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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 145 records · Page 8Linked to original sources
PubMed2000

Proprioception after total knee arthroplasty: a comparison with clinical outcome.

We determined proprioception in replaced and unreplaced arthrotic knees by measuring threshold levels for the perception of passive knee motion. In addition, results of these proprioception measurements were compared with the clinical outcomes in patients with a total knee arthroplasty. Threshold detection levels were significantly higher in the replaced than in the unreplaced knees. Moreover, detection-failure rates were significantly higher in the replaced knees as well. In contrast to this diminished movement sense in the replaced knees, clinical examination of these knees showed good or excellent outcome in all cases. A correlation between the clinical outcome and the ability to perceive passive motion in either patient group could not be found. We hypothesize that our findings may be due to the operative removal of intraarticular receptor-rich tissue that is affected by arthrosis. This would not only contribute to marked clinical improvements but also to a significant decrease in proprioception.

Activities of Daily Living↗
PubMed2000

NF-kappaB and AP-1 are responsible for inducibility of the IL-6 promoter by ionizing radiation in HeLa cells.

PURPOSE: To investigate the mechanisms leading to initiation by ionizing radiation of IL-6 transcription in HeLa cells. MATERIALS AND METHODS: HeLa cells were irradiated with X-rays at a dose rate of approximately 1 Gy/min or treated with TPA (100 ng/ml). Transient transfection analysis with truncated IL-6 promoter CAT constructs was used to identify the radiation-sensitive region within the IL-6 promoter/enhancer. RESULTS: For basal expression of the IL-6 gene in unirradiated control cells the presence of the binding site for the nuclear factor kappa B (NF-kappaB) and the multiple response elements (MRE) were necessary. After deletion of either the activator protein (AP)-1 or the MRE site, radiation-induced IL-6 promoter CAT activity was significantly reduced, whereas after deletion of the NF-kappaB site it was completely abolished. Maximal radiation-induced IL-6 promoter CAT activity was observed when the AP-1, NF-kappaB and MRE motifs were present. In electrophoretic mobility shift analyses (EMSA), X-ray-inducible activity was found for NF-kappaB and AP-1 at the MRE constitutive, but no inducible activities were detectable. The nuclear factor IL-6 (NF-IL6) element showed no specific radiation-responsive activity. CONCLUSIONS: These results demonstrate that NF-kappaB plays a major role in X-ray-inducible IL-6 expression in HeLa cells. The fact that IL-6 promoter activity was dramatically enhanced in the presence of the MRE and distal AP-1 binding motif is indicative of a cooperative mode of transcriptional activation involving all three transcription factor systems. These data provide new insights into the prodromal events of radiation-induced inflammation of epithelial cells and putatively the cutaneous radiation syndrome.

Binding Sites↗
PubMed2000

Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate.

Glucocorticoid receptor (GR) activation induces apoptosis of granule cells in the hippocampus. In contrast, neuroprotection is seen after mineralocorticoid receptor (MR) activation. To date there is no in vivo evidence for direct interactions between corticosteroids and any of the key regulatory molecules of programmed cell death. In this report, we show that the opposing actions of MR and GR on neuronal survival result from their ability to differentially influence the expression of members of the bcl-2 gene family; specifically, in the rat hippocampus, activation of GR induces cell death by increasing the ratio of the proapoptotic molecule Bax relative to the antiapoptotic molecules Bcl-2 or Bcl-x(L); the opposite effect is observed after stimulation of MR. The same results were obtained in both young and aged animals; however, older subjects (which were more susceptible to GR-mediated apoptosis) tended to express the antiapoptotic genes more robustly. Using a loss-of-function mouse model, we corroborated the observations made in the rat, demonstrating Bax to be essential in the GR-mediated cell death-signaling cascade. In addition, we show that GR activation increases and MR activation decreases levels of the tumor suppressor protein p53 (a direct transcriptional regulator of bax and bcl-2 genes), thus providing new information on the early genetic events linking corticosteroid receptors with apoptosis in the nervous system.

Aging↗
PubMed2000

Aligned microcontact printing of micrometer-scale poly-L-lysine structures for controlled growth of cultured neurons on planar microelectrode arrays.

We describe a method for producing high-resolution chemical patterns on surfaces to control the attachment and growth of cultured neurons. Microcontact printing has been extended to allow the printing of micron-scale protein lines aligned to an underlying pattern of planar microelectrodes. Poly-L-lysine (PL) lines have been printed on the electrode array for electrical studies on cultured neural networks. Rat hippocampal neurons showed a high degree of attachment selectivity to the PL and produced neurites that faithfully grew onto the electrode recording sites.

Animals↗
PubMed2000

Phospholamban: a major determinant of the cardiac force-frequency relationship.

The cardiac force-frequency relationship has been known for over a century, yet its mechanisms have eluded thorough understanding. We investigated the hypothesis that phospholamban, a potent regulator of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), determines the cardiac force-frequency relationship. Isolated left ventricular papillary muscles from wild-type (WT) and phospholamban knockout (KO) mice were stimulated at 2 to 6 Hz. The force-frequency relationship was positive in WT but negative in KO muscles, i.e., it was inverted by ablation of phospholamban (P < 0.01, n = 6 mice). From 2 to 6 Hz, relaxation accelerated considerably (by 10 ms) in WT muscles but only minimally (by 2 ms) in KO muscles (WT vs. KO: P < 0. 0001, n = 6). To show that the lack of frequency potentiation in KO muscles was not explained by the almost maximal basal contractility, twitch duration was prolonged in six KO muscles with the SERCA inhibitor cyclopiazonic acid to WT values. Relaxation still failed to accelerate with increased frequency. In conclusion, our results clearly identify phospholamban as a major determinant of the cardiac force-frequency relationship.

Animals↗
PubMed2000

Cloning, genomic sequence, and chromosome mapping of Scyb11, the murine homologue of SCYB11 (alias betaR1/H174/SCYB9B/I-TAC/IP-9/CXCL11).

A T-cell attracting CXC chemokine phylogenetically related to MIG and SCYB10 was recently characterized and termed SCYB11 (alias betaR1/H174/SCYB9B/I-TAC/IP-9/CXCL11). Here, we cloned the cDNA of the murine homologue of this protein, Scyb11, from interferon-gamma/lipopolysaccharide-stimulated RAW264.7 mouse macrophage-like cells. The nucleotide sequence of Scyb11 shares 63% identity with its human counterpart. It encodes a 100 amino acid immature protein of 11,265 Da which contains a putative signal peptide of 21 amino acids. The molecular mass of the mature protein was calculated to be 9,113 Da. Sequence identity of the murine and human SCYB11 proteins is 68%. Phylogenetic tree analysis of mouse CXC chemokines places SCYB11 together with the murine homologues of MIG and SCYB10 (Crg-2/muIP-10) on an individual branch. A genomic sequence was obtained by genome walking and subcloning DNA fragments from a BAC clone containing Scyb11. Like human SCYB11, Scyb11 contains 4 exons with intron/exon boundaries at positions comparable to the human gene. Whereas introns 2 and 3 are of similar length in the murine and human genes, intron 1 of Scyb11 contains 1,260 bp more than intron 1 of the human gene. Intron 1 of Scyb11 is also characterized by a 201-bp stretch with repetitive sequences of high cryptic simplicity. Using a BAC clone containing Scyb11, this gene could be mapped to chromosome 5 at position 5E3. Since human SCYB11 is localized on 4q21.2, this result confirms the mouse/human homology of the two chromosome regions.

Amino Acid Sequence↗
PubMed2000

Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone.

PURPOSE: Suramin is a novel agent that has demonstrated preliminary evidence of antitumor activity in hormone-refractory prostate cancer (HRPC). A prospective randomized clinical trial was designed to evaluate pain and opioid analgesic intake as surrogates for antitumor response in HRPC patients with significant, opioid analgesic-dependent pain. PATIENTS AND METHODS: A double-blind, placebo-controlled trial randomized patients to receive a 78-day, outpatient regimen of either suramin plus hydrocortisone (HC, 40 mg/d) or placebo plus HC. Treatment assignment was unblinded when either disease progression or dose-limiting toxicity occurred; placebo patients were allowed to cross-over to open-label suramin plus HC. In addition to pain and opioid analgesic intake, prostate-specific antigen (PSA) response, time to disease progression, quality of life, performance status, and survival were compared. RESULTS: Overall mean reductions in combined pain and opioid analgesic intake were greater for suramin plus HC (rank sum P =.0001). Pain response was achieved in a higher proportion of patients receiving suramin than placebo (43% v 28%; P =.001), and duration of response was longer for suramin responders (median, 240 v 69 days; P =.0027). Time to disease progression was longer (relative risk = 1.5; 95% confidence interval, 1.2 to 1.9) and the proportion of patients with a greater than 50% decline in PSA was higher (33% v 16%; P =.01) in patients who received suramin. Neither quality of life nor performance status was decreased by suramin treatment, and overall survival was similar. Most adverse events were of mild or moderate intensity and were easily managed medically. CONCLUSION: Outpatient treatment with suramin plus HC is well tolerated and provides moderate palliative benefit and delay in disease progression for patients with symptomatic HRPC.

Adult↗
PubMed2000

Occlusion: an orthodontic perspective.

In recent years, orthodontists have examined their concepts of occlusion. In current literature, at professional meetings, and in continuing education courses, one hears an ongoing discussion of condylar position and mandibular border movements in relation to occlusion. There is a wide variation in opinion as to whether dental occlusion and TMJ function are interdependent. The authors have adopted a dynamic concept of dental function to replace the traditional static view of molar relationship and incisor overlap. This article discusses how occlusion has evolved in orthodontics and reviews Andrews' six keys to ideal static occlusion, the goals of ideal dynamic occlusion, and the six signs of developing malocclusions. The authors also review the literature on the relationship between orthodontics, occlusion, and TMD.

Child↗
PubMed2000

Auditory language comprehension: an event-related fMRI study on the processing of syntactic and lexical information.

The functional specificity of different brain regions recruited in auditory language processing was investigated by means of event-related functional magnetic resonance imaging (fMRI) while subjects listened to speech input varying in the presence or absence of semantic and syntactic information. There were two sentence conditions containing syntactic structure, i.e., normal speech (consisting of function and content words), syntactic speech (consisting of function words and pseudowords), and two word-list conditions, i.e., real words and pseudowords. The processing of auditory language, in general, correlates with significant activation in the primary auditory cortices and in adjacent compartments of the superior temporal gyrus bilaterally. Processing of normal speech appeared to have a special status, as no frontal activation was observed in this case but was seen in the other three conditions. This difference may point toward a certain automaticity of the linguistic processes used during normal speech comprehension. When considering the three other conditions, we found that these were correlated with activation in both left and right frontal cortices. An increase of activation in the planum polare bilaterally and in the deep portion of the left frontal operculum was found exclusively when syntactic processes were in focus. Thus, the present data may be taken to suggest an involvement of the left frontal and bilateral temporal cortex when processing syntactic information during comprehension.

Adult↗
PubMed1999

Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines.

The role of the calcium-binding protein, calbindin-D(28k) in potassium/depolarization-stimulated increases in the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release was investigated in pancreatic islets from calbindin-D(28k) nullmutant mice (knockouts; KO) or wild type mice and beta cell lines stably transfected and overexpressing calbindin. Using single islets from KO mice and stimulation with 45 mM KCl, the peak of [Ca(2+)](i) was 3.5-fold greater in islets from KO mice compared with wild type islets (p < 0.01) and [Ca(2+)](i) remained higher during the plateau phase. In addition to the increase in [Ca(2+)](i) in response to KCl there was also a significant increase in insulin release in islets isolated from KO mice. Evidence for modulation by calbindin of [Ca(2+)](i) and insulin release was also noted using beta cell lines. Rat calbindin was stably expressed in betaTC-3 and betaHC-13 cells. In response to depolarizing concentrations of K(+), insulin release was decreased by 45-47% in calbindin expressing betaTC cells and was decreased by 70-80% in calbindin expressing betaHC cells compared with insulin release from vector transfected betaTC or betaHC cells (p < 0.01). In addition, the K(+)-stimulated intracellular calcium peak was markedly inhibited in calbindin expressing betaHC cells compared with vector transfected cells (225 nM versus 1,100 nM, respectively). Buffering of the depolarization-induced rise in [Ca(2+)](i) was also observed in calbindin expressing betaTC cells. In summary, our findings, using both isolated islets from calbindin-D(28k) KO mice and beta cell lines, establish a role for calbindin in the modulation of depolarization-stimulated insulin release and suggest that calbindin can control the rate of insulin release via regulation of [Ca(2+)](i).

1-Methyl-3-isobutylxanthine↗
PubMed1999

Bronchodilation using combined urodilatin - albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial.

Urodilatin, the renal form of natriuretic peptide type A, induces bronchodilation, increasing intracellular cyclic guanosine monophosphate (cGMP), whereas the bronchorelaxant effect by b2-agonists is triggered by cyclic adenosine monophosphate (cAMP). The objective of this investigation is to demonstrate the efficacy of urodilatin in inducing bronchodilation, and to show this activity alone or in combination with albuterol. Therefore, a randomized, double-blind, placebo-controlled, dose-finding study with cross-over design was carried out including 12 stable, mild to severe (step 2 to 4, definition by NIH/NHLBI guideline 1997) asthmatics. 96 treatments were thus performed. The intervention was comprised of an intravenous infusion of urodilatin (0, 10, 30, or 60 ng/kg/min) combined with inhaled albuterol (0 or 200 microg). As primary objective, the increase in forced expiratory volume in one second (FEV subset1) was measured. - The trial shows that urodilatin at all applied doses or 200 microg albuterol significantly increases FEV subset1 (p < 0.05). Combination of urodilatin and albuterol treament significantly improves FEV subset1 (p < 0.05) compared to either monotherapy and results in maximum bronchodilation. - From the results, the following conclusions can be drawn. In stable asthmatics, the combined activation of cGMP- and cAMP-mediated pathways results in a significantly improved, maximal bronchodilation in comparison to either type of monotherapy. This shows that urodilatin combined with albuterol improves lung function and ameliorates the therapy in asthmatics.

Adult↗
PubMed1999

Effects of mutant and antisense RNA of phospholamban on SR Ca(2+)-ATPase activity and cardiac myocyte contractility.

BACKGROUND: The delayed cardiac relaxation in failing hearts has been attributed to a reduced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2). Phospholamban (PLB) inhibits SERCA2 activity and is therefore a potential target to improve the cardiac performance in heart failure. METHODS AND RESULTS: Mutants of PLB (Adv/mPLB) or antisense RNA of PLB (Adv/asPLB) was expressed in cardiac myocytes by recombinant adenovirus, and their effects on SERCA2 activity and myocyte contractility were studied. One mPLB, K3E/R14E, pentamerized with endogenous PLB in neonatal myocytes and resulted in a 45% increase in the affinity of SERCA2 for Ca(2+) and 27% faster diastolic Ca(2+) decline as determined by SR (45)Ca uptake assays and by indo 1-facilitated Ca(2+) transient measurement, respectively. Edge-detection analysis of adult myocyte contractility showed a 74% increase in fractional shortening, accompanied by 115% increase in velocity of relengthening and 25% decrease in time to half-maximal relengthening. In parallel, infection of neonatal cardiac myocytes by Adv/asPLB decreased the endogenous PLB level by 54%, which was associated with a 35% increase in Ca(2+) affinity of SERCA2 and 21% faster diastolic Ca(2+) decline. However, in adult cardiac myocytes, Adv/asPLB failed to significantly alter the endogenous PLB level, the SERCA2 activity, or most of the contractile parameters. CONCLUSIONS: K3E/R14E is a dominant negative mutant of PLB that disrupts the structural integrity and function of the endogenous PLB and consequently enhances SERCA2 activity and myocyte contractility. In neonatal myocytes, the decrease in steady-state abundance of PLB by asPLB also leads to increased SERCA2 activity.

Adenoviridae↗
PubMed1999

Parapoxviruses: potential alternative vectors for directing the immune response in permissive and non-permissive hosts.

Parapoxvirus (PPV) represents a genus of the poxviridae, and particularly PPV ovis (Orf virus, OV) seems to offer several potential advantages for the use of vector vaccine. Therefore, we started to investigate the genome of the highly attenuated OV strain D1701, which was only poorly characterised until now. Due to recombination of non-homologous sequences, part of the right hand end of the D1701 genome was duplicated and translocated to the opposite end of the genome. As a consequence gene deletion had occurred and the inverted terminal repeat region is increased. Results are described to identify viral genes, which are non-essential for virus replication and potentially influence viral pathogenesis, virulence, and host immunity. In more detail, we analysed the expression and functional activity of the OV-specific vascular endothelial growth factor (VEGF) gene homologue. Finally the construction and production of a D1701 mutant lacking the VEGF gene homologue is reported.

Animals↗
PubMed1999

Application of a peptide bank from porcine brain in isolation of regulatory peptides.

Over the past years, the introduction of biological assay systems, random peptide sequencing and orphan receptor screening has led to the isolation and identification of new regulatory peptides with potential clinical impact. We have developed a method for separating peptides into about 300 fractions from large amounts of porcine brain tissue. The preparation of this peptide bank consists of three steps including ultrafiltration followed by cation-exchange separation and reversed-phase chromatography. These fractions represent the peptide bank with desalted and lyophilized peptides from brain tissue. Molecular masses of the peptides in the fractions are determined by matrix-assisted laser desorption ionization MS and a mass data bank is subsequently generated. For systematic analysis of the peptides, a subsequent two-step purification procedure is followed by Edman sequencing resulting in the identification of different peptides. A survival assay with a neuronal cell line revealing the stimulatory and inhibitory activities is applied as a model to test the 300 fractions. This primary screen indicates that the biological activities of the extracted peptides are easily characterized and, moreover, can be related to the biochemical entities. We conclude that the established peptide bank is an efficient and useful tool for the isolation of regulatory brain peptides applying different purification strategies.

Animals↗
PubMed1999

Overexpression of sarcoplasmic reticulum Ca(2+)-ATPase improves cardiac contractile function in hypothyroid mice.

OBJECTIVE: Prolonged cardiac contraction and relaxation in hypothyroidism are in part related to diminished expression of the gene coding for the calcium pump of the sarcoplasmic reticulum (SERCA2a). Therefore, we examined whether or not transgenic SERCA2a gene expression in mice may compensate for the cardiac effects of hypothyroidism. METHODS: SERCA2a mRNA and protein were analyzed from hearts of euthyroid and hypothyroid mice of wild-type or SERCA2a transgene status. Contractile function was studied in isolated left ventricular papillary muscles. RESULTS: We found significant decreases of SERCA2a mRNA and protein levels in hearts of hypothyroid wild-type mice in comparison with euthyroid wild-type mice (controls). Papillary muscles from hypothyroid wild-type mice showed significant increases in time to peak contraction and relaxation times compared with controls. In contrast, SERCA2a mRNA and protein levels were significantly higher in hypothyroid SERCA2a transgenic mice than in hypothyroid wild-type mice. The transgene led to a functional improvement by compensating for the prolonged contraction and relaxation of papillary muscles. CONCLUSIONS: Our murine model of hypothyroidism revealed decreases in SERCA2a gene expression accompanied by prolonged contraction and relaxation of papillary muscles, and an improvement of the contractile phenotype due to compensated SERCA2a gene expression in SERCA2a transgenic mice.

Animals↗
PubMed1999

Porcine guanylin and uroguanylin: cDNA sequences, deduced amino acid sequences, and biological activity of the chemically synthesized peptides.

Guanylin and uroguanylin are structurally related intestinal peptide hormones which were purified from a limited number of mammals and are capable of activating the particulate guanylate cyclase-C. Although the biological functions of guanylin and uroguanylin are not yet clarified in detail, they are involved in the regulation of the intestinal water and electrolyte balance. In order to verify the general importance of this hormone system in mammals, we cloned the corresponding cDNAs from pig. Here, we present the nucleotide sequences and the deduced amino acid sequences representing porcine guanylin and uroguanylin. The expression patterns of the corresponding genes, as shown by Northern hybridization and RT-PCR analysis, resemble those of the human homologues. Further, we demonstrate the bioactivity of both porcine peptide hormones by inducing the intracellular cGMP production in human T84 cells and by ion transport experiments using porcine intestinal mucosa in the Ussing chamber.

Amino Acid Sequence↗
PubMed1999

On the geometry of a modern imaging diffractometer.

The geometry of a modern imaging diffractometer is discussed in detail. A method to find all relevant instrument parameters from the control single-crystal measurement data is proposed and the limitations of such a procedure are indicated. Optimization of the instrument parameters by the least-squares method is presented.

Journal Article↗