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Biomedical subjects

M Lindemann

Publications and source records attributed to M Lindemann.

At least 19 recordsLinked to original sources
PubMed2003

Effect of atorvastatin and clopidogrel on cellular immune function.

Lipid lowering therapy by statins and antiaggregation have become the basis of any anti-atherosclerotic prophylaxis either as primary or secondary prophylaxis. As several recent papers indicated immunosuppressive properties of statins we investigated changes in lymphocyte subpopulations, apoptosis markers, and cellular immune response towards mitogens after a short-term therapy with atorvastatin and clopidogrel. Nine healthy volunteers (four male, five female, age ranging from 26 to 43 years) were treated with 20 mg atorvastatin for 4 weeks and for 2 additional weeks with 20 mg atorvastatin and 75 mg clopidogrel after oral consent was given. Lymphocyte subpopulations were counted by flow cytometry. To assess cellular in vitro immune function, lymphocyte transformation tests with four mitogens (PHA, ConA, PWM, and OKT3) were performed. Absolute leucocyte counts remained unchanged as well as the granulocyte, monocyte, lymphocyte, and lymphocyte subpopulation counts. There were no detectable changes in markers of cell activation (HLA-DR, CD25, CD69, and CD86) or apoptosis (CD95, annexin). Cellular in vitro responses towards four mitogens did not show significant changes after atorvastatin nor after atorvastatin plus clopidogrel treatment.In conclusion, our data show that atorvastatin is not an immunosuppressive drug under therapeutical conditions.

Adult↗
PubMed2003

ELISpot: a new tool for the detection of nickel sensitization.

BACKGROUND: The standard assay for the clinical detection of contact allergy against nickel is the patch test. For research purposes, the in vitro lymphocyte transformation test (LTT) is mostly applied. However, the in vivo application of allergens includes the potential of sensitization, whereas the LTT demands 6 days of cell culture and radioactive labelling procedures. OBJECTIVE: The purpose of this study was to validate an enzyme-linked immunospot (ELISpot) assay to specifically detect cellular response against nickel sulphate in correlation with patch test, anamnestic data, and LTT results. METHODS: In probands with positive (n=60) and negative patch test results (n=19), cytokine ELISpot and LTT were performed in parallel using various concentrations of nickel sulphate, various numbers of responding peripheral blood mononuclear cells (PBMC), and various durations of cell cultures. RESULTS: Concentrations of 50 and 75 microM nickel sulphate were found to be optimal to stimulate in the ELISpot 4x10(5) and in the LTT 2x10(5) PBMC, respectively. An increase in ELISpot sensitivity was reached by pre-incubation with nickel sulphate for 24 h prior to transfer to ELISpot plates. In nickel-sensitive probands, an average precursor cell frequency of 19x10(5), 1.7x10(5), and 0.7x10(5) could be defined for IFN-gamma, IL-2, and IL-4 producing PBMC, respectively. In non-sensitive probands IFN-gamma producing cells were detectable, but with significantly lower frequency (2x10(5); P=0.004). The prior performance of patch tests had no significant effect on cytokine production or lymphocyte proliferation. Overall, the parameters patch test, anamnestic nickel allergy, ELISpot, and LTT results were positively correlated (P<0.05). CONCLUSIONS: Based on these experiments, the quantitative in vitro detection of cell-mediated reactions towards nickel as well as other heavy metal ions should be possible utilizing the above-described ELISpot assay.

Adolescent↗
PubMed2001

Delay estimation for cortico-peripheral relations.

In neurophysiology, time delays between concurrently measured time series are usually estimated from the slope of a straight line fitted to the phase spectrum. We point out that this estimate is valid only in the case in which, one signal is a mere time-delayed copy of the other one. We present a procedure for delay estimation that applies to a much wider class of systems with nontrivial phase spectrum like for example lowpass filters. The procedure is based on the Hilbert transform relation between the phase of a linear system and its log gain. The Hilbert transform relation is nonlocal in frequency space, a fact that limits its applicability to experimental data. We explore these limits, and demonstrate that the method is applicable to neurophysiological time series. We present the successful application of the Hilbert transform behavior method to concurrently recorded epicortical brain activity and peripheral tremor. We point out and explain physiologically unreasonable delay estimates given by the traditional method. Finally, we discuss the assumptions underlying the applicability of the Hilbert transform method in the neuroscience context.

Cerebral Cortex↗
PubMed2001

Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells.

The present paper summarizes the results of the second German consensus meeting on immunogenetic donor search for allotransplantation of hematopoietic stem cells held in Essen in November 1999 under the auspices of the German Society for Immunogenetics (DGI) and the German Working Party for Blood and Marrow Transplantation (DAG-KBT). Immunogeneticists and transplant physicians from all over the country agreed to update the national standards for: (1) search strategy including the role of unrelated and extended family donor search after unsuccessful core family donor search, (2) histocompatibility loci to be typed, (3) histocompatibility typing techniques to be used (HLA serology vs DNA-based HLA typing, cellular tests, serum cross-match), and (4) acceptable HLA mismatches in the context of a defined underlying disease, donor type, and conditioning regimen.

Aging↗
PubMed2001

The G protein beta3 subunit 825T allele is a genetic marker for enhanced T cell response.

The G protein beta3 subunit (GNB3) 825T allele is predictive of enhanced Gi protein activation. Studying the influence of C825T allele status on cellular in vitro immune responses towards recall antigens and interleukin-2 stimulation we observed a 2-4-fold, significantly increased proliferation in homozygous 825T (TT) vs. C825 allele (CC) carriers. Furthermore, lymphocyte chemotaxis and CD4(+) T cell counts of individuals with TT+TC genotypes were significantly enhanced compared to the CC genotype. In summary, it appears that C825T allele status is highly predictive of immunocompetence and could be a candidate gene in disorders associated with inadequate immune response.

Alleles↗
PubMed2001

The pathophysiology of tremor.

Tremor is defined as rhythmic oscillatory activity of body parts. Four physiological basic mechanisms for such oscillatory activity have been described: mechanical oscillations; oscillations based on reflexes; oscillations due to central neuronal pacemakers; and oscillations because of disturbed feedforward or feedback loops. New methodological approaches with animal models, positron emission tomography, and mathematical analysis of electromyographic and electroencephalographic signals have provided new insights into the mechanisms underlying specific forms of tremor. Physiological tremor is due to mechanical and central components. Psychogenic tremor is considered to depend on a clonus mechanism and is thus believed to be mediated by reflex mechanisms. Symptomatic palatal tremor is most likely due to rhythmic activity of the inferior olive, and there is much evidence that essential tremor is also generated within the olivocerebellar circuits. Orthostatic tremor is likely to originate in hitherto unidentified brainstem nuclei. Rest tremor of Parkinson's disease is probably generated in the basal ganglia loop, and dystonic tremor may also originate within the basal ganglia. Cerebellar tremor is at least in part caused by a disturbance of the cerebellar feedforward control of voluntary movements, and Holmes' tremor is due to the combination of the mechanisms producing parkinsonian and cerebellar tremor. Neuropathic tremor is believed to be caused by abnormally functioning reflex pathways and a wide variety of causes underlies toxic and drug-induced tremors. The understanding of the pathophysiology of tremor has made significant progress but many hypotheses are not yet based on sufficient data. Modern neurology needs to develop and test such hypotheses, because this is the only way to develop rational medical and surgical therapies.

Animals↗
PubMed2001

Amitriptyline enhances the central component of physiological tremor.

OBJECTIVES: Postural tremor is a regularly encountered side effect of amitriptyline which can be strong enough to cause discontinuation of therapy. The aim was to characterise amitriptyline induced tremor and to assess if the central or reflex component of physiological tremor was modulated by this drug. METHODS: The postural hand tremor was measured in 15 patients on a clinical rating scale, by power spectral analysis of accelerometer, forearm flexor, and extensor EMG before and after the beginning of amitriptyline treatment for major depression or chronic pain syndrome. A coherence analysis between flexor and extensor muscles on the same side was performed. RESULTS: There was a clinically visible increase in postural tremor in a third of these patients. The tremor amplitude measured by accelerometer total power increased in every patient under amitriptyline. The EMG synchronisation as reflected by significant peaks in the flexor or extensor spectrum generally occurring at higher frequencies (8-18 Hz) than the accelerometric tremor frequencies (6-11 Hz) did not change. The number of patients with a significant flexor-extensor coherence in the 7-15 Hz range increased significantly under amitriptyline, the frequency bands of significant coherence corresponded with the EMG frequencies, and both were independent of changes to the hand's resonant frequency by added inertia. CONCLUSIONS: An enhancement of postural tremor under amitriptyline is a common phenomenon although not always clinically apparent. The increase in EMG-EMG coherence indicates an increased common central drive to the motor units as its frequency is not influenced by peripheral resonance or reflex mechanisms. This is the first account of a drug induced enhancement of the central component of physiological tremor.

Amitriptyline↗
PubMed2000

Multiple oscillators are causing parkinsonian and essential tremor.

The tremors of Parkinson's disease (PD) and essential tremor (ET) are traditionally considered to depend on a central oscillator producing rhythmic activation of the motoneurones of all extremities. To test this hypothesis, we have compared electromyographic tremor activity in different muscles of the affected limbs using cross spectral analysis, including coherence and phase. Surface electromyographic recordings from both arms, legs, and the neck were analyzed in 22 patients with PD and 28 patients with ET. Volume conduction between neighboring muscles producing artificial "coherence" has been found to be an important methodologic problem. We have developed a mathematical test to exclude data that could distort the results. According to this test, 10% or 25% of muscle combinations from the same limb had to be excluded from further analysis in PD or ET, respectively. In both, patients with PD and ET, we found a considerable number of muscle combinations oscillating at virtually the same frequency (delta frequency <0.4 Hz) without showing a significant coherence. Thus, the frequency difference between different muscles is not sufficient to measure the correlation between two muscles. Significant coherencies between muscles within the same arm or leg were found in 70% or 90% of patients with PD or ET, respectively, whereas only one patient with PD and not a single patient with ET showed significant coherencies between muscles from different limbs. The phase between coherent muscles of the same arm of patients with PD showed a preference of either a reciprocal alternating pattern for antagonistic muscles in forearm flexor and upper arm extensor as opposed to a co-contraction pattern between the hand flexors and the triceps brachii. In patients with ET such clear differences were lacking. We conclude that multiple oscillators are responsible for the tremor in different extremities of patients with PD and ET. Differences between PD and ET concerning the phase relation within the arm may either be related to the topography within the basal ganglia or to differently involved-spinal pathways.

Arm↗
PubMed2000

The pathophysiology of parkinsonian tremor: a review.

Parkinsonian tremor is most likely due to oscillating neuronal activity within the CNS. Summarizing all the available evidence, peripheral factors only play a minor role in the generation, maintenance and modulation of PD tremor. Recent studies have shown that not a single but multiple oscillators are responsible. The most likely candidate producing these oscillations is the basal ganglia loop and its topographic organization might be responsible for the separation into different oscillators which, nevertheless, usually produce the same frequency. The neuronal mechanisms underlying these oscillations are not yet clear, but three hypotheses would be compatible with the presently available data from animal models and data recorded in patients. The first is a cortico-subthalamo-pallido-thalamic loop, the second is a pacemaker consisting of the external pallidum and the subthalamic nucleus, and the third is abnormal synchronization due to unknown mechanisms within the whole striato-pallido-thalamic pathway leading to a loss of segregation. Assuming the oscillator within the basal ganglia pathway, the mechanism of stereotactic surgery might be a desynchronization of the activity of the basal ganglia-thalamo-cortical or the cerebello-thalamo-cortical pathway.

Animals↗
PubMed2000

Determinants of physiologic tremor in a large normal population.

OBJECTIVES: It has been well established that peripheral mechanical resonant factors as well as central mechanisms may play a role in the generation of physiological tremor (PT). Furthermore it has been postulated that subject's attributes like age and sex might influence PT. The present study was designed to quantify these influences on PT in a large normal population. METHODS: Physiological hand and finger tremors were measured in a group of 117 normal subjects between 20 and 94 years of age using accelerometry and surface EMG recordings from the forearm flexor and extensor muscles. The hand tremor was measured in a postural position with and without weight, and the finger tremor was recorded with the arm outstretched, forearm supported and hand supported. Hand volume and grip force were measured in each subject. RESULTS: Hand tremor frequency (mean 7.7 Hz) was reduced significantly by added inertia (mean 5.2 Hz) and it was negatively correlated with hand volume while there was no correlation with grip force. Finger tremor showed, subject to the arm position, maximally 3 and at least two distinct frequency bands (1-4, 6-11 and 15-30 Hz) reflecting the resonance frequencies of the whole arm, the hand and the finger, respectively. A significant EMG peak was found in 50-80% of the recordings. This EMG synchronization gave rise to a corresponding accelerometer peak or a significant EMG-EMG coherence in about one-third of the population indicating a central component of PT because its frequency was unaffected by mechanical changes in the periphery. We did not find a significant influence of age on the tremor frequency, while the sex of the subjects slightly but significantly changed the frequency range of hand tremor. Multiple partial correlations revealed, however, that the only direct influence on hand tremor frequency is the hand volume indicating that the influence of sex on hand tremor frequency is an indirect effect produced by the significantly larger hands of male subjects. CONCLUSIONS: In conclusion, the main determinants of PT are the mechanical properties of the oscillating limb. Apart from the dominating peripheral resonance mechanism we found indications of an additional central component of PT in about one-third of the normal population. There was no age dependence of tremor frequency and it was shown that the influence of the subjects' sex on tremor frequency only represents an indirect mechanical effect.

Adult↗
PubMed2000

Chromium yeast affects growth performance and plasma traits but not carcass characteristics of growing-finishing pigs depending on the glycemic index.

Forty Swiss Large White pigs (barrows with 31.7 kg initial to 103.7 kg final BW) were equally and randomly assigned to one of four treatments (H0, H200, L0, L200) involving a combination of chromium supplementation (0 or 200 micrograms/kg) and glycemic index (high GI (H) or low GI (L)). Growth performance, energy and protein digestibility, carcass composition, and some plasma traits were investigated. The data indicated, that the substitution of dietary carbohydrates with fat and crude fibre (low GI) resulted in lower growth performance due to impaired energy digestibility. Moreover, the strong stimulation of insulin secretion due to the high and rapid availability of carbohydrates of the diets H0 and H200 caused increased carcass fat deposition. Chromium supplementation also affected plasma insulin and glucagon concentrations. Depending on glycemic index, chromium affected the growth performance. Daily gain was reduced in pigs of the L200 treatment compared to the L0 group. This finding indicated that the energy availability expressed as GI is one of several nutritional factors, which determine the efficacy of dietary chromium. We could not corroborate evidences that dietary chromium modifies the chemical composition of the whole carcass, but depending on GI, chemical composition of the longissimus muscle was affected.

Animal Feed↗
PubMed1999

Impact of localized radiotherapy on blood immune cells counts and function in humans.

Immune cells subsets were prospectively analyzed after localized radiotherapy (LRT). LRT reduced the levels of all lymphocyte subsets, with B-cells and naive T-cells being most sensitive. Lymphocyte function was suppressed, but still within the normal range. Rapid recovery of cytotoxic T-cells/natural killer cells after LRT and the functional suppression within normal levels explains the low incidence of infections after LRT.

Adolescent↗
PubMed1999

Indirect and direct simultaneous, comparative blood pressure measurements with the Bosotron 2 device.

Testing the accuracy of the automatic blood pressure measuring device Bosotron 2, we performed simultaneous, same-arm, comparative blood pressure measurements with three instruments (A, B, and C) of the device and by auscultation in the antecubital fossa by a trained observer in 24 volunteers each. The volunteers were evenly matched for age, sex, and blood pressure level. The mean systolic differences and their standard deviations (24 subjects each, n = 288 single measurements) were -1.32+/-3.8 mm Hg for instrument A, -0.99+/-3.9 mm Hg for instrument B, and -1.12+/-5.0 mm Hg for instrument C. The corresponding values for the diastolic differences were -2.71+/-4.4, -3.46+/-4.3, and -2.72+/-3.9 mm Hg, respectively. Combining the results for the three instruments, the comparison yielded a good accuracy (mean difference) and sufficient repeatability of the differences (standard deviation) for the systolic and diastolic blood pressures (systolic -1.14+/-4.3 mm Hg; diastolic -2.96+/-4.2 mm Hg). In addition to the British Hypertension Society protocol, in 33 patients with coronary artery disease the measurements using the three Bosotron 2 devices were compared with measurements within the aortic arch. The mean systolic/diastolic differences (+/-SD) were +1.45+/-4.3 and +7. 27+/-4.7 mm Hg for instrument A, +4.70+/-12.8 and +1.73+/-7.4 mm Hg for instrument B, and -3.74+/-8.0 and +5.61+/-2.6 mm Hg for instrument C. Combining the results of the three instruments, the blood pressure was determined to be only slightly higher (systolic +1.74+/-9.6 mm Hg; diastolic +4.87+/-5.6 mm Hg) by the Bosotron 2 R device as compared with the aortic arch pressure. The Bosotron 2 R device seems to be suitable for clinical use and for monitoring blood pressure during clinical-pharmacological studies.

Adolescent↗
PubMed1998

Regulation of mitogen-activated protein kinase phosphatase-1 in vascular smooth muscle cells.

Mitogen-activated protein (MAP) kinase cascades are major signaling systems by which cells transduce extracellular cues into intracellular responses. In general, MAP kinases are activated by phosphorylation on tyrosine and threonine residues and inactivated by dephosphorylation. Therefore, MAP kinase phosphatase-1 (MKP-1), a dual-specificity protein tyrosine phosphatase that exhibits catalytic activity toward both regulatory sites on MAP kinases, is suggested to be responsible for the downregulation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK), and p38 MAP kinase. In the present study, we examined the role of these MAP kinases in the induction of MKP-1 in vascular smooth muscle cells (VSMCs). Extracellular stimuli such as platelet-derived growth factor (PDGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and angiotensin II, which activated ERK but not SAPK/p38 MAP kinase, induced a transient induction of MKP-1 mRNA and its intracellular protein. In addition, PD 098059, an antagonist of MEK (MAP kinase/ERK kinase), the upstream kinase of ERK, significantly reduced the PDGF-induced activation of ERK and potently inhibited the expression of MKP-1 after stimulation with PDGF, thereby demonstrating the induction of MKP-1 in response to activation of the ERK signaling cascade. Furthermore, anisomycin, a potent stimulus of SAPK and p38 MAP kinase, also induced MKP-1 mRNA expression. This effect of anisomycin was significantly inhibited in the presence of the p38 MAP kinase antagonist SB 203580. These data suggest the induction of MKP-1, not only after stimulation of the cell growth promoting ERK pathway but also in response to activation of stress-responsive MAP kinase signaling cascades. We suggest that this pattern of MKP-1 induction may be a negative feedback mechanism in the control of MAP kinase activity in VSMCs.

Animals↗
PubMed1997

Detection of major and minor sex pheromone components by the male codling moth Cydia pomonella (Lepidoptera: Tortricidae).

Electroantennograms (EAGs) recorded from the antennae of male Cydia pomonella L. in response to stimulation with doses of the main sex pheromone component E8,E10-dodecadienol (Codlemone) ranging from 5ng to 500&mgr;g did not differ in their amplitudes from responses obtained to a synthetic 7-component pheromone blend containing the same absolute quantities of Codlemone. Based on differences in spike amplitudes obtained in Single Cell recordings (SCR), Sensilla trichodea on the antenna of males were found to contain at least three receptor neurone types. Two olfactory receptor neurones were tuned to Codlemone, while the third failed to be stimulated by Codlemone or by the minor components of the pheromone blend. As spike activity of the neurones in the S. trichodea stimulated by the 7-component blend did not differ from that of stimulation by Codlemone alone it appears that none of the receptor neurones is sensitive to any of the minor components tested. Scanning-electron-microscopical (SEM) examination of Sensilla auricillica on the antennae of Cydia males revealed two morphologically distinct types: rabbit eared shoehorn and regular shoehorn. SCR from these sensilla showed that only olfactory receptor neurones located in the rabbit-eared shoehorn type were tuned to the minor components. Differences in spike amplitudes (large, intermediate, small) allowed three types of neurones to be distinguished. Only the spike frequency of the intermediate receptor neurone was increased by application of the minor components E8-dodecenol, E9-dodecenol, dodecanol, tetradecanol, hexadecanol and E8,E10-dodecadienal. None were stimulated by Codlemone. These results are discussed in relation to the behavioural role of the minor pheromone components of C. pomonella.

Journal Article↗
PubMed1997

Association of the TNFa2 microsatellite allele with the presence of colorectal cancer.

Independently, our two groups collaborating in this report performed association studies to consider the influence of the TNF region within the human MHC on the presence of colorectal cancer. In the Glasgow Study, 84 colorectal cancer patients were compared with 91 controls at the TNFa microsatellite locus. Analysis of individual alleles by Fisher's exact test revealed a significant overrepresentation of the TNFa2 allele in the colorectal cancer group, after correcting for multiple comparisons. In the Essen Study, 47 colorectal cancer patients were compared with 117 matched controls, and the hypothesis of TNFa2 overrepresentation in colorectal cancer was confirmed. These data provide evidence for the involvement of the TNF locus in the pathogenetic etiology of colorectal cancer.

Alleles↗