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  • 1995-1999  (313)
  • 1999  (313)
  • Human  (119)
  • Immunohistochemistry  (100)
  • Life and Medical Sciences  (96)
  • Nuclear reactions
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  • 1995-1999  (313)
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Keywords
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 127 (1999), S. 83-94 
    ISSN: 1432-1106
    Keywords: Key words Target interception ; Reaching ; Grasping ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 127 (1999), S. 207-212 
    ISSN: 1432-1106
    Keywords: Key words Attention ; Distractor interference ; Path deviation ; Horse race model ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 103
    ISSN: 1432-1106
    Keywords: Key words Reach to grasp ; Human ; Perturbation ; Kinematics ; Motor control ; Parkinson’s disease ; Elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 104
    ISSN: 1432-1912
    Keywords: Key words Blood pressure ; Endothelium ; Human ; Mesenteric artery ; Rat ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 105
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Rhadomyosarkom ; Klassifizierung ; Immunhistochemie ; Genetik ; Prognose ; Key words Rhabdomyosarcoma ; Classification ; Immunohistochemistry ; Genetics ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence.The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called ’International Classification of Rhabdomyosarcoma’ includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.
    Notes: Zusammenfassung Rhabdomyosarkome stellen eine heterogene Gruppe von ganz verschiedenartigen, histogenetisch wohl nicht zusammengehörenden Tumoren dar. Nach der heute verwendeten „Internationalen Klassifikation” der Rhabdomyosarkome werden neben der Unterteilung in embryonalen und alveoläre Rhabdomyossarkome auch Subtypen des embryonalen RMS identifiziert (botryoider und leiomyomatöser Subtyp), die durch eine günstigere Prognose und durch die Notwendigkeit einer weniger aggressive Therapie gekennzeichnet sind. Durch Einsatz von verschiedenen histologischen und immunhistochemischen Färbungen ist die Identifizierung der verschiedenen Typen der RMS heute möglich und auch zwingend notwendig, da die einzelnen Entitäten nach ganz unterschiedlichen Therapieprotokollen behandelt werden. Der Nachweis typischer molekulargenetischer Veränderungen kann in der Unterscheidung insbesondere von embryonalen und alveolären RMS hilfreich sein. In der Regel ist die Abgrenzung zwischen diesen beiden Entitäten auch an konventionell gefärbten Schnittpräparaten möglich. Die Identifizierung von alveolären RMS mit einer t(1;13)-Translokation könnte in Zukunft eine große Bedeutung haben, da diese genetische Veränderung möglicherweise mit einer günstigeren Prognose assoziert sein könnte als die t(2;13)-Translokation.
    Type of Medium: Electronic Resource
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  • 106
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Pleomorphes Adenom ; Äußerer Gehörgang ; Zeruminom ; Differentialdiagnose ; Immunhistochemie ; Key words Pleomorphic adenomas ; Meatus acusticus externus ; Ceruminoma ; Differential diagnosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A tumor was removed from the right external auditory canal of a 69-year old female patient. The histopathological and immunhistochemical evaluation revealed a pleomorphic adenoma (mixed tumor). The differential diagnosis of the tumors derived from the ceruminal glands, their clinical and prognostic implications as well as the histogenesis of pleomorphic adenomas in this localization are discussed.
    Notes: Zusammenfassung Bei einer 69jährigen Patientin wurde aus dem rechtsseitigen äußeren Gehörgang ein Tumorknoten exstirpiert. Die histopathologische und immunhistochemische Untersuchung ergab ein pleomorphes Adenom (Mischtumor). Die Differentialdiagostik der von den Zeruminaldrüsen abgeleiteten Tumoren, deren klinisch-prognostische Konsequenz sowie die Histogenese der pleomorphen Adenome in dieser besonderen Lokalisation werden erörtert.
    Type of Medium: Electronic Resource
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  • 107
    ISSN: 1432-2072
    Keywords: Key words Marijuana ; Human ; THC ; Withdrawal ; Dependence ; Tolerance ; Subjective effect ; Performance ; Food intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 108
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 141 (1999), S. 395-404 
    ISSN: 1432-2072
    Keywords: Key words Marijuana ; Dependence ; Withdrawal ; Human ; Tolerance ; Subjective effect ; Performance ; Residential laboratory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 109
    ISSN: 1432-2072
    Keywords: Key words Aggression ; Tryptophan ; Serotonin ; Human ; Diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 110
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Human ; Self-administration ; D1 agonist ; Subjective effect ; Craving ; Cardiovascular effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 111
    ISSN: 1432-2072
    Keywords: Key words Methadone maintenance treatment ; Chiral analysis ; Methadone ; Plasma ; Urine ; Abused drug ; Daily variation ; Rating scales ; Dose-adjustment ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 112
    ISSN: 1432-2072
    Keywords: Key words MDMA ; Ecstasy ; Human ; EEG ; Power ; Coherence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 113
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 145 (1999), S. 162-174 
    ISSN: 1432-2072
    Keywords: Key words Opioid blockade ; Buprenorphine ; Naltrexone ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 145 (1999), S. 39-51 
    ISSN: 1432-2072
    Keywords: Key words Zaleplon ; Triazolam ; Benzodiazepine ; Hypnotics ; Learning ; Memory ; Abuse potential ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 115
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Drug discrimination ; Training conditions ; Testing conditions ; Three-choice procedure ; Subjective effect ; Human ; Smoking status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 116
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 146 (1999), S. 111-118 
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Heroin dependence ; Opioid dependence ; Human ; Opioid withdrawal ; Treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 117
    ISSN: 1432-2072
    Keywords: Key words Alcohol effect ; Impulsivity ; Working memory ; Executive function ; High-risk ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 118
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    Psychopharmacology 147 (1999), S. 200-209 
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Flumazenil ; Precipitated withdrawal ; Antagonist ; Physical dependence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 119
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    Psychopharmacology 147 (1999), S. 266-273 
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Lorazepam ; Human ; Memory ; Auditory priming ; Visual priming ; Explicit memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 120
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    Experimental brain research 128 (1999), S. 578-582 
    ISSN: 1432-1106
    Keywords: Key words Prehension ; Binocular ; Vergence ; Distance perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 121
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    Keywords: Key words Coordination ; Posture ; Movement ; Anticipatory postural adjustments ; Axial synergy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 122
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    Keywords: Key words Spasticity ; Gait ; Spinal cord ; Human ; Clonidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 123
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    Experimental brain research 124 (1999), S. 422-428 
    ISSN: 1432-1106
    Keywords: Key words Lifting forces ; Size-weight illusion ; Microgravity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Individuals usually report for two objects of equal mass but different volume that the larger object feels lighter. This so-called size-weight illusion has been investigated for more than a century. The illusion is accompanied by increased forces, used to lift the larger object, resulting in a higher initial lifting speed and acceleration. The illusion holds when subjects know that the mass of the two objects is equal and it is likely that this also counts for the enlarged initial effort in lifting a larger box. Why should this happen? Under microgravity, subjects might be able to eliminate largely the weight-related component of the lifting force. Then, if persistent upward scaling of the weight-related force component had been the main cause of the elevated initial lifting force under normal gravity, this elevated force might disappear under microgravity. On the other hand, the elevated initial lifting effort in the large box would be preserved if it had been caused mainly by a persistent upward scaling of the force component, necessary to accelerate the object. To test whether the elevated initial lifting effort either persists or disappears under microgravity, a lifting experiment was carried out during brief periods of microgravity in parabolic flights. Subjects performed whole-body lifting movements with their feet strapped to the floor of the aircraft, using two 8-kg boxes of different volume. The subjects were aware of the equality of the box masses. The peak lifting forces declined almost instantaneously with approx. a factor 9 in the first lifting movements under microgravity compared with normal gravity, suggesting a rapid adaptation to the loss of weight. Though the overall speed of the lifting movement decreased under microgravity, the mean initial acceleration of the box over the first 200 ms of the lifting movement remained higher (P=0.030) in the large box (1.87±0.127 m/s2) compared with the small box (1.47±0.122 m/s2). Under normal gravity these accelerations were 3.30±0.159 m/s2 and 2.67±0.159 m/s2, respectively (P=0.008). A comparable trend was found in the initial lifting forces, being significant in the pooled gravity conditions (P=0.036) but not in separate tests on the normal gravity (P=0.109) and microgravity (P=0.169) condition. It is concluded that the elevated initial lifting effort with larger objects holds during short-term exposure to microgravity. This suggests that upward scaling of the force component, required to accelerate the larger box, is an important factor in the elevated initial lifting effort (and the associated size-weight illusion) under normal gravity.
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  • 124
    ISSN: 1432-1106
    Keywords: Key words Microneurography ; Peripheral nerve ; Pacinian afferent ; Cutaneous mechanoreceptor ; Vibrotactile stimuli ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 µm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors.
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  • 125
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Reaching ; Anticipatory postural control ; EMG ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study focused on the developmental changes of postural adjustments accompanying reaching movements in healthy infants. We made a longitudinal study of ten infants between 6 and 18 months of age. During each session multiple surface electromyograms of arm, neck, trunk and leg muscles at the right side of the body were recorded during right-handed reaching movements in two positions (”upright sitting” in an infant chair and ”long-leg” sitting without support). Simultaneously the whole session was recorded on video. Comparable data were present from the same infants at 3–5 months. Additionally, 18 infants (8–15 months) were assessed once during similar reaching tasks, but in these infants electromyographic activity of the trunk and neck muscles at both sides of the body were recorded. Our data revealed two transitions in the development of postural adjustments. The first transition was present around 6 months of age. At this age the postural muscles were infrequently activated during reaching movements. At 8 months ample postural activity reappeared and the infants developed the ability to adapt the postural adjustments to task-specific constraints such as arm movement velocity or the sitting position at the onset of the reaching movement. The second transition occurred between 12 and 15 months. Before 15 months the infants did not show consistent anticipatory postural activity, but from 15 months onwards they did, particularly in the neck muscles.
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  • 126
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    Experimental brain research 126 (1999), S. 536-544 
    ISSN: 1432-1106
    Keywords: Key words Magnetic brain stimulation ; Afferent input ; Motor cortex ; Plasticity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previously, we had described a technique for investigating probable GABAergic cortical inhibitory circuits in conscious man using transcranial magnetic stimulation. This type of inhibition has been termed intracortical inhibition. During voluntary contraction, activity in the circuits responsible for this inhibition is reduced. The mechanism by which this reduction in activity is brought about is unknown. However, evidence exists to suggest that afferent input may be, at least in part, responsible for the reduction in inhibition. The experiments described here were designed to investigate this possibility further. The results of these experiments showed that afferent input, produced by electrical peri- pheral-nerve stimulation, reduced the level of intracortical inhibition. Also, motor imagery, which activates similar brain regions as overt movement, but does not result in afferent input, failed to produce significant changes in intracortical inhibition. We conclude from these results that afferent input is capable of altering activity in cortical inhibitory circuits. The relevance of these findings to the mechanisms involved in cortical reorganisation is discussed.
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  • 127
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    Experimental brain research 126 (1999), S. 556-562 
    ISSN: 1432-1106
    Keywords: Key words Acceleration ; Ocular microtremor ; Eye movements ; Partial coherence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel technique for the study of human eye movements was used to investigate the frequency components of ocular drift and microtremor in both eyes simultaneously. The tangential components of horizontal eye accelerations were recorded in seven healthy subjects using light-weight accelerometers mounted on scleral contact lenses during smooth pursuit movements, vestibulo-ocular reflexes and eccentric gaze with and without fixation. Spectral peaks were observed at low (up to 25 Hz) and high (60–90 Hz) frequencies. A multivariate analysis based on partial coherence analysis was used to correct for head movement. After correction, the signals were found to be coherent between the eyes over both low- and high-frequency ranges, irrespective of task, convergence or fixation. It is concluded that the frequency content of ocular drift and microtremor reflects the patterning of low-level drives to the extra-ocular muscle motor units.
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  • 128
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    Keywords: Key words Suprathreshold heat pain ; Adapting temperature ; Temporal parameters ; Spinal dorsal horn neuron ; Descending control ; Rat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of stimulus temperature rise rate (2.5ºC/s, 5.0ºC/s, and 10.0ºC/s), adapting (baseline) temperature (25ºC, 30ºC, and 35ºC), and duration of peak stimulus temperature (1.0 s, 2.5 s, 5.0 s, and 10.0 s) on responses evoked by noxious heat stimuli of suprathreshold intensity was studied in wide dynamic range (WDR) neurons of the rat spinal dorsal horn. The spinal neuronal responses were compared with human psychophysical data obtained using the same stimuli. Noxious heat stimuli with a peak temperature of 54ºC were applied with a contact thermostimulator to the glabrous skin of the hindfoot in rats or to the palmar skin in humans. With the highest ramp rate and the highest adapting temperature, the sensory and spinal neuronal response latencies were decreased more than expected on the basis of the change in physical parameters of the stimulus. The magnitudes of sensory and spinal neuronal response were independent of the stimulus ramp rate, whereas pain magnitude estimates and spinal neuronal impulse counts evoked by the same peak stimulus temperature were increased with an increase in the adapting stimulus temperature. The onset latencies of pain reactions and spinal neuronal responses were independent of the peak stimulus duration, whereas the latency of the maximum discharge in spinal neurons increased with prolongation of the peak stimulus. The sensory magnitude estimate of pain and the neuronal impulse count were increased with increase in stimulus duration. Following spinalization, the spinal neuronal responses were stronger and the stimulus duration-dependent increase in the impulse count developed faster. Moreover, the peak frequency of spinal neuronal response increased significantly with prolongation of the heat stimuli after spinalization, but not in animals with an intact spinal cord. The results indicate that stimulus rise rate, stimulus duration, and the adapting temperature are important factors in determining the sensory and spinal neuronal responses to high-intensity heat stimuli. The changes in the total impulse counts evoked by varying supraliminal heat stimuli in spinal dorsal horn WDR neurons corresponded well with the changes in pain magnitude estimates in humans. Also, the changes in spinal neuronal response onset latencies were accompanied by corresponding changes in onset latencies of human pain reactions but not with pain magnitude estimates. The effect of spinalization indicated that descending pathways control not only the response magnitude in the spinal dorsal horn WDR neurons but also the temporal characteristics of the spinal neuronal response.
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  • 129
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    Experimental brain research 125 (1999), S. 521-524 
    ISSN: 1432-1106
    Keywords: Key words Light touch ; Sway ; Centre of pressure ; Hand force ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has previously been shown that light contact with the finger tip on a fixed surface reduces centre of pressure (CoP) fluctuations in the frontal plane when standing in an unstable posture with the feet in line (tandem Romberg stance). Positive cross-correlations between horizontal finger forces and CoP fluctuations with finger forces exhibiting a phase lead suggest the hand provides sensory input for postural stability. The present study investigates whether this is the case for normal posture. We report reduced CoP fluctuations in the sagittal plane when light touch is permitted during normal bipedal stance. Moreover, we find positive crosscorrelations between finger tip forces and CoP fluctuations which are of similar magnitude and phase lag to those observed in tandem Romberg stance. This shows the utility of hand touch input for regulation of normal upright posture as well as inherently unstable postures such as tandem Romberg.
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  • 130
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    European journal of clinical pharmacology 55 (1999), S. 349-352 
    ISSN: 1432-1041
    Keywords: Key words Ischaemic stroke ; Vinpocetine ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: To determine whether vinpocetine decreases short- and long-term case fatality and proportion of dependent survivors if administered within 2 weeks of stroke onset. Methods: All published and unpublished trials were attempted to be identified using the standard search strategy of the Cochrane Collaboration Stroke Review Group, using MEDLINE searches performed with all known manufacturer code names and trade names of vinpocetine and by contacting manufacturers of vinpocetine to give information of all randomised controlled trials on vinpocetine in stroke. Researchers who participated in trials on vinpocetine in Hungary were asked for further information. Only truly randomised, unconfounded clinical trials that compared the effect of vinpocetine to either placebo or another reference treatment for acute stroke where treatment started no later than 14 days after stroke onset were eligible for inclusion. Data synthesis and analysis was performed using the Cochrane Review Manager software (RevMan version 3.0). Results: Among the identified studies on vinpocetine in stroke, only one fulfilled the selection criteria for inclusion in the review. No death occurred in the study groups and no statistically significant difference was found in dependency between the treatment and the placebo groups. No adverse effects were reported. Conclusions: Based on only one small randomised controlled unconfounded study, presently there is not enough evidence to decide whether the administration of vinpocetine does or does not decrease case fatality and dependency in acute stroke.
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  • 131
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    Experimental brain research 128 (1999), S. 353-368 
    ISSN: 1432-1106
    Keywords: Key words Multijoint arm ; Simulations ; Muscle torques ; Kinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Adults are able to reach for an object for the first time with appropriate direction, speed, and accuracy. The rules by which the nervous system is able to set muscle activities to accomplish these outcomes are still debated and, indeed, the sensitivity of kinematics to variations in muscle torques is unknown for complex arm movements. As a result, this study used computer simulations to characterize the effects of change in muscle torque on initial hand path. The same change was applied to movements towards 12 directions in the horizontal plane, and changes were systematically manipulated such that: (1) torque amplitude was changed at one joint, (2) timing of torque was changed at one joint, and (3) amplitude and/or timing was changed at two joints. Results showed that simultaneous changes in torque amplitude at shoulder and elbow joints affected initial speed uniformly across direction. These results add to conclusions from previous experimental and modeling work that the simplest rule to produce a desired change in speed for any direction is to scale torque amplitude at both joints. In contrast, all simulations showed nonuniform effects on initial path direction. For some regions of the workspace, initial path direction was little affected by either a ±30% change in amplitude or a ±100-ms change in timing, whereas for other regions the same changes produced large effects on initial path direction. These findings suggest that the range of possible torque solutions to achieve a particular initial path direction varies within the workspace and, consequently, the requirements for an accurate initial path will vary within the workspace.
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  • 132
    ISSN: 1432-1106
    Keywords: Key words Aiming movements ; Target size ; Inertial load ; Strategies ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments are reported that investigated the effects of target size and inertial load on the control of rapid aiming movements. Based on kinematic profiles, movements were partitioned into their preprogrammed initial impulse- and feedback-based error correction phases. Electromyographic (EMG) rise rates were examined to investigate whether participants used a speed-sensitive or speed-insensitive control strategy. The results from both experiments showed that initial impulse velocity and EMG rise rates varied as a function of target size, i.e., a speed-sensitive strategy. This was the case whether participants were allowed to make error corrections to their movements (experiment 1) or were instructed to produce initial impulses that hit the target (experiment 2). Both experiments also showed that initial impulse velocity and endpoint variability were inversely related to inertial load. The results from experiment 2 indicated that, while the manipulation of inertial load had no effect on EMG rise rates for movements to a large target, EMG slopes were modulated between inertial load conditions when the target was small.
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  • 133
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    Keywords: Key words Vibration-induced kinesthetic illusions ; Antagonist vibratory response ; Motor units ; Wrist extensor muscles ; Human ; Microelectromyography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In humans, vibration applied to muscle tendons evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response or AVR). The aim of the present study was to investigate the neurophysiological mechanisms underlying such a motor response. For that purpose, we analyzed the relationships between the parameters of the tendon vibration (anatomical site and frequency) and those of the illusory movement perceived (direction and velocity), as well as the temporal, spatial, and quantitative characteristics of the corresponding AVRs (i.e., surface EMG, motor unit firing rates and activation latencies). Analogies were supposed between the characteristics of AVRs and voluntary contractions. The parameters of the AVR were thus compared with those of a voluntary contraction with similar temporal and mechanical characteristics, involving the same muscle groups as those activated by vibration. Wrist flexor muscles were vibrated either separately or simultaneously with wrist extensor muscles at frequencies between 30 and 80 Hz. The illusory movement sensations were quantified through contralateral hand-tracking movements. Electromyographic activity from the extensor carpi radialis muscles was recorded with surface and intramuscular microelectrodes. The results showed that vibration of the wrist flexor muscle group induced both a kinesthetic illusion of wrist extension and a motor response in the extensor carpi radialis muscles. Combined vibration of the two antagonistic muscle groups at the same frequency evoked neither kinesthetic illusion nor motor activity. In addition, vibrating the same two antagonistic muscle groups at different frequencies induced both a kinesthetic illusion and a motor response in the muscle vibrated at the lowest frequency. The surface EMG amplitude of the extensor carpi radialis as well as the motor unit activation latency and discharge frequency were clearly correlated to the parameters of the illusory movement evoked by the vibration. Indeed, the faster the illusory sensation of movement, the greater the surface EMG in these muscles during the AVRs and the sooner and the more intense the activation of the motor units of the wrist extensor muscles. Moreover, comparison of the AVR with voluntary contraction showed that all parameters were highly similar. Mainly slow motor units were recruited during the AVR and during its voluntary reproduction. That the AVR is observed only when a kinesthetic illusion is evoked, together with the similarities between voluntary contractions and AVRs, suggests that this vibration-induced motor response may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms.
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  • 134
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    Experimental brain research 124 (1999), S. 351-362 
    ISSN: 1432-1106
    Keywords: Key words Saccadic adaptation ; Gaze ; Short term adaptation ; Transfer to hand movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated whether and how adaptive changes in saccadic amplitudes (short-term saccadic adaptation) modify hand movements when subjects are involved in a pointing task to visual targets without vision of the hand. An experiment consisted of the pre-adaptation test of hand pointing (placing the finger tip on a LED position), a period of adaptation, and a post-adaptation test of hand pointing. In a basic task (transfer paradigm A), the pre- and post-adaptation trials were performed without accompanying eye and head movements: in the double-step gaze adaptation task, subjects had to fixate a single, suddenly displaced visual target by moving eyes and head in a natural way. Two experimental sessions were run with the visual target jumping during the saccades, either backwards (from 30 to 20°, gaze saccade shortening) or onwards (30 to 40°, gaze saccade lengthening). Following gaze-shortening adaptation (level of adaptation 79±10%, mean and s.d.), we found a statistically significant shift (t-test, error level P〈0.05) in the final hand-movement points, possibly due to adaptation transfer, representing 15.2% of the respective gaze adaptation. After gaze-lengthening adaptation (level of adaptation 92±17%), a non-significant shift occurred in the opposite direction to that expected from adaptation transfer. The applied computations were also performed on some data of an earlier transfer paradigm (B, three target displacements at a time) with gain shortening. They revealed a significant transfer relative to the amount of adaptation of 18.5±17.5% (P〈0.05). In the coupling paradigm (C), we studied the influence of gaze saccade adaptation of hand-pointing movements with concomitant orienting gaze shifts. The adaptation levels achieved were 59±20% (shortening) and 61±27% (lengthening). Shifts in the final fingertip positions were congruent with internal coupling between gaze and hand, representing 53% of the respective gaze-amplitude changes in the shortening session and 6% in the lengthening session. With an adaptation transfer of less than 20% (paradigm A and B), we concluded that saccadic adaptation does not ”automatically” produce a functionally meaningful change in the skeleto-motor system controlling hand-pointing movements. In tasks with concomitant gaze saccades (coupling paradigm C), the modification of hand pointing by the adapted gaze comes out more clearly, but only in the shortening session.
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  • 135
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Silent period ; Voluntary motor drive ; Motor threshold ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation.
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  • 136
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Multijoint movement ; Movement synergy ; Stroke ; Laterality ; Redundancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies have shown that in neurologically normal subjects the addition of trunk motion during a reaching task does not affect the trajectory of the arm endpoint. Typically, the trunk begins to move before the onset and continues to move after the offset of the arm endpoint displacement. This observation shows that the potential contribution of the trunk to the motion of the arm endpoint toward a target is neutralized by appropriate compensatory movements of the shoulder and elbow. We tested the hypothesis that cortical and subcortical brain lesions may disrupt the timing of trunk and arm endpoint motion in hemiparetic subjects. Eight hemiparetic and six age-matched healthy subjects were seated on a stool with the right (dominant) arm in front of them on a table. The tip of the index finger (the arm endpoint) was initially at a distance of 20 cm from the midline of the chest. Wrist, elbow, and upper body positions as well as the coordinates of the arm endpoint were recorded with a three-dimensional motion analysis system (Optotrak) by infrared light-emitting diodes placed on the tip of the finger, the styloid process of the ulna, the lateral epicondyle of the humerus, the acromion processes bilaterally, and the sternal notch. In response to a preparatory signal, subjects lifted their arm 1–2 cm above the table and in response to a ”go” signal moved their endpoint as fast as possible from a near to a far target located at a distance of 35 cm and at a 45° angle to the right or left of the sagittal midline of the trunk. After a pause (200– 500 ms) they moved the endpoint back to the near target. Pointing movements were made without trunk motion (control trials) or with a sagittal motion of the trunk produced by means of a hip flexion or extension (test trials). In one set of test trials, subjects were required to move the trunk forward while moving the arm to the target (”in-phase movements”). In the other set, subjects were required to move the trunk backward when the arm moved to the far target (”out-of-phase movements”). Compared with healthy subjects, movements in hemiparetic subjects were segmented, slower, and characterized by a greater variability and by deflection of the trajectory from a straight line. In addition, there was a moderate increase in the errors in movement direction and extent. These deficits were similar in magnitude whether or not the trunk was involved. Although hemiparetic subjects were able to compensate the influence of the trunk motion on the movement of the arm endpoint, they accomplished this by making more segmented movements than healthy subjects. In addition, they were unable to stabilize the sequence of trunk and arm endpoint movements in a set of trials. It is concluded that recruitment and sequencing of different degrees of freedom may be impaired in this population of patients. This inability may partly be responsible for other deficits observed in hemiparetic subjects, including an increase in movement segmentation and duration. The lack of stereotypic movement sequencing may imply that these subjects had deficits in learning associated with short-term memory.
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  • 137
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    Experimental brain research 126 (1999), S. 134-138 
    ISSN: 1432-1106
    Keywords: Key words Upper limb ; Posture ; Geometric constraints ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Significant debate exists regarding the neural strategies underlying the positioning and orienting of the hand during voluntary reaching movements of the human upper extremity. Some authors have suggested that positioning and orienting are controlled independently, while others have argued that a strong interdependence exists. In an effort to address this uncertainty, our study employed computer simulations to examine the impact of physiological limitations of joint rotation on the proposed independence of hand position and orientation. Specifically, we analyzed the effects of geometric constraints on final arm postures using a 7 degree-of-freedom model of the human arm. For 20 different hand configurations within the attainable workspace, we computed sets of achievable joint angles by applying inverse kinematics. From each set, we then calculated the locus of possible elbow positions for the particular final hand posture. When the joints were allowed 360° of rotation, the loci formed complete circles; however, when joint ranges were limited to physiological values, the extent of the loci decreased to an average arc angle of 54.6° (±27.9°). Imposition of joint limits also led to practically linear relationships between joint angles within a solution set. These theoretical results suggest a requirement for coordinated interaction between control of the joints associated with hand position and those involved with hand orientation in order to ensure attainable joint trajectories. Furthermore, it is conceivable that some of the correlations observed between joint angles in the course of natural reaching movements result from geometric constraints.
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  • 138
    ISSN: 1432-1106
    Keywords: Key words Lumbar motoneurons ; Immunohistochemistry ; Light microscopy ; GABA and glycine colocalization ; Stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The distribution of γ-aminobutyric acid (GABA) and/or glycine-immunoreactive (IR) terminal-like structures apposed to somatic and dendritic membrane of lumbar α-motoneurons in column 2 was examined in 1- and 3-week-old kittens and in the adult cat. This quantitative study was carried out using a postembedding technique on semithin sections and a stereological method, the disector. Analysis of immunoreactive terminals showed that the percentages of GABA-IR and glycine-IR terminals (these populations include terminals containing both GABA and glycine) apposed to somatic and proximal dendritic compartments of α-motoneurons are almost the same in kittens, while in the adult glycinergic innervation becomes predominant. This change results from: (1) the decrease in numbers of GABA-IR terminals contacting the somatic compartment between 3 weeks and adult stage, while the numbers of glycine-IR terminals show no significant changes after birth and the numbers of terminals containing both neurotransmitters (GABA-IR+glycine-IR) present transient changes and (2) the postnatal increase in the dendritic compartment, in numbers of GABA-IR, glycine-IR and GABA-IR+glycine-IR terminals; the increase being larger for glycine-IR terminals. Furthermore, using a postembedding immunogold technique, observations by electron microscopy showed that GABA-IR P boutons apposed to M boutons can already be identified at 1 week after birth.
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  • 139
    ISSN: 1432-1106
    Keywords: Key words Paired-pulse transcranial magnetic stimulation ; Threshold hunting ; Intracortical inhibition ; Intracortical I-wave facilitation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Short-interval, paired-pulse transcranial magnetic stimulation (TMS) is usually used to demonstrate intracortical inhibition. It was shown recently that with short-interval, paired-pulse TMS a facilitation – called intracortical I-wave facilitation – can also be demonstrated. It was the aim of this study to investigate which stimulus conditions lead to intracortical inhibition and what conditions yield an intracortical I-wave facilitation in a hand muscle of normal subjects. Paired-pulse TMS responses with an interstimulus interval of 1.2 ms were obtained from the abductor digiti minimi muscle of four normal subjects. A threshold-hunting paradigm with hunting through first or second stimulus variation was used to obtain a curve of threshold-pair strengths. All subjects showed two branches of stimulus interaction on this diagram. If the first stimulus of a threshold pair was below approximately 65% of resting motor threshold it modified the response primarily due to the second stimulus through intracortical inhibition. However, if the first stimulus of a threshold pair exceeded approximately 65% of resting motor threshold it became responsible for the spinal action-potential initiation. The subsequent second stimulus served as a ”booster” for the ongoing intracortical I-wave activity, making it impossible to observe the intracortical inhibition evoked by the first stimulus.
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  • 140
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    Experimental brain research 127 (1999), S. 355-370 
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Motion ; Functional imaging ; Human ; Flicker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional magnetic resonance imaging was used to map motion responsive regions of the human brain by contrasting passive viewing of moving and stationary randomly textured patterns. Regions were retained as motion responsive if they reached significance either in the group analysis or in the majority of hemispheres in single-subject analysis. They include well-known regions, such as V1, hMT/V5+, and hV3A, but also several occipito-temporal, occipito-parietal, parietal, and frontal regions. The time course of the activation was similar in most of these regions. Motion responses were nearly identical for binocular and monocular presentations. Flicker-induced-activation introduced a dichotomy amongst these motion responsive regions. Early occipital and occipito-temporal regions responded well to flicker, while flicker responses gradually vanished as one moved to occipito-parietal and then parietal regions. Finally, over a more than four-fold range, stimulus diameter had little effect on the motion activations, except in V1.
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  • 141
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    Experimental brain research 128 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Eye-hand coordination ; Human ; Saccade ; Vision ; Bimanual coordination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300±39 ms for the predictive condition versus 394±53 ms for the non-predictive condition, P〈0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.
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  • 142
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    Experimental brain research 129 (1999), S. 241-246 
    ISSN: 1432-1106
    Keywords: Key words Selective attention ; Visual attention ; Putamen ; Orienting ; Positron emission tomography ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used positron emission tomography (PET) in ten subjects to study the brain regions involved in voluntary shifts of attention. For six scans, subjects performed a visual target detection task in which the location of the target was indicated in advance on some proportion of trials by the appearance of an arrow cue at fixation. The informative cues were successful in speeding reaction time to the target. Blood flow in the left putamen was correlated with the proportion of informative cues provided within a scan. We discuss this finding in terms of three possible interpretations: attentional shifts, response inhibition, and motor preparation related to the use of the right hand to respond. Blood flow in cortical regions commonly associated with attention was not related to cue ratio, a finding that may reflect automatization of the processes involved in interpreting and using the cues.
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  • 143
    ISSN: 1432-1106
    Keywords: Key words Frontal eye field ; Saccade ; Efference copy ; Spatial short-term memory ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Physiological studies in monkeys have shown that the frontal eye field (FEF) is involved in the preparation and triggering of purposive saccades. However, several questions of FEF function remain unclear: the role of the FEF in visual short-term memory, its ability to update its spatial map and its role in reflexive saccade inhibition. We have addressed these issues in a patient with a small acute ischemic lesion whose location corresponded very accurately to the region of the left FEF according to the most recent cerebral blood flow studies. An initial study was conducted on days 7 and 8 after the stroke, i.e., before substantial recovery. A first group of paradigms (smooth pursuit, simple saccade tasks) was performed to assess FEF dysfunction. In a second group of paradigms, (1) visual short-term memory was tested by means of memory-guided saccade paradigms with short and long delays (1 and 7 s), (2) spatial updating abilities were tested by a double-step saccade task and two memory-guided saccade tasks in which the central fixation point was displaced during the memorization delay, and (3) reflexive saccade inhibition was tested by the antisaccade task. Results show that the FEF is involved in short-term memorization of the parameters of the forthcoming memory-guided saccade encoded in oculocentric coordinates. Normal results in the antisaccade task suggest that the FEF is not involved in reflexive saccade inhibition.
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  • 144
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    Experimental brain research 129 (1999), S. 378-390 
    ISSN: 1432-1106
    Keywords: Key words Manual tracking ; Microgravity ; Visuomotor transformation ; Adaptation ; Human ; Spaceflight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A series of step-tracking experiments was conducted before, during, and after a 3-week space mission to assess the effects of prolonged microgravity on a non-postural motor-control task. In- and post-flight accuracy was affected only marginally. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movements was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. The observed in-flight decrements in peak velocity and peak acceleration point to an underestimation of mass, in agreement with the re-interpretation hypothesis of Bock et. al. Post-flight no reversals of the in-flight changes (negative aftereffects) were found. Instead, there was a general slowing down, which could be due to post-flight physical exhaustion.
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  • 145
    ISSN: 1432-1106
    Keywords: Key words Elbow movement ; Motor learning ; Reaction time ; Kinematics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Learning of a motor task, such as making accurate goal-directed movements, is associated with a number of changes in limb kinematics and in the EMG activity that produces the movement. Some of these changes include increases in movement velocity, improvements in end-point accuracy, and the development of a biphasic/triphasic EMG pattern for fast movements. One question that has remained unanswered is whether the time course of the learning-related changes in movement parameters is similar for all parameters. The present paper focuses on this question and presents evidence that different parameters evolve with a specific temporal order. Neurologically normal subjects were trained to make horizontal, planar movements of the elbow that were both fast and accurate. The performance of the subjects was monitored over the course of 400 movements made during experiments lasting approximately 1.5 h. We measured time-related parameters (duration of acceleration, duration of deceleration, and movement duration) and amplitude-related parameters (peak acceleration, peak deceleration, peak velocity), as well as movement distance. In addition, each subject’s reaction time and EMG activity was monitored. We found that reaction time was the parameter that changed the fastest and that reached a steady baseline earliest. Time-related parameters decreased at a somewhat slower rate and plateaued next. Amplitude-related parameters were slowest in reaching steady-state values. In subjects making the fastest movements, a triphasic EMG patterns was observed to develop. Our findings reveal that movement parameters change with different time courses during the process of motor learning. The results are discussed in terms of the neural substrates that may be responsible for the differences in this aspect of motor learning and skill acquisition.
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  • 146
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    Experimental brain research 125 (1999), S. 50-60 
    ISSN: 1432-1106
    Keywords: Key words Pointing errors ; Remembered target Navigation ; Active self-movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied pointing movements to remembered visual targets in a completely darkened room with and without self-made step movements in order to investigate in which coordinate system and to what extent target representations relative to the body are updated for self-induced egomotion. A small red-light-emitting diode on the fingertip provided visual feedback about fingertip position at all times. We asked subjects to make pointing movements that started 2 s after disappearance of a visual target. In this interval of 2 s the subject did or did not make a step. The pointing errors without a step showed that subjects undershot faraway targets in a systematic way, whereas they sometimes overshot nearby targets. We found that the step causes larger pointing errors both in amplitude and direction with a bias in the direction of the step. We explored three different versions of a descriptive model in which polar coordinates were used to describe the pointing movement, and in which either Cartesian or polar coordinates were used to update target position relative to the shoulder for the step. The results suggest that incorporation of the step displacement in the new target position relative to the subject is done in a Cartesian frame of reference. Moreover, the amplitude of the step displacement tends to be underestimated by subjects.
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  • 147
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    Experimental brain research 125 (1999), S. 109-114 
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Visual pathways ; Illusions ; Prehension ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Visual size illusions have been shown to affect perceived object size but not the aperture of the hand when reaching to those same objects. Thus, vision for perception is said to be dissociated from vision for action. The present study examines the effect of visual-position and visual-shape illusions on both the visually perceived center of an object and the position of a grasp on that object when a balanced lift is required. The results for both experiments show that although the illusions influence both the perceived and the grasped estimates of the center position, the grasp position is more veridical. This partial dissociation is discussed in terms of its implications for streams of visual processing.
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  • 148
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    Experimental brain research 125 (1999), S. 302-312 
    ISSN: 1432-1106
    Keywords: Key words Overarm throwing ; Finger opening ; Proprioceptive feedback ; Perturbations ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Accuracy in an overarm throw requires great precision in the timing of finger opening. We tested the hypothesis that finger opening in an overarm throw is triggered by proprioceptive feedback from elbow extension or wrist flexion. The hypothesis was tested in two ways: first, by unexpectedly perturbing elbow extension or slowing wrist flexion and determining whether changes occurred in finger opening, and second, by measuring the latency from the start of these joint rotations to the start of finger opening. Subjects threw balls fast and accurately from a sitting or standing position while joint rotations were recorded with the search-coil technique. Elbow extension was unexpectedly blocked near the start of forward motion of the hand by a rope attached to the wrist that passed through a catch mechanism located behind the subject. In spite of a slowing or complete block of elbow extension, and in some cases a replacement of elbow extension by elbow flexion, finger opening always occurred and at the same latency as for normal throws. Wrist flexion was slowed in seven of eight subjects when subjects changed from throwing with a light ball (14 g, 70 mm diam.) to a heavy ball (210 g, 65 mm diam.). For the first throw with the heavy ball, this slowing was neither fully anticipated by the subject nor compensated for by the changed proprioceptive feedback associated with the slowing. Consequently, the timing of finger opening was unchanged and (to the surprise of the thrower) the ball went high. Furthermore, in unperturbed throws with tennis balls, the latency from onset of wrist flexion or elbow extension to onset of finger opening was too short for either to have triggered finger opening (across subjects means were 4 ms for wrist flexion and 21 ms for elbow extension). In additional analysis, no relation was found between the time of onset of earlier occurring rotations at the shoulder and the time of onset of finger opening. We concluded that, although a role for all proprioceptive feedback in triggering finger opening cannot be disproved by these experiments, it can be ruled out for feedback arising from elbow extension and wrist flexion, and it seems unlikely for feedback arising from events occurring very early in the throw. The more likely possibility is that finger opening in an overarm throw is triggered by a central command based on an internal model of hand trajectory.
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  • 149
    ISSN: 1432-1106
    Keywords: Key words Corticospinal tract ; Handedness ; Spinal premotoneurones ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles . Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.
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  • 150
    ISSN: 1432-0851
    Keywords: Key words In vitro immunisation ; MUC1 ; Human ; antibodies ; Phage display ; Carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently described an efficient method to study the human humoral immune response in vitro and to generate isotype-switched, antigen-specific human B cells, which has allowed us to produce high-affinity IgG antibodies against different peptides. In an attempt to study the in vitro immune response against self-antigens, such as tumour-associated antigens, this protocol was used to immunise resting human peripheral blood B cells with a peptide epitope from the human-adenocarcinoma-associated antigen, MUC1. After the two-step in vitro immunisation, the secondary immunised cultures were tested for MUC-1-specific antibodies by enzyme-linked immunosorbent assay (ELISA). Phage molecular libraries were subsequently constructed, using the variable parts of Ig genes derived from cells taken from ELISA-positive wells. The libraries were selected on the MUC1 core peptide. Antigen-specific Fab fragments, specific for the self antigen MUC1, were found in the library of secondary immunised IgG+ B cells and these antibodies were evaluated by BIAcore analysis. The specific Fab fragments exhibited an unusually rapid dissociation rate constant and the overall response frequency was lower, as compared to other antibodies generated by this protocol, which might be explained by the repetitive nature of the core peptide used for immunisation.
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    Archives of toxicology 73 (1999), S. 7-14 
    ISSN: 1432-0738
    Keywords: Key words Organophosphates ; Acetylcholinesterase ; Oximes ; Human ; Reactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl-AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLö 7, respectively. Aging (t 1/2 3.7 h) and spontaneous reactivation (t 1/2 0.7 h) occurred concomitantly, with the portion of the aged enzyme being dependent on the presence of excess inhibitor. Calculation of steady-state AChE activity in the presence of inhibitor and oxime revealed that obidoxime was superior to pralidoxime. In addition, organophosphate concentrations up to 10−6 M (paraoxon-methyl) and 10−4 M (oxydemeton-methyl) could be counteracted at clinically relevant oxime concentrations (10 μM). These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be attributed to megadose intoxications and to prolonged time intervals between poison uptake and oxime administration. The potency of the oximes to reactivate dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower (t 1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status.
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    Virchows Archiv 435 (1999), S. 574-579 
    ISSN: 1432-2307
    Keywords: Key words Melanoma ; Matrix metalloproteinases ; Collagenase ; Gelatinase ; Stromelysin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The matrix metalloproteinases (MMPs) are considered to have an important role in connective tissue degradation and have been implicated in the mechanisms of tumour invasion and metastatic spread. We have used immunohistochemistry to examine and compare the tissue distributions of collagenase-1 (MMP-1), gelatinase A (MMP-2) and stromelysin-1 (MMP-3) in 18 specimens of malignant melanoma, viz. 10 superficial spreading and 8 nodular melanomas. MMPs-1, -2 and -3 were demonstrated within melanoma and host tissue cells, especially at the periphery of some tumours, but were usually restricted to less than 10% of total melanoma cells. The MMPs were absent from ’normal’ skin tissue distant from the tumour. MMP-2 was localised to discrete groups of cells and was especially evident at the epidermal:tumour interface, whereas MMP-3 was mainly confined to the deeper margins of melanoma. No regular pattern of MMP expression was observed for either the superficial spreading or the nodular melanomas. The variable distributions of the MMPs suggested that enzyme expression was subject to local microenvironmental regulation, possibly in response to matrix components and the cellular heterogeneity observed at the tumour margins. These in situ observations add weight to the concept that specific MMPs contribute to the mechanisms of tumour invasion.
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    Virchows Archiv 435 (1999), S. 580-589 
    ISSN: 1432-2307
    Keywords: Abstract Adrenal cortex ; Adrenal tumour ; Innervation ; Immunohistochemistry ; Neuronal markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The innervation of the human adrenal gland and of cortical lesions was studied in sections of cortical tissue (n=10), hyperplastic cortical tissue (n=3), and tissue from cortical adenomas (n=5) and carcinomas (n=6). The presence and distribution of nerve structures containing neuronal markers indicating sympathetic and parasympathetic innervation were studied by immunohistochemistry and the co-existence and co-localization patterns of the different markers by immunofluorescence. The cortex and hyperplastic cortical tissue had a moderate to rich supply of nerve structures containing the typical neuronal markers: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), small vesicle synaptic protein type 2 (SV2), and nerves showing immunoreactivity to the adrenergic marker tyrosine hydroxylase (TH). All these immunoreactive nerves were located predominantly adjacent to blood vessels, but also among parenchymal cells. The cortex showed numerous nerve structures containing the neuropeptide substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal protein (VIP), but few nerves containing these peptides were seen in hyperplastic cortical tissue. Typical markers were occasionally observed in cortical adenomas but were not found in carcinomas, except in a few cases where PGP 9.5 and NSE were present, but only adjacent to necrotic areas. Nerves containing NPY and VIP occurred in varying numbers in both adenomas and carcinomas. NPY- and VIP-immunoreactive nerve structures were seen mostly alongside blood vessels. There were several types of co-existence. For instance, NSE/VIP-, TH/VIP- and TH/NPY-immunoreactive nerve structures were often seen in the same trunk, but were only partly co-localized.
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  • 154
    ISSN: 1432-2307
    Keywords: Key words Sclerosing hepatic carcinoma ; Hypercalcaemia ; Parathyroid hormone-related protein (PTHrP) ; Immunohistochemistry ; In situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 69-year-old man had a hepatic tumour occupying the left and half of the right lobe, with portal vein thrombus. There were hypercalcaemia and hypophosphataemia with increased nephrogenous cyclic adenosine monophosphate; bone metastases were excluded. Serum parathyroid hormone-related protein (PTHrP) was elevated, but no increase in intact parathyroid hormone (PTH) or vitamin D3 metabolites was found. At autopsy the histological features were typical of sclerosing hepatic carcinoma. By immunohistochemistry PTHrP was detected in cancer cell nests but not in the fibrous stroma. PTHrP transcripts were demonstrated by in situ hybridization using a polymerase chain reaction (PCR)-derived single-stranded DNA probe. Tumour cells expressed AE1 and CA19-9 (markers for cholangioepithelium) and CEA (for bile canaliculi). Electron microscopy revealed microvilli on the apical surface, and secretory granules 100 nm in diameter were observed. These findings indicate that this case is one of cholangiocellular sclerosing hepatic carcinoma. The interaction between cancer and stromal cells may be the cause of PTHrP overexpression.
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  • 155
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    Virchows Archiv 435 (1999), S. 428-433 
    ISSN: 1432-2307
    Keywords: Key words Pituitary adenomas ; Growth hormone- producing adenomas ; Immunohistochemistry ; Mitochondria ; Oncocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  An immunohistochemical study to demonstrate oncocytes in nongonadotrophic pituitary adenomas was performed. The adenomas were 10 prolactinomas, 2 ACTH-producing adenomas (ACTHomas), and 28 growth hormone-producing adenomas (GHomas); we also studied 5 pituitary oncocytomas. GHomas were divided into two groups: GHomas with (GHomas-1) and without (GHomas-2) fibrous bodies. A small number of solitary large cells showed intense cytoplasmic granular reactivity for mitochondrial protein and cytochrome oxidase, resembling oncocytes in oncocytomas. The proportions of the mitochondrial protein-positive cells ranged from zero to 2.1% (0.3±0.4%). They were more frequent in GHomas, GHomas-1 in particular, than other types of adenomas (P〈0.01), and were mostly negative in prolactinomas and ACTHomas. In multivariate analysis, the proportions showed positive correlation with age (P〈0.01) and the Ki-67 (MIB-1) labeling index (P〈0.01) and tended to increase in number with recurrence (P〈0.05). In GHomas, these cells were more common in cases with low basal GH level (P〈0.01) and large tumor volume (P〈0.01). We consider that these cells represent oncocytes existing in varying numbers in adenomas. We suggest that oncocytic change in nongonadotrophic adenomas indicates poor differentiation and/or some aggressiveness, which lead to a decrease in the endocrine activity of the tumor.
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  • 156
    ISSN: 1432-2072
    Keywords: Key words Cannabinoids ; THC ; Dronabinol ; Binocular depth inversion ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic Δ9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The time-course of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.
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  • 157
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    Psychopharmacology 143 (1999), S. 339-346 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Smoking ; Naltrexone ; Opiates ; Mechanism ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The role of endogenous opiate systems in cigarette smoking remains unclear. In laboratory animals, opiate antagonists block many of the effects of nicotine, but in humans they do not consistently alter smoking behavior. Objective: This study explored the effects of naltrexone, alone and in combination with nicotine, on smoking behavior. Methods: In a double-blind, double-dummy, within-subjects design, 19 regular smokers received four treatments of 1 week duration: naltrexone tablet (50 mg) plus placebo skin patch, placebo tablet plus nicotine skin patch (21 mg/24 h), naltrexone tablet plus nicotine skin patch, and placebo tablet plus placebo skin patch. During each treatment, subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory, and to their own brand of cigarette smoked ad libitum outside the laboratory. Results: Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving, negative affect, and rates of ad lib smoking, and potentiated the aversiveness of a cigarette. Naltrexone reversed these effects of the nicotine patch, and produced negative effects on mood. Conclusions: The blockade of nicotine’s effects by naltrexone supports a role for opioid mechanisms in cigarette smoking.
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  • 158
    ISSN: 1432-2072
    Keywords: Key words Alternative reinforcers ; Heroin ; Human ; Intranasal ; Intravenous ; Opioids ; Performance ; Progressive ratio ; Reinforcing effect ; Self-administration ; Subjective effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight heroin-dependent individuals, maintained on divided daily doses of oral morphine, participated in a 2.5-week inpatient study comparing the effects of intranasal (IN) (placebo, 12.5, 25, 50, 100 mg) and intravenous (IV) (placebo, 6.25, 12.5, 25, 50 mg) heroin. Each morning, participants received $20 and a sample dose of heroin, and each afternoon they had the opportunity to self-administer all or part of the morning heroin dose or money amount. Participants responded under a modified progressive-ratio schedule (PR 50, 100, 200, 400, 800, 1200, 1600, 2000, 2400, 2800) during a ten-trial self-administration task. During each trial, participants could respond for 1/10th of the heroin dose or 1/10th of the money amount. The total amount of heroin and/or money chosen during the self-administration task was given at the end of the task. Thus, participants received drug and/or money twice each day: once during the morning sample session and once during the afternoon self-administration session. Participants received IV solution and IN powder simultaneously during each dosing; only one route contained active drug. Heroin produced dose-related increases in break point values by both routes of administration. Although IV heroin was approximately four-fold more potent than IN heroin, the maximal break point values for both routes were not significantly different. A similar difference in potency between the IV and IN routes was found for several ratings of subjective effects (e.g., “I feel a good drug effect,”“I feel high”), but maximal subjective ratings were lower for IN compared to IV heroin. These results suggest that the reinforcing efficacy of heroin is similar by the two routes of administration, but that IN heroin is less potent than IV heroin. The results also underscore the importance of evaluating drug self-administration in the evaluation of the abuse liability of drugs.
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  • 159
    ISSN: 1432-2072
    Keywords: Key words MDMA (3 ; 4-methylenedioxymethamphetamine) ; Serotonin ; Psychopathology ; Human ; Rat ; Prepulse inhibition ; Habituation ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers. Objective: In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies. Methods: Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA. Results: As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects. Conclusions: This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
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  • 160
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    Knee surgery, sports traumatology, arthroscopy 7 (1999), S. 177-183 
    ISSN: 1433-7347
    Keywords: Key words Knee joint ; Human ; Anterior knee pain ; Innervation ; Substance-P fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract The etiology of pain in anterior knee pain syndrome is a matter of controversy. The normal, articular cartilage is aneural, so defects in the surface are not thought to produce pain. Some authors have sought the origin of the pain in soft tissue structures around the knee. Knowledge of the distribution of nociceptive nerve fibers around the knee would provide insight for treating anterior knee pain syndrome. Twenty consecutive patients (28 knees), all women, with anterior knee pain syndrome (group I) participated in the study. For comparison we used two groups of patients: 20 patients with an osteoarthritic knee (group II) and 20 patients with anterior cruciate ligament rupture or meniscal lesion with no history of pain in the anterior compartment (group III). Immunohistochemical techniques using a monoclonal antibody to substance-P (SP) were employed to identify nociceptive fibers. For statistical analyses we used the one-way ANOVA test, which was corrected with the LSD test, at the level of significance P 〈 0.05. Results of the study demonstrate that SP-immunoreactive nerve fibers are widespread within the soft tissues around the knee. These tissues include the retinaculum, synovium, fat pad and, in some circumstances, bone. In cases of anterior knee pain, the presence of neuropeptide-containing fibers was statistically significant in the medial retinaculum (P 〈 0.005) and in the fat pad (P 〈 0.001) compared to group III, and compared to group II (P 〈 0.05 and P 〈 0.007, respectively). For lateral retinaculum this relationship was not so statistically strong (P 〈 0.02) and was equal in comparison between anterior knee pain patients (group I) and group II or group III. There were no statistically significant differences in the distribution of substance-P nerve fibers in the fat pad, lateral and medial retinaculum or synovium between groups II and III. The results of this study provide immunohistochemical evidence suggesting that pain may originate in the fat pad and medial retinaculum of many patients with anterior knee pain syndrome.
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  • 161
    ISSN: 1573-4943
    Keywords: Human ; aldehyde dehydrogenase ; 4-trans-(N,N-dimethylamino)cinnamaldehyde ; binding ; incorporation ; stoichiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract 4-trans-(N,N-Dimethylamino)cinnamaldehyde (DACA) is a chromophoric substrate of aldehyde dehydrogenase (EC 1.2.1.3) whose fate can be followed during catalysis. During this investigation we found that DACA also fluoresces and that this fluorescence is enhanced and blue-shifted upon binding to aldehyde dehydrogenase. Binding of DACA to aldehyde dehydrogenase also occurs in the absence of coenzyme. Benzaldehyde (a substrate), acetophenone (a substrate-competitive inhibitor), and the substrate-competitive affinity reagent bromoaceto-phenone interfere with DACA binding. Thus, DACA binds to the active site and can be employed for titration of active aldehyde dehydrogenase. Both E1 and E2 isozymes, which are homotetramers, bind DACA with dissociation constants of 1–4 μM with a stoichiometry of 2 mol DACA/mol enzyme. The stoichiometry of enzyme–acyl intermediate was also found to be 2 mol DACA/mol enzyme for both E1 and E2 isozymes. Thus, both enzymes appear to have only two substrate-binding sites which participate in catalysis. The level of enzyme–acyl intermediate remained constant at different pH values, showing that enhancement of velocity with pH was not due to altered DACA–enzyme levels. When the reaction velocity was increased even further by using 150 μM Mg2+ the intermediate level was decreased, suggesting that both increased pH and Mg2+ promote decomposition of the DACA–enzyme intermediate. Titration with DACA permits study of aldehyde substrate catalysis before central complex interconversion.
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  • 162
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Naloxone ; Dose ratio ; Opiate dependence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.
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  • 163
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Craving ; Cytidine ; CDP-choline ; Human ; Medication ; Drug dependent ; Citicoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The administration of cytidine-5′-diphosphate choline (CDP-choline, citicoline) to animals increases the rate of membrane phospholipid synthesis and elevates brain dopamine levels. Because cocaine dependence has been associated with increases in brain phospholipid precursors, as well as depletion of dopamine within the central nervous system, the present outpatient study was conducted to assess the safety of citicoline (500 mg bid) and to determine if short-term treatment alters mood states and cocaine craving in subjects with a history of cocaine dependence. In addition, measures of drug craving and mood states after presentation of cocaine-related cues were collected on two occasions: before and after 14 days of double-blind treatment with either citicoline or placebo. Subjects did not experience any side effects and citicoline treatment was associated with decreases in self-reported mood states associated with cocaine craving. These preliminary data are encouraging and suggest that citicoline warrants further study as a promising potential treatment for cocaine abuse and dependence that is devoid of side effects.
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  • 164
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    Psychopharmacology 142 (1999), S. 149-157 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Craving ; Smoking ; Rapid smoking ; Cigarette ; Self-report ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Craving is thought to play an important role in maintaining regular smoking patterns in current smokers, and in leading to relapse in smokers attempting to quit. Within the scientific community however, the concept is surrounded by controversy. In an effort to 1) identify interventions that can reliably influence cigarette cravings, and 2) assess the relationship between cigarette craving and smoking behavior, effects of aversive rapid smoking (up to nine cigarettes with puffs taken every 6 s) on self-reported craving and subsequent smoking behavior were compared to effects of self-paced smoking or no smoking. Subjects (n = 14) engaged in a rapid, self-paced or no smoking procedure at the start of three separate sessions. Craving levels, measured repeatedly during the next 3 h of no smoking, were significantly lower after rapid smoking than after either self-paced or no smoking. Measures of subsequent smoking behavior (latency to first cigarette, number of cigarettes, number of puffs) did not differ systematically across conditions. Thus, craving was reliably suppressed by aversive rapid smoking, but craving scores did not predict actual smoking behavior.
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  • 165
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Alprazolam ; Placebo ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8–30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.
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  • 166
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; Programmed cell death ; Ductular proliferation ; Biliary decompression ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A complex molecular network controls cell homeostasis by inducing apoptosis or proliferation. The balance of Bcl-2 and Bax, members of a protein family, determines whether a cell will become immortal (Bcl-2) or will undergo apoptosis (Bax). To determine the role of Bcl-2 and Bax during proliferation of biliary epithelial cells (BEC) after bile duct ligation (BDL) and their regression after biliary decompression we induced hyperplasia of BEC by BDL in male rats. Regression of hyperplastic BEC by way of apoptosis was induced by biliary decompression through a Roux-en-Y biliodigestive anastomosis. To quantify apoptosis a modified TUNEL assay was used. Expression of Bcl-2 and Bax was visualized by immunohistochemistry and quantified stereologically. BEC increased from 〈1% to 〉20% after BDL; this increase was associated with overexpression of Bcl-2 in up to 30% of hyperplastic BEC. After biliodigestive anastomosis, apoptotic BEC increased from 〈0.1% to a peak of 5.4% after 1 day to reach baseline again 1 week after decompression. This was associated with de novo appearance of Bax. The interaction between Bcl-2 and Bax triggers apoptosis in BEC and acts as a cell rheostat in BEC hyperplasia and its involution after biliary decompression.
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  • 167
    ISSN: 1432-2307
    Keywords: Key words Rhabdomyosarcoma ; Aorta ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an intimal sarcoma presenting as an aortic aneurysm. A 68-year-old man suffered from chest pain and speech disturbance. Computed tomography showed a sacciform aneurysm of the aorta, which was resected, revealing a polypoid tumour measuring 1.5×2×2.5 cm projecting into the lumen. This proved to be a poorly differentiated high-grade sarcoma having morphological, immunophenotypic and ultrastructural features consistent with rhabdomyosarcomatous differentiation. Primary sarcomas of the aorta are extremely rare. Many cases have been diagnosed as ”intimal” on the basis of their site of origin, and they are not easy to classify from their histological pattern. Electron microscopy and the use of a more comprehensive panel of immunohistochemical markers should be applied in the histological classification of ”intimal” sarcoma.
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  • 168
    ISSN: 1432-2307
    Keywords: Key words Human ; Cytochrome P450 2C ; Cytochrome P450 3A ; Immunohistochemistry ; Neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Organ and cellular distribution and expression constancy of microsomal cytochrome P450 (CYP) 2C and 3A in humans were studied with new polyclonal antibodies to CYP2C (MP-1) and 3A (NF-2) active in formalin-fixed, paraffin-embedded tissues. Antibodies were raised against purified human CYP2C9 and CYP3A4. On western blotting, MP-1 reacted with 2C8, 2C9, 2C18 and 2C19, and NF-2 with 3A4. In both frozen and paraffin sections, hepatocytes showed diffuse immunoreactivity with MP-1 and centrilobular staining with NF-2. Inparaffin sections of 40 kinds of nonneoplastic tissues, epithelium of the small and large intestine, bile duct, nasal mucosa, kidney and adrenal cortex stained positively with both MP-1 and NF-2 antibodies. Epithelium of gastric fundic glands, salivary glands, tracheobronchial glands, Brunner’s glands, the prostate, uterine cervix and nasopharynx showed definite reactivity with MP-1. Epithelium of the gastric mucosa with intestinal metaplasia, duodenum, gallbladder and intercalated ducts of the pancreas and chief cells of the parathyroid and the corpus luteum of the ovary reacted with NF-2. Among the neoplastic tissues, MP-1 reacted with pleomorphic adenoma of the salivary gland and carcinomas of six different organs, and NF-2 with those of 7 different organs. These results indicate that CYP2C and CYP3A are distributed widely and organ specifically, as well as being variably expressed in neoplastic and normal states.
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  • 169
    ISSN: 1432-0878
    Keywords: Key words Apoptosis ; p53 ; Ischemia ; Enterocytes ; Proliferation ; Differentiation ; ISEL ; Glomeruli ; Mouse (Balb/c) ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Morphological changes associated with apoptosis are closely correlated with the expression of specific proteins. However, the cause-effect relationships between the expression of these proteins and DNA degradation are barely known. For studying expression of apoptosis-related proteins in relation to different degrees of DNA fragmentation, the small intestine with its spatially organized continuum of proliferation, differentiation and death is a very useful preparation. Enterocytes towards the apex of the villi become increasingly susceptible to apoptosis. Here, this ”apoptotic gradient” is used to demonstrate the presence of BAX and BCL-2 proteins in the cytoplasm of cells at the onset of apoptosis. In semithin serial sections of the small intestine, BAX, BCL-2 and DNA fragmentation were demonstrated. BAX and BCL-2 are always colocalized and only in cells with fragmented DNA. The gradient of BAX or BCL-2 staining is similar to the gradient of DNA fragmentation. Immunoreactivity for BCL-2 or BAX is most intense in cells that are prone to become apoptotic next in the course of cellular turnover but not in cells in an advanced apoptotic state, showing strongly condensed chromatin. When using the same technique on semithin sections of kidney biopsies, containing epithelia with low cellular turnover, we found DNA fragmentation mainly in the epithelial cells of the distal tubules. Similar to the situation in the enterocytes, BAX staining was confined to the cytoplasm of epithelial cells with a moderate degree of DNA fragmentation and reduced in epithelial cells with a high degree of DNA fragmentation. In contrast to the situation in the small intestine, very low levels of BCL-2 were found. The results suggest that expression of BCL-2 and BAX is related to cell damage as indicated by DNA fragmentation but not to advanced stages of cellular death, as indicated by chromatin condensation and cellular shrinkage.
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  • 170
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    Cell & tissue research 296 (1999), S. 433-437 
    ISSN: 1432-0878
    Keywords: Key words Nitric oxide ; Vasoactive intestinal polypeptide (VIP) ; Immunohistochemistry ; Enteric nervous system ; Crocodylus porosus (Crocodilia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The aim of this study was to investigate the distribution of nitric oxide synthase (NOS)-containing nerve cells in the gastrointestinal tract of a reptile and to compare it with the pattern in other vertebrate classes. In the estuarine crocodile, Crocodylus porosus, NOS-positive nerve cell bodies and fibres were found in all regions of the gut examined. Most myenteric microganglia contained one or several NOS-immunoreactive neurons together with unlabelled neurons. The majority of the neurons were multipolar, ranging from 10 to 25 µm in diameter. Both the circular and the longitudinal muscle layers were innervated by NOS-immunoreactive nerve fibres, which mostly ran parallel to the muscle fibres. In addition, small blood vessels in the submucosa and on the serosal surface of the gut were innervated by NOS-immunoreactive fibres. Double labelling with antisera to NOS and vasoactive intestinal peptide (VIP) revealed three neuronal subpopulations. A small proportion of the NOS-immunoreactive cells also contained immunoreactivity to VIP while a majority of the VIP-immunoreactive cells were NOS immunoreactive. There were more nerve fibres showing VIP immunoreactivity than fibres with NOS immunoreactivity, although most of the latter also contained immunoreactivity to VIP. VIP-immunoreactive fibres often surrounded the NOS-immunoreactive nerve cells. These results suggest that neuronally released nitric oxide is likely to be involved in the control of gastrointestinal motility in the crocodile as in most other vertebrate species.
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  • 171
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    Cell & tissue research 296 (1999), S. 587-597 
    ISSN: 1432-0878
    Keywords: Key words Hyaluronic acid ; Immunohistochemistry ; Inter-alpha-trypsin inhibitor ; Localization ; Mouse (CD-1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The direct interaction of hyaluronic acid (HA) and heavy chain (HC) of the inter-alpha-trypsin inhibitor (IαI) family plays a critical role in the organization and stabilization of the extracellular matrix. The aim of the present investigation was to elucidate the distribution of the IαI HC and HA in adult mouse tissues. An immunohistochemical method using a rabbit polyclonal antibody raised against mouse IαI heavy-chain peptide and a specific probe for HA (biotinylated HA-binding protein) was used to demonstrate an immunolocalization of IαI HC and HA. Distribution and localization of HA was of three types, namely, colocalization with IαI HC itself (cartilaginous tissue and ovary), localization around IαI HC immunostaining (lung, intestine and skeletal muscle), and localization at a small distance from IαI HC or a different distribution pattern (brain, liver, skin and kidney). These results indicate that IαI HC could function as an HA-rich matrix stabilizer on the cells of cartilage and maturing ovary, in which IαI HC shows colocalization with its predominant ligand, HA.
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  • 172
    ISSN: 1432-0878
    Keywords: Key words Avian pineal organ ; Pinopsin ; Cell differentiation ; Tissue culture ; Immunohistochemistry ; Quail embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The avian pineal organ contains several types of photoreceptors with different photopigments: rhodopsin, iodopsin, and pinopsin. We have previously examined the differentiation of both rhodopsin-like and iodopsin-like immunoreactive cells during pineal development in quail embryos to determine the onset of synthesis of specific proteins and their cellular localization. In the present study, we have performed pinopsin immunohistochemistry on in-vivo developing and in-vitro cultured pineal organs of quail embryos. The results were compared with those obtained with rhodopsin and iodopsin immunohistochemistry. In the developing pineal organs, pinopsin immunoreactivity was detected at embryonic day 8, i.e. five days earlier than rhodopsin-like and iodopsin-like immunoreactivities. It was localized exclusively in the protrusions extending into the lumen throughout development, whereas rhodopsin-like and iodopsin-like immunoreactivities were usually found both in cell bodies and processes. These differences were also observed under two different types of culture conditions (dissociated cell culture and organ culture) indicating that, in the avian pineal organ, the expression pattern of the pinopsin gene is basically different from those of the other two pineal photopigments. The present study suggests that pineal cells have a mechanism for the polarized transport of pinopsin molecules.
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  • 173
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    Cell & tissue research 296 (1999), S. 607-617 
    ISSN: 1432-0878
    Keywords: Key words Gastrointestinal tract ; Respiratory tract ; Urogenital tract ; Immunohistochemistry ; In situ hybridization ; mRNA ; Pig (Swedish Landrace × Yorkshire)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The antisecretory factor, AF, is a 41-kDa protein, cloned and sequenced from a human pituitary library. AF is a potent inhibitor of experimental intestinal hypersecretion in rats and pigs. An antiserum against the C-terminal of the truncated, recombinantly produced AF protein was raised in rabbits. The affinity-purified antiserum was used to study the expression of AF in mucosal membranes and in the pituitary gland of the pig; distinctly stained cells were found in lymphoid cells in the connective tissue of all parts of the gastrointestinal, respiratory and urinary tracts. Cytoplasmic AF was demonstrated in endocrine and epithelial cells in the pituitary gland. In situ hybridisation with a digoxigenin-labelled mRNA probe also demonstrated specific cytoplasmic staining in epithelial and lymphoid cells in all of these tissues. The cells stained by either method were similarly distributed topographically within the tissues. The results suggest that a specific defined cell population in these various tissues possesses the capability of both synthesising and storing the AF protein within the cellular cytoplasmic compartment.
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  • 174
    ISSN: 1432-0878
    Keywords: Key words Vascular endothelial growth factor ; flt-1 ; flk-1 ; Embryonic implantation ; Immunohistochemistry ; In situ hybridization ; Reverse transcription/polymerase chain reaction ; Golden hamster (Mesocricetus auratus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and its receptors (flt-1 and flk-1) during the peri-implantation period (days 3, 4, 5, 6 and 7 post coitus) in the golden hamster was investigated by in situ hybridization, immunohistochemistry and the reverse transcription/polymerase chain reaction (RT-PCR). Three days after mating, in situ hybridization and immunohistochemical staining revealed weak VEGF expression only in the uterine epithelium; this expression was similar to that seen at oestrus. Flt-1 but no flk-1 immunoreactivity was observed. At day 4, the subepithelial stroma and embryo displayed immunoreactivity for VEGF and flt-1, whereas endothelial cells expressed both flt-1 and flk-1. At day 5, immunoreactivity for both VEGF and its receptors was detected in decidual cells and vascular endothelial cells. Only a few embryonic cells expressed VEGF mRNA but strong signals were noted in decidual cells. The patterns of VEGF and VEGF receptor expression were the same in the day-6 and day-7 embryos and decidua, except for an increase in intensity as development progressed. Based on these findings, we conclude that, in addition to its known actions on endometrial angiogenesis and tissue swelling, VEGF may also facilitate the proliferation and differentiation of the endometrium and help to sustain the avascular embryo during this early stage of development.
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  • 175
    ISSN: 1432-0878
    Keywords: Key words Vesicle protein ; Physin ; Secretory carrier-associated membrane protein ; Vesicle-associated membrane protein ; Synaptobrevin ; Expression ; Liver ; Bovine ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The cell-type restricted expression of cytoplasmic microvesicle membrane protein isoforms may be a consequence of the functional adaptation of these vesicles to the execution of specialized processes in cells of different specialization. To characterize the expression of the vesicle protein pantophysin, an isoform of the synaptic vesicle proteins synaptophysin and synaptoporin, we have prepared and characterized antibodies useful for the immunological detection of pantophysin in vitro and in situ. Using these reagents, we show by immunoblot analyses that pantophysin expression is not homogeneous but differs significantly between various bovine tissues. Furthermore, these differences are not exactly paralleled by the expression of other vesicle proteins of the SCAMP (secretory carrier-associated membrane protein) and VAMP (vesicle-associated membrane protein) types that have previously been localized to pantophysin vesicles in cultured cells. By immunofluorescence microscopy, pantophysin expression is seen predominantly in non-neuroendocrine cells with pronounced membrane traffic. Pantophysin staining codistributes with SCAMP and VAMP immunoreactivities in most instances but differs in some. Remarkably, pantophysin staining in liver is restricted to cells surrounding sinusoids and is not detectable in hepatocytes, similar to that of the SCAMP and VAMP isoforms as detected by our reagents in tissue sections.
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  • 176
    ISSN: 1432-0878
    Keywords: Key words Basal lamina ; Immunohistochemistry ; Confocal laser microscopy ; Cochlea ; Mongolian gerbil ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Bridging structures between discrete capillaries in the stria vascularis of the cochlea were studied morphologically in gerbils and rats. Serial thin sections for transmission electron microscopy revealed (1) that elongated cells surrounded by the basal lamina provided the structural basis for the bridging structure, (2) that the basal lamina surrounding the elongated cell extended to the basal lamina around the capillary endothelial cell, (3) that the electron density of the cytoplasm was similar to that of the pericytes around the capillaries, and (4) that the cell was attached to the capillaries at both ends only. Visualization of the basal lamina by immunofluorescent methods revealed (1) that capillaries were often bent at the site of attachment of the bridging cell, (2) that the bridging cell bifurcated occasionally, and (3) that the density of the bridging cell was much higher in the stria vascularis than in the underlying spiral ligament. Filamentous actin visualized by fluorescent phalloidin was not apparent in the bridging cell. We propose that the bridging cell provides mechanical strength to the tortuous capillary network in the stria vascularis and participates in the specific function of the stria vascularis in cooperation with other types of cells.
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  • 177
    ISSN: 1432-0878
    Keywords: Key words Harderian gland ; Tryptophan hydroxylase ; Serotonin ; Immunohistochemistry ; Rat (Wistar) ; Syrian hamster ; Mesocricetus auratus ; Djungarian hamster ; Phodopus sungorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The Harderian gland is considered as being an extrapineal source of melatonin. In most rodents, the Harderian gland contains two epithelial cell types (I and II). The aim of this study has been to define which cell type is involved in indoleamine synthesis. The presence and localization of serotonin (melatonin precursor) and tryptophan hydroxylase (the rate-limiting enzyme for serotonin synthesis) have been investigated by immunohistochemistry in male Wistar rats, Syrian hamsters and Djungarian hamsters. The results of the present study show that immunoreactivity for tryptophan hydroxylase and serotonin is confined to the type I cell, suggesting that this cell type is involved in indoleamine synthesis in the rodent Harderian gland.
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  • 178
    ISSN: 1432-0878
    Keywords: Key words Mammary gland ; Differentiation ; Neoplasia ; Homeodomain ; Cancer ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  In the mouse mammary gland, homeobox gene expression patterns suggest roles in development and neoplasia. In the human breast, we now identify a family of Iroquois-class (IRX) homeobox genes. One gene, IRX-2, is expressed in discrete epithelial cell lineages being found in ductal and lobular epithelium, but not in myoepithelium. Expression is absent from associated mesenchymal adipose stroma. During gland development, expression is concentrated in terminal end buds and terminal lobules and is reduced in a subset of epithelial cells during lactation. In contrast to observations for many homeobox genes in the mouse mammary gland in which homeobox gene expression is lost on neoplastic progression, IRX-2 expression is maintained in human mammary neoplasias. Data suggest IRX-2 functions in epithelial cell differentiation and demonstrate regulated expression during ductal and lobular proliferation as well as lactation.
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  • 179
    ISSN: 1432-0878
    Keywords: Key words Cytokine ; ELISA ; FACScan ; Lipids ; Macrophage ; Monocyte ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Diabetes (type I and type II) affects approximately 13 million people in the United States. Delayed and incomplete healing of wounds can be a major problem for diabetic patients. Macrophages are an important cell in the complex process of wound repair representing the major source of cytokines throughout the wound-healing process. Cytokines mediate many of the cellular responses critical to timely wound repair. It has been suggested that diabetes impairs wound healing through disruption of local cytokine production. Our previous in vivo studies in rats demonstrated that diabetes-induced and diet-induced hyperlipidemia cause changes in macrophage phenotype and function (Iacopino 1995; Doxey et al. 1998), suggesting that alterations in macrophage cytokine profiles represent the cellular/molecular mechanism responsible for delayed wound healing. The purpose of this study was to investigate how monocyte maturation/differentiation and cytokine production were altered by serum lipids in an in vitro system using human cells. Commercially prepared purified human monocytes were cultured and exposed to serum lipids. Phenotypic analysis of differentiated macrophages was then performed by flow cytometry and fluorescent microscopy using surface antigens specific for various macrophage subsets. Selected cytokines in conditioned medium were assayed using commercial human enzyme-linked immunosorbent assay (ELISA) kits. We demonstrate that serum lipids cause an increase in monocytic differentiation leading to an inflammatory macrophage phenotype rather than a reparative/proliferative phenotype. We also show that serum lipids cause a generalized decrease in macrophage cytokine production using interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), platelet-derived growth factor (PDGF), and transforming growth factor beta 1 (TGF-β1) as marker cytokines. Our present in vitro results using human cells confirm our previous in vivo studies in the rat and support the hypothesis that diabetes-induced hyperlipidemia alters the monocyte differentiation process resulting in changes of macrophage subsets and cytokine release at the wound site, ultimately impairing the wound-healing process.
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  • 180
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    Cell & tissue research 296 (1999), S. 489-497 
    ISSN: 1432-0878
    Keywords: Key words Nitric oxide synthase isoforms I ; III ; Neurosphere ; Immunohistochemistry ; Nestin ; Embryonic brain striatum ; Mouse (Balb/c)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Nitric oxide (NO) is a gaseous, radical molecule that plays a role in various physiological processes in the nervous system such as learning and hippocampal plasticity. It is generated from l-arginine by nitric oxide synthases (NOS), which come in three isoforms depending on the tissue of origin, namely inducible-NOS (iNOS in macrophages), endothelial-NOS (eNOS in endothelial cells) and neural-NOS (nNOS in neural cells). We used epidermal growth factor (EGF)-responsive nestin-positive neural precursor cells originating from the mouse E16 embryonic striatum, and studied the relative expression of NOS isoforms probed with isoform-specific antibody using the avidin-biotin immunohistochemical method. Our data revealed both nNOS and eNOS to be expressed in both neurospheres and desegregated neural precursor cells. However, iNOS signals were virtually undetectable in both cell categories. When the neural precursor cells were carried in the presence of poly-l-ornithine (PLO), there was a strong induction of the expression of iNOS proteins, indicating the possibility that this isoform is amenable to modulation by extracellular cues. These preliminary results suggest both nNOS and eNOS to be important in the physiology of neural precursor cells, and that iNOS might also play a role at certain stages in the life of these cells.
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  • 181
    ISSN: 1432-0878
    Keywords: Key words Cultured epidermis ; Keratinocyte ; Epithelialization ; Wound healing ; Human ; Mouse (NMRI)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Sheets of cultured allogeneic human keratinocytes have been used for the treatment of burns and chronic leg ulcers but there has been no animal assay for the therapeutic action of these cultures. In order to analyze the effects of frozen cultures of human keratinocytes on wound healing, we have developed such an assay based on the rate of repair of full-thickness skin wounds in immunocompetent NMR1 mice. Reepithelialization of the control wounds, originating from the murine epithelium at the edge of the wound, occurred at a constant rate of advance of 150 µm/day. When frozen cultured human epidermal sheets were thawed at room temperature for 5–10 min and applied to the surface of the wound, the murine epithelium advanced at 267 µm/day. Most wounds treated with frozen cultures completely healed after 10 days, whereas most control wounds required 16 days. The accelerated reepithelialization did not depend on the presence of proliferative human keratinocytes in the frozen cultures. The cultures also promoted early formation of granulation tissue and laminin deposition over the surface of the wound bed. This simple assay should permit quantitative analysis of the effects on healing exerted not only by cultured cells, but also by proteins and small molecules.
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  • 182
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    Cell & tissue research 297 (1999), S. 111-117 
    ISSN: 1432-0878
    Keywords: Key words P2X receptor ; Immunohistochemistry ; Duodenum ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Immunohistochemical techniques were performed on freshly frozen sections of the duodenum of the rat using specific polyclonal antibodies to unique peptide sequences of P2X1–7 receptors. Of the antibodies to the seven known P2X receptor subtypes that mediate extracellular signalling by nucleotides, three reacted with discrete structures in the duodenal villus of the rat. Anti-P2X1 reacted with the capillary plexus in the intestinal villus, which did not extend to the crypt region, suggesting that nucleotides may be involved in the uptake and transport of metabolites. Anti-P2X5 immunostained the membranes of the narrow ”stem” of villus goblet cells, where the nucleus and cell organelles reside, possibly influencing synthesis and release of mucins. P2X7 receptor immunoreactivity was only seen in the membranes of enterocytes and goblet cells at the tip of the villus, where cells are exfoliated into the lumen, consistent with earlier findings that P2X7 is involved in apoptotic events. Thus, in complex structures such as the intestinal villus, purinoceptors appear to participate in several and diverse signalling functions.
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  • 183
    ISSN: 1432-0878
    Keywords: Key words Interleukin-18 ; Hyperosmotic conditions ; Epithelial cells ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Interleukin-18 is a novel multifunctional cytokine, which enhances natural killer cell activity and promotes the induction of cytokine production, including that of interferon-γ by T cells and antitumor effects. Interleukin-18 is produced by cells of several different tissues (e.g., macrophages, keratinocytes, osteoblasts, and intestinal epithelium); however, it is unclear what physiological conditions or stimuli induce interleukin-18 production. To determine physiological conditions for the production of interleukin-18, we have examined the effect of mannitol-induced hyperosmotic conditions on normal human umbilical vein endothelial cells (HUVEC) and eight established human epithelial-like cell lines (Intestine 407, Caco-2, A253, HeLa, SCC25, HT1197, ACHN, A549). Hyperosmotic conditions induced interleukin-18 immunoreactivity in all the human cell lines tested, as detected by immunocytochemistry. The enhanced interleukin-18 production was also observed when mannitol was replaced with NaCl as the inducer of hyperosmotic stress. Enzyme-linked immunosorbent assays revealed that interleukin-18 concentrations in cell extracts were significantly increased by hyperosmotic conditions. Reporter gene assays also revealed that hyperosmotic conditions stimulated transcriptional activity of the interleukin-18 promoter. These results show for the first time that hyperosmotic stress is a stimulator of interleukin-18 production in epithelial-like cells.
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  • 184
    ISSN: 1432-0878
    Keywords: Key words Chloride cells (mitochondria-rich cells) ; Teleost larvae ; Osmoregulation ; Immunohistochemistry ; Quantification ; Ultrastructure ; Oreochromis mossambicus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Integumental and branchial chloride cells of tilapia larvae (Oreochromis mossambicus) were studied at the light-microscopical and ultrastructural level. Total numbers and distribution of chloride cells were quantified after immunostaining of cross sections of the entire larvae with an antibody against the α-subunit of Na+/K+-ATPase. The majority (66%) of Na+/K+-ATPase-immunoreactive (ir) cells, i.e. chloride cells, of freshwater tilapia larvae were located extrabranchially up to 48 h after hatching. Five days after hatching, the majority (80%) of chloride cells were found in the buccal cavity. Transfer of 24-h-old larvae to 20% sea water speeded up this process; 24 h after transfer (i.e. 48 h after hatching), the majority (59%) of chloride cells were located in the buccal cavity. The branchial chloride cell population of 24-h- and 120-h-old larvae consisted of immature, mature, apoptotic and necrotic chloride cells. However, relatively more immature chloride cells were observed in freshwater larvae (42–63%) than in (previously studied) freshwater adults (21%), illustrating the developmental state of the gills. After transfer to sea water, the incidence of degenerative chloride cells did not change. Furthermore, the incidence of immature cells had decreased and a new subtype of chloride cells, the ”mitochondria-poor” cells, appeared more frequently. These mitochondria-poor chloride cells were characterised by an abundant tubular system and relatively few mitochondria, which were aligned at the border or concentrated in one part of the cytoplasm. Most of these cells did not contact the water. The function of their enhanced appearance after seawater transfer is unknown.
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  • 185
    ISSN: 1432-0878
    Keywords: Key words α1-Microglobulin ; Bikunin ; Inter-α-trypsin inhibitor ; Mast cells ; Trypstatin ; Urinary trypsin inhibitor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We recently reported that the rat mast cell proteinase inhibitor trypstatin is genetically identical with the second half of inter-α-trypsin inhibitor light chain (ITI-LC), also known as bikunin or urinary trypsin inhibitor (UTI). In this study, therefore, immunoreactivities of mast cells of various human tissues were examined with three antibodies, anti-human ITI-LC, anti-ITI, which recognizes mainly heavy chains or the sugar moiety of ITI, and anti-α 1-microglobulin (α1mG). ITI-LC immunoreactivity was strongly found in mast cells in the connective tissues of various organs except for those of the propria mucosae of small intestine. Neither anti-ITI antibody nor anti-α1mG antibody reacted with mast cells in various tissues. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, α1mG/ITI-LC mRNA was not detected in the skin and tongue, and only weakly in small intestine, although ITI-LC immunoreactivity was strongly detected in these tissues. Furthermore, the mRNA was not expressed in cultured human mast cells. These results suggest that ITI-LC protein is stored in the granules of human connective tissue mast cells, though is not produced by them.
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  • 186
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    Cell & tissue research 297 (1999), S. 163-168 
    ISSN: 1432-0878
    Keywords: Key words Acid release ; Stomach ; Antibody ; Immunohistochemistry ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The tetradecapeptide somatostatin (SRIF) has an inhibitory action on acid secretion in the stomach. It has been suggested that somatostatin may act directly on parietal cells as well as indirectly via histamine-producing cells. A family of high affinity membrane-bound receptors, which are termed sst1–sst5 receptors, mediates the physiological effects of somatostatin. On the basis of functional studies it has been suggested that somatostatin may mediate its actions in the stomach by activation of a somatostatin sst2 receptor type. Two splice variants of the rat sst2 receptor exist, sst2(a) and sst2(b), which differ in length and composition of their intracellular carboxy termini. To date, little information is available on the distribution of the somatostatin sst2(b) receptor in any peripheral tissue. Here we show for the first time the localisation of this receptor isoform in the rat oxyntic mucosa, where the receptor protein was found to be present in parietal cells. This is in contrast to sst2(a) receptor, which was localised to enterochromaffin-like cells and nerve fibres. The differential localisation of the receptor isoforms to two key cell types, parietal cells and enterochromaffin-like cells, may explain how somatostatin inhibits acid secretion by more than one mechanism.
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  • 187
    ISSN: 1432-0878
    Keywords: Key words Osteoblasts ; Extracellular matrix ; Transforming growth factor-β1 ; Basic fibroblast growth factor ; Apert’s syndrome ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The phenotype of Apert osteoblasts differs from that of normal osteoblasts in the accumulation of macromolecules in the extracellular matrix. Apert osteoblasts increase type I collagen, fibronectin and glycosaminoglycans secretion compared with normal osteoblasts. Because the extracellular matrix macromolecule accumulation is greatly modulated by transforming growth factor-β1, we examined the ability of normal and Apert osteoblasts to secrete transforming growth factor-β1 by CCL-64 assay and to produce transforming growth factor-β1 by analysis of the mRNA expression of transforming growth factor-β1. Northern blot analysis revealed an increased amount of transforming growth factor-β1 mRNA expression in Apert osteoblasts compared with normal ones. Moreover, the level of the active transforming growth factor-β1 isoform was higher in Apert than in normal media. In pathologic cells, the increase in transforming growth factor-β1 gene expression was associated with a parallel increase in the factor secreted into the medium. The level of transforming growth factor-β1 was decreased by the addition of basic fibroblast growth factor. Transforming growth factor-β1 is controlled temporally and spatially during skeletal tissue development and produces complex stimulatory and inhibitory changes in osteoblast functions. We hypothesise that in vitro differences between normal and Apert osteoblasts may be correlated to different transforming growth factor-β1 cascade patterns, probably due to an altered balance between transforming growth factor-β1 and basic fibroblast growth factor.
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  • 188
    ISSN: 1432-0878
    Keywords: Key words Calbindin ; Hertwig’s epithelial root sheath ; Epithelial rest of Malassez ; Preodontoblast ; Periodontal fibroblast ; Immunohistochemistry ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The present study was undertaken to examine the localization of calbindin D28k (CB)-like immunoreactivity (-LI) during the root formation of the rat molar. In the adult rat, CB-LI was detected in some of the cells of the epithelial rest of Malassez at the bifurcational region and in certain cells between the root dentin and cementum at the apical region. These cells had indented nuclei and many tonofilaments, and cementocytes lacked CB-LI. Moreover, CB-LI was observed in the periodontal fibroblasts in the alveolar half of the apical region. During root formation, the cells in the Hertwig’s epithelial root sheath (HERS) lacked CB-LI, but most fragmented cells along the root surface began to express CB-LI when HERS was disrupted. Preodontoblasts and odontoblasts at the apical portion of the root also showed CB-LI. After the formation of cellular cementum, the CB-immunoreactive (-IR) cells were entrapped between the root dentin and cementum in the apical portion of the root. The number of CB-IR cells at the root surface decreased gradually, while that between the root dentin and cementum increased. The fibroblasts in the periodontal ligament began to express CB-LI after commencement of the occlusion, and the number and the staining intensity of CB-IR fibroblasts increased gradually with the passage of time. The present results suggest that CB may play an important role in the survival of the epithelial cells, in the cellular responses of periodontal fibroblasts against mechanical forces caused by the occlusion, and in the initial mineralization by the odontoblasts through the regulation of intracellular Ca2+ concentration.
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  • 189
    ISSN: 1432-0878
    Keywords: Key words Endothelin ; Endothelin receptors ; Endothelin-converting enzyme ; Ovary ; In situ hybridization ; Human ; Cynomolgus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The endothelin system is composed of three endothelin isoforms (ET-1, ET-2, and ET-3), the endothelin receptors ETA and ETB, and the endothelin-converting enzyme (ECE). Besides having a major vasoactive role, endothelins have roles in different cell types at a local level. We investigated the presence of the different components of the endothelin system in primate ovaries. Human ovaries and gonadotropin-stimulated monkey ovaries were studied using immunohistochemistry for endothelin, and in situ hybridization with probes for ET-1, ET-2, ET-3, ETA and ETB receptors, and ECE. ET-1 and ETA receptors were detected in endothelial cells and vascular smooth muscle cells, respectively, in stromal vessels adjacent to follicles and corpora lutea. ETB receptors and ET-1 were found in the endothelial cells of capillaries of corpora lutea. ECE was present in internal theca cells of secondary, de Graaf, atretic follicles, and in luteinized granulosa cells of the corpora lutea. The endothelin system components are present in or around the follicles of human and monkey ovaries. Although the components are not expressed in the same cell types, they are synthesized, mainly in follicles, by cells that are in close proximity. Thus, the endothelin system could act in a paracrine manner. ECE expression in steroid-producing cells changes its compartmentalization during follicle maturation.
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  • 190
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    Cell & tissue research 295 (1999), S. 297-305 
    ISSN: 1432-0878
    Keywords: Key words Trophoblast ; Macrophages ; Placenta ; Cell culture ; Paracrine regulation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In view of the accumulating evidence for paracrine mechanisms regulating trophoblast function, we tested the hypothesis that placental macrophages affect trophoblast activity in a paracrine fashion. Trophoblast was isolated from 17 term placentas (–IP). One aliquot of cells was further immunopurified (+IP) using an HLA class I antibody. This increased the proportion of trophoblast (+IP 〉97%; –IP ∼70%) as identified by rigorous immunocytochemistry. Most (∼70%) non-trophoblast cells in –IP were macrophages. The cells were cultured for 5 days with a daily medium change. In addition, +IP cells from seven placentas were cultured with lipopolysaccharide (LPS)-stimulated or -unstimulated macrophage-conditioned media. The concentrations of lactate, trophoblast-specific hormones, human chorionic gonadotropin-β (hCG-β) and human placental lactogen (hPL), of several prostanoids and of endothelin-1 and angiotensin II were determined in the culture media. The accumulated amounts of substances released into the culture media, corrected for the greater proportion of trophoblast in +IP cultures, were on average two- to threefold higher (hCG-β: 18-fold) in +IP than in –IP, with the exception of endothelin-1,2 (no change), angiotensin II (–70%) and 6-keto-prostaglandin-F1α (–40%). [3H]leucine incorporation into the trichloroacetic acid (TCA)-precipitable pool measured on day 5 was twofold higher in +IP than in –IP. Addition of conditioned media reverted these changes. The data demonstrate that placental macrophages in culture affect trophoblast biosynthetic activity in a paracrine fashion. We conclude that macrophages are important regulators of trophoblast activity.
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  • 191
    ISSN: 1432-0878
    Keywords: Key words Enteric innervation ; Immunohistochemistry ; Nitric oxide synthase ; Galanin ; Striated muscle ; Esophagus ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The relationship between nitric oxide synthase (NOS)- and galanin-immunoreactive nerve terminals and the origin of NOS-immunoreactive nerve terminals on the motor endplates in the striated muscles of the rat esophagus was investigated. Double immunohistochemical staining revealed a dual innervation of motor endplates by calcitonin gene-related peptide (CGRP)-immunoreactive axons and by axons that were immunoreactive for both NOS and galanin. On average, 91% of NOS terminals were galanin immunoreactive. NOS-immunoreactive fibers were revealed at 67% of endplates, identified by the presence of CGRP terminals. The left vagus and superior laryngeal nerve were cut and 15 days allowed for terminals to degenerate. This caused a significant loss of CGRP fibers, but did not affect the density of innervation of the striated muscle by NOS-immunoreactive fibers. Thus the NOS/galanin fibers are deduced to originate from ganglia in the esophageal wall. This is supported by our observation of numerous NOS-immunoreactive nerve cell bodies in the myenteric ganglia of the esophagus, 74% of which were galanin immunoreactive. There were no CGRP-immunoreactive nerve cell bodies in the wall of the esophagus.
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  • 192
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    Cell & tissue research 295 (1999), S. 537-551 
    ISSN: 1432-0878
    Keywords: Key words Decapod ; Invertebrate ; Monoamine ; Immunohistochemistry ; Procambarus clarkii ; Pacifastacusleniusculus (Crustacea)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We used whole-mount immunocytochemistry to characterize the distribution of serotonin in the stomatogastric nervous systems of seven species of crayfish representing three genera from the family Cambaridae (Orconectes, Cambarus, and Procambarus) and one from the family Astacidae (Pacifastacus). In all species, we observed serotonin-like immunoreactivity in four gastropyloric receptor (GPR) neurons located in the lateral ventricular nerves, with one pair of neurons in each nerve. As in other crustaceans, the GPR axons project to the stomatogastric ganglion and to the bilateral commissural ganglia. In three crayfishes, we observed the GPR axons crossing the commissural ganglia, and extending toward the thoracic nervous system. This feature was most clearly and consistently seen in Pacifastacus leniusculus. The number of stained somata in the commissural ganglia varied among crayfish species from two (in Procambarus clarkii) to five (in Pacifastacus leniusculus). The largest soma (the L cell) displayed both serotonin- and tyrosine hydroxylase-like immunoreactivity in all species, suggesting that serotonin and dopamine are cotransmitters in this cell. The inferior esophageal nerve and a branch of this nerve (the inner labral nerve) contained several axons with serotonin-like immunoreactivity. These axons were clearly present in only one species (Procambarus clarkii). Serotonin acts as a neuromodulator of rhythms produced by circuits in the crab and lobster stomatogastric ganglion, and is likely to play a similar role in crayfish. Differences are apparent in the distribution of serotonin among crayfish species and between crayfish and other crustaceans, and could result in differences in the physiological action of this modulator.
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  • 193
    ISSN: 1432-0878
    Keywords: Key words Cerebrovascular development and injury ; Hemangioma ; Angiogenesis ; Immunocytochemistry ; Adhesion molecules ; Conventional transmission and high-voltage electron microscopy ; Mouse (C57BL ; SJL/J) ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Blood vessels from the vasculature of mouse brains during postnatal development and from human brain tumors (hemangiomas) removed at biopsy were examined immunocytochemically by transmission electron microscopy (TEM) or high-voltage transmission electron microscopy (HVEM) to determine the expression of intercellular adhesion molecule-1 (ICAM-1). In the mouse brains, ICAM-1 was shown to be initially expressed on the luminal and abluminal endothelial cell (EC) surfaces on day 3 after birth. ICAM-1 intensity increased on the luminal EC surfaces and labeled vesiculotubular profiles (VTS, defined in the present report) between days 5 and 7. After 2 weeks and at 6 months after birth, ICAM-1 labeling was weak or absent on the luminal EC surfaces. The hemangiomas presented a strong ICAM-1 reaction product on the luminal EC surfaces of small and large blood vessels associated with the VTS, with a weaker labeling of the abluminal or adventitial aspects of larger blood vessels. TEM of vesiculovacuolar structures (VVOs) within ECs from arteries and veins also demonstrated reaction product for ICAM-1 labeling. Three-dimensional stereo-pair images in the HVEM enhanced the visualization of gold particles that were attached to the inner-delimiting membrane surfaces of EC VTS, and VVOs, respectively. These observations raise the possibility that the neonatal leukocytes and tumor cells may utilize these endothelial structures as a route across the developing and injured blood-brain barrier (BBB).
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  • 194
    ISSN: 1432-0878
    Keywords: Key words Atherosclerosis ; Culture model ; Endothelial cell ; Endothelin-1 ; Oxidized LDL ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We investigated the structural and functional properties of human umbilical vein endothelial cells (HUVECs) cultured on a two-chamber culture model system using an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs cultured on the model system exhibited several features similar to those of in vivo vessels, including formation of the intercellular junctional devices and expression of tight junction-associated protein ZO-1 and adherence junction-associated protein α-catenin. Furthermore, we found that HUVECs had a property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount of synthesized ET-1 was found in the lower well, designated as the basal side. When HUVECs were incubated with either native low-density lipoproteins (nLDLs) or oxidized LDLs (oxLDLs) at a concentration of 100 μg/ml, ET-1 secretion was significantly increased, dependent on the cell side (apical vs basal) on which the nLDLs or oxLDLs were loaded. When the LDLs were loaded on the apical side, the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL) and 61% (oxLDL), whereas it was accompanied by a concomitant decrease of ET-1 on the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the basal side, however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side, with a 26% simultaneous decrease of ET-1 on the opposite side for both nLDLs and oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1 secretion from HUVECs on the opposite side of the well on which HDLs were loaded; there was a 57% decrease on the basal side when HDLs were loaded on the apical side, and a 46% decrease on the apical side when loaded on the basal side. These results indicate that modulation of ET-1 secretion from ECs by lipoproteins is virtually dependent on the place (apical vs basal) where these proteins are present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a polarized pattern suggests that ET-1 may be involved in pathophysiological processes such as atherogenesis.
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  • 195
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 295 (1999), S. 151-158 
    ISSN: 1432-0878
    Keywords: Key words Class II MHC-positive cells ; Human leukocyte antigen-DR ; Dental pulp ; Dendritic cells ; Macrophages ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution and ultrastructure of class II major histocompatibility complex (MHC)-positive cells were investigated in human dental pulp, employing immunohistochemistry using an anti-human leukocyte antigen (HLA)-DR-monoclonal antibody. HLA-DR-immunopositive cells, appearing spindle-like or dendritic in profile, were densely distributed throughout the dental pulp. Under the electron microscope, these cells exhibited various sizes of vesicles containing clear or opaque contents, multivesicular bodies and characteristic fine tubulovesicular structures in their cytoplasm. Some reactive cells possessed coated pits and vesicles including electron-dense materials, indicating an active endocytosis. At the periphery of the pulp tissue, the HLA-DR-immunopositive cells were predominantly situated in the subodontoblastic layer, with some located in the odontoblast layer and/or predentin and extending their cytoplasmic processes into the dentinal tubules. Cell processes of these cells occasionally made contact with several odontoblast processes in the same way as the nerve fibers in the predentin. These cells never contained the typical phagosomes frequently observed in the HLA-DR-immunoreactive macrophages in the subodontoblastic layer and the pulp core. The results suggest that the HLA-DR-immunopositive cells in the odontoblast layer and/or predentin have some regulatory function on the odontoblasts under physiological conditions, in addition to their involvement in the initial defense reaction after tooth injury.
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  • 196
    ISSN: 1432-0878
    Keywords: Key words Proopiomelanocortin ; Post-translational processing ; Novel neuropeptides ; Immunohistochemistry ; HPLC analysis ; Oncorhynchus mykiss (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Several vertebrate species which underwent duplication of their genome, such as trout, salmon and Xenopus, possess two proopiomelanocortin (POMC) genes. In the trout, one of the POMC molecules, called POMC-A, exhibits a unique C-terminal extension of 25 amino acids which has no equivalent in other POMCs characterized so far. This C-terminal peptide contains three pairs of basic residues, suggesting that it may be the source of novel regulatory peptides. The aim of the present study was to investigate the occurrence of these peptides in the brain of the trout Oncorhynchus mykiss by using specific antibodies raised against two epitopes derived from the C-terminal extension of POMC-A, i.e., EQWGREEGEE and YHFQ-NH2. Immunohistochemical labeling of brain sections revealed the presence of EQWGREEGEE- and YHFQ-NH2-immunoreactive cell bodies in the anterior part of the nucleus lateralis tuberis of the hypothalamus. Immunoreactive fibers were observed in the dorsal hypothalamus, the thalamus, the telencephalon, the optic tectum and the medulla oblongata. In contrast, no labeling was detected using antibodies against the non-amidated peptide YHFQG. Biochemical characterization was performed by combining high-performance liquid chromatography (HPLC) analysis with radioimmunoassay (RIA) quantification. Two peptides exhibiting the same retention time as synthetic EQWGREEGEE and ALGERKYHFQ-NH2 were resolved. However, no peptide co-eluting with YHFQ-NH2 or YHFQG could be detected. These results demonstrate that, in the trout brain, post-translational processing of POMC-A generates the two decapeptides EQWGREEGEE and ALGERKYHFQ-NH2. The wide distribution of immunoreactive fibers in the diencephalon, telencephalon, optic tectum and medulla oblongata suggests that these peptides may exert neurotransmitter and/or neuromodulator activities.
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  • 197
    ISSN: 1432-0878
    Keywords: Key words Central nervous system ; Immunohistochemistry ; In situ hybridization ; Leech excitatory peptide ; Neuropeptide ; Whitmania pigra (Annelida)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We have recently isolated a myoactive peptide, called leech excitatory peptide, belonging to the GGNG peptide family from two species of leeches, Hirudo nipponia and Whitmania pigra. Immunohistochemistry and in situ hybridization were employed to localize leech excitatory peptide-like peptide(s) and its gene expression in the central nervous system of W. pigra. A pair of neuronal somata were stained by both immunohistochemistry and in situ hybridization in the supraesophageal, subesophageal, and segmental ganglia. In addition, several other neurons showed positive signals by either immunohistochemistry or in situ hybridization in these ganglia. An immunoreactive fiber was observed to run in the anterior root of segmental ganglion 6, which is known to send axons to the sexual organs, though we failed to detect immunoreactivity in possible target tissues. Antiserum specificity was established by enzyme-linked immunosorbent assay using different leech excitatory peptide-related peptides. Leech excitatory peptide elicited muscular contraction of isolated preparations of penis and intestine at concentrations of 10–8 M. These results suggest that leech excitatory peptide is a neuropeptide modulating neuromuscular transmission in multiple systems, including regulation of reproductive behavior.
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  • 198
    ISSN: 1432-0878
    Keywords: Key words Glucocorticoid receptor (GR) ; Immunohistochemistry ; In situ hybridization ; Pituitary ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract By means of double immunohistochemical techniques and a nonradioisotopic in situ hybridization method, we determined the colocalization pattern of glucocorticoid receptor (GR) and pituitary hormones and the GR messenger RNA (mRNA) expression in the pituitaries of Wistar adult male rats. Immunoreactivity for GR was detected in the nuclei of cells in the anterior and posterior pituitary. Double immunohistochemistry revealed that the colocaliza- tion of GR and anterior pituitary hormones occurred in almost 99% of the growth hormone (GH)-producing cells and adrenocorticotropic hormone (ACTH)-producing cells, and in 67% of the thyroid stimulating hormone (TSH)-producing cells. Almost all of the folliculostellate cells (93%), marginal layer cells (94%) in the anterior pituitary, and pituicytes (96%) in the posterior pituitary immunostained for S100 protein antibody were also immunostained with GR. GR mRNA was abundant in the cytoplasm of anterior and intermediate pituitary cells but scattered sparsely in that of the posterior pituitary. These results suggest that glucocorticoids directly influence certain pituitary cells in order to regulate cell function, including the synthesis and/or secretion of hormones.
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  • 199
    ISSN: 1615-6102
    Keywords: Cumulus oophorus ; Ovarian follicle ; Fertilization ; Ultrastructure ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The fine structure of the human cumulus oophorus has been reviewed on the basis of scanning and transmission electron microscopic observations as well as of immunofluorescence data. Tissues sampled from preovulatory ovarian follicles and cumulus-enclosed oocytes and fertilized eggs (collected from the oviduct or obtained during in vitro fertilization procedures) have been evaluated from a microtopographic and morphodynamic point of view in order to better clarify the possible role of this population of cells. In particular, the following aspects have been studied and discussed: the presence of multiple close contacts (modulated by the interposition of the zona pellucida) between the oocyte surface and the long microvillous evaginations projecting from the inner aspect of corona cells surface (through these structures the intraovarian cumulus oophorus may control oocyte growth and metabolism up until the time of ovulation); the occurrence of different subpopulations of cells (steroid-synthetic cells, cells producing adhesive proteins, leukocytes, macrophages) in the postovulatory, extraovarian cumulus oophorus surrounding oocytes, zygotes and early developing embryos. All these elements found in the cumulus mass may positively act, through their paracrine activities, on the chemical composition of the microenvironment in which fertilization occurs.
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  • 200
    ISSN: 1615-2573
    Keywords: Smooth muscle cell ; Heterogeneity ; Coronary artery ; Human ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The arterial media is composed of a heterogeneous population of smooth muscle cells (SMCs). Recently, the properties of SMCs were observed to be heterogeneous not only among individual cells but also among arteries of the same vascular bed. To test the hypothesis that a site-specific heterogeneity exists in the SMCs of human coronary arteries, we examined the expression of desmin, vimentin, calponin, and high-molecular-weight (h-) caldesmon in arteries of various sizes. Specimens of arteries were obtained at autopsy from 12 patients: 6 adults (67 ± 4 years old); 3 younger adults (26 ± 2 years old); and 3 neonates. The size of the arteries was estimated by the number of SMC layers of the media. The expression was compared in SMCs of large arteries (〉10 layers in adults, 〉5 layers in neonates), medium-sized arteries (5–10 layers in adults, 3–5 SMC layers in neonates), and small arteries (〈3 layers). In adults, the percentage of arteries positive for desmin was lower in the small (17% ± 3%) and medium-sized arteries (44% ± 12%) than in the large arteries (94% ± 6%) (P 〈 0.01). The percentage of arteries positive for calponin was also lower in the small (18% ± 2%) and medium-sized arteries (66% ± 5%) than in the large arteries (100%) (P 〈 0.01). The percentage for vimentin and h-caldesmon did not differ among large, medium-sized, and small arteries. These observations in adults were similar to those in younger adults or neonates. The phenotypes of medial SMCs are vessel sizedependent in human coronary arteries. This finding should be important for understanding the site-specific characteristics of vascular function in the regulation of myocardial perfusion or those of vascular responses to environmental changes.
    Type of Medium: Electronic Resource
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