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  • Electronic Resource  (41)
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  • 2000-2004  (41)
  • 1960-1964
  • Human
  • 1
    ISSN: 1530-0358
    Keywords: Barostat ; Colon ; Human ; Ileus ; Manometry ; Motility ; Postoperative ; Rectum ; Surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of hepato-biliary-pancreatic surgery 7 (2000), S. 575-579 
    ISSN: 1436-0691
    Keywords: Key words Precancerous conditions ; Pancreatic duct adenocarcinoma ; Hamster ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 3
    ISSN: 1432-2307
    Keywords: Keywords Lung ; Ozone ; Centriacinar ; Human ; Autopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Medical electron microscopy 33 (2000), S. 109-114 
    ISSN: 1437-773X
    Keywords: Key words Ciliogenesis ; Ciliated cell ; Abnormal cilia ; Basal body ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 5
    ISSN: 1432-0533
    Keywords: Key words Skeletal muscle ; Human ; Differentiation ; Protein kinase C ; Isozymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 6
    ISSN: 1432-0568
    Keywords: Keywords Granulosa cells ; Ontogeny ; Ovary ; Rete ovarii ; Cytokeratin ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 292 (2000), S. 9-15 
    ISSN: 1432-069X
    Keywords: Key words Epidermal T cells ; Function ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: Key words Erythropoietin ; Endogenous ; Blood volume ; Human ; Intraoperative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Allograft-inflammatory factor-1 ; Microglia response factor-1 ; Macrophage-inhibiting factor ; related-protein-8/S100A8 ; Traumatic brain injury ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 10
    ISSN: 1432-0851
    Keywords: Keywords Melanoma ; Antigens ; Cytotoxic ; T lymphocytes ; Human ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 11
    ISSN: 1432-1211
    Keywords: Key words MHC class III region ; Mouse ; Human ; G7c ; Lung tumor susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 51 (2000), S. 487-488 
    ISSN: 1432-1211
    Keywords: Key words Immunoglobulin ; J segments ; IGKJ genes ; Alleles ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 73 (2000), S. 479-487 
    ISSN: 1432-1246
    Keywords: Key words Biological monitoring ; Formate ; Formic acid ; Human ; Methanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 147 (2000), S. 339-346 
    ISSN: 1432-2072
    Keywords: Key words Sibutramine ; d-Amphetamine ; Abuse potential ; Subjective effect ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 15
    ISSN: 1432-2072
    Keywords: Key words Haloperidol ; Dopamine ; Receptor occupancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 149 (2000), S. 24-33 
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Conditioning ; Cardiovascular effect ; Subjective effect ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 17
    ISSN: 1432-1106
    Keywords: Key words Visual perception ; Object recognition ; Functional magnetic resonance imaging ; Neuroimaging ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 18
    ISSN: 1432-0738
    Keywords: Key words Diethylhexylphthalate ; Peroxisome proliferation ; Hepatocarcinogenesis ; Species differences ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 19
    ISSN: 1432-0738
    Keywords: Key words Organophosphate ; Acetylcholinesterase ; Oximes ; Human ; Reactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurology 247 (2000), S. I28 
    ISSN: 1432-1459
    Keywords: Key words Motor neurone ; Astrocyte ; Human ; Tissue culture ; ALS ; Glutamate ; Calcium ; SOD-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Liver transplantation ; Rejection ; Tacrolimus ; Human ; Child
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Pituitary ; Human ; Somatotroph ; Thyrotroph hyperplasia ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Child's nervous system 16 (2000), S. 235-241 
    ISSN: 1433-0350
    Keywords: Key words Magnetic resonance spectroscopy ; Epilepsy ; Brain metabolism ; GABA ; N-Acetyl aspartate ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Knee surgery, sports traumatology, arthroscopy 8 (2000), S. 180-185 
    ISSN: 1433-7347
    Keywords: Keywords Proprioception ; Equilibrium ; Posture ; Reproducibility of results ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: 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
    Keywords: Key words cDNA ; Human ; Cathepsin P ; Propeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Cerebral blood flow velocity ; EEG ; Caffeine ; Withdrawal ; Physical dependence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Opioids ; Self-administration ; Progressive ratio ; Drug abuse ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Basal systemic nitric oxide production rate ; Fasting ; Human ; Plasma nitrate ; Single-compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Heat shock protein ; Antibody ; Vascular disease ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Temporal summation ; Repeated electrical stimulation ; Experimental pain ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    European journal of applied physiology 83 (2000), S. 106-115 
    ISSN: 1439-6327
    Keywords: Key words Central fatigue ; Muscle fatigue ; Human ; Motor cortex ; Motoneuron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Fatigue ; Glenohumeral joint ; Human ; Occupational musculoskeletal problems ; Proprioception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    European journal of applied physiology 81 (2000), S. 210-213 
    ISSN: 1439-6327
    Keywords: Key words Cross-sectional area ; Exercise ; Human ; Reflex sympathetic activity ; Skeletal muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Local cold ; Extremities ; Cold induced vasodilatation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Eccentric-concentric actions ; Electromyography ; Gastrocnemius muscle ; Soleus muscle ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Key words Bed rest ; Resistance training ; Skeletal muscle ; Physiological cross-sectional area ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Journal of mammary gland biology and neoplasia 5 (2000), S. 351-364 
    ISSN: 1573-7039
    Keywords: Human ; breast cancer ; premalignant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    International urology and nephrology 32 (2000), S. 109-117 
    ISSN: 1573-2584
    Keywords: Aging ; Nephrosclerosis ; Arteriolosclerosis ; Hypertension ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: 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
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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
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    Human evolution 15 (2000), S. 99-112 
    ISSN: 1824-310X
    Keywords: Development ; Ontogeny ; Growth ; Brain ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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
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    Medical & biological engineering & computing 38 (2000), S. 454-464 
    ISSN: 1741-0444
    Keywords: Optic nerve ; Human ; Self-sizing spiral cuff electrode ; Finite elements method ; Fibre model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: 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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