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M Krause

Publications and source records attributed to M Krause.

At least 37 records · Page 2Linked to original sources
PubMed2004

Fullerene quantum gyroscope.

We report the observation of quantized rotational states of a diatomic C2 unit in solid endohedral fullerene C(2)Sc(2)@C(84). The rotational transitions induce a periodic line pattern in the low energy Raman spectrum. The rotational constant B and the C-C distance were found to be 1.73 cm(-1) and 0.127 nm, respectively. Density functional calculations revealed an intrinsic rotational barrier of the order of only a few meV for the C2 unit. The Schrödinger equation involving the potential barrier was solved and the Raman tensor matrix elements were calculated, yielding good quantitative agreement with the experiment. To our best knowledge this is the first intrinsic rotational spectrum of a diatomic plane molecular rotor.

Journal Article↗
PubMed2004

Repopulation of moderately well-differentiated and keratinizing GL human squamous cell carcinomas growing in nude mice.

PURPOSE: It has been suggested that, reminiscent of the regulated proliferative response of normal squamous epithelium, squamous cell carcinomas that have preserved characteristics of differentiation have a greater repopulation capacity during fractionated irradiation than undifferentiated tumors. The aim of the present study was to investigate repopulation in moderately well-differentiated and keratinizing GL human squamous cell carcinomas in nude mice. METHODS AND MATERIALS: GL human squamous cell carcinomas were transplanted s.c. into the right hind leg of NMRI nu/nu mice. Irradiation was performed with 5.4 Gy fractions under clamp hypoxia or with 2 Gy fractions under ambient conditions. Six, 12, or 18 fractions were given daily, every second day, or every third day. Graded top-up doses were applied under clamp hypoxia to determine the tumor control dose 50% (TCD(50)). A total of 20 TCD(50) assays were performed and analyzed using maximum-likelihood techniques. RESULTS: With an increasing number of daily 5.4 Gy fractions under clamp hypoxia, the top-up TCD(50) values decreased significantly from 50.9 Gy (95% CI: 47, 54) after single doses to 0 Gy after 18 fractions. For the same number of fractions, the top-up TCD(50) increased with increasing overall treatment time. The results are consistent with a constant repopulation rate with a clonogenic doubling time (T(clon)) of 12.7 days (8.6, 16.8). Under ambient blood flow, the top-up TCD(50)s for daily 2 Gy fractions decreased significantly, but were less pronounced than for 5.4 Gy fractions under clamp hypoxia. For a given number of fractions under ambient conditions, the top-up TCD(50)s did not increase significantly with overall treatment time, except for irradiation with 12 fractions in 36 days compared to 12 and 24 days. The T(clon) value from these data was 24.0 days (11.6, 36.4). CONCLUSION: Our data demonstrate a slow but significant rate of repopulation of clonogenic tumor cells during fractionated irradiation of GL human squamous cell carcinomas under clamp hypoxia without indication of a change of the repopulation rate during treatment. Less pronounced repopulation was observed for irradiation under ambient conditions, which might be explained by preferential survival of hypoxic and therefore nonproliferating cells. Taken together with our previous studies on poorly differentiated FaDu tumors (Petersen et al., IJROBP 2001;51:483-493), the results support important heterogeneity of kinetics and mechanisms of repopulation, in particular of the influence of the oxygenation status of surviving clonogenic cells on the repopulation rate during fractionated irradiation, in different experimental squamous cell carcinoma.

Algorithms↗
PubMed2004

Multipole induced splitting of metal-cage vibrations in crystalline endohedral D2d-M2@C84 dimetallofullerenes.

Metal-carbon cage vibrations of crystalline endohedral D2d-M2@C84 (M=Sc,Y,Dy) dimetallofullerenes were analyzed by temperature dependent Raman scattering and a dynamical force field model. Three groups of metal-carbon cage modes were found at energies of 35-200 cm(-1) and assigned to metal-cage stretching and deformation vibrations. They exhibit a textbook example for the splitting of molecular vibrations in a crystal field. Induced dipole-dipole and quadrupole-quadrupole interactions account quantitatively for the observed mode splitting. Based on the metal-cage vibrational structure it is demonstrated that D2d-Y2@C84 dimetallofullerene retains a monoclinic crystal structure up to 550 K and undergoes a transition from a disordered to an ordered orientational state at a temperature of approximately 150 K.

Journal Article↗
PubMed2004

Chronic necrotizing pulmonary aspergillosis complicated by pneumothorax.

A 61-year-old man presented with left-sided pneumothorax. On the chest computed tomograghy (CT), severe bilateral emphysema and left-sided pleural thickening were seen. His pneumothorax was drained with a chest tube. Because of a persistent air leakage, video-thoracoscopic wedge-resection of the suspected fistula and muscle-sparing minithoracotomy with extensive wedge resections of the left upper lobe were performed. Biopsy specimens showed micronodular mycetomas with septate hyphae highly suggestive of Aspergillus. The fungus destructed the lung tissue without vessel invasion. The patient had not been taking immunosuppressant drugs and had no prior opportunistic infections. Itraconazole was begun, the lung was expanded and the patient recovered. We propose that extensive resection of affected lung tissue in combination with long-term antifungal therapy with itraconazole is a valuable therapeutic option in patients with a complicated course of chronic necrotizing pulmonary aspergillosis (CNPA).

Antifungal Agents↗
PubMed2004

Adjuvant inhibition of the epidermal growth factor receptor after fractionated irradiation of FaDu human squamous cell carcinoma.

BACKGROUND AND PURPOSE: Experiments performed by others have shown that inhibition of EGFR before and after single dose irradiation prolonged growth delay and improved local tumour control. This suggests that adjuvant EGFR inhibition can inactivate clonogens that survived irradiation. To test this hypothesis local tumour control was investigated after fractionated radiotherapy and adjuvant EGFR-TK inhibition. MATERIALS AND METHODS: FaDu hSCC xenografts were irradiated with 30 fractions in 6 weeks with total doses of 30-100Gy. After the end of fractionated irradiation, BIBX1382BS was administered daily orally over a time period of 75 days. Tumour volumes were determined two times per week, the volume doubling time during adjuvant treatment was calculated for progressing and recurrent tumours. Local tumour control was investigated 120 days after end of irradiation. RESULTS: Adjuvant BIBX1382BS significantly reduced the tumour growth rate but did not improve local tumour control. The TCD(50) values were 66.1Gy (95% C.I.: 59; 73Gy) after adjuvant BIBX1382BS treatment and 67.9Gy (61; 75Gy) for control tumours (P=0.9). CONCLUSIONS: These data indicate that, although growth of recurrent tumour cells after irradiation is dependent on the EGFR pathway, tumour cells retain their clonogenic potential despite of EGFR inhibition. The results imply also that a decreased tumour growth rate does not necessarily allow conclusions on enhanced inactivation of clonogenic cells when antiproliferative drugs are combined with radiation.

Animals↗
PubMed2004

Sympathetic and parasympathetic activation in heart rate variability in male hypertensive patients under mental stress.

Disturbed sympathetic and also parasympathetic activity of the autonomic nervous system points to pathological alterations in the cardiovascular system. Untreated hypertensive subjects were examined with respect to the question of whether an increase in sympathetic activity necessarily goes along with a reduction in parasympathetic activity, and whether 'delayed' recovery behaviour after mental stress could be an indicator of a disturbed cardiovascular function. In 20 male hypertensive (HT) and 20 normotensive (NT) subjects (control group), heart rate variability (HRV) was compared during rest and under mental stress. The testing procedure consisted of the following phases: habituation, arithmetic tasks without and with interference, recovery. HRV was analysed using the trigonometric regressive spectral analysis (TRS). Proceeding from the total variance (ms2), the weighted averaged frequency (Hz) and the variance parts (ms2) in the frequency bands 'low frequency' (LF-band: 0.04-0.15 Hz) and 'high frequency' (HF-band: 0.15-0.40 Hz) were explored. The variance part modulated by spontaneous breathing within the HF-band was assessed additionally. The variance part in the LF-band under mental stress was significantly increased in the HT group (P<0.01). Activity in the HF-band (without the respiration-dependent part) under mental stress did not differ between both groups, whereas the breathing-modulated part of variance in the HF-band was reduced in the HT subjects. During the recovery period in the HT group, the weighted averaged frequency was still elevated compared to baseline, and the variance part in the LF-band was increased, which may point to delayed recovery behaviour. In addition, by using a discriminant analysis 85% of all subjects were reclassified to the original groups, all HT subjects being assigned 'correctly'. Spectral variance parameters enable early discovery of altered cardiovascular regulation. Respiration influences variance in the HF-band in hypertensive subjects and should therefore be paid attention to. The variance part in the LF-band, weighted averaged frequency and the respiration-modulated variance in the HF-band turned out to be the most valid parameters for the differentiation between NT and HT subjects.

Adult↗
PubMed2004

Differentiation status of human squamous cell carcinoma xenografts does not appear to correlate with the repopulation capacity of clonogenic tumour cells during fractionated irradiation.

PURPOSE: To investigate the magnitude and kinetics of repopulation in a moderately well differentiated UT-SCC-14 human squamous cell carcinoma [hSCC] in nude mice. This question is of interest because clinical data indicate a higher repopulation capacity in those SCC that have preserved characteristics of differentiation, which appears to be in contrast to results on FaDu and GL hSCC previously reported from this laboratory. METHODS AND MATERIALS: UT-SCC-14 tumours were transplanted subcutaneously into the right hind leg of NMRI nu/nu mice. Fractionated radiation treatments were delivered, either under clamped hypoxia at 5.4 Gy/fraction or under ambient conditions (consistent with an OER of 2.7). Tumours were irradiated every day, every 2nd day, or every 3rd day with 6, 12 or 18 fractions. 1, 2 or 3 days after the last fraction, graded top-up-doses under clamped conditions were given for the purpose of estimating the 50% tumour control dose (TCD50). A total of 22 TCD50 assays were performed and analysed using maximum likelihood techniques. RESULTS: The data demonstrate a slow but significant repopulation of clonogenic cells during fractionated irradiation of UT-SCC-14 hSCC. The results under hypoxic conditions are consistent with a constant repopulation rate, with a clonogenic doubling time (Tclon) of 15.6 days (95% CI: 9.7, 21.4). This contrasts with ambient conditions where Tclon was 68.5 days (95% CI: 124, 161). Both Tclon values are longer than the 6-day volume doubling time of untreated tumours. CONCLUSIONS: Less pronounced repopulation for irradiation under ambient compared to clamped hypoxic conditions might be explained by preferential survival of hypoxic and therefore non-proliferating clonogenic cells. Taken together with previous studies on poorly differentiated FaDu and moderately well differentiated GL hSCC, the results are consistent with considerable variability in the magnitude and kinetics of repopulation in different experimental squamous cell carcinomas, and with a relationship between reoxygenation and repopulation during fractionated irradiation. The differentiation status of hSCC growing in nude mice does not to appear to correlate with the proliferative capacity of clonogenic tumour cells during treatment. The results do not support the hypothesis gained from clinical data of higher repopulation in well-differentiated tumours.

Animals↗
PubMed2004

Analysis of the S810L point mutation of the mineralocorticoid receptor in patients with pregnancy-induced hypertension.

OBJECTIVE: A missense mutation at codon 810 (Ser --> Leu) of the mineralocorticoid receptor was recently observed in a family with early manifestation of hypertension. Our objective was to determine if this mineralocorticoid receptor alterations is prevalent in patients with pregnancy-induced hypertension. METHODS: Thirty-eight women with hypertension during pregnancy were tested for the mineralocorticoid receptor gene mutation. DNA was extracted out of blood leucocytes. PCR and automated DNA sequencing were used to analyze exon 6 for the S810L missense mutation. Anamnestical data concerning cardiovascular risk factors and family history were evaluated with a questionnaire. Pregnancy course and outcome were documented in all cases. RESULTS: In 33 patients with pregnancy-induced hypertension and in five patients with exacerbation of preexisting hypertension in pregnancy no point mutations were found at codon 810 in exon 6. CONCLUSIONS: Our data suggest that the S810L missense mutation of the mineralocorticoid receptor does not play a major role in the etiology of pregnancy-induced hypertension in a German /Turkish population.

Codon↗
PubMed2004

Facial expression recognition and subthalamic nucleus stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor signs in Parkinson's disease. However, clinical studies suggest that DBS of the STN may also affect cognitive and emotional functions. OBJECTIVE: To study the impact of STN stimulation in Parkinson's disease on perception of facial expressions. RESULTS: There was a selective reduction in recognition of angry faces, but not other expressions, during STN stimulation. CONCLUSIONS: The findings may have important implications for social adjustment in these patients.

Adult↗
PubMed2003

Progressive arm weakness and tonic hand spasm from multifocal motor neuropathy in the brachial plexus.

A 50-year-old waitress presented with a 10-year history of progressive weakness in her right arm without atrophy and with tonic hand spasms suggesting a central motor disorder. Electromyography, however, disclosed chronic neurogenic changes including fasciculations and atypical cramps. Isolated motor conduction block in the right brachial plexus suggested a variant of multifocal motor neuropathy. Strength recovered and cramps disappeared after intravenous immunoglobulins. Motor neuropathies may thus manifest with features of central motor disorders.

Action Potentials↗
PubMed2003

Measurement of plasma corticosterone and fecal glucocorticoid metabolites in the chicken (Gallus domesticus), the great cormorant (Phalacrocorax carbo), and the goshawk (Accipiter gentilis).

A method for the non-invasive measurement of glucocorticoid metabolites in feces of chickens was established and validated. After high-performance liquid chromatography (HPLC) the presence of at least two fecal immunoreactives was demonstrated, one co-eluting with authentic corticosterone, whereas the second substance migrates close to corticosterone sulphate. We investigated the relationship between corticosterone in blood plasma obtained by a vena brachialis catheter and fecal samples in groups of five chickens after an ACTH and a dexamethasone injection to stimulate and to suppress adrenal activity. A control group received a saline injection. After ACTH plasma cortisol concentrations increased 16-fold after 1.5 h to levels between 19 and 38 ng/ml and dropped to pre-treatment levels (1.1-2.5 ng/ml) 4h after stimulation. Dexamethasone did not result in a distinct suppression of adrenocortical activity and plasma corticosterone dropped only slightly below pre-treatment levels. The concentrations in fecal metabolites corresponded to the changes in the levels of biological active hormone in plasma. Fecal peak excretion (105-295 ng/g) was obtained with a delay of approximately 4 h compared to plasma. The profile obtained after ACTH challenge reflected a broader and dampened pattern of glucocorticoid secretion and provided a more integrated measure of adrenal activity. Dexamethasone treatment did not induce a measurable decrease in fecal metabolites and concentrations fluctuated around a mean of 30.0+/-9.9 ng/g, almost identical to those obtained from the saline treatment group (29.4+/-13.9 ng/g). In a separate experiment the effect of an alternative capture method (remote-controlled injection system) was investigated in cormorants. Plasma corticosterone measurements revealed a significantly diminished stress reaction compared to traditional trapping (1.24+/-0.78 vs. 10.9+/-12.1 ng/ml). Investigations whether goshawk nestlings infected with Trichomas gallinae differ in fecal corticosterone metabolite concentrations compared to healthy subjects revealed no significant changes. However, a significant correlation was found between the glucocorticoid metabolite concentrations and the number of nestlings per nest. The demonstration that adrenal activity can be detected by the assay is a prerequisite that ecologically meaningful levels of imposed stress can be validated. Therefore, non-invasive measurements of fecal metabolites are a promising perspective to monitor stress in birds.

Adrenocorticotropic Hormone↗
PubMed2003

Viability of the myocardium after twenty-four-hour heart conservation--a preliminary study.

BACKGROUND: Orthotopic heart transplantation following ischemic times beyond four hours is associated with increased risk of early graft failure. The use of modern myocardial preservation strategies could enable safe transplantation after long-term conservation. In this study, we tested a new myocardial protection regime in an experimental model of 24 h storage. METHODS: Orthotopic heart transplantations (n=15) were performed in a pig model. Donor hearts were flushed with Bretschneider solution, excised, and stored for 24 hours at 4 degrees C. During implantation, controlled reperfusions with substrate-enriched leukocyte-depleted blood cardioplegia were performed after each anastomosis. Blood cardioplegia contained 1 mmol/l of the Na(+)-H(+)-exchange inhibitor HOE 642 and 100 mg/l of adenosine. Controlled reperfusion was continued with leukocyte-depleted blood for 20 min. A microaxial pump was inserted after heart transplantation and circulatory assistance was maintained for five hours to prevent right heart failure. RESULTS: No initial graft failure could be observed. Thirteen hearts could be weaned from extracorporeal circulation. Due to bleeding problems, kidney and lung failure only five hearts could be included in the final analysis. Hemodynamics of these hearts remained stable with epinephrine at 0.1 micro g/kg/min. Myocardial oxygen consumption 20 min after start of reperfusion (5.3+/-2.0 ml/100 g/min) did not differ significantly versus baseline (6.8+/-2.0 ml/100 g/min). Oxygen extraction six hours after heart transplantation was also well preserved compared to baseline (58.0+/-10.2 versus 49.2+/-8.8 %). Histological examination six hours after transplantation using luxol fast blue staining revealed that only 1.0 % of the myocytes were irreversibly damaged. CONCLUSIONS: The data indicate full viability of the myocardium after 24 h conservation. The preservation technique described could contribute to the extension of conservation times in heart transplantation and enable transplantation of marginal donor hearts.

Animals↗
PubMed2003

[Mechanical circulatory assist devices in acute and chronic heart failure].

The clinical use of mechanical circulatory assist devices as bridge to transplantation has been proved as life-saving therapy in a large population of patients. Learning from the clinical experience the construction of the blood pumps has been markedly improved over the last years. The better outcome of the patients has enabled a broader use of ventricular assist devices. The novel axial pumps are designed for long-term circulatory support. After further reduction of device related complications (first of all thromboembolic events) these systems may provide a future alternative to heart transplantation.

Contraindications↗
PubMed2003

Impact of increased cell loss on the repopulation rate during fractionated irradiation in human FaDu squamous cell carcinoma growing in nude mice.

PURPOSE: To determine the impact of increased necrotic cell loss on the repopulation rate of clonogenic cells during fractionated irradiation in human FaDu squamous cell carcinoma in nude mice. MATERIALS AND METHODS: FaDu tumours were transplanted into pre-irradiated subcutaneous tissues. This manoeuvre has previously been shown to result in a clear-cut tumour bed effect, i.e. tumours grow at a slower rate compared with control tumours. This tumour bed effect was caused by an increased necrotic cell loss with a constant cell production rate. After increasing numbers of 3-Gy fractions (time intervals 24 or 48 h), graded top-up doses were given to determine the dose required to control 50% of the tumours (TCD50). All irradiations were given under clamp hypoxia. RESULTS: With increasing numbers of daily fractions, the top-up TCD50 decreased from 37.9 Gy (95% CI: 31; 45) after single dose irradiation to 14.1 Gy (8; 20) after irradiation with 15 fractions in 15 days. Irradiation with 18 daily 3-Gy fractions controlled more than 50% of the tumours without a top-up dose. After irradiation with six fractions every second day, the top-up TCD50 decreased to 26.9 Gy (22; 32). No further decrease of the TCD50 was observed after 12 and 18 irradiations every second day. Assuming a constant increase of TCD50 with time, the calculated doubling time of the clonogenic tumour cells (Tclon) was 7.8 days (4.4; 11.3). The Tclon calculated for FaDu tumours growing in pre-irradiated tissues was significantly longer (p=0.0004) than the Tclon of 5.1 days (3.7; 6.5) determined under the same assumptions in a previous study for FaDu tumours growing in normal subcutaneous tissues. CONCLUSIONS: Increased necrotic cell loss by pre-irradiation of the tumour bed resulted in longer clonogen doubling times during fractionated radiotherapy of human FaDu squamous cell carcinoma. This implies that a decreased necrotic cell loss might be the link between reoxygenation and repopulation demonstrated previously in the same tumour model.

Animals↗
PubMed2003

Selective inhibition of the epidermal growth factor receptor tyrosine kinase by BIBX1382BS and the improvement of growth delay, but not local control, after fractionated irradiation in human FaDu squamous cell carcinoma in the nude mouse.

PURPOSE: To investigate the effect of BIBX1382BS, an inhibitor of the epidermal growth factor receptor tyrosine kinase, on proliferation and clonogenic cell survival of FaDu human squamous cell carcinoma in vitro, and on tumour growth and local tumour control after fractionated irradiation over 6 weeks in nude mice. FaDu human squamous cell carcinoma is epidermal growth factor receptor positive and significant repopulation during fractionated irradiation was demonstrated in previous experiments. MATERIALS AND METHODS: Receptor status, receptor phosphorylation, cell cycle distribution, cell proliferation and clonogenic cell survival after irradiation were assayed with and without BIBX1382BS (5 microM) in vitro. Tumour volume doubling time, BrdUrd and Ki67 labelling indices and apoptosis were investigated in unirradiated tumours growing in NMRI nude mice treated daily with BIBX1382BS (50 mg kg(-1) body weight orally) or carrier. Tumour growth delay and dose-response curves for local tumour control were determined after irradiation with 30 fractions within 6 weeks. RESULTS: BIBX1382BS blocked radiation-induced phosphorylation of the epidermal growth factor receptor and reduced the doubling time of FaDu cells growing in vitro by a factor of 4.9 (p=0.008). Radiosensitivity in vitro remained unchanged after incubation with BIBX1382BS for 3 days and decreased moderately after 6 days (p=0.001). BIBX1382BS significantly reduced the volume doubling time of established FaDu tumours in nude mice by factors of 2.6 when given over 15 days (p<0.001) and 3.7 when applied over 6 weeks (p<0.001). When given simultaneously to fractionated irradiation, growth delay was significantly prolonged by an average of 33 days (p=0.003). Local tumour control was not improved by BIBX1382BS. The radiation doses necessary to control 50% of the tumours locally were 63.6 Gy (95% confidence interval 55; 73) for irradiation alone and 67.8 Gy (60; 77) for the combined treatment (p=0.5). CONCLUSIONS: Despite clear antiproliferative activity in rapidly repopulating FaDu human squamous cell carcinoma and significantly increased tumour growth delay when combined with fractionated irradiation, local tumour control was not improved by BIBX1382BS. The results do not disprove that epidermal growth factor receptor inhibition might enhance the results of radiotherapy. However, the results imply that further preclinical investigations using relevant treatment schedules and appropriate endpoints are necessary to explore the mechanisms of action and efficacy of such combinations.

Animals↗
PubMed2003

Ultrafractionation in A7 human malignant glioma in nude mice.

PURPOSE: Low-dose hyperradiosensitivity (HRS) has been demonstrated in numerous cell lines in vitro, including a number of radioresistant human malignant glioma cell lines such as A7. The aim of our experiment was to show whether HRS can be exploited by using ultrafractionated irradiation (UF) to improve local control of A7 tumours growing in nude mice. Extrapolation of the in vitro results predict a 3.7-fold difference in the efficacy of UF compared with conventional fractionation (CF). MATERIAL AND METHODS: Subcutaneuously growing A7 tumours were irradiated either with UF (126 fractions in 6 weeks, 0.4 Gy per fraction) or CF (30 fractions in 6 weeks, 1.68 Gy per fraction). The total dose was 50.4 Gy in both experimental arms. Fractionated irradiations were given under ambient conditions and followed by graded top-up doses under clamp hypoxia. Endpoints were tumour growth delay and local tumour control 180 days after the end of treatment. RESULTS: UF resulted in a significant decrease of tumour growth delay and in a significant increase of the top-up TCD(50) compared with CF (40.0 Gy [95% CI 29; 61 Gy] versus 28.3 Gy [24; 35 Gy], p=0.047). CONCLUSIONS: Despite a pronounced HRS phenomenon in vitro, UF was significantly less effective than CF in A7 human malignant glioma in nude mice. These results neither disprove the existence of HRS nor do they exclude a possible clinical value of UF. The findings rather indicate that simplistic extrapolation from results obtained after single-dose exposure or few fractions in vitro is not sufficient to predict outcome of UF in vivo and that comprehensive evaluation of novel treatment options in animal models continues to be an essential requirement for clinical translation.

Animals↗