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Biomedical subjects

M Möller

Publications and source records attributed to M Möller.

At least 37 records · Page 2Linked to original sources

Loss of expression of HDAC-recruiting methyl-CpG-binding domain proteins in human cancer.

Dysregulation of CpG-methylation is a common feature of many human cancers and tumour suppressor genes can be silenced by hypermethylation. Recently, 2 methyl-CpG-binding domain proteins have been linked to gene inactivation by their ability to recruit co-repressors and HDAC-activity to methylated gene promoters. Here, we have analysed mRNA expression of these genes, MeCP2 and MBD2, in a wide variety of primary human tumours. In solid tumours, expression levels of MBD2 (57/71) and MeCP2 (64/71) were significantly reduced in the majority of primary tumours as detected by quantitative real-time RT-PCR. Western blot analyses of MeCP2 in matched tumour-normal samples of patients with non-small-cell lung cancer (NSCLC) indicated reduced protein in a significant percentage of patients. In acute myelogenous leukaemia (n = 26), expression levels were only slightly reduced and did not differ between samples analysed at diagnosis or at the time of relapse. In early-stage NSCLC (n = 70) expression of MeCP2 and MBD2 was significantly lower in squamous cell carcinoma than in adenocarcinoma or large cell carcinoma (P = 0.03 and P = 0.01). To further elucidate the mechanisms of gene regulation, we analysed MeCP2 and MBD2 regulation during haematopoietic differentiation. No significant changes in MeCP2 or MBD2 expression were found when NB4 cells were differentiated toward granulocytes suggesting that neither differentiation nor cell cycle status were relevant for the reduced expression of these genes in human cancer. In conclusion, the significant loss of MeCP2 and MBD2 expression in human cancers suggests a potential role of this phenomenon in the development of solid human tumours.

Cell Differentiation↗

Synthesis, aggregation, and adsorption phenomena of shape-persistent macrocycles with extraannular polyalkyl substituents.

The synthesis of shape-persistent macrocycles based on the phenyl-ethynyl backbone containing various extraannular alkyl side chains is described. Although compound solubility increases with increasing size of the side groups, decreasing the solvent polarity induces aggregation of the rings by nonspecific interactions. This was investigated by proton NMR spectroscopy. The magnitude of aggregation can be varied by using solvent mixtures of different hexane content, supporting the model of a solvophobic effect. From 1,2,4-trichlorobenzene solution the macrocycle 1c adsorbs at the surface of highly oriented pyrolitic graphite (HOPG). The two-dimensional order of the structure was investigated by scanning tunneling microscopy (STM) revealing the formation of a two-dimensional lattice of p1(2)mm symmetry with lattice parameters A = 3.6 nm, B = 5.7 nm, and Gamma = 74 degrees.

Journal Article↗

A combined study of tumor-related brain lesions using MEG and proton MR spectroscopic imaging.

The purpose of this study is to localize, in cases of brain tumors, pathological magnetic brain activities and to analyze metabolic alterations in functionally abnormal lesions using magnetoencephalography (MEG) and proton magnetic resonance spectroscopic imaging (1H MRSI). The study focused on 10 healthy volunteers and seven patients with common brain tumors, namely astrocytic tumor and meningioma. In spontaneous MEG, the pathological brain activities (slow, fast waves and spikes) were localized using a single equivalent dipole model. After the results of MEG and 1H MRSI were superimposed onto the corresponding MR images, the signal intensities of spectroscopically visible metabolites were analyzed in the regions where the dipoles of the pathological activities were concentrated. Increased slow wave activity was observed in four cases and fast wave or spike activity was significantly increased in one case. These pathological activities were localized in surrounding regions of the bulk of tumors, where mild reduction of N-acetyl aspartate (NAA) and slight accumulation of lactate (Lac) consistently existed. Preserved cortical areas, which are indicated by residual NAA, might be able to generate pathological magnetic activities under lactic acidosis. Such areas could be understood as a border zone between normal and seriously damaged brain tissue by tumors or associated brain edema. This combined technique with the different modalities gives insight into functional as well as metabolic aspects of pathological brain conditions.

Adult↗

Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea.

Collapsibility of the upper airways has been identified as an important pathogenic factor in obstructive sleep apnea (OSA). Objective measures of collapsibility are pharyngeal critical pressure (Pcrit) and resistance of the upstream segment (Rus). To systematically determine the effects of sleep stage and body position we investigated 16 male subjects suffering from OSA. We compared the measures in light sleep, slow-wave sleep, REM sleep and supine vs. lateral positions. The pressure-flow relationship of the upper airways has been evaluated by simultaneous readings of maximal inspiratory airflow (Vimax) and nasal pressure (p-nCPAP). With two-factor repeated measures ANOVA on those 7 patients which had all 6 situations we found a significant influence of body position on Pcrit (p<0.05) whereas there was no significant influence of sleep stage and no significant interaction between body position and sleep stage. When comparing the body positions Pcrit was higher in the supine than in the lateral positions. During light sleep Pcrit decreased from 0.6 +/- 0.8 cm H2O (supine) to -2.2 +/- 3.6 cm H2O (lateral) (p<0.01), during slow-wave sleep Pcrit decreased from 0.3 +/- 1.4 cm H2O (supine) to -1.7 +/- 2.6 (lateral) (p<0.05) and during REM sleep it decreased from 1.2 +/- 1.5 cm H2O to -2.0 +/- 2.2 cm H2O (p<0.05). Changes in Rus revealed no body position nor sleep-stage dependence. Comparing the different body positions Rus was only significantly higher in the lateral position during REM sleep (p<0.05). The results indicate that collapsibility of the upper airways is not mediated by sleep stages but is strongly influenced by body position. As a consequence lower nCPAP pressure is needed during lateral positions compared to supine positions.

Adult↗

New approach to localize speech relevant brain areas and hemispheric dominance using spatially filtered magnetoencephalography.

We used a current localization by spatial filtering-technique to determine primary language areas with magnetoencephalography (MEG) using a silent reading and a silent naming task. In all cases we could localize the sensory speech area (Wernicke) in the posterior part of the left superior temporal gyrus (Brodmann area 22) and the motor speech area (Broca) in the left inferior frontal gyrus (Brodmann area 44). Left hemispheric speech dominance was determined in all cases by a laterality index comparing the current source strength of the activated left side speech areas to their right side homologous. In 12 cases we found early Wernicke and later Broca activation corresponding to the Wernicke-Geschwind model. In three cases, however, we also found early Broca activation indicating that speech-related brain areas need not necessarily be activated sequentially but can also be activated simultaneously. Magnetoencephalography can be a potent tool for functional mapping of speech-related brain areas in individuals, investigating the time-course of brain activation, and identifying the speech dominant hemisphere. This may have implications for presurgical planning in epilepsy and brain tumor patients.

Adult↗

Correlation of sensorimotor activation with functional magnetic resonance imaging and magnetoencephalography in presurgical functional imaging: a spatial analysis.

In this study we investigated the spatial heterotopy of MEG and fMRI localizations after sensory and motor stimulation tasks. Both methods are frequently used to study the topology of the primary and secondary motor cortex, as well as a tool for presurgical brain mapping. fMRI was performed with a 1.5T MR system, using echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI activation was determined with a cross-correlation analysis. MEG source localization was performed with a single equivalent current dipole model and a current density localization approach. Distances between MEG and fMRI activation sites were measured within the same anatomical 3-D-MR image set. The central region could be identified by MEG and fMRI in 33 of 34 cases. However, MEG and fMRI localization results showed significantly different activation sites for the motor and sensory task with a distance of 10 and 15 mm, respectively. This reflects the different neurophysiological mechanisms: direct neuronal current flow (MEG) and secondary changes in cerebral blood flow and oxygenation level of activated versus non activated brain structures (fMRI). The result of our study has clinical implications when MEG and fMRI localizations are used for pre- and intraoperative brain mapping. Although both modalities are useful for the estimation of the motor cortex, a single modality may err in the exact topographical labeling of the motor cortex. In some unclear cases a combination of both methods should be used in order to avoid neurological deficits.

Adolescent↗

[Effect of walking speed on pressure distribution of orthopedic shoe technology].

Lesions to the diabetic foot have various causes. However, there is broad consensus that excessive plantar pressure plays a major role in the chain of events leading to ulcerations and gangrenes. During walking, on the other hand, peak values of plantar pressure are likely to increase with velocity even in therapeutic shoes. Therefore, the question arises whether a moderate velocity should be recommended to diabetic patients to reduce the risk of foot lesions. In this study, two velocities were compared for different types of therapeutic footwear. The velocities selected were considered moderate (0.7 m/s) and normal (1.3 m/s) for diabetic patients. A specially designed mathematical algorithm (velocity normalization) provided the pressure distributions from a common set of measurements: seven trials at different velocities for each subject and each type of footwear. Ten test subjects with healthy feet were studied. The shoes were ready-made and all had a midfoot rocker. The following four conditions were tested: flexible or rigid outsole respectively in combination with a flat insole or molded foot bed respectively. Pressure distribution measurements were performed with the Pedar in-shoe system, and the Pedar software package was used for analysis. The foot was divided into six regions: first toe, second to fifth toes, metatarsal region, medial midfoot, lateral midfoot, and heel. Only peak pressures were taken into account. Gait velocity was found to have an effect on plantar pressure distribution, mainly in the toes and heel region. Peak pressure in the heels increased significantly by about 20%. In the toe region, the increase was about the same, but was not statistically significant. At a higher velocity, pressure even slightly decreased in the midfoot region. The percentage variation was similar for all four conditions. Thus, walking slowly prevented the foot from high peak pressures, and the combination of rigid outsole and molded foot bed was best suited for both slow and higher velocities.

Acceleration↗

Tissue expansion for repair of severely complicated Achilles tendon ruptures.

We report on two patients with severely complicated Achilles tendon ruptures (ATR), including re-rupture, postoperative deep infection and subsequent tissue loss. Tissue expansion was used to facilitate tendon reconstruction and to ensure good healing potential with skin closure without tension. Tissue expansion is a valid option in patients with complicated ATR. The outcome for the two patients described here was good, with improved function and no major complications.

Achilles Tendon↗

Plantar flexor muscle function in open and closed chain.

In the present study, the torque or work produced during isometric, pure concentric and eccentric-concentric plantar flexions, performed in sitting, standing and prone were measured. The electromyographic (EMG) activity was measured from the soleus, gastrocnemius medialis, tibialis anterior and rectus femoris muscles. The isometric tests showed the highest torques in the standing test. The rectus femoris and gastrocnemius activities were lower in the prone than in the standing test. The sitting test showed lower activities in all muscles of the lower leg compared with the standing test. No differences in work between the prone and sitting tests were found during the concentric phases. Higher rectus femoris activity in the eccentric-concentric test and lower activity in the triceps surae during the concentric phases were seen in the sitting compared with the prone test. We conclude that tests of overall functional ability should be performed in the standing position while specific tests of the plantar flexors should be performed in the prone position.

Adult↗

[Treatment costs in initially underestimated infections of the hand].

Summary. Infections that develop as a complication of minor injuries to the hand, frequently are underestimated by the patient or by the physician initially consulted. Between 1990 and 2000, we have treated 172 in-patients as a result of this underestimation. In a retrospective study we have tried to evaluate the economic consequences. According to our results, treatment costs of 210,000 D-Mark could have been saved, if adequate treatment had been initiated on time.

Adolescent↗

Asthma care and factors affecting medication compliance: the patient's point of view.

OBJECTIVE: To identify important factors that can influence patient compliance with prescribed medication and to elucidate aspects of asthma care from the patient's point of view. DESIGN: Field investigation; the interviewer used a semi-structured questionnaire. SETTING: Patients with asthma in primary health care settings in Sweden. STUDY PARTICIPANTS: A sample of 77 patients was randomly selected from 11 primary health care centres in southern Sweden; 63 of these patients participated in the study. CONCLUSION: The factors of importance for self-reported compliance with prescribed medication were age, gender, duration of the disease, the attitude of the staff and information/education about asthma. The patients expressed important aspects of care, and these are in accordance with how an asthma nurse practice functions in Sweden.

Adult↗

Acute rupture of tendon Achillis. A prospective randomised study of comparison between surgical and non-surgical treatment.

In a prospective, randomised, multicentre study, 112 patients (99 men and 13 women, aged between 21 and 63 years) with acute, complete rupture of tendo Achillis were allocated either to surgical treatment followed by early functional rehabilitation, using a brace, or to non-surgical treatment, with plaster splintage for eight weeks. The period of follow-up was for two years. Evaluation was undertaken by independent observers and comprised interviews, clinical measurements, isokinetic muscle performance tests, heel-raise tests and an overall outcome score. The rate of rerupture was 20.8% after non-surgical and 1.7% after surgical treatment (p < 0.001). Surgical and non-surgical treatment produced equally good functional results if complications were avoided. However, the rate of rerupture after non-surgical treatment was unacceptably high.

Achilles Tendon↗

Evolution of morphological novelty: a phylogenetic analysis of growth patterns in Streptocarpus (Gesneriaceae).

Streptocarpus shows great variation in vegetative architecture. In some species a normal shoot apical meristem never forms and the entire vegetative plant body may consist of a single giant cotyledon, which may measure up to 0.75 m (the unifoliate type) or with further leaves arising from this structure (the rosulate type). A molecular phylogeny of 87 taxa (77 Streptocarpus species, seven related species, and three outgroup species) using the internal transcribed spacers and 5.8S region of nuclear ribosomal DNA suggests that Streptocarpus can be divided into two major clades. One of these broadly corresponds to the caulescent group (with conventional shoot architecture) classified as subgenus Streptocarpella, whereas the other is mainly composed of acaulescent species with unusual architecture (subgenus Streptocarpus). Some caulescent species (such as S. papangae) are anomalously placed with the acaulescent clade. Available cytological data are, however, completely congruent with the two major clades: the caulescent clade is x = 15 and the acaulescent clade (including the caulescent S. papangae) is x = 16 (or polyploid multiples of 16). The genera Linnaeopsis, Saintpaulia, and Schizoboea are nested within Streptocarpus. The sequenced region has evolved, on average, 2.44 times faster in the caulescent clade than in the acaulescent clade and this is associated with the more rapid life cycle of the caulescents. Morphological variation in plant architecture within the acaulescent clade is homoplastic and does not appear to have arisen by unique abrupt changes. Instead, rosulate and unifoliate growth forms have evolved several times, reversals have occurred, and intermediate architectures are found. An underlying developmental plasticity seems to be a characteristic of the acaulescent clade and is reflected in a great lability of form.

DNA, Plant↗

Helicobacter pylori induces DNA damage in vitro.

A close association between Helicobacter pylori infection and the development of gastric adenocarcinoma in humans has been demonstrated. Therefore, the direct induction of DNA damage by H. pylori was investigated here using the in vitro micronucleus assay. After 5 days of incubation with bacterial lysate a dose-dependent formation of micronuclei was found, which was not limited to cytotoxic protein concentrations and was not observed after treatment with Escherichia coli lysate (control). This induction of DNA damage may be a link between chronic H. pylori infection and development of adenocarcinoma of the stomach.

Animals↗

Function after Achilles tendon rupture in the elderly: 25 patients older than 65 years followed for 3 years.

We retrospectively analyzed the function after Achilles tendon rupture in 25 patients older than 65 years, 3 (1-5) years after the initial treatment. The patients' median age at the time of injury was 71 (65-86) years. The initial management was surgical in 14 patients and non-surgical (8-week immobilization) in 10, 1 patient was not treated. The ratio of the number of heel-raises on the injured to the uninjured side was median 0.64 (0-1.14), showing a reduction in performance. However, in both surgically- and non-surgically-treated patients, the subjective impairment was mild, and the patients were able to perform most walking activities. Only 9 patients reached their previous activity level. Co-morbidity was frequent: 17 patients had other diseases that affected their performance. 14 complications occurred in 11 patients. 5 patients sustained a rerupture (4 following initial closed treatment with plaster), 1 a deep venous thrombosis and 4 had superficial infections requiring antibiotic treatment. 1 patient sustained a fibular nerve injury following compression by the plaster cast and another a sural nerve injury during the operation. 2 patients had symptoms due to adhesions between the tendon and the skin. We conclude that Achilles tendon rupture in patients older than 65 years reduces lower limb function and that complications are common following surgical and non-surgical treatment.

Achilles Tendon↗

Changes in balance performance in physically active elderly people aged 73-80.

In our hospital in 1989 a series of 30 healthy elderly people participated in a study to evaluate the effect of physical training on improving balance. Thereafter, the majority of the people in this group continued with some kind of balance training. Seven years later we followed up 17 of the people who had participated in the original study. We wanted to evaluate the balance performance of these physically active elderly people (mean age 80.5 years) and compare it with their balance performance 7 years previously. Balance was found to be significantly impaired compared with 1989 in four out of six static balance tests. The time required to walk 30 m had increased significantly. The subjective ratings of vertigo and balance problems had not changed significantly, neither had the number of correct steps when walking forwards on one line and backwards between two lines. In dynamic posturography, the test with sway-referenced visual cues showed improved postural control, but no change in sway was seen in the other five sensory conditions. When sudden backward translations of the platform occurred, increased latencies of force response were seen.

Aged↗