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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 55 records · Page 3Linked to original sources
PubMed2004

Cytotoxic and antimicrobial coumarins from Mammea africana.

Six coumarin derivatives [three 4-phenylcoumarins (Mammea A/AA, Mammea A/BA and MAB 3), two 4-n-propylcoumarins (Mammea B/BB and Mammea B/BA) and one 4-n-pentylcoumarin (Mammea C/OB)], 1,5-dihydroxyxanthone and 1-methoxy-5-hydroxyxanthone have been isolated from the stem bark of Mammea africana Sabine collected in Cameroon. Although known, the structures of the coumarin derivatives were confirmed by spectral analysis, including two-dimensional nuclear magnetic resonance. All the coumarin compounds showed noteworthy cytotoxicity against the human 9-KB cell line. Both of the 4-n-propylcoumarins were also found to exhibit significant activity against Staphylococcus aureus.

Anti-Bacterial Agents↗
PubMed2004

[Molecular biology of haemostasis: fibrinogen, factor XIII].

Genetic defects of fibrinogen are caused by a broad spectrum of mutations in one of the three structural genes FGA, FGB and FGG. They result in complete or partial lack of plasma fibrinogen (a- or hypofibrinogenaemia) or in structural abnormalities affecting protein function (dysfibrinogenaemia). In contrast to afibrinogenaemia mainly caused by nonsense, frameshift, and splice site mutations resulting in substantially truncated polypeptide chains (mainly Aalpha), in hypo- and dysfibrinogenaemias missense mutations lead to the exchange of single amino acids as dominating underlying defect. In the cases with quantitative disorders, bleeding with various degrees of severity is generally observed. Dysfibrinogenaemia is associated with both bleeding or thrombosis or even a combination of haemorrhagic and thromboembolic symptoms. About one half of the dysfibrinogenaemic cases is clinically asymptomatic. The plasmatic factor XIII (FXIII) is a heterotetramer composed of two A and two B subunits encoded by two different genes. FXIII deficiency is associated with bleeding, wound dehiscence and recurrent spontaneous abortions. The most frequent form is caused by defects in the A subunit with a broad spectrum of underlying mutations. Defects of the B subunit are very rare and were molecularly elucidated in only a few cases.

Amino Acid Substitution↗
PubMed2004

A simulation model for small-area cancer incidence rates.

OBJECTIVES: Cancer epidemiologists are often asked by members of the interested public about possible associations between suspected carcinogens and apparently increased small-area cancer incidence rates. Frequently, no systematic incidence differences can be demonstrated. Nevertheless, it is necessary to address public concerns about suspected cancer clusters. To facilitate explanations about the large random variation of small-area tumor incidence, we implemented a software simulation tool in R. METHODS: Under the assumption of no cancer causes other than chance, the tool simulates a small village population with an average number of five inhabitants per house and allows graphical visualisation of ten streets with 100 houses. Published age-specific incidence and mortality data are used for event sampling based on the binomial distribution. Program parameters include sample size, age distribution, cancer incidence, and mortality rates. RESULTS: On average, 22 percent (2.2/10) of all houses per street have been inhabited by at least one cancer patient during the last five years in our simulated small village. A situation where all (10) houses in a street have been inhabited by at least one cancer patient during the last five years appears to be very rare (less than one in a million streets). CONCLUSIONS: Our software tool can be used effectively for numerical and graphical visualisation of small-area tumour incidence and prevalence rates due to chance alone. The explanation of basic epidemiological concepts to members of the public can help to increase public motivation and support for population-based cancer registration. Our simulation tool can be used to support this goal.

Adolescent↗
PubMed2003

Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23.

The orphan receptor ChemR23 is a G-protein coupled receptor (GPCR) with homology to neuropeptide and chemoattractant receptors. Tazarotene, a synthetic retinoid activating retinoic acid receptor (RAR), up-regulates tazarotene-induced gene-2 (TIG2). The function and molecular target of this protein are now described. By means of reverse pharmacology screening using a peptide library generated from human hemofiltrate, we have isolated and identified TIG2 as the natural ligand of ChemR23 and report the specific molecular form of the bioactive, circulating TIG2, representing the amino-acid residues 21 to 154 of the 163 amino acid-containing prepropeptide. Based on the expression pattern of ChemR23 and TIG2, the physiological role in bone development, immune and inflammatory responses and the maintenance of skin is now being investigated.

Amino Acid Sequence↗
PubMed2003

MRI in acute subarachnoid haemorrhage; findings with a standardised stroke protocol.

There is doubt as to whether acute haemorrhage is visible on MRI. We carried out MRI within 6 h of symptom onset on five patients with minor (low Hunt and Hess grades 1 or 2) subarachnoid haemorrhage (SAH) diagnosed by CT to search for any specific pattern. We used our standard stroke MRI protocol, including multiecho proton density (PD)- and T2-weighted images, echoplanar (EPI) diffusion- (DWI) and perfusion- (PWI) weighted imaging, and MRA. In all cases SAH was clearly visible on PD-weighted images with a short TE. In four patients it caused a low-signal rim on the T2*-weighted source images of PWI, and DWI revealed high signal in SAH. In the fifth patient SAH was perimesencephalic; susceptibility effects from the skull base made it impossible to detect SAH on EPI DWI and T2*-weighted images. Perfusion maps were normal in all cases. MRA and conventional angiography revealed an aneurysm in only one patient. Stroke MRI within 6 h of SAH thus shows a characteristic pattern.

Adult↗
PubMed2003

Self-affine fractal variability of human heartbeat interval dynamics in health and disease.

The complexity of the cardiac rhythm is demonstrated to exhibit self-affine multifractal variability. The dynamics of heartbeat interval time series was analyzed by application of the multifractal formalism based on the Cramèr theory of large deviations. The continuous multifractal large deviation spectrum uncovers the nonlinear fractal properties in the dynamics of heart rate and presents a useful diagnostic framework for discrimination and classification of patients with cardiac disease, e.g., congestive heart failure. The characteristic multifractal pattern in heart transplant recipients or chronic heart disease highlights the importance of neuroautonomic control mechanisms regulating the fractal dynamics of the cardiac rhythm.

Circadian Rhythm↗
PubMed2003

Fractal dynamics in circadian cardiac time series of corticotropin-releasing factor receptor subtype-2 deficient mice.

Non-linear fractal analysis of circadian 24 hr heartbeat interval time series was performed in corticotropin releasing factor receptor-subtype 2 (CRFR2) deficient mice. We hypothesized that, as a result of its central as well as its peripheral expression, CRFR2 would mediate or interfere with the circadian rhythmicity. The dynamical properties of cardiac interbeat intervals were expected to be different between CRFR2 (+/+) and CRFR2 (-/-) mice when studied over an extended circadian 24 hr cycle. The dynamics of neurocardiac control were found to remain remarkably stable throughout the circadian cycle. In disagreement with the initial hypothesis, the dynamical properties underlying the cardiac control process were common to both CRFR2 (+/+) and CRFR2 (-/-) mice suggesting that control of heart rate does not rely on the elaborate interaction of the CRFR2-sensor and its intrinsic feedback arrangement. Lack of expression of CRFR2 would not compromise cardiac control and its dynamical output or is subserved by other, unknown mechanisms. Functional integrity of CRFR2 would not constitute an indispensable requirement of physiologic cardiac control. The circadian rhythm of heart rate is generated centrally and is independent of expression of CRFR2. While 'normal' strain C57BL/6N mice exhibit a circadian dark/light cycle of heart rate, absence of circadian fluctuations in transgenic CRFR2-mice (both +/+ and -/-) and 'normal' strain C57BL/6J mice points at the importance of other deficiencies that may be related to a common genetic background. Mutant mice that share a common 129SvJ- or C57BL/6J-derived genetic background may not present an optimal model for physiological studies of cardiovascular control.

Algorithms↗
PubMed2003

Circular polarization of ion fluorescence completing the analysis of resonant Xe* 4d(-1)(5/2)6p Auger decay.

The relative contributions of the partial electron waves emitted in the Auger decay of the Xe* 4d(-1)(5/2)6p(J(*)=1) resonance have been determined by fluorescence polarimetry after excitation with circularly polarized synchrotron radiation. The analysis of circularly polarized fluorescence of the photoion leads to an independent determination of the orientation parameters for all states of the Xe II 5p(4)6p multiplet. The present study provides, in combination with data on the angular distribution and spin polarization of the Auger electrons, complete quantum mechanical information on the resonant Auger decay, i.e., branching ratios and relative phases of the Auger decay amplitudes.

Journal Article↗
PubMed2003

Early outcome and cost-effectiveness of endoscopic versus open carpal tunnel release: a randomized prospective trial.

Proponents of endoscopic carpal tunnel release have been advocating the technique for more than 10 years but there is still debate about its efficacy, safety and cost-effectiveness. We have performed a randomized, prospective, blind trial to compare early outcome after single portal endoscopic or open carpal tunnel surgery and to assess the cost-effectiveness of the procedures. There were no significant differences in symptom and functional activity scores, grip strength or anterior carpal pain in the first 3 months. For those in employment, we found a statistically significant difference between the two treatment groups with the endoscopic group returning to work, on average, 8 (95% CI, 2-13 days) days sooner than the open group. This translates into a cost saving to industry. There were no major neurovascular complications in either group. On the basis of these findings, we recommend that endoscopic carpal tunnel release should be considered in the employed as a cost-effective procedure, but perhaps not in the general population as a whole.

Activities of Daily Living↗
PubMed2003

Proteus syndrome.

A 34-year-old male patient was referred with a recalcitrant leg ulcer overlying an extensive vascular malformation, which had led several times to septic soft tissue infections. During his infancy he had been diagnosed to have Klippel-Trenaunay syndrome. Clinical examination revealed asymmetric hypertrophy of the lower extremities, an extensive portwine stain on the more severely affected left limb as well as prominent venous varicosities of both legs. Hands and feet showed striking cerebriform palmoplantar hypertrophy, and macrodactily with syndactily of several fingers. All toes had been amputated in early childhood due to extreme overgrowth and currently the patient walked on his forefeet in a prominent pes equinus deformity. Further symptoms consisted in several lipomas at both arms, another portwine stain at the left hemithorax and a single café-au-lait spot at the left scapula. Angio-magnetic resonance imaging scans of both legs showed an extensive venous-lymphatic vascular malformation involving the whole subcutis and infiltrating the muscle. The chronic wound was interpreted as venous stasis ulceration. Local percutaneous sclerotherapy of the dilated veins underneath the ulcer was discussed, but considered to carry a relevant risk of skin necrosis with consecutive progression of the wound. A conventional split-skin graft led to complete wound healing. Since, the patient consequently wears custom-made compression stockings and remained free from recurrences. The syndromatic constellation of palmoplantar overgrowth, multiple lipomas, giant fingers and toes, limb overgrowth, venous-lymphatic malformation and a café-au-lait spot led to the diagnosis of Proteus syndrome. The possible aetiology, clinical manifestations, differential diagnosis and management of this rare disorder are discussed.

Adult↗
PubMed2003

Cluster of TRIM genes in the human MHC class I region sharing the B30.2 domain.

The major histocompatibility complex (MHC), a region of high gene density, contains a large number of genes relevant to the immune response, belonging to different multigenic families. We studied the genomic organization and polymorphism of a set of genes in the MHC class I region containing the tripartite motif (TRIM), consisting of a RING domain, B-box and coiled coil region, and a B30.2-like domain. A cluster of seven genes at 6p21.33 and two related family members telomeric of the cluster were characterized. All MHC-encoded TRIM-B30.2 genes showed moderate levels of polymorphism, affecting predominantly the RING and B-box domains. In terms of structure, the genes varied by the loss of partial and, in some cases, complete domains. They were strongly conserved in exons 2, 3 and 4, which form the coiled-coil region. The last exon, encoding the B30.2-like domain, is shared with the otherwise unrelated butyrophilin-like (BTN) genes, located 4.3 Mb telomeric of the TRIM-B30.2 cluster. The data are consistent with multiple, ancient duplications giving rise to a set of related genes.

Amino Acid Motifs↗
PubMed2003

Endothelial nitric oxide synthase (ecNOS) 4 a/b gene polymorphism and carotid artery intima-media thickness in type-1 diabetic patients.

AIM: To study putative associations of the ecNOS 4 a/b polymorphism with carotid artery intima-media thickness (IMT) and diabetic complications in young type-1 diabetic patients. METHODS: Study participants were 147 type-1 diabetic patients (56 men and 91 women), mean age 30.1 +/- 6.6 years (range 14 - 44), with a diabetes duration of 13.1 +/- 8.1 years. HbA1c, albuminuria, and lipid status were assessed by standard laboratory techniques, the ecNOS 4 a/b genotype was determined by polymerase chain reaction with subsequent polyacrylamide gel electrophoresis. The patients were categorized according to the presence or absence of hypertension, nephropathy and retinopathy. The IMT, which can be used to estimate early stages of arteriosclerosis, was measured by high-resolution ultrasonography. RESULTS: The ecNOS genotypes were distributed as follows: 7.5 % a/a, 30.6 % a/b, and 61.9 % b/b. The IMT values did not differ between the patients with various ecNOS genotypes (a/a: 0.62 +/- 0.13; a/b: 0.63 +/- 0.21; b/b: 0.63 +/- 0.13; all: 0.63 +/- 0.15 mm). The prevalence of retinopathy was significantly higher in patients with the b/b genotype (odds ratio: 2.4 vs. a/a+a/b; 95 % CI, 1.1 - 5.3). CONCLUSIONS: Our results do not support the hypothesis that the ecNOS 4 a/b polymorphism interacts with the development of early carotid arteriosclerosis in young type-1 diabetic patients, but they give grounds to assume that in these patients it could influence the occurence of diabetic retinopathy.

Adolescent↗
PubMed2002

Strong, polarized Balmer-alpha fluorescence after resonant core excitation of HCl.

Visible-UV fluorescence has been analyzed after resonant Cl 2p core excitation of HCl molecules. The dispersed fluorescence spectra are dominated by emissions from atomic fragments. In particular, an intense and polarized Balmer H(alpha) line is observed after photoexcitation of the 2p(-1)nl Rydberg states. The excited hydrogen atoms are efficiently produced in the resonant Auger process and the subsequent dissociation of high lying HCl+ states. The experimental results, complemented by a time-resolved measurement of the H(alpha) decay, point to a universal mechanism for the production of H( n = 3) atoms in the dissociation of innershell excited HCl molecules.

Journal Article↗
PubMed2002

Glial cell line-derived neurotrophic factor up-regulates GTP-cyclohydrolase I activity and tetrahydrobiopterin levels in primary dopaminergic neurones.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurones against toxic and physical damage. In addition, GDNF promotes differentiation and structural integrity of dopaminergic neurones. Here we show that GDNF can support the function of primary dopaminergic neurones by triggering activation of GTP-cyclohydrolase I (GTPCH I), a key enzyme in catecholamine biosynthesis. GDNF stimulation of primary dopaminergic neurones expressing both tyrosine 3-monooxygenase and GTPCH I resulted in a dose-dependent doubling of GTPCH I activity, and a concomitant increase in tetrahydrobiopterin levels whereas tyrosine 3-monooxygenase activity was not altered. Actinomycin D, asan inhibitor of de novo biosynthesis, abolished any GDNF-mediated up-regulation of GTPCH I activity. However, GTPCH I mRNA levels in primary dopaminergic neurones were not altered by GDNF treatment, suggesting that the mode of action for that up-regulation is not directly connected to the regulation of GTPCH I transcription. We conclude that GDNF, in addition to its action in structural differentiation, also promotes differentiation regarding expression and enzymatic activity of a crucial component in the dopaminergic biosynthetic pathway.

Animals↗
PubMed2002

CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted imaging results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) has become a commonly used imaging modality in stroke centers. The value of this method as a routine procedure is still being discussed. In previous studies, CT was always performed before DWI. Therefore, infarct progression could be a reason for the better result in DWI. METHODS: All hyperacute (<6 hours) stroke patients admitted to our emergency department with a National Institutes of Health Stroke Scale (NIHSS) score >3 were prospectively randomized for the order in which CT and MRI were performed. Five stroke experts and 4 residents blinded to clinical data judged stroke signs and lesion size on the images. To determine the interrater variability, we calculated kappa values for both rating groups. RESULTS: A total of 50 patients with ischemic stroke and 4 patients with transient symptoms of acute stroke (median NIHSS score, 11; range, 3 to 27) were analyzed. Of the 50 patients, 55% were examined with DWI first. The mean delay from symptom onset until CT was 180 minutes; that from symptom onset until DWI was 189 minutes. The mean delay between DWI and CT was 30 minutes. The sensitivity of infarct detection by the experts was significantly better when based on DWI (CT/DWI, 61/91%). Accuracy was 91% when based on DWI (CT, 61%). Interrater variability of lesion detection was also significantly better for DWI (CT/DWI, kappa=0.51/0.84). The assessment of lesion extent was less homogeneous on CT (CT/DWI, kappa=0.38/0.62). The differences between the 2 modalities were stronger in the residents' ratings (CT/DWI: sensitivity, 46/81%; kappa=0.38/0.76). CONCLUSIONS: CT and DWI performed with the same delay after onset of ischemic stroke resulted in significant differences in diagnostic accuracy. DWI gives good interrater homogeneity and has a substantially better sensitivity and accuracy than CT even if the raters have limited experience.

Acute Disease↗
PubMed2001

Neurons in the monoaminergic nuclei of the rat and human central nervous system express FA1/dlk.

The gene DLK1 encodes a member of the epidermal growth factor (EGF) superfamily, delta-like (dlk). When exposed in vivo to the action of an unknown protease, this type 1 membrane protein generates a soluble peptide referred to as Fetal antigen 1 (FA1). By acting in juxtacrine as well as paracrine/autocrine manners, both forms have been shown to be active in the differentiation/proliferation process of various cell types. In adults, FA1/dlk has been demonstrated mainly within (neuro) endocrine tissues. In this study we investigated the presence of FA1/dlk in other parts of the developing and adult rat and human CNS. Using immunocytochemistry and in situ hybridization we found that in both species FA1/dlk was expressed in neurons of the Edinger-Westphal's nucleus as well as in substantia nigra, ventral tegmental area (VTA), locus coeruleus and in certain parts of the raphe nuclei.

Aged↗
PubMed2001

Reactivity of the inversely polarized phosphaalkenes RP=C(NMe2)2 (R = tBu, Me3Si, H) towards arylcarbene complexes [(CO)5M=C(oEt)Ar] (Ar= Ph, M = Cr, W; Ar = 2-MeC6H4, 2-MeOC6H4, M = W).

The reaction of the arylated Fischer carbene complexes [(CO)5M=C(OEt)Ar] (Ar=Ph; M = Cr, W; 2-MeC6H4; 2-MeOC6H; M = W) with the phosphaalkenes RP=C(NMe2), (R=tBu, SiMe3) afforded the novel phosphaalkene complexes [[RP=C(OEt)Ar]M(CO)5] in addition to the compounds [(RP=C(NMe2)2]M(CO)5]. Only in the case of the R = SiMe3 (E/Z) mixtures of the metathesis products were obtained. The bis(dimethylamino)methylene unit of the phosphaalkene precursor was incorporated in olefins of the type (Me2N)2C=C(OEt)(Ar). Treatment of [(CO)5W=C(OEt)(2-MeOC6H4)] with HP=C(NMe2)2 gave rise to the formation of an E/Z mixture of [[(Me2N)2CH-P=C(OEt)(2-MeOC6H4)]W(CO)5] the organophosphorus ligand of which formally results from a combination of the carbene ligand and the phosphanediyl [P-CH(NMe2)2]. The reactions reported here strongly depend on an inverse distribution of alpha-electron density in the phosphaalkene precursors (Pdelta Cdelta+), which renders these molecules powerfu] nucleophiles.

Journal Article↗