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Biomedical subjects

T Meyer

Publications and source records attributed to T Meyer.

At least 163 records · Page 9Linked to original sources
PubMed2000

Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II.

Synaptic plasticity is thought to be a key process for learning, memory and other cognitive functions of the nervous system. The initial events of plasticity require the conversion of brief electrical signals into alterations of the biochemical properties of synapses that last for much longer than the initial stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin-dependent protein kinase IIalpha (CaMKII), sequentially translocates to postsynaptic sites, undergoes autophosphorylation and gets trapped for several minutes until its dissociation is induced by secondary autophosphorylation and phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation for several minutes. This suggests that trapping of CaMKII by its targets and priming of CaMKII translocation may function as biochemical memory mechanisms that change the signaling capacity of synapses.

Aniline Compounds↗
PubMed2000

Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum.

BACKGROUND: Despite numerous therapeutic options the treatment of common warts and molluscum contagiosum remains unsatisfactory for both patients and physicians. Imiquimod, a novel topical immune response modifier, has been successfully used for the treatment of external anogenital warts. OBJECTIVES: We aimed to evaluate the safety, tolerance and efficacy of imiquimod for the treatment of common cutaneous warts and mollusca that were resistant to previous therapeutic interventions. METHODS: Imiquimod 5% cream was self-applied by the patients to the warts or mollusca once daily for 5 days per week and left in place overnight. Assessment for response and the occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 16 weeks. RESULTS: Twenty-eight of 50 (56%) patients with warts achieved a total clearance (n = 15; 30%) or a > 50% reduction in wart size (n = 13; 26%) after a mean treatment period of 9.2 weeks. Twelve of 15 (80%) patients with mollusca achieved a total clearance (n = 8; 53%) or a > 50% reduction in molluscum size (n = 4; 27%). There was no difference in response with regard to gender, human immunodeficiency virus serostatus or atopic predisposition. CONCLUSIONS: Patient-applied 5% imiquimod cream holds promise as an effective treatment of common warts and mollusca in a difficult-to-treat patient population.

Adolescent↗
PubMed2000

Detection of human papillomavirus and response to topical 5% imiquimod in a case of stucco keratosis.

Stucco keratosis is a skin disorder with papular warty lesions that usually appear on the lower limbs in elderly people. The aetiology, pathogenesis and treatment is still a matter of debate. We report a 75-year-old non-immunosuppressed man with extensive lesions all over his body, which had not responded to curettage or electrodesiccation. To determine the possible role of human papillomavirus (HPV) in stucco keratosis, we used nested polymerase chain reaction (PCR) to identify HPV DNA in the lesions. To include a broad range of both cutaneous and mucosal HPV types, PCR was performed with two sets of degenerate primers. Using this approach we detected HPV types 9, 16, 23b, DL322 and a variant of HPV type 37 in multiple stucco keratoses. Imiquimod (5% cream), a new compound that modifies the immune response by stimulating production of cytokines, applied overnight, three times a week for 5 weeks, resulted in resolution of all treated lesions.

Aged↗
PubMed2000

Role of tumour markers in monitoring epithelial ovarian cancer.

Currently the only tumour marker to have a well-defined and validated role in the management of ovarian cancer is CA125. Changes in the level of CA125 can be used as a reliable indication of response or progression according to various criteria, but it does not yet have a clear place in diagnosis or prognosis. Its value as part of a screening tool and during routine follow-up remain the subject of ongoing trials. Other markers remain experimental and do not have a well-defined contribution to make at present.

Biomarkers, Tumor↗
PubMed2000

The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial.

BACKGROUND: A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia, the Panic and Agoraphobia Scale (P & A). The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients (panic attacks, avoidance, anticipatory anxiety, disability and worries about health). The application of this scale in a double-blind placebo-controlled panic disorder trial is described. At the same time, the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy. METHODS: Patients with Panic disorder (DSM-IV) were randomly assigned to three treatment modalities: running (n=45), clomipramine (n=15) or placebo (n=15). Treatment efficacy was measured with the Panic and Agoraphobia Scale (P & A) and other rating scales. RESULTS: According to the P & A and other scales, both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment. Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise. The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability. CONCLUSIONS: The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments. Analysis of the scales five subscores may help to understand mechanisms of action of panic disorder treatments.

Agoraphobia↗
PubMed2000

Influence of glutaraldehyde fixation on the detection of SLA-I and II antigens and calcification tendency in porcine cardiac tissue.

OBJECTIVE: Immunological effects have been addressed as key factors for the long-term results of biological porcine aortic prostheses. In this study we investigated the influence of glutaraldehyde fixation on the expression of SLA (swine leucocyte antigens) and the calcification of porcine cardiac tissue. DESIGN: Deparaffinized sections obtained from porcine aortic tissue were fixed in a buffered glutaraldehyde solution for 1, 2, 3, 24 and 72 hours, respectively, and finally immunostained with monoclonal anti-SLA class I antibody 2.27-3a and anti-SLA-II antibody MSA3. Sixteen samples from fixed porcine cardiac tissue and, for comparison, 8 samples from leaflets of Toronto-SPV and Freestyle valves were implanted subcutaneously in 10 Wistar rats for 12 weeks and their calcium content was measured by atomic absorption spectrophotometry. RESULTS: SLA-I epitopes were no longer detectable using anti-SLA-I antibodies after fixation for 3 h. The SLA-II antigens remained detectable after longer fixation period. Short-time fixation resulted in marked calcification of the porcine cardiac tissue and to destruction of the SLA-I epitopes, whereas, even after longer fixation time, the epitopes of the SLA-II antigen remain unaffected. CONCLUSION: Chelate formation due to glutaraldehyde treatment provides protection against calcification. Short-time fixed porcine cardiac tissue has a tendency towards a greater degree of calcification than longer fixation periods. Based on the present results, it is pointless to set the length of fixation to switch off the immunogenicity.

Animals↗
PubMed2000

Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined combined pulmonary emphysema and lung fibrosis.

The simultaneous occurrence of pulmonary fibrosis and emphysema may present considerable problems in clinical assessment. Recent studies have shown that Aerosol Derived Airway Morphometry (ADAM) and Aerosol Bolus Dispersion (ABD) are changed in patients with pulmonary emphysema. This study was performed to assess the effect of simultaneous lung fibrosis in patients with emphysema on ADAM and ABD. ADAM and ABD measurements were performed in 20 patients with lone high resolution CT scan (HRCT) confirmed emphysema (E), and compared to those in 15 emphysematics with HRCT-confirmed superimposed pulmonary fibrosis (FE). In both groups the peripheral effective airspace dimension (EAD) (E: 0.63 +/- 0.20 mm; FE: 0.60 +/- 0.27 mm, N.S.) was increased by more than a factor of two compared to that of healthy subjects (0.28 +/- 0.05 mm) (p < 0.001). Patients with E showed a significantly higher bolus dispersion than patients with FE (724 +/- 122 cm3 vs. 546 +/- 80 cm3; p < 0.001). However, in patients with FE, bolus dispersion was still significantly higher than in previously published control groups of healthy subjects (546 +/- 80 cm3 vs. 455 +/- 68 cm3; p < 0.001). The results of this study confirm that ADAM and ABD are powerful tools for identifying emphysema even in patients with superimposed pulmonary fibrosis.

Aerosols↗
PubMed2000

Frequency and spectrum of HPV types detected in cutaneous squamous-cell carcinomas depend on the HPV detection system: a comparison of four PCR assays.

BACKGROUND: The association of human papillomavirus (HPV) with cutaneous squamous-cell carcinomas (SCCs) has been described recently, but the frequency and spectrum of HPV types identified differed substantially in distinct studies. OBJECTIVE: Comparison of different PCR assays with respect to sensitivity and range of HPV types detected. METHOD: Cutaneous SCC were analyzed for HPV DNA using both consensus PCR assays with degenerate primers and PCR assays with nondegenerate primers derived from HPV types 5 and 8. RESULTS: HPV DNA was found in 50% of SCC specimens using degenerate primers. The rate of HPV-DNA-positive specimens increased to 69% when PCR assays with nondegenerate primers were applied in addition. The spectrum of HPV types detected with each of the PCR assays differed considerably. CONCLUSIONS: The frequency and spectrum of HPV types detected in cutaneous SCC strongly depends on the HPV detection system used and urges the need for standardization of HPV detection and typing in skin lesions in order to characterize HPV types predominating in distinct tumors.

Aged↗
PubMed2000

Therapeutic impact of exercise on psychiatric diseases: guidelines for exercise testing and prescription.

Aerobic exercise seems to be effective in improving general mood and symptoms of depression and anxiety in healthy individuals and psychiatric patients. This effect is not limited to aerobic forms of exercise. There are almost no contraindications for psychiatric patients to participate in exercise programmes, provided they are free from cardiovascular and acute infectious diseases. However, very little is known about the effects of exercise in psychiatric disease other than those in depression and anxiety disorders. A few reports indicate the need for controlled investigations in psychotic and personality disorders. Unfortunately, no general concept for a therapeutic application of physical activity has been developed so far. Reliance on submaximal measures is highly recommended for fitness assessment. Monitoring of exercise intensity during training sessions is most easily done by measuring the heart rate using portable devices (whereas controlling the exact workload may be preferable for scientific purposes). Appropriate pre- and post-training testing is emphasised to enable adequate determinations of fitness gains and to eventually allow positive feedback to be given to patients in clinical settings.

Adult↗
PubMed2000

PKC412--a protein kinase inhibitor with a broad therapeutic potential.

The staurosporine derivative PKC412 was originally identified as an inhibitor of protein kinase C (PKC) and subsequently shown to inhibit other kinases including the kinase insert domain receptor (KDR) (vascular endothelial growth factor receptor, VEGF-R2), the receptor of platelet-derived growth factor, and the receptor for the stem cell factor, c-kit. PKC412 showed a broad antiproliferative activity against various tumor and normal cell lines in vitro, and was able to reverse the Pgp-mediated multidrug resistance of tumor cells in vitro. Exposure of cells to PKC412 resulted in a dose-dependent increase in the G2/M phase of the cell cycle concomitant with increased polyploidy, apoptosis and enhanced sensitivity to ionizing radiation. PKC412 displayed a potent antitumor activity as single agent and was able to potentiate the antitumor activity of some of the clinically used cytotoxins (Taxol and doxorubicin) in vivo. The combined treatment of PKC412 with loco-regional ionizing irradiation showed significant antitumor activity against tumors which are resistant to both ionizing radiation and chemotherapeutic agents (dysfunctional p53). The finding that PKC412 is an inhibitor of the VEGF-mediated cellular signaling via inhibition of KDR and PKC in vitro is consistent with the in vivo inhibition of VEGF-dependent angiogenesis in a growth factor implant model. Orally administered PKC412 also strongly inhibited retinal neovascularization as well as laser-induced choroidal neovascularization in murine models. In summary, PKC412 may suppress tumor growth by inhibiting tumor angiogenesis in addition to directly-inhibiting tumor cell proliferation via its effects on PKC and/or other protein kinases. PKC412 is currently in Phase I clinical trials for treatment of advanced cancer as well as for the treatment of ischemic retinopathy.

Angiogenesis Inhibitors↗
PubMed2000

Preimplant ultrastructure and calcification tendency of various biological aortic valves.

BACKGROUND AND AIM OF THE STUDY: In recent years a number of fixation and anti-calcification methods have been developed, but little is yet known about the calcification process of biological valves. The aims of this study were to: (i) perform a systematic ultrastructural investigation on various biological valves; and (ii) determine the extent of calcification of these valves in a subcutaneous rat model. METHODS: The following porcine aortic prostheses were investigated: Toronto-SPV, Intact, Freestyle, Mosaic and Hancock-II. Samples taken from the valve leaflets, and in the case of the Freestyle and Toronto-SPV valves also from the aortic wall, were examined ultrastructurally using scanning and transmission electron microscopy. Other samples were implanted subcutaneously in Wistar rats for 12 weeks. The calcium content of the samples was measured using atomic absorption spectrophotometry. RESULTS: All valves examined showed a considerable loss of the endothelial cover. Significant changes in valve ultrastructure were also detected. With regard to calcium content, two valve groups could be distinguished (p <0.05): (i) those with high calcium content, e.g. Toronto-SPV and Intact (>40 mg/g dry tissue); and (ii) those with low calcium content, e.g. Mosaic, Freestyle and Hancock-II (<5 mg/g). CONCLUSION: Fixation methods have pronounced effects on the ultrastructural integrity of bioprostheses. The degenerative calcification of bioprostheses can be effectively inhibited by glutaraldehyde-free fixation and anti-calcification treatments.

Animals↗
PubMed2000

[When each person thinks he is less exposed to risks than others, but more receptive to health prevention messages].

Comparative optimism consists of projecting oneself into a situation that is advantageous in relation to others. This is observed in the estimation of future risks, as well as in the evaluation of prevention messages: people who consider themselves less exposed to risks but more receptive than others to prevention messages. Our experimental research, which included a sample of 523 people, examines the effect of prevention messages on comparative optimism regarding future risks such as automobile accidents, domestic accidents or infectious diseases. Three independent variables were tested: the framing of messages, the context of judgement, and the target of comparison. The framing of messages consisted of centering the arguments on losses resulting from the absence of prevention or on the benefits of prevention. The context allowed for the evaluation of the perception of risks with or without a prevention message or reading instructions. People should have indicated if they were more or less likely to be at risk compared to someone close to them (a friend) or to an abstract entity (someone of their generation). Our study shows that the preliminary attention to prevention messages diminishes comparative optimism relative to future risks when the target of comparison is abstract, and the instruction increases the personal implication; it increases the comparative optimism regarding future risks when the comparison is to someone familiar and the messages are framed negatively. The discussion relates to the applications of these results for the conception and evaluation of prevention messages.

Adolescent↗
PubMed1999

The RNA of the glutamate transporter EAAT2 is variably spliced in amyotrophic lateral sclerosis and normal individuals.

Impaired re-uptake of synaptic glutamate, and a reduced expression of the glutamate transporter EAAT2 have been found in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Two splice forms of the EAAT2 RNA resulting from retention of intronic sequences (EAAT2/Int) and deletion of one protein coding exon (EAAT2/C1) have been reported to account for the EAAT2 protein loss in ALS. In this study we investigated the presence of two known (EAAT2/C1; EAAT2/Int) and three novel (EAAT2/C2-4) EAAT2 RNA in motor cortex of 17 ALS cases and 11 controls. Reverse transcription and PCR were carried out to amplify the complementary DNA of the complete and variably spliced EAAT2 transcripts. Nested PCR was followed to generate amplicons specific for EAAT2/C1-4 and EAAT2/Int. EAAT2/Int was detected in 59% of ALS specimens as compared to 36% of controls showing a trend but no statistical significance of a more frequent expression in ALS (Type I error 24.6%). EAAT2/C1-4 were found to be equally expressed in ALS patients and controls. Our results indicate that the involvement of EAAT2 transcripts in ALS is unlikely to be primary, and more complex than previously recognized. Alterations of quantitative expression of distinct EAAT2 splice forms in ALS cannot be excluded from this study and remain to be investigated.

Aged↗
PubMed1999

A versatile microporation technique for the transfection of cultured CNS neurons.

The application of molecular techniques to cultured central nervous system (CNS) neurons has been limited by a lack of simple and efficient methods to introduce macromolecules into their cytosol. We have developed an electroporation technique that efficiently transfers RNA, DNA and other large membrane-impermeant molecules into adherent hippocampal neurons. Microporation allowed the use of either in vitro transcribed RNA or cDNA to transfect neurons. While RNA transfection yielded a higher percentage of transfected neurons and produced quantitative co-expression of two proteins, DNA transfection yielded higher levels of protein expression. Dextran-based calcium indicators also were efficiently delivered into the cytosol. Microporated neurons appear to survive poration quite well, as indicated by their morphological integrity, electrical excitability, ability to produce action potential-evoked calcium signals, and intact synaptic transmission. Furthermore, green fluorescent protein (GFP)-tagged marker proteins were expressed and correctly localized to the cytosol, plasma membrane, or endoplasmic reticulum. The microporation method is efficient, convenient, and inexpensive: macromolecules can be introduced into most adherent neurons in a 3 mm2 surface area while requiring as little as 1 microl of the material to be introduced. We conclude that the microporation of macromolecules is a versatile approach to investigate signaling, secretion, and other processes in CNS neurons.

Animals↗
PubMed1999

Selective GRB2 SH2 inhibitors as anti-Ras therapy.

Given the key role of Ras in the mitogenic signaling by receptor tyrosine kinases, several targets upstream of Ras may prove to be excellent targets for drugs in the treatment of cancer caused by oncogenic tyrosine kinases. CGP78850 is a potent competitor of Grb2 SH2-phosphopeptide interactions. This inhibitor has been obtained by rational drug design and is specific toward the Grb2 SH2 vs. other SH2 domains and the PTB domain of SHC in vitro. Accordingly, CGP78850 blocks epidermal growth factor receptor (EGFR)-Grb2 and Shc-Grb2 interactions in living cells. It also inhibits the growth of cells transformed by receptor tyrosine kinases, which transmit a proliferative signal through Grb2 to Ras, but not cells transformed by oncogenic Raf or cells that contain activating Ras mutations. Moreover, our results demonstrate that, in cells overexpressing receptor tyrosine kinases, such as the EGFR, Grb2 SH2 inhibitors induce expression of the cell cycle inhibitors p21(Waf1/Cip1/CAP1) and p27(Kip1) and reverse transformation.

3T3 Cells↗
PubMed1999

Antisense oligonucleotides against receptor kinase GRK2 disrupt target selectivity of beta-adrenergic receptors in atrial myocytes.

K+ channels composed of GIRK subunits are predominantly expressed in the heart and various regions of the brain. They are activated by betagamma-subunits released from pertussis toxin-sensitive G-proteins coupled to different seven-helix receptors. In rat atrial myocytes, activation of K(ACh) channels is strictly limited to receptors coupled to pertussis toxin-sensitive G-proteins. Upon treatment of myocytes with antisense oligodesoxynucleotides against GRK2, a receptor kinase with Gbetagamma binding sites, in a fraction of cells, K(ACh) channels can be activated by beta-adrenergic receptors. Sensitivity to beta-agonist is insensitive to pertussis toxin treatment. These findings demonstrate a potential role of Gbetagamma binding proteins for target selectivity of G-protein-coupled receptors.

Animals↗