papillomavirus 16 E6 and E7 plasmid to produce an immortal keratinocyte line “HEK001”. Lymphocyte migration and adhesion to HEK001 was assessed in calcein fluorimetric assays. ETC migrated towards HEK001 three to four times more than DTC. ETC adhered to HEK001 two to four times more than DTC. The proportion of ETC expressing the cutaneous lymphocyte-associated antigen was greater than that of DTC (26% and 1%, respectively). The keratinocyte line HEK001 expressed ICAM-1 following stimulation with TNF-α or IFN-γ and following coculture with autologous cutaneous T cells. A blocking anti-ICAM-1 antibody reduced DTC and ETC adhesion to HEK001 by 30% and 50%, respectively. Therefore, cutaneous T cells may upregulate keratinocyte ICAM-1 expression which mediates adhesion to autologous keratinocytes. These results are consistent with the hypothesis that the ETC and DTC populations are distinct. Both directed migration (epidermotropism) and selective retention may be involved in the development and maintenance of the ETC population in normal human skin.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Annals of hematology 79 (2000), S. 183-186 
    ISSN: 1432-0584
    Schlagwort(e): Key words Erythropoietin ; Endogenous ; Blood volume ; Human ; Intraoperative
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  There is accumulating evidence of a relationship between changes in intravascular blood volume and endogenous erythropoietin (EPO) levels. In this study, eight healthy adult American Society of Anesthesiologists class-I patients due for prolonged elective surgery were randomised either to preoperative hypervolaemic haemodilution using hydroxyethyl starch, followed by intraoperative crystalloid infusion, or to standard intraoperative normovolaemic fluid balance management using crystalloids (control group). Electrolytes, creatinine, urea, osmolality, urine output and blood gases were monitored pre- and intraoperatively for 6 h, Comparable cardiopulmonary and renal homeostasis were maintained in both groups. We found that central venous pressure increased and EPO levels decreased, both significantly, in the hypervolaemic haemodilution group relative to controls. There were no significant intergroup changes in any other parameters. By controlling for other known determinants of EPO levels, our data indicate a relationship between EPO levels and changes in intravascular blood volume in humans, supporting the notion of EPO as a volume-regulated, and possibly volume-regulating, hormone.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-0533
    Schlagwort(e): Key words Allograft-inflammatory factor-1 ; Microglia response factor-1 ; Macrophage-inhibiting factor ; related-protein-8/S100A8 ; Traumatic brain injury ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Intracellular calcium (Ca2+) has been shown to function as second messenger and to be associated with activation of different cell types including microglia. Previously, in human focal cerebral infarctions an early expression of macrophage-related protein-8 (MRP8/ S100A8), a member of the Ca2+-binding S100-protein family, in microglia has been reported. On the other hand, a delayed activation of microglia was observed following traumatic brain injury (TBI). We therefore examined immunohistochemically microglial expression of MRP8 and allograft inflammatory factor-1 (AIF-1), identical to microglial response factor-1 (mrf-1) and ionized calcium binding adaptor molecule-1 (iba1) in human brains after TBI and in control brains. Both, MRP8 and AIF-1 are Ca2+-binding peptides which have been associated with microglial activation in experimental models and in human cerebral infarctions. Detection of AIF-1 in controls confirmed constitutive expression of this peptide in a subset of microglial cells. After TBI, the density of AIF-1+ microglia did not increase significantly. Lesional expression of AIF-1 did not significantly differ from other brain regions. Furthermore, following TBI, we found no significant differences in the density of AIF-1+ microglia as compared to controls. Microglial MRP8 expression was not detectable in controls and within the first 3 days post TBI, but increased rapidly after 3 days post TBI, suggesting a subpopulation of microglial cells to be AIF-1–/MRP8+. We conclude that the delayed expression of MRP8 and the lack of AIF-1 up-regulation in microglia after TBI is in contrast to ischemic brain lesions and might reflect different activation cascades of microglia.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-0851
    Schlagwort(e): Keywords Melanoma ; Antigens ; Cytotoxic ; T lymphocytes ; Human ; Immunotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Melanoma-reactive HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) lines generated in vitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pmel17/gp100. However, a subset of melanomas fail to be lysed by these T cells. In the present report, four different HLA-A*0201+ melanoma cell lines not lysed by melanoma-reactive allogeneic CTL have been evaluated in detail. All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pmel17/gp100, gp75/trp-1, and MART-1/Melan-A. This concordant loss of multiple MDP explains their resistance to lysis by melanoma-reactive allogeneic CTL and confirms that a subset of melanomas may be resistant to tumor vaccines directed against multiple MDP-derived epitopes. All four melanoma lines expressed normal levels of HLA-A*0201, and all were susceptible to lysis by xenoreactive-peptide-dependent HLA-A*0201-specific CTL clones, indicating that none had identifiable defects in antigen-processing pathways. Despite the lack of shared MDP-derived antigens, one of these MDP-negative melanomas, DM331, stimulated an effective autologous CTL response in vitro, which was restricted to autologous tumor reactivity. MHC-associated peptides isolated by immunoaffinity chromatography from HLA-A1 and HLA-A2 molecules of DM331 tumor cells included at least three peptide epitopes recognized by DM331 CTL and restricted by HLA-A1 or by HLA-A*0201. Recognition of these CTL epitopes cannot be explained by defined, shared melanoma antigens; instead, unique or undefined antigens must be responsible for the autologous-cell-specific anti-melanoma response. These findings suggest that immunotherapy directed against shared melanoma antigens should be supplemented with immunotherapy directed against unique antigens or other undefined antigens, especially in patients whose tumors do not express MDP.
    Materialart: Digitale Medien
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  • 11
    ISSN: 1432-1211
    Schlagwort(e): Key words MHC class III region ; Mouse ; Human ; G7c ; Lung tumor susceptibility
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 51 (2000), S. 487-488 
    ISSN: 1432-1211
    Schlagwort(e): Key words Immunoglobulin ; J segments ; IGKJ genes ; Alleles ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    International archives of occupational and environmental health 73 (2000), S. 479-487 
    ISSN: 1432-1246
    Schlagwort(e): Key words Biological monitoring ; Formate ; Formic acid ; Human ; Methanol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A toxicokinetic (TK) model was developed to describe the inhalation exposure in humans to methyl formate (MF), a catalyst used in foundries, and to discuss biological monitoring. The TK model consisted of four compartments: MF, the metabolites – methanol (MeOH) and formic acid (FA) – and, in addition, a urinary compartment describing the saturable reabsorption of FA. Levels of MeOH and FA in urine, from an experimental study (100 ppm MF, 8 h at rest), validated the present model. The TK model describes well the general behaviour of MeOH and FA in urine after MF exposure. A nonlinear and a linear relationship respectively, was predicted between MF exposure and FA or MeOH excretion in urine, and this has previously been seen after occupational MF exposure. The present model has been modified to simulate MeOH exposure as well. Generally low exposures (concentration or exercise) produce only marginal increases in FA urinary excretions, but when exposure is elevated, urinary FA excretion increases because of saturation in the mechanism of reabsorption. Using FA urinary excretion as the critical indicator, because of its link to health effects, an occupational exposure limit value for MF of no greater than 50 ppm should be selected (based on predictions with the TK model). MeOH in urine can be considered as a biomarker for MF at low exposure, because of lower background values and of a linear relationship with exposure. At higher exposures, however, FA could be used as a biomarker as it becomes progressively more sensitive. But the use of biological monitoring for MF is difficult because of individual variations in background values. Under the present state of knowledge both FA and MeOH should be used to estimate only group exposures, rather than individual exposures.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 147 (2000), S. 339-346 
    ISSN: 1432-2072
    Schlagwort(e): Key words Sibutramine ; d-Amphetamine ; Abuse potential ; Subjective effect ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Sibutramine (Meridia) is a serotonin and norepinephrine reuptake inhibitor marketed for weight control. Previous studies demonstrated low abuse potential for 20 and 30 mg sibutramine (doses near the therapeutic range); however, no data existed on supratherapeutic doses. This study, therefore, examined 25 and 75 mg sibutramine in humans compared to d-amphetamine (20 mg) as a positive control and placebo as a negative control. Objectives: The study examined the acute subjective, reinforcing, and physiological effects of sibutramine to assess its abuse liability. Methods: Twelve polydrug abusers with no history of drug dependence participated in this double-blind, inpatient/outpatient study. Volunteers participated in four drug sessions, in which they completed subjective effects scales including the Profile of Mood States (POMS), Visual Analog Scales (VAS), and the Addiction Research Center Inventory (ARCI). The Multiple Choice Procedure (MCP) was used to evaluate reinforcing efficacy. Results: Sibutramine 25 mg produced subjective effects that were indistinguishable from placebo. Sibutramine 75 mg produced significant unpleasant effects, such as Anxiety, Confusion, and decreased Vigor. On the MCP, volunteers chose to give up an average of $4.04 from their study pay rather than receive the higher dose of sibutramine again. In contrast, d-amphetamine 20 mg produced positive mood changes and was well liked. Conclusions: These data indicate sibutramine lacks amphetamine-type abuse liability when administered acutely.
    Materialart: Digitale Medien
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  • 15
    ISSN: 1432-2072
    Schlagwort(e): Key words Haloperidol ; Dopamine ; Receptor occupancy ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Positron emission tomography (PET) is increasingly being used to study dopamine receptor occupancy and the clinical effects of antipsychotic medication. Dopamine D2 receptor occupancy has been shown to predict several clinical effects of antipsychotic medication including therapeutic response, motor and endocrine side-effects. Plasma levels may be used as a surrogate marker for central occupancy if the relationship between these two measures may be accurately described. This study was designed to test the capacity of a previously derived relationship equation (%D2 occupancy=plasma level/ED50+plasma level, where ED50= 0.40 ng/ml) to predict striatal D2 occupancy from plasma level. Twenty-one patients receiving treatment with low dose haloperidol underwent a 11C-raclopride PET scan to measure D2 occupancy. The D2 occupancy levels were accurately predicted by use of the previously generated equation with only a small degree of error (3.89% CI 0.45–7.33). Predicted and measured D2 occupancy values correlated closely (Pearson’s r=0.864, P=0.003). The study indicates that reliable prediction of D2 occupancy from plasma levels is possible. This provides a potentially useful surrogate measure of D2 occupancy for research and possibly clinical practice, as the routine use of PET to measure occupancy levels is not feasible.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 149 (2000), S. 24-33 
    ISSN: 1432-2072
    Schlagwort(e): Key words Cocaine ; Conditioning ; Cardiovascular effect ; Subjective effect ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Clinical data suggest that stimuli paired with cocaine use acquire emergent stimulus effects, such as the ability to elicit cocaine craving. Objectives: The purpose of this study was to determine the conditioned effects of neutral stimuli paired with cocaine smoking. Methods: Eight experienced adult cocaine smokers participated in 22 experimental sessions while residing on a Clinical Research Center. One set of cues (CS–) was paired with placebo smoked cocaine and one set of cues (CS+) was paired with 25 mg smoked cocaine. Results: After 18 training trials, the effects of cocaine on heart rate and ratings of ”anxious” were greater, and skin temperature and ratings of ”tired” were smaller when compared to the effects of cocaine after the first training trial. When instructed to select a cue to experience after training, seven of eight participants selected the CS+, while only three of the participants selected the CS+ prior to training, i.e., the CS+ functioned as a conditioned reinforcer. Presentation of the CS+ alone without cocaine during extinction trials increased HR, SP, and ratings of ”anxious””tired”, and ”I want cocaine” and decreased skin temperature. These changes elicited by presentation of the CS+ decreased over the course of the extinction sessions. Conclusions: The present results indicate that classical conditioning is one mechanism by which stimuli paired with cocaine acquire emergent stimulus effects.
    Materialart: Digitale Medien
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  • 17
    ISSN: 1432-1106
    Schlagwort(e): Key words Visual perception ; Object recognition ; Functional magnetic resonance imaging ; Neuroimaging ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Electrophysiologic and functional imaging studies have shown that the visual cortex produces differential responses to the presence or absence of structure within visual textures. To further define and characterize regions involved in the analysis of form, functional magnetic resonance imaging (fMRI) was used to detect changes in activation during the viewing of four levels of isodipole textures. The texture levels systematically differed in the density of visual features such as extended contours and blocks of solid color present within the images. A linear relationship between activation level and density of structure was observed in the striate cortex of human subjects. This finding suggests that a special subpopulation of striate cortical neurons participates in the ability to extract and process structural continuity within visual stimuli.
    Materialart: Digitale Medien
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  • 18
    ISSN: 1432-0738
    Schlagwort(e): Key words Diethylhexylphthalate ; Peroxisome proliferation ; Hepatocarcinogenesis ; Species differences ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Diethylhexylphthalate (DEHP) is a phthalate plasticizer that belongs to the peroxisome proliferator (PP) class of rodent nongenotoxic hepatocarcinogens. Previously, we have shown that MEHP (a principal metabolite of DEHP and the proximal PP) induced DNA synthesis and suppressed apoptosis in rat but not in human hepatocytes in vitro. Here, we present further studies of species differences in response to DEHP. In rats, 4 days of exposure to DEHP (950 mg/kg per day by gavage) induced peroxisomal β-oxidation, DNA synthesis and suppressed apoptosis. In contrast, there was no response of guinea pig liver to DEHP. In rat hepatocytes in vitro, MEHP (250, 500 and 750 μM) induced peroxisomal β-oxidation, DNA synthesis and suppressed apoptosis. In contrast to the pleiotropic response noted in rat hepatocytes, there was no response of human hepatocytes to 250, 500 or 750 μM MEHP. PPs activate the peroxisome proliferator activated receptor alpha (PPARα) that binds to DNA at peroxisome proliferator response elements (PPREs) within the promoters of PP-responsive genes such as rat acyl CoA oxidase (ACO). However, the human ACO gene promoter differs at three bases within the PPRE from the rat ACO promoter and appears refractory to PPs. To address species differences in response to DEHP at the molecular level, we used promoter-reporter gene assays to compare the ability of MEHP to induce gene expression from the rat or the human ACO promoter. MEHP gave a concentration-dependent increase in reporter gene expression from the rat ACO gene promoter with either mouse or human PPARα. In contrast, the human ACO promoter was unable to drive MEHP-induced gene transcription irrespective of the species origin of PPARα. These data provide further weight of evidence at the cellular and molecular levels for a lack of risk to human health from the phthalate DEHP.
    Materialart: Digitale Medien
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  • 19
    ISSN: 1432-0738
    Schlagwort(e): Key words Organophosphate ; Acetylcholinesterase ; Oximes ; Human ; Reactivation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The reactivation of organophosphate-inhibited acetylcholinesterase (AChE) by oximes inevitably results in the formation of highly reactive phosphoryloximes (POX), which are able to re-inhibit the enzyme. In this study, the dependence of POX formation on AChE concentration was investigated with sarin-inhibited human erythrocyte AChE (EryAChE). A marked dependence was found with obidoxime but not with the experimental oxime HI 6, suggesting great differences in the decomposition rates of the respective POXs. At a physiological erythrocyte content the reactivation of EryAChE was markedly affected by POX with obidoxime and pralidoxime (2-PAM) but not with the newer oximes HI 6 and HLö 7. Addition of extensively dialysed, sarin-treated human plasma reduced the reactivation by obidoxime and 2-PAM even more. Obidoxime and 2-PAM were superior to HI 6 and HLö 7 in reactivating butyrylcholinesterase (BChE). This effect was pronounced in diluted plasma, but was obscured in concentrated plasma, probably because of re-inhibition by the generated POX. Addition of native erythrocytes to sarin-treated plasma resulted in marked inhibition of EryAChE in the presence of obidoxime, suggesting a higher affinity of the POX for EryAChE. The results indicate that obidoxime and 2-PAM may reactivate sarin-inhibited AChE insufficiently due to re-inhibition by the POX formed. In addition, the re-inhibition of EryAChE may be aggravated by the POX that is produced during BChE reactivation. These reactions must be regarded as therapeutically detrimental and disqualify those oximes which are capable of forming stable POX by reactivation of BChE.
    Materialart: Digitale Medien
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neurology 247 (2000), S. I28 
    ISSN: 1432-1459
    Schlagwort(e): Key words Motor neurone ; Astrocyte ; Human ; Tissue culture ; ALS ; Glutamate ; Calcium ; SOD-1
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Defining the basis of the selective cell vulnerability of motor neurones (MN) represents the key issue in amyotrophic lateral sclerosis (ALS), and tissue culture models are the ideal system for the identification of the MN specific features at the single cell level. Neurone-astrocyte metabolic interactions, which have a critical role in MN through glutamatergic toxicity, have been mostly defined in vitro. Ca++ metabolism, which appears to play a critical role in inducing MN loss in ALS, has been successfully studied using in vitro cell models. Furthermore, primary cultures demonstrated that apoptotic or necrotic death of neurones after injury depends upon the cell energetic status. Superoxide dismutase-1 (SOD-1) mutations were successfully expressed in cultured rodent MNs, providing a critical assay to sequence the molecular processes responsible for MN degeneration due to the identified genetic defect. The recent identification of genes that separate humans from apes further increases the value of the human in vitro models to better understand specific human cellular properties. Purified human MNs and astrocytes can today be obtained from the human embryonic spinal cord anterior horns. Interactions at the single cell level can be dissected using the cDNA amplification techniques. The effects of molecules affecting MN survival, neurite extension, and metabolism can easily be defined in vitro, gaining a critical mass of information of immediate clinical application in the treatment of patients affected by ALS. Understanding the properties of human MNs in vitro represents today a significant and critical tool that can easily be reached after extension of the available knowledge from non-primate to human research. Human MN culture studies can greatly contribute to identifying the primitive critical cellular events responsible for the MN degeneration observed in ALS and to gaining crucial information ¶on new therapeutical agents.
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  • 21
    ISSN: 1432-2277
    Schlagwort(e): Key words Liver transplantation ; Rejection ; Tacrolimus ; Human ; Child
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rejection and efficacy of rescue therapy with tacrolimus were evaluated in 50 children who underwent primary, ABO-compatible, liver transplantation. Six patients who died within the first week and one child who underwent retransplantation from an ABO-incompatible donor were excluded from the study. No patient or graft were lost due to rejection. We observed 48 episodes of rejection in 33 patients. Fourteen patients required conversion to tacrolimus for steroid-resistant rejection with resolution of rejection. One of these children developed PTLD. Other indications for conversion were neurotoxicity and hirsutism. One patient developed blindness of unknown origin after the conversion. Other side effects of tacrolimus were minor and resolved by lowering the dose. Five patients developed rejection after conversion; all achieved resolution with either steroid therapy or increase of tacrolimus dose. In conclusion, our study confirms that tacrolimus is an effective rescue therapy for paediatric liver transplantation.
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  • 22
    ISSN: 1432-2307
    Schlagwort(e): Key words Pituitary ; Human ; Somatotroph ; Thyrotroph hyperplasia ; Immunocytochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In patients with protracted primary hypothyroidism, the pituitary is enlarged due to the lack of feedback inhibition by thyroid hormone. In the present work, adenohypophysial biopsies from three women with protracted primary hypothyroidism were investigated by routine histology, immunocytochemistry, double immunostaining, immunoelectron microscopy, and combined immunocytochemistry – in situ hybridization. These methods confirmed the presence of massive thyrotroph hyperplasia and the formation of ”thyroidectomy” or ”thyroid deficiency” cells. A number of thyroidectomy cells were found to be immunoreactive for growth hormone (GH). Double immunostaining and immunoelectron microscopy revealed the presence of bihormonal cells containing both GH and thyroid stimulating hormone (TSH). Immunostaining combined with in situ hybridization revealed GH immunoreactive cells expressing TSH mRNA as well as TSH immunopositive cells expressing GH mRNA. Our findings provide conclusive evidence that somatotrophs may transform to thyrotrophs. Thus, in addition to multiplication of thyrotrophs, transdifferentiation of GH cells to thyrotrophs contributes to the increase of TSH-producing cells. The presence of such bihormonal cells best termed ”thyrosomatotrophs” supports the concept that adenohypophysial cells are not irreversibly committed to the production of one single hormone and that their phenotype can change in response to functional demand.
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Child's nervous system 16 (2000), S. 235-241 
    ISSN: 1433-0350
    Schlagwort(e): Key words Magnetic resonance spectroscopy ; Epilepsy ; Brain metabolism ; GABA ; N-Acetyl aspartate ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The current applications of magnetic resonance spectroscopy (MRS) in the clinical management of epileptic patients are reviewed. A major contribution of MRS to epilepsy is its ability to determine lateralisation before surgical resection of the diseased brain region. Phosphorus-31 and proton single-voxel MRS identify abnormalities in high-energy metabolism, neuronal function and neurotransmitter levels, but information can only be obtained from restricted regions of the brain. Spectroscopic imaging techniques (also known as chemical shift imaging) provide a metabolic mapping of the whole brain. They expand the range of applications of MRS to other types of epilepsy (neocortical, frontal) than temporal lobe epilepsy, which is the most often studied. Also, spectral editing techniques in proton MRS make it possible to detect and monitor drug-induced variations of GABA in the human brain, opening new insights into patient response to drug therapy of epilepsy. MRS is playing an increasing role in the noninvasive characterisation and management of epileptic patients.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Knee surgery, sports traumatology, arthroscopy 8 (2000), S. 180-185 
    ISSN: 1433-7347
    Schlagwort(e): Keywords Proprioception ; Equilibrium ; Posture ; Reproducibility of results ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Sportwissenschaft
    Notizen: Abstract The Kinesthetic Ability Trainer (KAT 2000) is a balance platform designed for training and functional testing of the neuromuscular control system. Forty healthy and sports-active persons were tested and 1 month later retested to investigate the reliability of the KAT 2000 testing “one-leg static balance” and “two-leg dynamic balance”. A significant improvement at retesting on the same day was seen in both tests; furthermore the dynamic test result improved significantly with retesting 1 month later. The data obtained made it possible to calculate the 95% confidence limits for an unchanged test result for a single person and a group of persons. The results show a clear learning effect when the persons are retested, especially in the dynamic test. The KAT 2000 can be used as a tool for testing groups of persons both in short- and long-term studies, but it cannot be used for testing single persons due to the great variance in the test results. Further investigations involving injured persons are needed to determine the range of improvement after intervention.
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  • 25
    ISSN: 1432-2013
    Schlagwort(e): Key words cDNA ; Human ; Cathepsin P ; Propeptide
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A cDNA encoding a novel human putative member of the papain family of cysteine peptidases has been cloned. The protease, named cathepsin P, is synthesized as a preproprotein. The presumed propeptide of 38 amino acids is followed by a 242-residue mature protein. The mature protease region is 30% identical to human papain-like cathepsins, with all the residues important for catalysis conserved. No similarity was observed in the propeptide region. On the contrary, the proenzyme shares 51-87% residues with some precursors of cysteine proteases from other species that have not yet been characterized. They all show a nearly completely conserved “CYTRED motif” in the propeptide region, not present in other members of the family, and could therefore constitute a distinct subfamily.
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  • 26
    ISSN: 1432-2072
    Schlagwort(e): Key words Cerebral blood flow velocity ; EEG ; Caffeine ; Withdrawal ; Physical dependence ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Cessation of daily caffeine consumption produces a withdrawal syndrome comprised of subjective symptoms and functional impairment. Few controlled studies have examined the physiological effects of caffeine withdrawal. Objective: The present study examined the effect of caffeine withdrawal on cerebral blood flow velocity and quantitative EEG. Methods: Ten volunteers reporting moderate caffeine intake (mean 333 mg/day) participated in this double-blind study. Subjects completed several tests when maintaining their normal diet (baseline period) and during two 1-day periods during which they consumed caffeine-free diets and received capsules containing placebo (placebo test session) or caffeine (caffeine test session) in amounts equal to their baseline daily caffeine consumption. Blood flow velocity was determined for four arteries: right and left middle (MCA), and right and left anterior (ACA) cerebral arteries using pulsed transcranial Doppler sonography. EEG was recorded for 3 min from eight scalp sites while subjects sat, with eyes closed, in a sound-attenuated electronically shielded chamber. Subjective effects were assessed with questionnaires. Results: Results showed an effect of the placebo (21-h withdrawal) condition compared to the caffeine condition. Placebo significantly increased the mean velocity, systolic velocity and diastolic velocity (cm/s) in all four cerebral arteries. In the MCA, the pulsatility index was significantly decreased following placebo. Placebo significantly increased EEG theta power. Placebo also produces subjective effect changes, including increases in heavy feelings in arms and legs and decreases in ability to concentrate. The caffeine and baseline conditions produced similar results on both the physiological and subjective measures. Conclusion: Cessation of daily caffeine consumption produced changes in cerebral blood flow velocity and quantitative EEG. These changes may be related to classic caffeine withdrawal symptoms of headache, drowsiness and decreased alertness.
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  • 27
    ISSN: 1432-2072
    Schlagwort(e): Key words Opioids ; Self-administration ; Progressive ratio ; Drug abuse ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Although most opioid self-administration research has been conducted with laboratory animals, such research with humans is necessary to answer questions unique to human drug-taking behavior. Objective: We investigated the influence of morphine dose and an alternative non-drug reinforcer on choice between morphine versus money and examined the relationship between drug-reinforced behavior and subjective euphoria. Methods: Five male opioid users participated in the 7-week study. During the first 5 weeks, a single dose of morphine (0, 4, 8, 16, or 32 mg/70 kg) was available each week. On Monday, subjects received an IM injection of the dose tested that week. On Tuesday, Thursday, and Friday, subjects could work for morphine or money under a second-order, progressive ratio schedule. For each primary ratio completed on the drug lever, subjects earned one-ninth of the available drug dose, and for each ratio completed on the money lever, subjects earned $1. Total amount of drug earned was administered in a single IM injection at the end of the session; money earned was credited to the subject’s account. Results: As morphine dose increased, responding for drug increased in an orderly manner and responding for money decreased. During the final phase of the study, the lowest and highest doses that maintained drug responding for each subject were repeated, and the value of the alternative reinforcer was increased to $2 per ratio. This manipulation was associated with decreased drug-maintained responding at the lowest, but not the highest, reinforcing dose of morphine. Conclusion: The progressive ratio, concurrent access procedure may be useful in predicting the outcome of drug abuse treatment interventions that use alternate reinforcement strategies.
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  • 28
    ISSN: 1615-2573
    Schlagwort(e): Key words Basal systemic nitric oxide production rate ; Fasting ; Human ; Plasma nitrate ; Single-compartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract It is of great interest and value to evaluate the systemic nitric oxide (NO) production rate in humans under various conditions. However, the currently available estimation methods are troublesome and time-consuming. We thus aimed at developing a simple method to estimate the basal systemic NO production rate in humans based on a steady-state analysis, i.e., a balance between the systemic NO production rate and the total nitrate elimination rate. Plasma nitrate concentrations of young healthy volunteers (n = 7 in group 1; n = 9 in group 2) were measured for 2 days. In group 1, all subjects had the same meals for 7 days prior to the plasma nitrate measurement. In group 2, all subjects were allowed free diets. The plasma nitrate concentrations were highly influenced by dietary nitrite/nitrate intake in both groups and reached the steady-state levels after 14-h fasting. Accordingly, the basal systemic NO production rates were estimated from the plasma nitrate concentrations after 14-h fasting (group 1, 630 ± 37 nmol min−1 = 0.78 ± 0.03 μmol kg−1 h−1; group 2, 597 ± 45 nmol min−1 = 0.66 ± 0.05 μmol kg−1 h−1, P = not significant vs group 1). These estimated values were comparable to the values obtained by other methods. In conclusion, the present estimation method with 14-h fasting using a single-compartment analysis was found to be a simple approach to quantitative evaluation and intra- and interindividual comparisons of the basal systemic NO production rates in humans.
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  • 29
    ISSN: 1615-2573
    Schlagwort(e): Key words Heat shock protein ; Antibody ; Vascular disease ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Heat shock proteins (Hsp) are families of phylogenetically conserved molecules that have a range of cytoprotective and intracellular functional roles. Reactivity to heat shock proteins has been implicated in the development of autoimmune disease and tissue expression of heat shock proteins and increased levels of anti-Hsp antibodies have also been reported in vascular disease. This study compared circulating levels of Hsp60 and Hsp70 and antihuman Hsp60, antihuman Hsp70, and antimycobacterial Hsp65 antibodies in peripheral (PVD) and renal (RVD) vascular disease with those in age- and sex-matched controls. Levels of Hsp70 were higher in both PVD (median 580 vs 40; P 〈 0.01) and RVD (median 160 vs 0; P 〈 0.03), whereas there were no differences in Hsp60 levels. Anti-Hsp60 antibody levels were elevated in PVD (146 vs 81 arbitrary units/ml; P 〈 0.04), but not RVD. This is the first study to demonstrate increased levels of circulating Hsp70 in pathological disease states; however, its physiological role remains to be determined.
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  • 30
    ISSN: 1439-6327
    Schlagwort(e): Key words Temporal summation ; Repeated electrical stimulation ; Experimental pain ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the present human study, we aimed to investigate the facilitation of both the subjective pain responses, and the withdrawal reflex to consecutive transcutaneous electrical stimuli as measures of temporal summation. The frequency (0.5–20 Hz) and intensity (0.4–0.8 times the reflex threshold,  ×RT) of the electrical stimuli were systematically varied. When using repeated stimulation, the stimulus intensity that evoked pain was lower than that required by a single stimulus (temporal summation). Temporal summation leading to pain was found to depend significantly upon both frequency and intensity (e.g. stimulation at 1 Hz caused summation at 0.8 × RT, whereas stimulation at 20 Hz caused summation at 0.6 × RT). The strongest reflex facilitation, and hence the strongest pain intensity was obtained for stimulation at 10–20 Hz at an intensity of 0.8 × RT. In conclusion, the results of the present human study demonstrate clearly that a stimulus that is perceived as a localised, repetitive tactile tap can be integrated and cause severe pain. This suggests that pathologically generated sparse nociceptive afferent activity causes strong pain by central integration. This might be one mechanism to explain why clinical conditions can become excruciatingly painful despite the fact that the pathophysiological changes seem to be marginal (e.g. minor nerve trauma).
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of applied physiology 83 (2000), S. 106-115 
    ISSN: 1439-6327
    Schlagwort(e): Key words Central fatigue ; Muscle fatigue ; Human ; Motor cortex ; Motoneuron
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Fatigue is a reduction of maximal muscle force or power that occurs with exercise. It is accompanied by changes at multiple levels in the motor pathway and also by changes in the discharge patterns of muscle afferents. Changes in afferent firing can lead to altered perceptions and can also act on the efferent pathway. Changes in the motor pathway include slowing of motor unit firing rates during sustained maximal voluntary contractions (MVCs). Muscle responses to stimulation at different levels of the motor pathway also change. Transcranial magnetic stimulation of the motor cortex and stimulation of descending tracts in the spinal cord in human subjects show an increase in the response of the cortex and a decrease in response of the motoneuron pool during sustained MVCs. In addition, the silent period following magnetic stimulation is prolonged. During relaxation after fatiguing exercise, muscle responses to stimulation of the motor cortex are initially facilitated and are then depressed for many minutes, whereas responses to descending tract stimulation are initially depressed but recover over about 2 min. Although some of the loss of force of fatigue does occur through inadequate drive to the muscle, it is not clear which, if any, of the changes described in the cortex or the motoneurons are responsible for loss of maximal voluntary force and thus contribute to fatigue. Changes may be associated with muscle fatigue without causing it.
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  • 32
    ISSN: 1439-6327
    Schlagwort(e): Key words Fatigue ; Glenohumeral joint ; Human ; Occupational musculoskeletal problems ; Proprioception
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Repetitive work to fatigue is soundly associated with work-related musculoskeletal disorders (WMSD), although the underlying mechanisms are poorly understood. In the present study, we tested the hypothesis that fatiguing work leads to proprioceptive deficits, which can be an initiating factor for the occurrence of WMSD. Thus, the position sense of the shoulder was determined for 13 males and 13 females before and after performing repetitive low-intensity arm work to fatigue in a simulated occupational setting. From a starting position of 45° to the sagittal plane, position sense tests consisted of subjects attempting to actively reproduce target positions of horizontal movements to 15° and 30° (shoulder adduction) and to 60° and 75° (shoulder abduction). An analysis of variance revealed that the absolute error was significantly increased following fatigue for the subjects as a group (P 〈 0.001). Furthermore, females had an overall higher error than males (P 〈 0.01). No difference in error was detected for the shorter movements versus the longer movements. However, the overall absolute error for adduction was significantly higher than for abduction (P 〈 0.001). The results of the present study support the hypothesis of diminished proprioceptive acuity following low-intensity work to fatigue. A reduction in position sense acuity could lead to impairment in motor control, which would further impact on position sense. Thus, a vicious cycle may be activated that might result in WMSD. The poorer position sense acuity observed for females may contribute to the explanation of why females demonstrate a higher incidence of WMSD than males.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    European journal of applied physiology 81 (2000), S. 210-213 
    ISSN: 1439-6327
    Schlagwort(e): Key words Cross-sectional area ; Exercise ; Human ; Reflex sympathetic activity ; Skeletal muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This research was performed to study how the cross-sectional area (CSA) changes in the skeletal muscles of exercising (E-leg) and contralateral non-exercising (N-leg) legs and to evaluate to what extent changes in CSA mirror changes in blood flow or extravascular water displacement. Seven healthy volunteers performed plantar flexion exercise at three different exercise intensities for 10 min each. Six plantar flexions followed by a 2-s rest in between allowed repeated measurement of the blood flow to the lower limbs by duplex ultrasonography in the popliteal artery and CSA by magnetic resonance imaging. The CSA was measured using manual planimetry at rest and after 3 and 9 min of the exercise periods. The CSA increased in the E-leg by 4.5% and decreased in the N-leg by −2.4%, from rest to highest exercise intensity. Post-exercise imaging of the E-leg showed a bi-phasic recovery of CSA with a rapid phase followed by a slower phase while the blood flow very rapidly returned almost to basal. The time course of the post-exercise decrease indicated that about 50% of the increase in CSA at the highest exercise intensity might have been a result of extravascular water displacement and 50% of an increase in the vasculature volume related to the flow increase. The CSA reduction in N-leg seems to have been related to vasoconstriction, probably mainly of the capacitance vessels since blood flow was not reduced.
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  • 34
    ISSN: 1439-6327
    Schlagwort(e): Key words Local cold ; Extremities ; Cold induced vasodilatation ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Hand cooling is a cold pressor test, which induces general sympathetic stimulation. This cooling procedure is often performed to investigate cold induced vasodilatation (CIVD) in one finger. To investigate the effects of this sympathetic stimulation on local CIVD, 12 subjects immersed either the right index finger (T1), right hand (T2) or left hand and right index finger (T3) for 30 min in water at 5°C followed by 15-min recovery. Skin temperature and skin blood flow (Q˙ sk) measured by laser Doppler flowmetry on the right index finger, as well as heart rate (f c) and mean arterial blood pressure ( ), were continuously monitored during the three tests. Cutaneous vascular conductance was calculated as Q˙ sk/ . Concentrations of plasma noradrenaline (NA) and adrenaline (AD) were measured at different times during the tests. The results showed no cardiovascular change in T1, whereas f c and increased significantly at the beginning of both T2 and T3. Similarly, sympathetic stimulation was reflected in the NA concentrations, which increased significantly (P 〈 0.01) during T2 and T3 after 5 min of immersion, and remained elevated until the recovery period. The AD concentration did not change during the three tests. During T2, the CIVD appeared later and slower in comparison with T1 [CIVD onset: 12.81 (SEM 2.30) min in T2 and 5.62 (SEM 0.33) min in T1] . During T3, the CIVD onset was not delayed compared to T1 [6.38 (SEM 0.67) min], but the rewarming was lower [+5.40 (SEM 0.86)°C in T3 and +9.10 (SEM 1.31)°C in T1]. These results showed that CIVD could be altered by sympathetic stimulation but it also appeared that the onset of CIVD could be influenced by local cooling, independently of the general sympathetic stimulation.
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  • 35
    ISSN: 1439-6327
    Schlagwort(e): Key words Eccentric-concentric actions ; Electromyography ; Gastrocnemius muscle ; Soleus muscle ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The objective of this study was to investigate muscle and tendon stiffness in the triceps surae muscles in patients who had previously had a stroke. The participants were 12 men showing slight to moderate degrees of muscle tonus in the affected leg. All patients showed minimal or no overt clinical motor symptoms, and all walked without mechanical aid. Muscle strengths in isometric and isokinetic activities were measured, as was passive resistance during plantarflexion in each leg. Walking speed was also measured. Evaluations of physical performance and muscle tone were made. Muscle and tendon stiffness was calculated from measurements whilst passively stretching during electrical stimulation, separately for each leg. Muscle strength was significantly higher in the non-affected than in the affected leg. Muscle stiffness was significantly higher in the affected leg than in the non-affected leg. Tendon stiffness was significantly higher in the non-affected than in the affected leg. The higher muscle stiffness in the affected leg might enhance the possibility for storing elastic energy during preactivation. Lower tendon stiffness in the affected leg might reduce the development of fatigue in movements at low velocities.
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  • 36
    ISSN: 1439-6327
    Schlagwort(e): Key words Bed rest ; Resistance training ; Skeletal muscle ; Physiological cross-sectional area ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of this study was to investigate the effects of resistance training on the morphological and functional properties of human lower limb muscles during 20 days of 6° head-down-tilt bed rest. Nine men were randomly assigned to the resistance training group (BR-Tr, n=5) or the non-training, control group (BR-Cont, n=4). Isometric leg-press exercises were performed: 3 s × 30 repetitions (30 s rest between repetitions) daily for 20 days during the bed-rest period. Serial axial magnetic resonance images were taken from the right thigh and leg muscles, and muscle volume, muscle length, and fibre length were estimated. The physiological cross-sectional areas (PCSAs) of the knee extensor, knee flexor, ankle plantarflexor, and ankle dorsiflexor (tibialis anterior) muscle groups were determined as muscle volume multiplied by the cosine of the angle of fibre pennation divided by fibre length. Maximum voluntary contraction (MVC) during knee extension was measured. No significant changes were observed in the PCSA of the knee extensor muscles in BR-Tr group, whereas the PCSA in the BR-Cont group decreased by 7.8%. The PCSA of the knee flexor and plantarflexor muscles in the BR-Tr group and BR-Cont group significantly decreased after bed rest (knee flexors, 10.2% and 11.5%; plantarflexors, 13.0% and 12.8%, respectively). However, in both groups bed rest had no effect on the muscle volume and PCSA of the tibialis anterior. MVC was maintained by resistance training in the BR-Tr group (decreased by 1%). In contrast, a decline of strength was observed in the BR-Cont group (−16%), but this result was not statistically significant. These results suggest that isometric leg-press training prevents the deconditioning (i.e. atrophy and decline of strength) of the knee extensor muscle group.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 351-364 
    ISSN: 1573-7039
    Schlagwort(e): Human ; breast cancer ; premalignant
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Most human invasive breast cancers (IBCs)4 arise from preexisting benign lesions. There are many types of benign lesions in the human breast and only a few appear to have significant premalignant potential (atypical hyperplasias and in situ carcinomas). These lesions are relatively common and only a small proportion progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect evidence based on epidemiological studies. Although lesions within specific categories look alike, they must possess morphologically silent biological differences motivating some to remain stable and others to progress. Understanding the biological changes responsible for the development and progression of premalignant disease is a very active area of medical research. Progress in this area may provide new opportunities for breast cancer prevention by providing strategies to treat premalignant lesions before they develop or become cancerous. A large number of biological features have been evaluated in this setting during the past decade. This review discusses a few features that appear to be particularly important and have been studied in a relatively comprehensive manner.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    International urology and nephrology 32 (2000), S. 109-117 
    ISSN: 1573-2584
    Schlagwort(e): Aging ; Nephrosclerosis ; Arteriolosclerosis ; Hypertension ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Arterial intimal fibroplasia in renal interlobular arteries but not arteriolar hyalinization was reported to be proportional to the rise of blood pressure with age in the data from all populations examined so far. New findings from Japan offer further insights into the disparities between the two types of renovasculopathy, both of which are called by the same name, `arteriolosclerosis'. PAS stained paraffin sections were prepared from specimens obtained atautopsy in Tokyo and New Orleans, emphasizing basal subjects, i.e. those with no cause of deathknown to be related to hypertension. Severities of fibroplastic vasculopathy, in units of intimal thickness as % of outer diameter, and hyaline vasculopathy, in units of affected arterioles per cm2 of tissue sectional area, were measured morphometrically. Blood pressure data were taken from published population surveys. Fibroplastic renovasculopathy was found to provide a proxy for mean blood pressure (MBP) when comparing groups of men and women of various age groups in the USA and Japan. Hyaline renovasculopathy did not reproduce these patterns. Some of these findings confirm similar results from prior studies, and this reproducibility increases confidence that a true biological difference may exist between these populations.
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  • 39
    ISSN: 1573-0603
    Schlagwort(e): Albumin ; Bronchial cells ; Chemoprevention ; Ecto-cervical cells ; Growth inhibition ; Hepatocytes ; Human ; In vitro ; Keratinocytes ; Mammary epithelial cells ; Mitochondrial function ; Normal ; Oral mucosal cells ; PCNA ; Prostate epithelial cells ; Renal cells ; Toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The Human Epithelial Cell Cytotoxicity (HECC) Assay for determining organ specific cytotoxicity uses human epithelial cells from eight different human tissues, including: skin, mammary, prostate, renal, bronchial, oral, ecto-cervix, and liver. Although the initial studies using this assay were conducted using cancer chemopreventive agents, the HECC Assay can also be used to evaluate other types of drugs, personal care products, environmental chemicals, and potential toxicants. Human epithelial cells at an early passage are seeded into multi-well dishes. The cells are exposed to multiple concentrations of a test agent for a three day period. The concentration ranges for test agents in the assay are determined in a preliminary assay using an exposure of five days and log dilutions from the highest soluble concentration. At the end of the exposure period, the cultures are evaluated for inhibition of growth. In the HECC Assay, cultures are exposed for three days. At the end of the exposure period, the cultures are evaluated for inhibition of growth, mitochondrial function, and PCNA expression or albumin synthesis (hepatocytes). Data are analyzed to determine the concentration that inhibited and point by 50 percent (TC50). Values for each agent in each target epithelial cell line or culture and the target tissue specific sensitivity are compared to determine the relative sensitivity of each epithelial cell line to the test agent.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    Human evolution 15 (2000), S. 99-112 
    ISSN: 1824-310X
    Schlagwort(e): Development ; Ontogeny ; Growth ; Brain ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The human has the most complex brain of the primates group. Their development is prolonged beyond birth and it is not completed structurally nor neurochemically until age of 20 years. Decades later, degenerative phenomena begin to be evident, that little by little will drive us to death. At the end of the life, 113 grams aproximate of cerebral mass are lost. The endowment of furrows and convolutions are fixed before birth, while the cerebral surface ends up having values next to the adult at 2 years. However the cerebral weight reaches its maximum at the 20 year-old decade. A first phase of neuronal death appears during the prenatal life, which is continued by another postnatal phase, and it ends with the definitive number of neurons. However, along life, the number of neurons decreases little by little at the time of the neuroglial cells increase. Much about brain knowledge at the moment is difficult to apply to the cranial endocasts, although approaches from the MNR are hopeful.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    Medical & biological engineering & computing 38 (2000), S. 454-464 
    ISSN: 1741-0444
    Schlagwort(e): Optic nerve ; Human ; Self-sizing spiral cuff electrode ; Finite elements method ; Fibre model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The aim of the study is to determine which of the existing myelinated mammalian nerve fibre models better fits experimental data resulting from electrical stimulation of the human optic nerve and from propagation velocity measured on primates. The macroscopic electric potential is computed in a 3D, inhomogeneous and anisotropic nerve model. The Chiu-Sweeney (CS) and the Schwarz-Wesselink (SW) membrane descriptions are then considered. Variations in parameters that are not well established (encapsulation-tissue thickness, nerve-fascicle conductivity, geometric and electrochemical fibre cable parameters) are taken into account. Results demonstrate that the SW model predictions are in better agreement with the experimental data than those of the CS model, although thresholds are still too high. When channel densities are varied, the SW model turns out to be more robust than the CS model. For a suitable leakage channel density value (about 8% of the original one), the SW model predicts a conduction velocity of 11.4ms−1 and an excitation threshold of 0.055 mA (for 0.1 ms pulse duration), which is in very good agreement with experimental values (11 ms−1 and 0.055 mA). Potassium current in the SW model is necessary for stability. Introduction of a potassium-like current can restore stability in the CS system.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    Surgical and radiologic anatomy 21 (1999), S. 139-141 
    ISSN: 1279-8517
    Schlagwort(e): Anatomy ; Human ; Cross-section ; Computer-assisted instruction ; Education ; Medical
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The NPAC visible human viewer (NPAC VHV), graphical interface written in JAVA, freely accessible by the Web, allows the display of anatomic cross-sections of the Visible Human Project developed by the National Library of Medicine. In April 1997, the Medical Media Library of Lyons undertook the construction of a French-language mirror site of the NPAC VHV. The aim of this work is to evaluate first year utilisation of this site. From May 1st, 1997 to April 30th, 1998, the mirror site was consulted 34,752 times. In 45.14% of cases, the request came from France, in 4.42% of cases from Belgium, in 3.98% from Canada and in 2.12% from Switzerland. Other connections came either from a country responsible for fewer than 1% of connections or from unidentified computers. Data analysis showed a peak of connections between 15:00 and 17:00, and an increased number of connections from September to March 1998. The NPAC VHV is housed in 5 sites in the world. It is a software very simple to use. As the figures have no legends, it is more appropriate for group teaching than for self-teaching.
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  • 43
    ISSN: 1437-1596
    Schlagwort(e): Key words Poisoning ; Benfuracarb ; Carbofuran ; Human ; Blood ; Urine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Notizen: Abstract We describe here three cases involving acute fatalities due to benfuracarb ingestion and the forensic toxicological implications. Benfuracarb, a carbamate insecticide and its main metabolite carbofuran, were detected using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS) after extraction with ethyl acetate and then quantified using gas chromatography (GC) equipped with NPD. The blood levels of benfuracarb and carbofuran were in the range of 0.30∼2.32 μg/ml and 1.45∼1.47 μg/ml, respectively. Benfuracarb was not detected in urine, but carbofuran was detected in the range of 0.53∼2.66 μg/ml.
    Materialart: Digitale Medien
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 125 (1999), S. 389-396 
    ISSN: 1432-1106
    Schlagwort(e): Key words Neck muscles ; Vibration ; Proprioception ; Sound localization ; Space perception ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The effect of transcutaneous vibration of the posterior neck muscles on the lateralization of dichotic sound was investigated in human subjects. Two-alternative forced-choice (left/right) judgements were made on acoustic stimuli presented with different interaural level differences via headphones during neck-muscle vibration. A shift of the subjective auditory median plane toward the side contralateral of vibration was found, indicating that the sound was perceived as shifted toward the side of vibration. The mean magnitude of the vibration-induced intracranial shift was 1.5 dB. The results demonstrate a neck-proprioceptive influence on sound lateralization and suggest that this proprioceptive input is used for a central-nervous transformation of auditory spatial coordinates onto a body-centered frame of reference.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 125 (1999), S. 435-439 
    ISSN: 1432-1106
    Schlagwort(e): Key words Transcranial magnetic stimulation ; Plasticity ; Synchronization ; Motor system ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We used focal transcranial magnetic stimulation to examine the effects of 120 synchronized thumb and foot movements on the motor output map of the right abductor pollicis brevis muscle (APB) (experiment 1). To evaluate the performance, the latencies between the onset of the electromyographic activity (EMG) of the two muscles were measured. As control, 120 asynchronous thumb and foot movements were performed (experiment 2). Exclusively in experiment 1, the center of gravity (CoG) of the output map moved medially in the direction of the foot representation area (mean 7 mm, P〈0.05) and returned into its original location within 1 h. In experiment 2, the CoG remained unchanged (mean displacement, 0.68 mm into a lateral direction; not significant). The effect in experiment 1 was independent of an improvement in performance. We conclude that a short-lasting training of synchronous movements induces modulations of motor output maps which probably occur due to interactions between hand and foot representation areas in the motor cortex.
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    Journal of comparative physiology 185 (1999), S. 297-304 
    ISSN: 1432-1351
    Schlagwort(e): Key words Odor coding ; Learning ; Enhanced sensitivity ; Rabbit ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The olfactory system is faced with a particular problem – the high dimensionality and inherent unpredictability of the chemical world. Most natural odorants encountered in everyday life are complex mixtures of many different volatiles. This means that from the outset the olfactory system has to contend with a great and often unpredictable diversity of molecules, making it difficult for stable primary features of the chemical world to be mapped onto the sensory surface. One solution to such unpredictability is provided by learning. Learning confers flexibility, enabling individuals of a given species to acquire and make use of the most appropriate information in a particular environment. Two examples of this are presented: learning of maternal odors in neonatal rabbits, including evidence that the sensory surface itself may be influenced by environmental conditions so as to enhance sensitivity to molecules of particular ecological relevance, and cross-cultural human studies suggesting that experience with everyday odors influences not only the way these are evaluated, but also their perceived intensity. It is concluded that an adequate understanding of odor coding and olfactory function will not be possible without taking such experience-dependent factors into account.
    Materialart: Digitale Medien
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  • 47
    ISSN: 1432-2307
    Schlagwort(e): Key words Peroxisomes ; Hepatocellular tumors ; Immunocytochemistry ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A significant reduction of catalase activity, a peroxisomal marker enzyme, occurs in human hepatic neoplasias, but no information is available on other peroxisomal proteins. We have studied by means of immunohistochemistry four specific proteins of peroxisomes (catalase and three enzymes of lipid β-oxidation) in human hepatocellular tumors of various differentiation grades from adenoma to anaplastic carcinoma. In all tumors, except the adenomas, the tumor cells contained fewer peroxisomes than extrafocal hepatocytes and the reduction of antigenic sites in the tumor types generally correlated with the degree of tumor dedifferentiation as assessed by classical histopathological criteria. Two poorly differentiated tumors had no detectable peroxisomes at all. There were no major differences in the intensities of the immunocytochemical staining for all four studied peroxisomal antigens in different tumors, suggesting that the neoplastic transformation affects the biogenesis of the entire organelle and not merely the individual peroxisomal enzyme proteins. Some tumors exhibited a distinct peripheral distribution of peroxisomes. In cases with associated liver cirrhosis, the hepatocytes in the adjacent liver showed marked peroxisome proliferation, forming large perinuclear aggregates, occupying occasionally the entire cytoplasm. Taken together, our observations indicate that peroxisomes are significantly altered in both hepatocellular tumors and liver cirrhosis and, thus, could be responsible for some of the metabolic derangements observed in those disease processes.
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  • 48
    ISSN: 1432-2307
    Schlagwort(e): Key words p21 ; p53 ; Colon ; Immunohistochemistry ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.
    Materialart: Digitale Medien
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  • 49
    ISSN: 1434-0879
    Schlagwort(e): Key words Alpha-1-microglobulin ; Calcium oxalate ; Crystallization ; ELISA ; Human ; Urine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the past few years, alpha-1-microglobulin (α1m) has been copurified from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have purified α1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was purified with an anti-α1m antibodies CNBr-activated sepharose column. Two molecular species of α1m of respectively 30 and 60 kDa were purified. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-α1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the first test, the presence of α1m of 30 kDa (8 μg/ml) in a medium containing 0.76 mM CaCl2 (with 45Ca) and 0.76 mM Ox(NH4)2 inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of α1m of 30 kDa in a medium containing 4 mM CaCl2 and 0.5 mM Na2Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modification of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary α1m concentration was significantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 ± 0.29 vs 5.34 ± 1.08 mg/l respectively, P = 0.01). The decreased concentration of α1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 199 (1999), S. 45-56 
    ISSN: 1432-0568
    Schlagwort(e): Key words Skin ; Proteoglycan ; Development ; Human ; Fetal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The extracellular matrix of human fetal skin differs substantially from that of adult skin. Fetal skin contains sparse amounts of fibrillar collagen enmeshed in a highly hydrated amorphous matrix composed of hyaluronan and sulfated proteoglycans. Both fetal and adult skin contain two major interstitial proteoglycans that are extracted by chaotrophic agents and detergents. These are the large chondroitin sulfate proteoglycan versican and the small dermatan sulfate proteoglycan decorin. For this study, proteoglycans extracted from fetal and adult skin were compared on Western blots to determine the relative amounts of versican. Decorin present in the same samples provided an internal standard for these studies. Fetal skin differed from adult skin in that it contained a significantly higher proportion of versican than did adult skin. Immunohistochemical studies compared early-fetal with mid-fetal skin and found that versican was a significant component of the interstitial extracellular matrix at both of these stages of skin development. However, by the mid-fetal period, interstitial versican became restricted to the upper half of the dermis, although versican also continued to be highly expressed around hair follicles, glands, and vasculature in the lower half of the dermis. Fetal skin extracts differed from an adult skin extract by the presence of a 66-kDa protein immunologically related to versican and by the absence of a 17-kDa core protein of a proteoglycan related to decorin. Both of these molecular species may represent degradation products of their respective proteoglycans. Monoclonal antibodies which detect epitopes in native chondroitin sulfate glycosaminoglycan chains recognized versican extracted from fetal skin. However, the tissue distribution of these antigens did not entirely conform to that for versican core protein, suggesting that versican in different regions of the skin may be substituted with glycosaminoglycan chains with different microchemistries. The results of these studies indicate that human fetal skin is structurally different from adult skin in terms of both the distribution and the composition of the large, aggregating chondroitin sulfate proteoglycan versican.
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  • 51
    ISSN: 1432-0533
    Schlagwort(e): Key words Amantadine ; Human ; N-methyl-d-aspartate ; Phencyclidine ; Postmortem brain
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Low doses of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists induce morphological alterations in neurons of the cingulate gyrus and retrosplenial cortex of the rat. Neuronal cell death may result at higher doses. These effects are a major concern with regard to the introduction of new NMDA receptor antagonists into clinical trials. Amantadine is an uncompetitive NMDA receptor antagonist, which has been in clinical use for many years. In the present study we have looked for possible morphological alterations like necrosis in postmortem human brain tissue of patients previously treated with amantadine. Formalin-fixed tissue samples were taken from the hippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on previous amantadine medication and of 11 controls. Histopathological examination of sections was performed blind. All brains except one revealed either nonspecific age-related or cerebrovascular changes or other neurodegenerative disorders including Alzheimer’s, Parkinson’s or Lewy body disease. In conclusion, histopathological examination of the hippocampus, retrosplenial cortex, and cingulate gyrus of human brain did not reveal changes suggested to be specific for previous amantadine treatment.
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  • 52
    ISSN: 1432-0533
    Schlagwort(e): Key words Purkinje cell ; Cerebellum ; Development ; Inositol 1 ; 4 ; 5-triphosphate type 1 receptor ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.
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  • 53
    ISSN: 1432-069X
    Schlagwort(e): Key words Chronic diabetic wounds ; Human ; fibroblasts ; Wound healing ; Cell culture ; Proliferation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Patients with diabetes mellitus experience impaired wound healing often resulting in chronic foot ulcers. Hospital discharge data indicate that 6–20% of all diabetic individuals hospitalized (mostly with type 2 diabetes) have a lower extremity ulcer. Maintaining glucose levels at acceptable levels (below 10 mmol/l) is considered to be an important part of the clinical treatment, but the exact mechanism by which diabetes delays wound repair is not yet known. We studied this phenomenon by determining the potential of fibroblasts isolated from the ulcer sites of four patients with non-insulin-dependent diabetes mellitus to proliferate in vitro. Controls were fibroblasts isolated from normal skin of the upper leg of five healthy age-matched volunteers and of six non-insulin-dependent diabetes patients. Proliferative capacity was analysed by evaluation of plates after trypsinization and [3H]thymidine incorporation. Fibroblast morphology was studied by light and transmission electron microscopy. Diabetic ulcer fibroblasts, measured by [3H]thymidine incorporation, proliferated significantly more slowly than the nonlesional control fibroblasts (P 〈 0.00047) and age-matched control fibroblasts (P 〈 0.00003). After culturing the fibroblasts for a prolonged period in high-glucose (27.5 mM) and low-glucose (5.5 mM, i.e. physiological) medium, this difference in proliferation rate between diabetic ulcer fibroblasts and nonlesional diabetic fibroblasts remained (P 〈 0.0001 for high-glucose and P 〈 0.0009 for low-glucose on day 7). Fibroblast proliferation in all three groups was slightly lower in high-glucose than in low-glucose medium, although not significantly at any time-point. Light microscopy showed diabetic ulcer fibroblasts to be large and widely spread. Transmission electron microscopy of cultured diabetic ulcer fibroblasts and nonlesional diabetic skin fibroblasts revealed a large dilated endoplasmic reticulum, a lack of microtubular structures and multiple lamellar and vesicular bodies. These results show a diminished proliferative capacity and abnormal morphology of fibroblasts derived from diabetic ulcers of non-insulin-dependent diabetes patients.
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    Archives of dermatological research 291 (1999), S. 247-252 
    ISSN: 1432-069X
    Schlagwort(e): Key words T cell activation ; Nickel ; Human ; Interferon-gamma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Contact hypersensitivity to nickel is the most common form of allergic contact dermatitis. To gain insight into the induction of this frequent disease, T cell reactivity towards nickel was investigated in “nonallergic” individuals defined as those with no skin manifestations and a negative patch test towards NiSO4. Surprisingly, we found that nickel induced proliferation of peripheral blood mononuclear cells (PBMC) from 16 of 18 adult individuals tested. This activation was specific, and no stimulation of PBMC was observed using control stimulants at equimolar concentrations. Furthermore, the NiSO4-induced activation required the presence of professional antigen-presenting cells. To describe the functional capacity of the nickel-inducible T cells, cytokine release was investigated in both nickel-allergic and nonallergic individuals. The T cells from both groups released interferon-γ but no interleukin-4 upon stimulation with nickel, suggesting that the functional capacities of these cell populations were similar in nickel-allergic and nonallergic individuals. Thus, at this level, no qualitative differences could be demonstrated between T cells obtained from nickel-allergic and nonallergic individuals.
    Materialart: Digitale Medien
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  • 55
    ISSN: 1432-069X
    Schlagwort(e): Key words ORS cells ; Melanocytes ; Human ; Organotypic cultures ; Melanosomes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred “through racial barriers”. Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 49 (1999), S. 438-445 
    ISSN: 1432-1211
    Schlagwort(e): Key words PA28 ; Proteasome ; Gene structure ; Evolution ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Two proteasome activators PA28α and β, which have been implicated in antigen processing for loading class I MHC molecules, are synthesized in response to Ifn-γ. The human genes encoding these activators (PSME1 and PSME2, respectively) were analyzed by sequencing. Each gene comprised 11 exons, consistent with gene duplication during vertebrate evolution. The intron/exon organization of both genes was highly conserved, the major difference being the absence of the exon encoding the lysine and glutamic acid-rich 'KEKE' motif in PA28β. Two other genes of relevance to the immune system were located close to those for PA28 at 14q11.2 including ISGF3G, a protein involved in transcription after IFNα signalling. These sequences were also characterized.
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  • 57
    ISSN: 1432-1211
    Schlagwort(e): Key words NK cells ; Human ; Surface molecule ; Lectin superfamily ; NK gene complex
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Natural killer (NK) cells constitute the third major population of lymphocytes. They possess the inherent capacity to kill various tumor and virally infected cells and mediate the rejection of bone-marrow grafts in lethally irradiated animals. A large family of NK cell receptors belong to the C-type lectin superfamily and are localized to the NK gene complex on Chromosome (Chr) 6 in the mouse and Chr 12 in the human. Genes in the NK gene complex encode type II receptors and examples include the families of NKR-P1, Ly-49, and NKG2 receptors. Examples of other C-type lectin-like NK cell receptors that occur as individual genes are CD94, CD69, and AICL. Here we report the molecular characterization and chromosomal mapping of a human lectin-like transcript (LLT1) expressed on NK, T, and B cells and localized to the NK gene complex within 100 kilobases of CD69. The cDNA encodes a predicted protein of 191 amino acid residues with a transmembrane domain near the N-terminus and an extracellular domain of 132 amino acid residues with similarity to the carbohydrate recognition domain of C-type lectins. The predicted protein of LLT1 shows 59 and 56% similarity to AICL and CD69, respectively. The predicted protein does not contain any intracellular ITIM motifs, suggesting that LLT1 may be involved in mediating activation signals.
    Materialart: Digitale Medien
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 128 (1999), S. 539-542 
    ISSN: 1432-1106
    Schlagwort(e): Key words Silent period ; Transcranial magnetic stimulation ; Motor cortex ; Epidural recordings ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50–200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357±62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.
    Materialart: Digitale Medien
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  • 59
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 128 (1999), S. 550-556 
    ISSN: 1432-1106
    Schlagwort(e): Key words Selective attention ; Kinematics ; Human ; Visual pathways
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In solving the selection-for-action problem, it is believed that attentional mechanisms enable dominance of target over non-target objects. However, under some conditions, information from non-target objects ”interferes” with the action to a relevant target. We investigated the possibility that this interference may result when the irrelevant object activates a specific subset of visuomotor pathways. Participants reached to grasp three-dimensional stimuli while actively attending to a nearby flanker object. The means by which the flanker was presented was manipulated. This relevant object was illuminated either abruptly or gradually. The parvocellular pathway in early visual processing is equally activated in both conditions. The magnocellular pathway is strongly activated by abrupt presentation and weakly activated with gradual presentation of the flanker object. Kinematics of the reach-to-grasp action to the target showed signs of interference only in the sudden illumination condition. This suggests a dissociation between dorsal and ventral cortical streams in terms of relevance for action. Our data suggests that this effect is not due to early visual-pathway differences, but instead reveals a property of a transient object-based visual attention mechanism.
    Materialart: Digitale Medien
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 124 (1999), S. 1-7 
    ISSN: 1432-1106
    Schlagwort(e): Key words Temporal cortex ; Connectivity ; Human ; Interhemispheric transfer ; Talairach coordinates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The human anterior commissure is believed, by extrapolation from data obtained in macaque monkeys, to convey axons from the temporal and orbitofrontal cortex. Reports of interhemispheric transfer and sexual dimorphism related to the anterior commissure, however, make more precise data on the human anterior commissure desirable. We investigated the connectivity of the human anterior commissure in six adults (male and female) that had circumscribed hemispheric lesions in temporal, frontal, parietal or occipital cortices or in infrapallidal white matter using the Nauta for anterogradely degenerating axons. Axons originating in the inferior part of temporal or occipital lobes, occipital convexity and possibly central fissure and prefrontal convexity were found to cross the midsagittal plane in the anterior commissure. The largest contigent of commissural axons originated in the inferior part of the temporal lobe; it displayed a roughly topographic organization, preferentially running through the inferior part of the commissure. The inferior temporal contigent seemed to reach homotopic and heterotopic targets in the opposite hemisphere. Among the latter were the amygdala and possibly the orbitofrontal cortex. The present data suggest that the human anterior commissure conveys axons from much larger territories than expected from work on non-human primates. Similarly to the human and non-human primate corpus callosum, the anterior commissure is roughly topographically organized and participates in heterotopic connectivity.
    Materialart: Digitale Medien
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 126 (1999), S. 200-204 
    ISSN: 1432-1106
    Schlagwort(e): Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 124 (1999), S. 273-280 
    ISSN: 1432-1106
    Schlagwort(e): Key words Vestibular system ; Posture control ; Balance ; Cross-spectral analysis ; Coherency ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Galvanic vestibular stimulation serves to modulate the continuous firing level of the peripheral vestibular afferents. It has been shown that the application of sinusoidally varying, bipolar galvanic currents to the vestibular system can lead to sinusoidally varying postural sway. Our objective was to test the hypothesis that stochastic galvanic vestibular stimulation can lead to coherent stochastic postural sway. Bipolar binaural stochastic galvanic vestibular stimulation was applied to nine healthy young subjects. Three different stochastic vestibular stimulation signals, each with a different frequency content (0–1 Hz, 1–2 Hz, and 0–2 Hz), were used. The stimulation level (range 0.4–1.5 mA, peak to peak) was determined on an individual basis. Twenty 60-s trials were conducted on each subject – 15 stimulation trials (5 trials with each stimulation signal) and 5 control (no stimulation) trials. During the trials, subjects stood in a relaxed, upright position with their head facing forward. Postural sway was evaluated by using a force platform to measure the displacements of the center of pressure (COP) under each subject’s feet. Cross-spectral measures were used to quantify the relationship between the applied stimulus and the resulting COP time series. We found significant coherency between the stochastic vestibular stimulation signal and the resulting mediolateral COP time series in the majority of trials in 8 of the 9 subjects tested. The coherency results for each stimulation signal were reproducible from trial to trial, and the highest degree of coherency was found for the 1- to 2-Hz stochastic vestibular stimulation signal. In general, for the nine subjects tested, we did not find consistent significant coherency between the stochastic vestibular stimulation signals and the anteroposterior COP time series. This work demonstrates that, in subjects who are facing forward, bipolar binaural stochastic galvanic stimulation of the vestibular system leads to coherent stochastic mediolateral postural sway, but it does not lead to coherent stochastic anteroposterior postural sway. Our finding that the coherency was highest for the 1- to 2-Hz stochastic vestibular stimulation signal may be due to the intrinsic dynamics of the quasi-static postural control system. In particular, it may result from the effects of the vestibular stimulus simply being superimposed upon the quiet-standing COP displacements. By utilizing stochastic stimulation signals, we ensured that the subjects could not predict a change in the vestibular stimulus. Thus, our findings indicate that subjects can act as ”responders” to galvanic vestibular stimulation.
    Materialart: Digitale Medien
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  • 63
    ISSN: 1432-1106
    Schlagwort(e): Key words Locomotion ; Load ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Prior work from mammals suggests that load experienced by extensor muscles of the hindlimbs (i.e. Duysens and Pearson 1980; Pearson and Collins 1993; Fouad and Pearson 1997) or cutaneous afferents from the plantar surface of the foot (Duysens and Pearson 1976; Guertin et al. 1995) enhances activity in extensor muscles during the stance phase, and delays the onset of flexor activity associated with the swing phase. The presumed functional significance of this phenomenon is that extensor activity of the supporting limb during walking can: (a) reinforce the supporting function in proportion to the load experienced, and (b) prolong the stance phase until unloading of the limb has occurred. Whether a similar functional role exists for load-sensitive afferents during walking in the human is unknown. In this study, the effect of adding or removing a substantial load (30% of body weight) at the centre of mass was studied in healthy adult human subjects. Loads were applied near the centre of mass to avoid the need for postural adjustments which might confound the interpretation of the results. Subjects walked on a treadmill with either: (a) a sustained increase or decrease in load, or (b) a sudden unexpected increase or decrease in load. In general, subjects responded to the changes in load by changing the amplitude of the extensor electromyographic (EMG) bursts. For example, with sudden unexpected additions in load, the average increase in amplitude was 40% for the soleus across the stance phase, and 134% for the quadriceps during the early part of the stance phase. Extensor EMGs increased with both sustained and sudden increases in load. Extensor EMG durations also increased (average increase in duration of 4% for soleus with sudden loading, and 7% for sustained loading). Cycle duration hardly changed (average increase of 0.5% with both sudden and sustained loading). These results differ from those of infants subjected to a similar perturbation during supported walking. A large change in timing (i.e. an increase in the duration of the stance phase by 30% and the step cycle by 28%) was seen in the infants, with no change in the amplitude of the EMG burst (Yang et al. 1998). These results suggest that the central nervous system can control the timing and amplitude of extensor EMG activity in response to loading independently. Maturation of the two components most likely occurs independently. In the adult, independent control of the two components may provide greater flexibility of the response.
    Materialart: Digitale Medien
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 126 (1999), S. 235-251 
    ISSN: 1432-1106
    Schlagwort(e): Key words Motor learning and memory ; Perseveration ; Prefrontal cortex ; Reversal learning ; Basal ganglia ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The ability to inhibit previously learned visuomotor associations is essential for efficient learning of novel behaviors. While the neural basis of the system that might control interactions between competing motor memories is not known, it has been demonstrated that animals with ventral and orbital prefrontal cortex (PFC) deficits have particular difficulties in learning to withhold responses to previously conditioned sensory stimuli. Here we measured regional cerebral blood flow (rCBF), using positron emission tomography, during learning of a novel motor task that required inhibition of a previously learned motor memory. Subjects (n=24) learned reaching movements in a force field (field A). After a variable time interval, some subjects (n=15) learned to reach in a field with a reversed pattern of forces (field B). When the time interval was short (10 min), learning in field B was coincident with a reactivation of regions that had become initially activated during learning in field A: the left putamen and bilaterally in the dorsolateral PFC. Behaviorally, this was accompanied with perseveration that lasted for hundreds of movements, suggesting an instantiation of the internal model for field A during learning in field B. Neither the reactivation nor the perseveration were observed in a different group of subjects that learned field B at 5.5 h. We found that the regions which significantly differentiated the two groups during learning of B were in the ventrolateral PFC (bilaterally): there were sharp decreases in rCBF here in the 5.5 group but not in the 10-min group. At 5.5 h motor learning again involved the striatum, but this time in the left caudate. Neither the caudate nor the ventral PFC had exhibited learning-related activity in field A. Instead, they showed changes in rCBF during the reversal of the learning problem when the previously acquired motor memory was successfully gated. The results demonstrate that: (1) perseveration of a competing motor memory may be linked to reactivation of the neural circuit that participated in acquiring that memory, and (2) the ventral PFC may play an important role in the inhibitory control of the competing motor memory.
    Materialart: Digitale Medien
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  • 65
    ISSN: 1432-1106
    Schlagwort(e): Key words Corpus callosum ; Interhemispheric transfer ; Positron emission tomography ; Split brain ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We studied with PET the intra- and interhemispheric pathways subserving a simple, speeded-up visuomotor task. Six normal subjects and one patient with a complete section of the corpus callosum (M.E.) underwent regional cerebral blood flow (rCBF) measurements under conditions of lateralized tachistoscopic visual presentations in a simple manual reaction time paradigm. Confirming previous behavioural findings, we found that on average crossed hand and/or hemifield conditions, i.e. those requiring an interhemispheric transfer of information, yielded a longer RT than uncrossed conditions. This difference (0.7 ms) was dramatically larger (45.6 ms) in the callosum-sectioned patient M.E. In normal subjects the cortical areas selectively activated in uncrossed and crossed conditions were different. In the former condition, most activation foci were anterior to the ventral anterior commissure (VAC) plane, whereas in the latter there was a prevalent parietal and occipital activation. This shows that a simple model in which the cortical visuo-motor pathways are similar in the intra- and the interhemispheric condition, with an extra callosal route for the latter, is too simplistic. Furthermore, these results suggest that the bulk of visuomotor interhemispheric transfer takes place through the widespread callosal fibres interconnecting the parietal cortices of the two hemispheres. The pattern of activation in the two crossing conditions was markedly different in M.E., in whom interhemispheric transfer might take place via his intact anterior commissure or subcortical commissures.
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 125 (1999), S. 43-49 
    ISSN: 1432-1106
    Schlagwort(e): Key words Proprioception ; Visual localization ; Visual context ; Multisensory integration ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In a previous study we investigated how the CNS combines simultaneous visual and proprioceptive information about the position of the finger. We found that localization of the index finger of a seen hand was more precise (a smaller variance) than could reasonably be expected from the precision of localization on the basis of vision only and proprioception only. This suggests that, in localizing the tip of the index finger of a seen hand, the CNS may make use of more information than proprioceptive information and visual information about the fingertip. In the present study we investigate whether this additional information stems from additional sources of sensory information. In experiment 1 we tested whether seeing an entire arm instead of only the fingertip gives rise to a more precise proprioceptive and/or visual localization of that fingertip. In experiment 2 we checked whether the presence of a structured visual environment leads to a more precise proprioceptive localization of the index finger of an unseen hand. In experiment 3 we investigated whether looking in the direction of the index finger of an unseen hand improves proprioceptive localization of that finger. We found no significant effect in any of the experiments. The results refute the hypothesis that the investigated effects can explain the previously reported very precise localization of a seen hand. This suggests that localization of a seen finger is based exclusively on proprioception and on vision of the finger. The results suggest that these sensory signals may contain more information than is described by the magnitude of their variances.
    Materialart: Digitale Medien
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 125 (1999), S. 139-152 
    ISSN: 1432-1106
    Schlagwort(e): Key words Reaching movements ; Direction ; Amplitude ; Initial kinematics ; Spatial variability ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The accuracy of reaching movements to memorized visual target locations is presumed to be determined largely by central planning processes before movement onset. If so, then the initial kinematics of a pointing movement should predict its endpoint. Our study examined this hypothesis by testing the correlation between peak acceleration, peak velocity, and movement amplitude and the correspondence between the respective spatial positions of these kinematic landmarks. Subjects made planar horizontal reaching movements to targets located at five different distances and along five radially arrayed directions without visual feedback during the movements.The spatial dispersion of the positions of peak acceleration, peak velocity, and endpoint all tended to form ellipses oriented along the movement trajectory. However, whereas the peaks of acceleration and velocity scaled strongly with movement amplitude for all of the movements made at the five target distances in any one direction, the correlations with movement amplitude were more modest for trajectories aimed at each target separately. Furthermore, the spatial variability in direction and extent of the distribution of positions of peak acceleration and peak velocity did not scale differently with target distance, whereas they did for endpoint distributions. Therefore, certain features of the final kinematics are evident in the early kinematics of the movements as predicted by the hypothesis that they reflect planning processes. However, endpoint distributions were not completely predetermined by the Initial kinematics. In contrast, multivariate analysis suggests that adjustments to movement duration help compensate for the variability of the initial kinematics to achieve desired movement amplitude. These compensatory adjustments do not contradict the general conclusion that the systematic patterns in the spatial variability observed in this study reflect planning processes. On the contrary, and consistent with that conclusion, our results provide further evidence that direction and extent of reaching movements are planned and determined in parallel over time.
    Materialart: Digitale Medien
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  • 68
    ISSN: 1432-1106
    Schlagwort(e): Key words Three-dimensional pointing ; Human ; Remembered targets
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The accuracy of visually guided pointing movements decreases with speed. We have shown that for movements to a visually defined remembered target, the variability of the final arm endpoint position does not depend on movement speed. We put forward a hypothesis that this observation can be explained by suggesting that movements directed at remembered targets are produced without ongoing corrections. In the present study, this hypothesis was tested for pointing movements in 3D space to kinesthetically defined remembered targets. Passive versus active acquisition of kinesthetic information was contrasted. Pointing errors, movement kinematics, and joint-angle coordination were analyzed. The movements were performed at a slow speed (average peak tangential velocity of about 1.2 m/s) and at a fast speed (2.7 m/s). No visual feedback was allowed during the target presentation or the movement. Variability in the final position of the arm endpoint did not increase with speed in either the active or the passive condition. Variability in the final values of the arm-orientation angles determining the position of the forearm and of the upper arm in space was also speed invariant. This invariance occurred despite the fact that angular velocities increased by a factor of two for all the angles involved. The speed-invariant variability supports the hypothesis that there is an absence of ongoing corrections for movements to remembered targets: in the case of a slower movement, where there is more time for movement correction, the final arm endpoint variability did not decrease. In contrast to variability in the final endpoint position, the variability in the peak tangential acceleration increased significantly with movement speed. This may imply that the nervous system adopts one of two strategies: either the final endpoint position is not encoded in terms of muscle torques or there is a special on-line mechanism that adjusts movement deceleration according to the muscle-torque variability at the initial stage of the movement. The final endpoint position was on average farther from the shoulder than the target. Constant radial-distance errors were speed dependent in both the active and the passive conditions. In the fast speed conditions, the radial distance overshoots of the targets increased. This increase in radial-distance overshoot with movement speed can be explained by the hypothesis that the final arm position is not predetermined in these experimental conditions, but is defined during the movement by a feedforward or feedback mechanism with an internal delay.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 125 (1999), S. 265-270 
    ISSN: 1432-1106
    Schlagwort(e): Key words Tendon reflexes ; Biceps femoris ; Gait ; Ia afferents ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  During gait it is generally accepted that there is a reduction in amplitude of H-reflexes as compared to standing. For short-latency stretch reflexes, however, it is less clear whether a similar reduction in reflex gain is present during locomotion. Stretches of constant amplitude are hard to produce under these circumstances and for this reason some previous studies on the biceps femoris (BF) have used ”reduced gait” in which the stimulated leg is stepping on the spot while the contralateral leg is walking on a treadmill. With this method it was possible to show that BF tendon jerk reflexes are larger at end swing and therefore are likely to contribute to the EMG burst normally occurring in that part of the step cycle when the BF is rapidly stretched. In the present study two questions were addressed: first, whether the reflex is different in size during gait compared to standing and, second, whether it is modulated in size during the gait cycle not only during reduced but also during normal gait. It was found that during both types of gait there was a general reflex depression with regard to the respective control values obtained during standing at similar EMG activity levels. In previous studies on soleus and quadriceps, discrepancies between EMG activity and reflex amplitude have been ascribed to changes in presynaptic inhibition of Ia terminals mediating the afferent volley of the reflex. Based on the data presented, this may also be true for the BF. In both normal and reduced gait the reflex was similarly modulated in size, showing a maximum at the end of swing. This similarity implies that reduced gait may be useful as an acceptable alternative for normal gait in studies on phase-dependent reflex modulation during locomotion.
    Materialart: Digitale Medien
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  • 70
    ISSN: 1432-1106
    Schlagwort(e): Key words Hyperventilation ; Magnetoencephalography ; Somatosensory cortex ; Auditory cortex ; Somatosensory evoked response ; Auditory evoked response ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  It is well established that voluntary hyperventilation (HV) slows down electroencephalographic (EEG) rhythms. Little information is available, however, on the effects of HV on cortical responses elicited by sensory stimulation. In the present study, we recorded auditory evoked potentials (AEPs) and magnetic fields (AEFs), and somatosensory evoked magnetic fields (SEFs) from healthy subjects before, during, and after a 3- to 5-min period of voluntary HV. The effectiveness of HV was verified by measuring the end-tidal CO2 levels. Long-latency (100–200 ms) AEPs and long-latency AEFs originating at the supratemporal auditory cortex, as well as long-latency SEFs from the primary somatosensory cortex (SI) and from the opercular somatosensory cortex (OC), were all reduced during HV. The short-latency SEFs from SI were clearly less modified, there being, however, a slight reduction of the earliest cortical excitatory response, the N20m deflection. A middle-latency SEF deflection from SI at about 60 ms (P60 m) was slightly increased. For AEFs and SEFs, the center-of-gravity locations of the activated neuronal populations were not changed during HV. All amplitude changes returned to baseline levels within 10 min after the end of HV. The AEPs were not altered when the subjects breathed 5% CO2 in air in a hyperventilation-like manner, which prevented the development of hypocapnia. We conclude that moderate HV suppresses long-latency evoked responses from the primary projection cortices, while the early responses are less reduced. The reduction of long-latency responses is probably mediated by hypocapnia rather than by other nonspecific effects of HV. It is suggested that increased neuronal excitability caused by HV-induced hypocapnia leads to spontaneous and/or asynchronous firing of cortical neurones, which in turn reduces stimulus-locked synaptic events.
    Materialart: Digitale Medien
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 124 (1999), S. 42-52 
    ISSN: 1432-1106
    Schlagwort(e): Key words Ocular tracking ; Oculomanual coordination ; Electromyography ; Internal model ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  When the eyes and arm are involved in a tracking task, the characteristics of each system differ from those observed when they act alone: smooth pursuit (SP) latency decreases from 130 ms in external target tracking tasks to 0 ms in self-moved target tracking tasks. Two models have been proposed to explain this coordination. The common command model suggests that the same command be addressed to the two sensorimotor systems, which are otherwise organized in parallel, while the coordination control model proposes that coordination is due to a mutual exchange of information between the motor systems. In both cases, the interaction should take into account the dynamic differences between the two systems. However, the nature of the adaptation depends on the model. During self-moved target tracking a perturbation was applied to the arm through the use of an electromagnetic brake. A randomized perturbation of the arm increased the arm motor reaction time without affecting SP. In contrast, a constant perturbation produced an adaptation of the coordination control characterized by a decrease in arm latency and an increase in SP latency relative to motor command. This brought the arm-to-SP latency back to 0 ms. These results support the coordination control model.
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 124 (1999), S. 287-294 
    ISSN: 1432-1106
    Schlagwort(e): Key words Magnetoencephalography ; V1 cortex ; V2 cortex ; V6 complex ; Horizontal meridian ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We recorded whole-scalp magnetoencephalographic (MEG) responses to black-and-white checkerboards to study whether the human cortical responses are quantitatively similar to stimulation of the lower and upper visual field at small, 0–6°, eccentricities. All stimuli evoked strongoccipital responses peaking at 50–100 ms (mean 75 ms). The activation was modeled with a single equivalent current dipole in the contralateral occipital cortex, close to the calcarine fissure, agreeing with an activation of the V1/V2 cortex. The dipole was, on average, twice as strong to lower than to upper field stimuli. Responses to hemifield stimuli that extended to both lower and upper fields resembled the responses to lower field stimuli in source current direction and strength. These results agree with psychophysical data, which indicate lower visual field advantage in complex visual processing. Parieto-occipital responses in the putative V6 complex were similar to lower and upper field stimuli.
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 126 (1999), S. 289-306 
    ISSN: 1432-1106
    Schlagwort(e): Key words Motor control ; Trajectory formation ; Coordination ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The degrees of freedom problem is often posed by asking which of the many possible degrees of freedom does the nervous system control? By implication, other degrees of freedom are not controlled. We give an operational meaning to ”controlled” and ”uncontrolled” and describe a method of analysis through which hypotheses about controlled and uncontrolled degrees of freedom can be tested. In this conception, control refers to stabilization, so that lack of control implies reduced stability. The method was used to analyze an experiment on the sit-to-stand transition. By testing different hypotheses about the controlled variables, we systematically approximated the structure of control in joint space. We found that, for the task of sit-to-stand, the position of the center of mass in the sagittal plane was controlled. The horizontal head position and the position of the hand were controlled less stably, while vertical head position appears to be no more controlled than joint motions.
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 124 (1999), S. 469-473 
    ISSN: 1432-1106
    Schlagwort(e): Key words Form from motion ; Visual development ; Visual acuity ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The development of dynamic vision was investigated in 400 healthy subjects (200 females and 200 males) aged between 4 and 24 years. The test consisted of a computer-generated random-dot kinematogram in which a Landolt ring was briefly presented as a form-from-motion stimulus. Motion contrast between the ring and background was varied in terms of the percentage of dots moving coherently within the ring in four levels (100%, 50%, 30%, and 20%). The subject’s task was to indicate the position of a gap in the ring (left, right, top, bottom). Results show a clear increase in performance with age for all motion contrast levels, with the greatest changes for the lowest levels. Adult performance was reached at the age of 15 years. Luminance-based static acuity measured with the Landolt test was poorly correlated with acuity for its form-from-motion analogue.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 124 (1999), S. 503-512 
    ISSN: 1432-1106
    Schlagwort(e): Key words Reaching movements ; Memory for positions ; Laterality ; Posture copying ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Many recent studies indicate that memory for final position is superior to memory for movement. There is ambiguity about what is meant by the term final position, however. Is it final spatial location or final posture? According to a recently proposed theory by Rosenbaum et al., which maintains that stored postures form the basis for movement planning, when people try to return to recently reached positions, they should try to adopt the postures they just occupied. An alternative view, which holds that movements are primarily planned with respect to spatial locations, predicts that subjects should tend to return to places in external space. We describe an experiment that tested these opposing predictions. The experiment relied on the notion that if people store and use postures, they should ”copy” the posture adopted with one arm to the other arm when possible. The results support this hypothesis.
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  • 76
    ISSN: 1432-1106
    Schlagwort(e): Key words Optokinetic nystagmus ; Positron emission tomography ; Visual motion ; Area V5 ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Positron emission tomography (PET) was used to address the issue of physiological changes in the cerebral cortex associated to optokinetic nystagmus (OKN) in humans. We studied regional cerebral blood flow in eight volunteers during reflexive induction of OKN by a pattern of dots moving unidirectionally (toward the left side). We used two control conditions, with subjects passively viewing either stationary or incoherently moving dots. This paradigm was designed in order to differentiate the OKN-related activations from blood flow changes related to visual motion. When compared with the stationary condition, OKN activated a set of occipital areas known to be sensitive to visual motion. Bilateral activation was found in the striate cortex (V1) and the parieto-occipital fissure, while area V5, the intraparietal sulcus, and the pulvinar were activated only in the left hemisphere. When compared with incoherent motion, OKN activated the V1 and the parieto-occipital fissure bilaterally and the right lingual gyrus, while a signal decrease was observed in the V5 region in both hemispheres. No significant signal changes were found in areas implicated in saccades or in processing vestibular information. These results indicate that processing of OKN-related information is associated with neural activity in a specific set of visual motion areas and suggest that this network can be asymmetrically activated by a strictly unidirectional stimulation. Results are also discussed in terms of the specific kinds of OKN-related information processing subserved by each area in this network.
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 126 (1999), S. 175-186 
    ISSN: 1432-1106
    Schlagwort(e): Key words Listing’s plane ; Vergence ; Binocular ; Eye movements ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Earlier studies have reported temporal rotation of Listing’s plane with convergence of the eyes causing torsion, which is dependent on eye elevation. The amount by which the planes rotate differs from study to study. To gain insight into the functional significance of the temporal tilt of Listing’s plane for vision, we examined whether the rotation of the plane depends on the visual conditions, namely on the stimuli driving vergence. In different conditions, accommodative vergence, disparity-vergence, combinations of disparity with accommodation or depth perception were used and the resulting rotation of Listing’s plane was measured. Our findings show, for the first time, that the relationship between convergence and Listing’s-plane temporal rotation depends on the stimuli driving vergence. When the stimulus contains only disparity cues, vergence and Listing’s plane rotate immediately and consistently among subjects. Accommodative vergence, the mutual couplings between vergence and accommodation, can influence the orientation of Listing’s plane, but they do so in a idiosyncratic way. The largest rotation was elicited by stereograms combining disparity-vergence with depth perception. These findings support the idea of a functional role of Listing’s plane rotation for binocular vision, perhaps for depth perception.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 126 (1999), S. 205-214 
    ISSN: 1432-1106
    Schlagwort(e): Key words Grip force ; Force control ; Parabolic flight ; Microgravity ; Hypergravity ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In the present study, grip forces exerted against a stationary held object were recorded during parabolic flights. Such flight maneuvers induce changes of gravity with two periods of hypergravity, associated with a doubling of normal terrestrial gravity, and a 20 s period of microgravity. Accordingly, the object’s weight changed from being twice as heavy as normally experienced and weightless. Grip-force recordings demonstrated that force control was seriously disturbed only during the first experience of hyper- and microgravity, with the grip forces being exceedingly high and yielding irregular fluctuations. Thereafter, however, grip force traces were smooth, the force level was scaled to the object’s weight under normal and high-G conditions, and the grip force changed in parallel with the weight during the transitions between hyper- and microgravity. In addition, during weightlessness, when virtually no force was necessary to stabilize the object, a low force was established, which obviously represented a reasonable safety margin for preventing possible perturbations. Thus, all relevant aspects of grip-force control observed under normal gravity conditions were preserved during gravity changes induced by parabolic flights. Hence, grip-force control mechanisms were able to cope with hyper- and microgravity, either by incorporating relevant receptor signals, such as those originating from cutaneous mechanoreceptors, or by adequately including perceived gravity signals into control programs. However, the adaptation to the uncommon gravity conditions was not complete following the first experience; finer tuning of the control system to both hyper- and microgravity continued over the measurement interval, presumably with a longer observation period being necessary before a stable performance can be reached.
    Materialart: Digitale Medien
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 129 (1999), S. 156-160 
    ISSN: 1432-1106
    Schlagwort(e): Key words Optokinetic nystagmus ; Depth-from-motion ; Transparent motion ; Ambiguous ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  When two visual patterns moving in opposite directions are superimposed, they appear to be at different depths and to slide over each other. Because the stimulus does not specify the depth-order between the surfaces, this transparent motion perception is essentially ambiguous. With prolonged observation, the perceived depth-order of the two moving surfaces reverses spontaneously. In the present study, the correlation between the perceived direction of transparent motion and optokinetic nystagmus (OKN) was examined. While viewing superimposed random-dot patterns moving in opposite horizontal or vertical directions, subjects attempted to fixate the center of the stimulus, while paying attention to either the near or far depth plane, and reported any changes of the direction of surface-motion at the attended depth. Even with attention focused on a particular depth, the spontaneous reversal of transparent motion perception still occurred. This indicates that the perceptual reversal may reflect a preattentive mechanism for depth-from-motion. Furthermore, the OKN slow-phase tended to be in the same direction as the perceived motion of the surface at the attended depth. These results support the idea that the mechanisms for OKN maintenance are sensitive to perception of depth-from-motion and, therefore, cortically mediated.
    Materialart: Digitale Medien
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  • 80
    ISSN: 1432-1106
    Schlagwort(e): Key words Reaching movements ; Grasping movements ; Prehension ; Manual control ; Computational model ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Reaching and grasping an object can be viewed as the solution of a multiple-constraint satisfaction problem. The constraints include contact with the object with the appropriate effectors in the correct positions as well as generation of a collision-free trajectory. We have developed a computational model that simulates reaching and grasping based on these notions. The model, rendered as an animation program, reproduces many basic features of the kinematics of human reaching and grasping behavior. The core assumptions of the model are: (1) tasks are defined by flexibly organized constraint hierarchies; (2) manual positioning acts, including prehension acts, are first specified with respect to goal postures and then are specified with respect to movements towards those goal postures; (3) goal postures are found by identifying the stored posture that is most promising for the task, as determined by the constraint hierarchy, and then by generating postures that are more and more dissimilar to the most-promising stored posture until a deadline is reached, at which time the best posture that was found during the search is defined as the goal posture; (4) depending on when the best posture was encountered in the search, the deadline for the search in the next trial is either increased or decreased; (5) specification of a movement to the goal posture begins with straight-line interpolation in joint space between the starting posture and goal posture; (6) if an internal simulation of this default movement suggests that it will result in collision with an obstacle, the movement can be reshaped until an acceptable movement is found or until time runs out; (7) movement reshaping occurs by identifying a via posture that serves as a body position to which the actor moves from the starting posture and then back to the starting posture, while simultaneously making the main movement from the starting posture to the goal posture; (8) the via posture is identified using the same posture-generating algorithm as used to identify the goal posture. These processes are used both for arm positioning and, with some elaboration, for prehension. The model solves a number of problems with an earlier model, although it leaves some other problems unresolved.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 127 (1999), S. 83-94 
    ISSN: 1432-1106
    Schlagwort(e): Key words Target interception ; Reaching ; Grasping ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The goal of the present study was to understand which characteristics (movement time or velocity) of target motion are important in the control and coordination of the transport and grasp-preshape components of prehensile movements during an interception task. Subjects were required to reach toward, grasp and lift an object as it entered a target area. Targets approached along a track at four velocities (500, 750, 1000 and 1250 mm/s) which were presented in two conditions. In the distance-controlled condition, targets moving at all velocities traveled the same distance. In the viewing-time-controlled condition, combinations of velocity and starting distances were performed such that the moving target was visible for 1000 ms for all trials. Analyses of kinematic data revealed that when, target distance was controlled, velocity affected all transport-dependent measures; however, when viewing time was controlled, these dependent measures were no longer affected by target velocity. Thus, the use of velocity information was limited in the viewing-time-controlled condition, and subjects used other information, such as target movement time, when generating the transport component of the prehensile movement. For the grasp-preshape component, both peak aperture and peak-aperture velocity increased as target velocity increased, regardless of condition, indicating that target velocity was used to control the spatial aspects of aperture formation. However, the timing of peak aperture was affected by target velocity in the distance-controlled condition, but not in the viewing-time-controlled condition. These results provide evidence for the autonomous generation of the spatial and temporal aspects of grasp preshape. Thus, an independence between the transport and grasp-preshape phases was found, whereby the use of target velocity as a source of information for generating the transport component was limited; however, target velocity was an important source of information in the grasp-preshape phase.
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 127 (1999), S. 207-212 
    ISSN: 1432-1106
    Schlagwort(e): Key words Attention ; Distractor interference ; Path deviation ; Horse race model ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  It has been suggested that, when movements are planned within cluttered environments, competing responses programmed to distracting stimuli are inhibited based on their relation to the action being performed. Further, as a result of this inhibition, the path of the movement made to the target object deviates away from the distractor. In contrast to the object avoidance hypothesis, the results of the present study show that, for aiming movements made in environments in which distractors are present, the path of the movement veers toward the distractor. Moreover, the effects of the distractors on the movement trajectory were independent of the direction of limb movement. These findings suggest that, when a distractor is not a potential physical barrier, a response to the distractor may be activated along with the target response and, owing to temporal advantages, cause a deviation of the movement trajectory toward the distractor.
    Materialart: Digitale Medien
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  • 83
    ISSN: 1432-1106
    Schlagwort(e): Key words Reach to grasp ; Human ; Perturbation ; Kinematics ; Motor control ; Parkinson’s disease ; Elderly
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study assessed the adaptive response of the reach-to-grasp movement of 12 Parkinson’s disease (PD) and 12 control subjects to a simultaneous perturbation of target object location and size. The main aim was to test further the reported dysfunction of PD subjects in the simultaneous activation of movement components. Participants were required to reach 30 cm to grasp a central illuminated cylinder of either small (0.7 cm) or large (8 cm) diameter. For a small percentage of trials (20/100) a visual perturbation was introduced unexpectedly at the onset of the reaching action. This consisted of a shift of illumination from the central cylinder to a cylinder of differing diameter, which was positioned 20° to the left (n=10) or to the right (n=10). The subject was required to grasp the newly illuminated cylinder. For the Parkinson’s disease subject group, the earliest response to this ’double’ perturbation was in the parameter of peak reaching acceleration, which was on average 50 ms earlier for ’double’ perturbed than for non-perturbed trials. The grasp component response followed more than 500 ms after the earliest transport response. For the control subjects initial signs of a response to the ’double’ perturbation were seen almost simultaneously in the transport parameter of peak arm deceleration, and in the manipulation parameter of maximum grip aperture, but these changes were not evident until more than 400 ms after movement onset. These results indicate that the basal ganglia can be identified as part of a circuit which is involved in the integration of parallel neutral pathways, and which exercise flexibility in the degree to which these components are ’coupled’ functionally. With basal ganglia dysfunction the activation of integration centres that at first gate the flow of information to the parallel channels of reach and grasp seems inefficient.
    Materialart: Digitale Medien
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 322-330 
    ISSN: 1432-1912
    Schlagwort(e): Key words Blood pressure ; Endothelium ; Human ; Mesenteric artery ; Rat ; Smooth muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K+ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca2+ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca2+-induced contractions in human arteries.
    Materialart: Digitale Medien
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 141 (1999), S. 385-394 
    ISSN: 1432-2072
    Schlagwort(e): Key words Marijuana ; Human ; THC ; Withdrawal ; Dependence ; Tolerance ; Subjective effect ; Performance ; Food intake
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral Δ9-tetrahydrocannabinol (THC) have been reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day residential study, male (n = 6) and female (n = 6) marijuana smokers worked on five psychomotor tasks during the day (0915–1700 hours), and in the evening engaged in private or social recreational activities (1700–2330 hours); subjective-effects measures were completed 10 times/day, and a sleep questionnaire was completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 2200 hours. Placebo THC was administered on days 1–3, 8–11, and 16–19. Active THC was administered on days 4–7 (20 mg qid) and on days 12–15 (30 mg qid). Both active doses of THC increased ratings of “High,”“Good Drug Effect,” and “Willingness to Take Dose Again” compared to baseline (days 1–3). THC also increased food intake by 35–45%, and decreased verbal interaction among participants compared to placebo baseline. Tolerance developed to the subjective effects of THC but not to its effects on food intake or social behavior. Abstinence from THC increased ratings of “Anxious,”“Depressed,” and “Irritable,” decreased the reported quantity and quality of sleep, and decreased food intake by 20–30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses of THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use.
    Materialart: Digitale Medien
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 141 (1999), S. 395-404 
    ISSN: 1432-2072
    Schlagwort(e): Key words Marijuana ; Dependence ; Withdrawal ; Human ; Tolerance ; Subjective effect ; Performance ; Residential laboratory
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Symptoms of withdrawal after oral Δ9-tetrahydrocannabinol (THC) administration have been reported, yet little is known about the development of dependence on smoked marijuana in humans. In a 21-day residential study, marijuana smokers (n = 12) worked on five psychomotor tasks during the day (0915–1700 hours), and in the evening engaged in recreational activities (1700–2330 hours); subjective-effects measures were completed 10 times/day. Food and beverages were available ad libitum from 0830 to 2330 hours. Marijuana cigarettes (0.0, 1.8, 3.1% THC) were smoked at 1000, 1400, 1800, and 2200 hours. Placebo marijuana was administered on days 1–4 . One of the active marijuana doses was administered on days 5–8, followed by 4 days of placebo marijuana (days 9–12). The other concentration of active marijuana cigarettes was administered on days 13–16, followed by 4 days of placebo marijuana (days 17–20); the order in which the high and low THC-concentration marijuana cigarettes were administered was counter-balanced between groups. Both active doses of marijuana increased ratings of “High,” and “Good Drug Effect,” and increased food intake, while decreasing verbal interaction compared to the placebo baseline (days 1–4). Abstinence from active marijuana increased ratings such as “Anxious,”“Irritable,” and “Stomach pain,” and significantly decreased food intake compared to baseline. This empirical demonstration of withdrawal from smoked marijuana may suggest that daily marijuana use may be maintained, at least in part, by the alleviation of abstinence symptoms.
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  • 87
    ISSN: 1432-2072
    Schlagwort(e): Key words Aggression ; Tryptophan ; Serotonin ; Human ; Diet
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Some studies have shown that sharp reduction of L-tryptophan (Trp) concentration in plasma results in increases in laboratory-measured aggression. Conversely, raising plasma Trp has blunted aggression. These effects are presumably due to impaired or enhanced serotonin synthesis and neurotransmission in the brain. In this study, the laboratory-measured aggressive behavior of eight men under both Trp depletion (T-) and Trp loading (T+) conditions was compared to their aggressive behavior under food-restricted control conditions (overnight fast without an amino acid beverage). Subjects were provoked by periodic subtraction of money which was attributed to a fictitious other participant, and aggression was defined as the number of retaliatory responses the subject made ostensibly to reduce the earnings of the (fictitious) other participant. Following ingestion of the T- beverage, aggressive responding was significantly elevated relative to the food-restricted control condition, and this increased aggressive behavior became more pronounced across behavioral testing sessions on a time-course which paralleled previously documented decreases in plasma Trp concentrations. In contrast, no changes were observed in aggressive responding under T+ conditions relative to food-restricted conditions. These within-subject behavioral changes under depleted plasma Trp conditions support earlier indications of a role of serotonin in regulating aggression.
    Materialart: Digitale Medien
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  • 88
    ISSN: 1432-2072
    Schlagwort(e): Key words Cocaine ; Human ; Self-administration ; D1 agonist ; Subjective effect ; Craving ; Cardiovascular effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: Data in laboratory animals suggest that D1 receptor agonists may have potential utility for the treatment of cocaine abuse. Objective: The effects of ABT-431, a selective agonist at the dopamine D1 receptor, on the reinforcing, cardiovascular and subjective effects of cocaine were investigated in humans. Method: Nine experienced cocaine smokers (8M, 1F), participated in nine self-administration sessions while residing on an inpatient research unit: three doses of ABT-431 (0, 2, 4 mg IV) were each given in combination with three doses of smoked cocaine (0, 12, 50 mg). ABT-431 was intravenously administered over a 1-h period immediately prior to cocaine self-administration sessions. A six-trial choice procedure (cocaine versus $5 merchandise vouchers) was utilized, with sessions consisting of: (a) one sample trial, where participants received the cocaine dose available that day, and (b) five choice trials, where participants chose between the available cocaine dose and one merchandise voucher. Results: ABT-431 did not affect the number of times participants chose to smoke each dose of cocaine, but produced significant dose-dependent decreases in the subjective effects of cocaine, including ratings of “High,”“Stimulated,” dose liking, estimates of dose value, “Quality,” and “Potency.” Furthermore, there was a trend for ABT-431 (4 mg) to decrease cocaine craving. ABT-431 also increased heart rate, while decreasing systolic and diastolic pressure at each dose of cocaine. Conclusions: These data suggest that D1 agonists may have potential utility for the treatment of cocaine abuse.
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  • 89
    ISSN: 1432-2072
    Schlagwort(e): Key words Methadone maintenance treatment ; Chiral analysis ; Methadone ; Plasma ; Urine ; Abused drug ; Daily variation ; Rating scales ; Dose-adjustment ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: One of the major problems in methadone maintenance treatment is to find optimal individual doses for the patients. Objective: The present study investigated whether the use of rating scales together with enantioselective analysis of l-methadone might facilitate dose adjustments in a clinical situation. Methods: Rating scales were used to evaluate subjective and objective signs of well-being in relation to plasma methadone concentrations in two groups of patients receiving methadone maintenance treatment. The first group (n = 25) was well-adjusted according to clinical observations and were satisfied with their methadone doses (86.2 ± 4.3 mg). The second group (n = 25) was in need of the methadone dose adjustment; they complained of low dosing, despite a dose level of 69.2 ± 4.0 mg/day. Results: Results indicated a significant correlation between dose and methadone concentration among dissatisfied patients only. The trough levels of d,l-methadone and l-methadone, as well as their elimination rates, were similar in the two groups of patients. There was a variable predominance of l- over d-methadone in plasma (ratio ≈1.2; range 0.7–3.6). Illicit use of drugs by the patients was related to the methadone dose and to satisfaction with the dose received. Increased illicit drug use among dissatisfied patients was successfully eliminated by raising the methadone dose. Subjective and objective ratings of the satisfied patients were quite stable throughout the evaluation period, whereas the ratings of the dissatisfied patients were unstable. These patients seemed to be more sensitive to low trough levels of methadone than the satisfied patients. Associations between the subjective and objective ratings and plasma methadone, along with background characteristics, were characterized by multiple regression analyses. The plasma concentrations of l-methadone were one of the most important explanatory variables in these analyses. Associations between well-being and methadone concentrations in plasma were stronger for l-methadone than for d,l-methadone. Conclusions: Selective measurements of the active isomer and the use of rating scales should be of clinical value when monitoring methadone maintenance treatment patients.
    Materialart: Digitale Medien
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  • 90
    ISSN: 1432-2072
    Schlagwort(e): Key words MDMA ; Ecstasy ; Human ; EEG ; Power ; Coherence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. Objective: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Methods: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject’s consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. Results: MDMA use was positively correlated with absolute power in the alpha (8–12 Hz) and beta (12–20 Hz) frequency bands, but not with the delta (1–3 Hz) or theta (4–7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. Conclusions: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs.
    Materialart: Digitale Medien
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 145 (1999), S. 162-174 
    ISSN: 1432-2072
    Schlagwort(e): Key words Opioid blockade ; Buprenorphine ; Naltrexone ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: One therapeutic benefit of mu opioid agonist or antagonist maintenance is the resultant attenuation of the effects of illicit opioids. It is important to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy. Objective: This study characterized the ability of buprenorphine to attenuate opioid effects during treatment initiation and discontinuation compared to naltrexone and placebo. Methods: Opioid-experienced volunteers (n = 8) participated in this 10-week, inpatient, double-blind, within-subject, crossover study. Five randomized conditions [buprenorphine (2 and 8 mg, sublingually), naltrexone (25 and 100 mg, PO) and placebo] were each examined during a 2-week period; the test drug was given for 7 days followed by a 7-day placebo wash-out. Cumulative doses of hydromorphone (0, 2 and 4 mg, IM, 45 min apart) were administered thrice-weekly corresponding with treatment and wash-out days 1, 3, and 5; behavioral, physiological and pharmacokinetic measures were collected. Results: Buprenorphine alone produced dose-related prototypic agonist effects during induction (i.e., positive mood, respiratory depression, miosis); tolerance developed only to the subjective effects. Buprenorphine 2 mg partially attenuated the effects of hydromorphone, while nearly complete attenuation was observed with 8 mg that lasted up to 72 h after discontinuation. Both naltrexone doses produced complete hydromorphone blockade after a single dose; blockade of the behavioral, but not physiological, effects persisted for 5 days after discontinuation of 100 mg. Conclusions: These data suggest that 2 mg buprenorphine is a sub-therapeutic maintenance dose, both buprenorphine 8 mg and naltrexone produce immediate and efficacious opioid blockade, and adequate protection against illicit opioids may be achieved with less-than-daily dosing.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 145 (1999), S. 39-51 
    ISSN: 1432-2072
    Schlagwort(e): Key words Zaleplon ; Triazolam ; Benzodiazepine ; Hypnotics ; Learning ; Memory ; Abuse potential ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Zaleplon, a pyrazolopyrimidine that is under development as a hypnotic, produces its pharmacological effects at the benzodiazepine-recognition site on the GABAA benzodiazepine-receptor complex. Unlike most benzodiazepines, zaleplon binds selectively to the BZ1 (ω1) subtype of the benzodiazepine receptor. The present study compared the acute subject-rated effects, performance-impairing effects, and abuse potential of zaleplon and triazolam, a triazolobenzodiazepine hypnotic, in 14 healthy volunteers with histories of drug abuse. Zaleplon (25, 50, and 75 mg), triazolam (0.25, 0.5, and 0.75 mg) and placebo were administered orally in this double-blind, crossover study. Zaleplon and triazolam produced comparable dose-related effects on several subject-rated drug-effect questionnaires. Zaleplon and triazolam also produced comparable dose-dependent decrements on several performance tasks including balance, circular lights, digit-enter and recall, DSST, picture recall/recognition and repeated acquisition. Same-day and next-day subject-rated measures reflecting abuse potential (e.g., drug liking, good effects, and monetary street value) also suggest that zaleplon and triazolam were comparable. The only notable between-drug difference observed in the present study was that the time-action function of zaleplon differed from that of triazolam. The onset time, time to maximum drug effect, and duration of action were shorter with zaleplon than triazolam. Thus, despite its non-benzodiazepine structure and unique benzodiazepine-receptor binding profile, the behavioral pharmacological profile of zaleplon is similar to that of triazolam.
    Materialart: Digitale Medien
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  • 93
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotine ; Drug discrimination ; Training conditions ; Testing conditions ; Three-choice procedure ; Subjective effect ; Human ; Smoking status
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Discrimination of a drug’s interoceptive stimulus effects often depends substantially on training and testing conditions. Objectives: We examined changes in nicotine discrimination behavior in humans as a function of lowering the training dose and of varying the discrimination testing procedure. Methods: Smokers and never-smokers (n=10 each) were initially trained to discriminate 20 µg/kg nicotine by nasal spray from placebo (0) and tested on generalization of discrimination responding across a range of doses from 0 to 20 µg/kg. Each subsequently learned to reliably discriminate progressively smaller doses of nicotine from placebo until his or her threshold dose for discrimination was identified (mean=2.7 µg/kg). A repeat testing of generalization responding across 0–20 µg/kg was then conducted, using placebo and the subject’s threshold dose as training doses. Generalization testing involved both two-choice and three-choice (novel response option) quantitative procedures. Results: A significant shift to the left was seen in nicotine-appropriate responding in the two-choice procedure when the nicotine training dose was lowered (i.e. from the first to the second test of generalization). In the three-choice procedure, however, there was no such leftward shift. Instead, in never-smokers, a flattening of nicotine-appropriate responding occurred with a lowering of the training dose, while novel-appropriate responding significantly increased. The subjective effects of ”head rush” and, in never-smokers only, ”jittery” also showed a shift to the left in their relationship with nicotine generalization dose when the training dose was lowered. Conclusions: These results confirm the importance of training and testing conditions on discrimination behavior and subjective drug responses within subjects and demonstrate the utility of the novel-response, three-choice procedure for assessing qualitatively different stimulus effects of novel drug doses.
    Materialart: Digitale Medien
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 146 (1999), S. 111-118 
    ISSN: 1432-2072
    Schlagwort(e): Key words Buprenorphine ; Heroin dependence ; Opioid dependence ; Human ; Opioid withdrawal ; Treatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing. Whether longer periods between dosing can be achieved is unknown. Objectives: To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication. Methods: Sixteen opioid-dependent outpatients each received three conditions (1) the maintenance dose of buprenorphine every 24 h, (2) double the maintenance dose every 48 h, and (3) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions. Each conditions was imposed in a random sequence for 21–22 days. Self report and observer measures were taken at 24-h intervals. Results: No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions. However, averaging effects across conditions may obscure important within-condition effects. When conditions were analyzed by individual days within a condition, several significant effects were observed. For example, 24 h after administration of triple the maintenance dose, significant effects were observed in eight opioid agonist measures. Also, 72 h after administration of triple the maintenance dose, significant effects were observed on four measures of withdrawal. Neither adverse medical reactions nor excessive opioid intoxication were observed. Conclusions: These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose, with only minimal withdrawal complaints. Importantly, this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses.
    Materialart: Digitale Medien
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  • 95
    ISSN: 1432-2072
    Schlagwort(e): Key words Alcohol effect ; Impulsivity ; Working memory ; Executive function ; High-risk ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Impulsivity is associated with increased risk for alcoholism. Alcohol also may increase impulsive behavior, although little is known about the processes underlying this effect. Objectives: This study tested a model proposing that the executive processes of working memory (WM) and conditional associative learning (CAL) modulate behavioral inhibition. Subjects had either a positive (FHP) or a negative (FHN) family history of alcoholism. Hypotheses were that alcohol would increase Go/No-Go impulsive responding but only in subjects with low working memory capacity (low-WM), low-CAL ability, or FHP for alcoholism. The model also predicted that WM and CAL modulate inhibitory responses to contingency reversal on a Go/No-Go task. Methods: A Go/No-Go learning task with a midway contingency reversal was administered to 71 FHP and 78 FHN subjects when sober and after drinking one of two moderate doses of alcohol. WM (digits backward) and CAL (conditional spatial association task) were also assessed when sober. Results: Alcohol resulted in more false alarms but only in low-WM subjects. Both WM and CAL modulated learning to inhibit behavior after contingency reversal, suggesting separate modulation mechanisms for WM and CAL. Subjects with low- capacity WM and subjects with low-capacity CAL ability had more difficulty learning response inhibition after contingency reversal. FHPs and FHNs did not differ in their response to alcohol. Conclusions: The results support our model of the modulatory role of WM and CAL in the ongoing regulation of behavioral inhibitory systems. The results also suggest that individuals with low capacity WM are more susceptible to alcohol’s effect of increasing impulsive behavior, suggesting that alcohol reduces the capacity of working memory to modulate response inhibition.
    Materialart: Digitale Medien
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 147 (1999), S. 200-209 
    ISSN: 1432-2072
    Schlagwort(e): Key words Benzodiazepine ; Flumazenil ; Precipitated withdrawal ; Antagonist ; Physical dependence ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Preclinical studies of the benzodiazepine antagonist flumazenil (Romazicon®) have contributed to the understanding of the physical dependence associated with chronic benzodiazepine use; when administered to animals chronically pretreated with benzodiazepines, flumazenil precipitates a withdrawal syndrome. However, few controlled clinical studies have been conducted. Objectives: The objective was to characterize the effects of flumazenil in long-term users of therapeutic doses of benzodiazepines. Methods: The acute physiological, participant-rated, and observer-rated effects of intravenously administered flumazenil (1 mg/70 kg) and caffeine (300 mg/70 kg; active drug control) were evaluated in an experimental group of 13 long-term users (mean 4.6 years) of low therapeutic doses (mean 11.2 mg/day diazepam equivalent) relative to a matched group of 13 volunteers without prior exposure to benzodiazepines in a double-blind, placebo-controlled, mixed design. Results: Whereas the experimental group did not differ from the control group with respect to the effects of placebo, and both groups showed some changes in response to caffeine (e.g., increased blood pressure and anxiety scores), only the experimental group showed considerable changes in physiological measures, participant ratings (e.g., increased ratings of dizziness, blurred vision, heart pounding, feelings of unreality, pins and needles, nausea, sweatiness, noises louder than usual, jitteriness, things moving, sensitivity to touch), and observer ratings in response to flumazenil; in addition, four participants developed panic attacks. Conclusions: This study clearly demonstrates that flumazenil can precipitate symptoms commonly associated with benzodiazepine withdrawal in chronic low-dose benzodiazepine users.
    Materialart: Digitale Medien
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  • 97
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 147 (1999), S. 266-273 
    ISSN: 1432-2072
    Schlagwort(e): Key words Benzodiazepine ; Lorazepam ; Human ; Memory ; Auditory priming ; Visual priming ; Explicit memory
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Lorazepam has been repeatedly shown to impair both explicit memory and perceptual priming, a form of implicit memory, in the visual domain. However, the effects of this benzodiazepine on priming in other perceptual domains, such as auditory priming, have never been explored. Objective:The present study investigated whether the deleterious effects of lorazepam on perceptual priming are restricted to the visual domain, or if they could be extended to the auditory domain. Methods: Thirty-two healthy volunteers were randomly assigned to two parallel groups, placebo and lorazepam 0.038 mg/kg. The drug was administered orally, following a double-blind procedure. In the same subjects, perceptual priming was assessed in the auditory and visual domains using similar word-stem completion tasks, and explicit memory was explored using a free- recall task. Results: Lorazepam markedly reduced free-recall performance for visually and auditorily presented words. Lorazepam equally impaired visual and auditory priming. In the auditory word-stem completion task, prior presentation of a word facilitated perception of its stem in the placebo group. This facilitation effect was not observed in the lorazepam group. The lorazepam-induced impairment of priming was not due to sedation or explicit contamination. Conclusion: These results indicate that the deleterious effects of lorazepam on priming are not restricted to the visual modality, but extend to the auditory modality.
    Materialart: Digitale Medien
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 128 (1999), S. 578-582 
    ISSN: 1432-1106
    Schlagwort(e): Key words Prehension ; Binocular ; Vergence ; Distance perception ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Human prehension requires accurate information on the properties of an object and on the position of the object relative to the body. In principle, prehension might be more accurate with binocular rather than monocular vision. Previous studies have shown that the kinematics of prehension are altered when one eye is covered. Unfortunately, the source of the useful binocular information cannot be established using this approach. In the current study, we used a perturbation technique to explore whether the human nervous system uses a signal from vergence in prehension. Perturbing vergence caused predictable changes in the kinematics of prehension. Our results thus provide clear evidence that the nervous system uses vergence information in the programming of prehensile movement.
    Materialart: Digitale Medien
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  • 99
    ISSN: 1432-1106
    Schlagwort(e): Key words Coordination ; Posture ; Movement ; Anticipatory postural adjustments ; Axial synergy ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The whole-body center of mass (CoM) has been classically regarded as the stabilized reference value for human voluntary movements executed upon a fixed base of support. Axial synergies (opposing displacements of head and trunk with hip segments) are believed to minimize antero-posterior (A/P) CoM displacements during forward trunk movements. It is also widely accepted that anticipatory postural adjustments (APAs) create forces of inertia that counteract disturbances arising from the moving segment(s). In the present study, we investigated CoM stabilization by axial synergies and APAs during a whole-body reaching task. Subjects reached towards an object placed on the ground in front of them in their sagittal plane using a strategy of coordinated trunk, knee, and hip flexion. The reaching task imposed constraints on arm-trajectory formation and equilibrium maintenance. To manipulate equilibrium constraints, differing conditions of distance and speed were imposed. The comparison of distance conditions suggested that axial synergies were not entirely devoted to CoM stabilization: backward A/P hip displacements reduced as head and trunk forward A/P displacements increased. Analysis of upper- and lower-body centers of mass in relation to the CoM also showed no strict minimization of A/P CoM displacements. Mechanical analysis of the effects of APAs revealed that, rather than acting to stabilize the CoM, APAs created necessary conditions for forward CoM displacement within the base of support in each condition. The results have implications for the CoM as the primary stabilized reference for posture and movement coordination during whole-body reaching and for the central control of posture and voluntary movement.
    Materialart: Digitale Medien
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  • 100
    ISSN: 1432-1106
    Schlagwort(e): Key words Spasticity ; Gait ; Spinal cord ; Human ; Clonidine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We studied the effect of the intrathecal (i.t.) injection of clonidine (30, 60 and 90 µg) on the polysynaptic spinal reflexes (PSR) elicited by electrical stimulation of flexor reflex afferents (FRA), monosynaptic reflex and gait of 11 subjects with spinal cord injuries. The effect of clonidine administration on gait velocity, stride amplitude and duration was measured in eight subjects who were able to walk. Five subjects were able to walk after intrathecal injection of clonidine and three were not able to stand up. Three subjects improved their gait velocity after clonidine administration; one (S6) increased his stride amplitude; the two others decreased their cycle durations. The tibialis anterior seemed to be more regularly activated during gait. Spasticity was reduced dramatically (P〈0.0001) after i.t. clonidine injection, but there was no statistically significant difference in the soleus H reflex (no effect on Hmax/Mmax). Clonidine administration decreased the amplitude of the early PSR (90–120 ms, N=4) and the threshold and maximal integrated EMG corresponding to the late response (140–450 ms, N=7). This effect was dose dependent (30, 60 and 90 µg). Placebo injection (N=4) caused no change. The changes in spinal reflexes, with a large reduction in spasticity, no change in motoneurone excitability and a large decrease in PSR, suggest that clonidine acts at a premotoneuronal level, possibly by presynaptic inhibition of group II fibres. The increase in gait velocity in three subjects could have been due to reduced spasticity or activation of spinal circuitry.
    Materialart: Digitale Medien
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