Bufadienolides from animal and plant sources.
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Biomedical subjects
Publications and source records attributed to B Kopp.
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OBJECTIVE: To continue and expand determination of the reliability, validity, and sensitivity to change of the Arm Motor Ability Test (AMAT), an instrument for assessing deficits in activities of daily living (ADL). DESIGN: The AMAT was administered twice to patients, with an interest interval of either 1 or 2 weeks, by one of two examiners assigned to patients in counterbalanced order. Patients' interest intervals and scores on the arm portion of the Motricity Index was unknown to the raters. SETTING: A referral inpatient neurological rehabilitation center. PATIENTS: Thirty-three subacute stroke inpatients with moderate to mild upper extremity motor deficit: median Motricity-Index-Arm score = 89, median chronicity = 43d, median age = 66yr; 12 were women. MAIN OUTCOME MEASURE AND RESULTS: The AMAT was developed in 1987, and interrater reliabilities at that time were found to range from .95 to .99. The present values for interrater reliability (2 scales) from videotaped test performance were: kappas = .68 to .77. Spearman correlations = .97 to .99. For performance time, interscorer reliability from videotaped test performance was .99. Homogeneities for the three AMAT measures for the total sample (Cronbach's alpha and split-half reliability) were .93 to .99. The test-retest reliabilities for the total sample were .93 to .99. The correlations to the Motricity-Index-Arm score were .45 to .61. The AMAT detected the difference in change occurring as a result of the passage of 1 versus 2 weeks in these subacute inpatients, presumably as a result of intensive therapy and/or spontaneous recovery, confirming the results of an earlier intervention study. CONCLUSION: The AMAT is an instrument with high interrater reliability, internal consistency, and sensitivity to change, as well as having satisfactory concurrent validity.
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We examined slow potentials, transient event-related potentials, and oscillatory-like responses in the electroencephalogram during aversive conditioning in humans, in order to determine what is happening in the neocortex when behavioral adaptations are learned. Pictures of an angry and a happy human face served as reinforced (CS+) and unreinforced (CS-) conditioned stimuli, respectively, in one group, and either the reversed condition or two discriminably different neutral faces in two other groups (total n = 48 subjects). The unconditioned stimulus (US) was intracutaneous shock delivered to the left hand 5 s after CS+ onset. The electroencephalographic (EEG) activity was recorded from Fz, Cz, Pz, C3, and C4, electromyographic (EMG) activity from bilateral forearm and corrugator muscles, and skin conductance from the right hand. During acquisition a negative slow potential developed after CS+ (not CS-), which was more pronounced when a neutral face served as CS+. Early (iCNV, initial contingent negative variation) and late (tCNV, terminal contingent negative variation) components of the slow-potential response were positively related to the magnitude of conditioned EMG responses. Differentiation of tCNV was larger when neutral faces signaled the US; iCNV persisted during extinction when a happy face served as CS+. Late-occurring event-related potentials (ERPs) elicited by the US diminished over conditioning, whereas short-latency US components and ERPs elicited by CS events did not. Fourier analysis revealed oscillatory ("gamma-band") activity between 30 and 40 Hz, which persisted up to 3 s after US delivery and diminished as conditioning progressed. Our findings indicate that learning is expressed in neocortical structures at the earliest stages of conditioning. The functional roles of the three types of EEG response in learning are discussed.
Forty-one bufadienolides were isolated from the bulbs of Urginea maritima agg. from Egypt; 26 of them are new natural compounds. Structure elucidation was performed by comparison with authentic substances or by means of 1H, 13C NMR and FAB mass spectroscopy. Sixteen of the glycosides derive from nine structurally new aglycones: 16 beta-hydroxy-scillarenin, 16 beta-O-acetyl- scillarenin, 12 beta-hydroxy-5 alpha-4,5-dihydro-scillirosidin, 16 beta- hydroxy-5 alpha-4,5-dihydro-scillirosidin, 16 beta-O-acetyl-5 alpha-4,5- dihydro-scillirosidin, 12 beta-hydroxy-scillirubrosidin, 16 beta-O-acetyl- scillirubrosidin, 9-hydroxy-scilliphaeosidine and 12 beta-hydroxy-desacetyl- scillirosidine.
Motor inhibition and its correlates in the event-related potential (ERP) are often studied in go/nogo tasks. However, go and nogo trials differ in their motor and their attentional requirements, rendering an interpretation of corresponding changes in ERP components difficult. As an alternative strategy to study motor inhibition, a hybrid choice-reaction go/nogo procedure involving selective response priming was used. Eighteen subjects performed the task. Response time (RT) and error measures as well as the lateralized readiness potential (LRP) indicated that responses were primed by flanker stimuli that were associated with one of the two possible responses. In nogo trials, selective response priming influenced the N2 amplitude whereas the P3 amplitude was unaffected. Because the N2 appeared irrespective of whether an erroneous response was correctable (in go trials) or not (in nogo trials), we conclude that the N2 reflects either the detection or the inhibition of an inappropriate tendency to respond.
Event-related potentials were recorded in a flanker task using arrowheads pointing to the left or to the right as targets and as congruent or incongruent flanker stimuli using squares as neutral flanker stimuli. The onset of the flanker stimuli preceded that of the target stimuli by 100 ms. Lateralized readiness potentials showed response activation below execution threshold in correspondence to the information conveyed by the flanker stimuli. Exclusively, the incongruent flanker condition provoked a N2c, which evolved closely synchronized to the erroneous response. Graded response analyses separating incongruent trials with weak, medium, and strong incorrect response activation revealed that the N2c amplitude covaried with the magnitude of the erroneous response. The N2c in the incongruent compatibility condition of the flanker task thus corresponds to the avoidance of inappropriate responses, possibly reflecting the inhibition of automatically but erroneously primed responses. The results are compatible with studies of error correction, suggesting that efference monitoring is a constituent of executive control.
In a pilot study we investigated the association between concentrations of various eicosanoids in menstrual blood with pain and oral contraceptive use. Menstrual fluid was collected on tampons by 12 women who did not use an oral contraceptive but suffered from slight primary dysmenorrhea and by three pain-free women who used an oral contraceptive. Eicosanoids (cyclooxygenase products: 6-ketoprostaglandin F1 alpha, thromboxane B2, prostaglandin E2, prostaglandin F2 alpha, 13,14-dihydro-15-ketoprostaglandin F2 alpha, 12-hydroxy-heptadecatrienoic acid; lipoxygenase products: 5-, 12-, 15-hydroxy-eicosatetraenoic acid (HETE), leukotriene B4, leukotriene C4, leukotriene D4, leukotriene E4) and female sex steroids (17 beta-estradiol and progesterone) were analyzed by the combined use of high-performance liquid chromatography and radioimmunoassay. 12-HETE was the main arachidonic acid metabolite. An increased metabolism of arachidonic acid was associated with pain, especially when synthesis of 12-HETE was elevated. Oral contraceptive use decreased the synthesis of prostaglandins as well as leukotrienes. The concordant changes of cyclooxygenase and lipoxygenase products in dysmenorrhea or in oral contraceptive use may be explained by an increased or decreased phospholipid metabolism, respectively.
Visual distractibility was studied in schizophrenic patients. Subjects had to respond to target stimuli while they ignored the visual context, which was either congruent, neutral, or incongruent with respect to the target stimulus. Eighteen schizophrenic patients and 18 healthy subjects performed this flanker task. Schizophrenic patients did not show increased distractibility compared with healthy subjects, and both groups showed the same attenuation of visual context effects when the spatial distance between target and flanker stimuli was increased. The two groups showed the same amount of interference by incongruent visual context. Thus, schizophrenic patients did not show enhanced distractibility, spatial extension of attention, or response competition. When flanker and target stimuli were redundant, the responses of schizophrenic patients were less accelerated than those of healthy subjects.
According to Frith (1987) the positive symptoms of schizophrenic patients result from an impaired central monitoring of their own actions. For motor behavior, this impairment implies deficient corrections of erroneous movements. Several studies found that schizophrenic patients did correct erroneous movements less frequently than various control groups. In these studies, movement errors were induced by instructing subjects to alternate between moving a joystick towards a target or away from it. In our study, 27 chronic schizophrenic patients, 27 healthy and 18 alcoholic controls were subjected to a similar task. Spatial and symbolic compatibility between stimuli and responses were varied in order to induce errors. Schizophrenic patients responded more slowly and took more time to reverse wrong movements than both control groups. They did not show fewer error corrections or increased correction latencies. These results did not support the supposed deficit in central monitoring of action. Schizophrenic patients exhibited more short latency movements with multiple changes of movement direction than the control groups. This may indicate a failure to inhibit the initiation of competing responses.
Deviant response patterns in experimental reaction time paradigms in schizophrenic probands are well documented. Although simple reaction times are strongly influenced by the current psychopathological status of the proband (e.g. florid psychotic patients versus remitted patients) these influences are less clear for measures obtained from more complex reaction time paradigms. These include the crossover paradigm (reaction time to stimuli presented after constant preparatory intervals in comparison to reaction time to stimuli presented after irregular preparatory intervals) and the modality shift paradigm (reaction time to a stimulus (light or tone) when the modality of the stimulus on the preceding trial was the same compared to when it was different). It is not clear if these peculiarities of response patterns occur as a consequence of the disease or if they represent vulnerability markers for schizophrenia. Both crossover reaction time and modality shift reaction time paradigms were applied to 56 drug free schizophrenics, 45 healthy siblings of these patients and 68 healthy controls. The results indicate that retarded reaction times and the occurrence of the crossover effect as well as of the modality shift effect distinguish schizophrenics and controls. Healthy siblings of schizophrenics differed from healthy controls with regard to the crossover effect but not with regard to the modality shift effect. Therefore only the crossover effect represents a vulnerability marker for schizophrenia. Correlations between the modality shift and the crossover effect revealed strong correlations in the schizophrenic group only.
Post-transfusion hepatitis was studied prospectively in 1,476 patients undergoing open-heart surgery between 1985 and 1988. Thirty-three (2.2%) patients suffered from post-transfusion hepatitis. Acute post-transfusion hepatitis was attributed to hepatitis B in one case and to hepatitis C in ten patients (0.7%). Four additional patients had preexisting serologic markers of hepatitis C. In 22 (1.5%) patients, hepatitis B or C was excluded as a cause of liver disease. Seroconversion for hepatitis C virus occurred from 3 weeks to more than 6 months after infection. Chronic hepatitis C developed in four patients. In addition, seroconversion to anti-HCV was observed in four patients with moderately elevated aminotransferases. In the control patients anti-HCV antibodies were found in 0.5%. The characteristics of acute hepatitis C after blood transfusion are shown and compared to 22 patients with acute hepatitis non-A, non-B, non-C. The etiology of these 22 cases is discussed.
Methods are described for the quantification of various eicosanoids (cyclooxygenase products: 6-KETO, TXB2, PGE2, PGF2 alpha, DHK; lipoxygenase products: 5-, 12-, 15-HETE, LTB4, LTC4, LTD4, LTE4) in menstrual blood collected by tampons. Samples were extracted with acidified ethanol. After purification by SEP-PACK C18 columns, the compounds were separated by reversed phase HPLC using a ternary gradient system. The eicosanoid concentrations of the fractionated eluents were measured by radioimmunoassay and corrected for recovery. 12-HETE was the most prominent metabolite of arachidonic acid in menstrual blood (mean: 1174 ng/g blood). With the exception of PGF2 alpha and TXB2 (mean: 343 and 212 ng/g blood, respectively) other eicosanoids were detected in remarkable lower concentrations.
Four cardenolides were isolated for the first time from the aerial parts of Adonis aestivalis. The compounds were identified by spectrometry and for 3-epi-periplogenin, helveticoside also by comparison with authentic substances. Two new cardenolides were structurally elucidated: strophanthidin-3-O-beta-D-digitoxosido-alpha-L-cymarosido-be ta-D-glucoside and strophanthidin-3-O-beta-D-digitoxosido-beta-D-digoxoside-bet a-D-diginosido-beta-D-glucoside.
Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings of drug-free schizophrenic probands revealed deficits has compared to 33 matched healthy controls in a blurred single target version of the Continuous Performance Test and in a multiple item version of the Span of Apprehension Test but not so in less difficult versions of both tests or in the time needed to react to stimuli with shifting modality.
An investigation of nine Malaysian dart poisons has confirmed that their main active components are cardenolides from Antiaris toxicaria (Pers.) Lesch. and alkaloids probably from different forms of Strychnos ignatii P. Bergius. It is not possible to determine the ethnic origin of the poisons from the results of the analyses on their own. Two new cardiac glycosides have been isolated and their structures determined as 12 beta-hydroxycannogenin 3 beta-O-beta-D-deoxygulopyranoside and 3 beta-O-alpha-L-rhamnopyranoside, respectively.