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T Meyer

Publications and source records attributed to T Meyer.

At least 109 records · Page 6Linked to original sources
PubMed2001

Residue mass plot and abundance plot: detection of isobaric interferences in DE-MALDI-TOF-mass spectra of complex polymer mixtures.

Mass spectra of complex polymer mixtures often disturbed by overlapping homologue peak series have been interpreted by means of the novel techniques of the residue mass plot and the abundance plot. The model substance used for the investigations is so far poorly characterized non-ionic emulsifier Cremophor EL (polyoxyl 35 castor oil) (CrEL), a heterogeneous polyethoxylate mixture. Because of its high amount of hydrophobic and hydrophilic components, CrEL was separated into two fractions, aqueous and methanolic, by cation exchange (CCaEx) chromatography. CrEL was then subjected to delayed extraction matrix-assisted laser desorption/ionization time of flight mass spectrometry (DE-MALDI-TOF-MS). Evaluation of the mass spectra was performed by comparing the residue masses of the homologue peak series with the calculated residue masses of potential components of the excipient cationized with Na+ and K+. A number of these series are overlapping because they differ in their theoretical residue masses by about 0.05 Da. The detection of these isobaric interferences was the basic requirement for our analysis method. This goal was achieved by high mass accuracy of the measurements (obtained by internal calibration) in combination with two newly developed evaluation methods, the residue mass plot and the abundance plot. Using this combined technique, generally applicable for complex polymer mixtures, it was shown that the aqueous CCaEx fraction contains hydrophobic components such as di- and triesters of ricinoleic acid and polyethylene glycol as well as glycerol polyoxyethylene di- and triricinoleates, whereas the methanolic fraction contains hydrophilic components, mainly polyethylene glycol (PEG) and glycerol polyoxyethylene ether. Moreover, free PEG was shown to consist of PEG 800 in contrast to the value of 600 Da described so far in literature.

Chromatography, Ion Exchange↗
PubMed2001

Identification of cylin-dependent kinase 1 inhibitors of a new chemical type by structure-based design and database searching.

We have selected cyclin-dependent kinase 1 (CDK1), an enzyme participating in the regulation of the cell cycle, as a target in our efforts to discover new antitumor agents. By exploiting available structural information, we designed an ATP-site directed ligand scaffold that allowed us to identify 4-(3-methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-ylamino)-benzenesulfonamide as a new potent inhibitor of CDK1 in a subsequent database search. The synthesis and testing of some analogues confirmed the interest of this class of compounds as novel CDK1 inhibitors.

Antineoplastic Agents↗
PubMed2001

Weekly cisplatin and oral etoposide as treatment for relapsed epithelial ovarian cancer.

BACKGROUND: Response rates to chemotherapy in relapsed, platinum resistant epithelial ovarian cancer remain poor. We have explored the effectiveness of weekly cisplatin combined with prolonged oral etoposide in this patient group. PATIENTS AND METHODS: Forty-two women with relapsed, advanced ovarian cancer were treated with cisplatin 60 mg/m2 on days 1, 8, 15, 29, 36 and 43 and oral etoposide 50 mg given from day 1-14 and day 29-43. In those who were responding and tolerating treatment (n = 13) oral etoposide 50 mg was continued for two further cycles (days 1-21 repeated every 28 days). The interval since last platinum containing chemotherapy was > 6 months in 28 patients and < 6 months in 16 patients. RESULTS: Thirty-six patients were evaluable for response according to CA 125 criteria giving an overall response rate of 44%. The response rate in evaluable patients declined with increasing numbers of previous treatments: 57% with one prior treatment, 42% with two, 40% with three or more. The response rate in patients who had received platinum chemotherapy within six months prior to treatment was 46%. The only significant non-haematological toxicity was nausea and vomiting in 4 patients who experienced greater than grade 2 toxicity. The number of patients experiencing haematological toxicity more than grade 2 was as follows: haemoglobin 3, white blood count 12, platelets 6. Sixteen patients had dose delays and two had dose reductions. CONCLUSION: We conclude that this short but intensive regimen provides worthwhile response rates, even in those patients who would ordinarily be considered refractory to platinum, and has an acceptable toxicity profile.

Adenocarcinoma, Clear Cell↗
PubMed2001

Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases.

BACKGROUND: Actinic keratoses (AK) are premalignant lesions, which are routinely treated by destructive procedures such as cryotherapy, electrodessication or topical 5-fluorouracil. OBJECTIVES: The aim of this study is to report six cases of AK treated with a potential new topical therapy, imiquimod. METHODS: Subjects included in this study had suffered with recurrent AK for between 5 and 16 years. All six men were treated with imiquimod 5% cream three times a week for 6-8 weeks. In the event of a local skin reaction treatment was modified to two times per week. RESULTS: All the AK lesions were successfully cleared after treatment with imiquimod cream 5% for 6-8 weeks. Histologically, no apparent signs of persisting AK could be detected, and no recurrences were reported during follow up. CONCLUSIONS: This study suggests that imiquimod may be useful as a new therapy for the treatment of actinic keratoses.

Administration, Cutaneous↗
PubMed2001

Fluorescence urethroscopy following instillation of 5-aminolevulinic acid: a new procedure for detecting clinical and subclinical HPV lesions of the urethra.

OBJECTIVE: To report early clinical experience with intraurethral instillation of 5-aminolevulinic acid (ALA) for the detection of clinical lesions (condyloma acuminata) and subclinical human papillomavirus (HPV) lesions of the urethra, not visible by conventional endoscopy. SUBJECTS AND SETTING: Eighty-four men with clinical diagnosis of condyloma acuminata were examined for urethral HPV lesions at the Department of Urology, Ludwig Maximilian University, Munich, Germany. METHODS: The anogenital areas of the patients were thoroughly examined using a magnifying glass before and after application of 5% acetic acid. Conventional as well as fluorescence urethroscopy were performed 1 h after topical application of 0.1% ALA for 15 min. A sensitive colour charge-coupled device camera for fluorescence video inspection was used with spectral analysis. Biopsies were taken for histological examination and HPV detection by polymerase chain reaction (PCR). RESULTS: Forty-three of 84 men attending our clinic for condyloma acuminata had clinical HPV lesions of the urethra. Condylomas of the proximal urethra were found by conventional endoscopy in eight patients. Fluorescence urethroscopy detected additional subclinical lesions in 13 men. All lesions were HPV infections of the urethra confirmed histologically or by PCR. In nine of these subclinical urethra lesions low-risk HPV types (HPV6, 11, 34) were found. Four lesions were associated with high-risk types (HPV18, 31,52,58). CONCLUSIONS: Fluorescence urethroscopy is a promising diagnostic procedure for detecting subtle clinical and subclinical HPV lesions of the urethra, that are normally not visualized by conventional endoscopy. Generally, urethroscopy is recommended in all cases of externally visible condylomas of the urethra after therapy.

Adolescent↗
PubMed2001

How large is the optic disc? Systematic errors in fundus cameras and topographers.

PURPOSE: To determine whether or not there are systematic differences in the areas of optic discs as measured by different machines using different measurement algorithms and whether racial or gender differences exist in optic disc area measurements. METHODS: We examined the results of twenty-three published studies on the size of normal optic discs of various patient populations. Studies differed in the type of instrument and method used to measure optic disc area, and the number, age, race and gender of subjects examined. Noticing that different machines exhibited statistically significant systematic differences in optic disc sizes of comparable populations, we computed a "normalization" factor for each machine based on these mean differences. Applying this normalization factor to the results, we then re-examined the differences between racial and gender groups. RESULTS: By comparing the results of mean optic disc areas of different racial groups made with different machines, and normalizing results according to those of the Zeiss fundus camera, we found the normalization factors for the following machines to be, Zeiss fundus camera: 1 (by definition), Rodenstock Optic Disc Analyzer (RODA): 1.51, Topcon fundus camera: 1.04, Heidelberg Retina Tomograph (HRT): 1.15 and TopSS scanning laser ophthalmoscope: 1.29. That is, to bring the results of area measurements made with a RODA machine in line with those made with a Zeiss fundus camera, one should multiply the former by the factor 1.51. Using the normalized results, we confirmed the findings of previous authors that the optic disc areas of black subjects were statistically significantly larger than those of white subjects (n-weighted mean effect = 0.556 +/- 0.142 S.E., n = 5). Further, the meta-analysis of various racial populations from five studies shows that males have significantly larger discs than females (n-weighted mean effect = 0.151 +/- .055 S.E., n = 9). CONCLUSION: Different machines and techniques give different results when populations of similar racial composition are measured. We recommend applying the above normalizing factors when comparing studies that employ different instruments.

Adolescent↗
PubMed2001

Tissue differentiation and cytokine synthesis during strain-related bone formation in distraction osteogenesis.

To investigate the contributions of various cytokines that are involved in mechanically related bone formation, we applied defined uniaxial strains in a rabbit model of mandibular elongation and examined the regenerating bone during early stages of dist raction osteogenesis by histomorphometry. We also measured serum concentrations of various cytokines during the distraction. Cell proliferation and differentiation indices correlated significantly (P<0.001) with the extent of load application. Serum concentrations of insulin-like growth factor-1 (IGF-1) decreased after osteotomy whereas transforming growth factor beta1 (TGFbeta1) showed a postoperative increase. Prostaglandin E2 (PGE2) concentrations were constant throughout the experimental period. Collagen degradation decreased slightly postoperatively and increased in samples exposed to higher magnitudes of strain. Our data show that it is the magnitude of mechanical strain that decides tissue response by a characteristic cell proliferation and differentiation. The operative trauma leads to inverse changes in serum concentrations of TGFbeta1 and IGF-1, thereby promoting the recruitment of osteoblastic precursor cells as well as collagen matrix synthesis.

Animals↗
PubMed2001

Microstructural investigations of strain-related collagen mineralization.

Distraction osteogenesis in rabbit mandibles after osteotomy can be used as an experimental model to study the microstructural features of mineralization of callus under defined mechanical loads. Our aim was to study the relation between the micromotions in the gap and the resulting features of mineralization of the matrix. We found that assembly of collagen and formation of crystals depended on the magnitude of the mechanical stress applied. At physiological bone strains (2000 microstrains), the callus had collagen type I in a mature bone-like extracellular arrangement, whereas at 20000 microstrains bundles were orientated predominantly towards the tension vector. Maximum loads (200000 microstrains) resulted in disorganized assembly of the collagen. Quantitative energy-dispersive analysis by X-rays confirmed that high strains were associated with substantially lower concentrations of calcium and phosphate. In contrast to bone-like apatitic formation of crystals at physiological strains, significantly fewer but larger crystals were detected by electron diffraction analysis in samples exposed to high strains. We suggest that mechanical stress regulates the assembly and mineralization of collagen during distraction osteogenesis.

Animals↗
PubMed2001

Mechanical tension in distraction osteogenesis regulates chondrocytic differentiation.

Differentiation of chondrocytes to cells of osteoblastic phenotype occurs during an interim period of bone development, fracture repair and distraction osteogenesis. To study the relationship between tension-stress and chondrogenesis, uniaxial strains (0 microstrains, 2000 microstrains, 20000 microstrains, 200000 microstrains, 300000 microstrains) were applied in a rabbit model of mandibular distraction osteogenesis. The results demonstrated that cell differentiation, apoptosis and tissue development in the newly formed gap tissue showed a correlation to the applied strain magnitudes. Only strains of 20000 microstrains resulted in a statistically significant (P<0.05) formation of cartilage struts with embedded chondrocyte-like cells. However, chondrocyte-like cells were rarely detected in samples distracted at lower or higher strain magnitudes. Osteoblasts appeared to replace cartilaginous matrix by mineralized bone matrix. The phenotypic change from chondrocytes to osteoblasts was accompanied by a decreased proteoglycan synthesis. a change in the expression from type II collagen towards type I and involved asymmetric cell divisions and apoptotic cell death. Therefore, we suggest that mechanical strain is an external stimulus responsible for phenotypic cell alterations.

Analysis of Variance↗
PubMed2001

[Measurement of the Fowler dead space in patients with pulmonary emphysema using C18O2].

In patients with lung emphysema, changes in lung volumes as well as changes in airway resistance are well known. The change in airway resistance is caused by obstruction of central airways, which is supposed to reduce the respiratory dead space. Until now, it was not possible to measure the respiratory dead space in patients with lung emphysema using the method of Fowler [2], because in this method distinction of the three phases of an inert gas expirogram is essential. While this distinction is easy in healthy subjects (fig. 1; expirogram 3), the separation of the three phases in patients with lung emphysema is not possible due to gradual transition of phase II into phase III in these patients (fig. 1; expirogram 2). The use of C18O2 as tracer gas allows to separate phase II and phase III even if the patients have severe emphysema (fig. 1; expirogram 1). CO2 labeled with the stable oxygen isotope 18O (C18O2) is completely taken up in the gas exchanging region of the lung, but not from the conducting airways. Therefore C18O2 is only expired from the dead space of the lung, but not from the alveolar region. Hence, C18O2 allows exact measurement of the respiratory dead space in patients with lung emphysema. 21 healthy nonsmoking subjects and 29 patients with clinical signs of lung emphysema participated in this study. There was a good correlation between respiratory dead space, measured by the use of Ar-gas and C18O2-gas in healthy subjects (fig. 2). This indicates, that the use of C18O2 is a valid method to measure the functional dead space. As expected, there was also a correlation between the airway resistance and respiratory dead space in patients with lung emphysema (fig. 3), but not in healty subjects. There was no significant difference of the mean values of the respiratory dead space between these two groups (223 +/- 43 ml in healthy subjects vs. 227 +/- 52 ml in patients), even though there were large differences in airway resistance (0.20 +/- 0.10 kPa/l/s vs. 0.49 +/- 0.27 kPa/l/s). This may be due to a loss of alveolar function in the area of the terminal bronchioli, which is typical for emphysematous patients. This entails a shift of functional dead space towards lung periphery and therefore causes an increase of the volume of functional dead space. But this enlargement may be compensated by the volume reduction, caused by the airway obstruction. Hence, these two oppositional mechanisms may result in only minimal change of dead space volume.

Adult↗
PubMed2001

Reliability of gas exchange measurements from two different spiroergometry systems.

Reliability of two different spiroergometric systems was investigated by comparing gas exchange measurements from two consecutive identical bicycle ergometer ramp exercise tests which were conducted after an initial habituation trial. Twenty-three healthy subjects (age: 25+/-5 years; weight: 71+/-10 kg; peak oxygen uptake: 55+/-9 ml x min(-1) x kg(-1)) took part in the study. One apparatus was a portable mixing chamber system (MetaMax I, Cortex, Leipzig, Germany), the other one a stationary spiroergometric device measuring in the breath-by-breath mode (MetaLyzer 3B, Cortex). There were no relevant systematic changes in gas exchange measurements and heart rate from test 1 to test 2. Intra-class reliability coefficients were 0.984 (oxygen uptake = VO2), 0.977 (carbon dioxide output = VCO2), and 0.973 (minute ventilation = VE) for the MetaMax I, and 0.969 (VO2), 0.964 (VCO2), and 0.953 (VE) for the MetaLyzer 3B. Bland-Altman plots revealed a slightly smaller variability of MetaLyzer 3B measurements compared to those of MetaMax I. It is concluded that the spiroergometric devices MetaMax I and MetaLyzer 3B represent reliable instruments for exercise testing in sports medical routine and research. This is important to decide if longitudinal changes in gas exchange measurements represent clinically meaningful differences in performance or merely inconsistencies of the measuring tool.

Adult↗
PubMed2001

Hemoglobin enhances tissue factor expression on human malignant cells.

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

Carcinoma, Transitional Cell↗
PubMed2001

Anaerobic exercise induces moderate acute phase response.

PURPOSE: It was intended to compare the immune reaction after single and repeated short bouts of anaerobic exercise. METHODS: Twelve unspecifically trained male subjects (27 +/- 2 yr, 75 +/- 2 kg, VO(2peak) 52 +/- 2 mL x min(-1) x kg(-1)) performed one 60-s all-out test (SMT) on a cycling ergometer and the same test followed by eight 10-s all-out tests every 5 min (AN-TS). These tests and one control day (Co-Day) were applied in randomized order. At rest and 15 min, 2 h, and 24 h after cessation of exercise the following venous blood parameters were determined: concentration of neutrophils and (CD16(+ -)) premacrophages (both flow-cytometrically), interleukin 6 and 8 (IL-6, IL-8), C-reactive protein (CRP) and cortisol. RESULTS: Two hours after cessation of exercise the neutrophils increased stronger after AN-TS than after SMT (P < 0.01). The peak in the number of premacrophages occurred earlier after SMT (15 min post; P < 0.01 to Co-Day) than after AN-TS (2 h post; P < 0.05 to Co-Day). IL-6 was elevated at 15 min and 2 h after AN-TS (P < 0.01 to SMT and Co-Day) but only slightly 2 h after SMT (P < 0.01 to Co-Day). There were no significant changes in IL-8. CRP was the only elevated parameter 24 h postexercise exclusively after AN-TS (P < 0.05 to Co-Day). CONCLUSIONS Repeated short anaerobic bouts of cycling lead to an acute phase response, which is more pronounced than after a single bout. Athletes should take care in performing such training sessions several times a week because signs of inflammation are detectable even 24 h after cessation of exercise.

Acute-Phase Reaction↗
PubMed2001

Regulation of microglia by CD4+ and CD8+ T cells: selective analysis in CD45-congenic normal and Toxoplasma gondii-infected bone marrow chimeras.

Microglia, the resident macrophage population of the central nervous system, is rapidly activated in murine Toxoplasma encephalitis (TE). However, the precise contribution of microglia to intracerebral immune reactions and the in vivo regulation of microglial activity are still poorly understood. To selectively analyse microglial reactions in TE, we have established a model of radiation-induced CD45-congenic bone marrow chimeras between CD45.2+ C57BL/6 (recipient) and CD45.1+ B6.SJL (donor) mice. These chimeras allow a differentiation of radioresistant CD45.2+ microglia from all other leukocytes, which exhibit the CD45.1+ haplotype. In the normal brain, microglia produced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10, and IL-15 mRNA. In TE, marked microglial activation was observed with a de novo expression of IL-12p40 and inducible nitric oxide synthase mRNA, upregulation of IL-1beta and TNF-alpha mRNA, a continuous production of IL-10, and IL-15 mRNA, an induction of major histocompatibility class I and II antigens, intercellular adhesion molecule-1, and leukocyte function-associated antigen-1. Furthermore, selective depletion of CD4+ and/or CD8+ T cells in the chimeras revealed that microglial cytokine production was critically regulated by CD8+T cells, whereas expression of cell surface molecules was less dependent on T cells. These findings demonstrate a specific regulation of microglia by T lymphocytes during the course of TE.

Animals↗
PubMed2001

Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma.

A loss of the glutamate transporter EAAT2 has been reported in the neoplastic transformation of astrocytic cells and astrocytoma. The RNA expression of EAAT2 and five 5'-regulatory splice variants was investigated to identify alterations of the post-transcriptional EAAT2 gene regulation in human astrocytic tumours. Three known (EAAT2, HBGTII, and HBGTIIC) and two novel (EAAT2/3 and EAAT2/31) EAAT2 transcripts originating from alternative splicing of 5'-regulatory sequences were subject to an RNA expression analysis using reverse transcription and competitive PCR. Specimens of astrocytoma World Health Organisation (WHO) grade I-IV in 14 patients and control brain tissue obtained from three normal persons were studied. The main EAAT2 RNA was found to be equally expressed in normal human brain and astrocytic tumour samples. By contrast, the expression pattern of four 5'-variants of the transporter transcript was altered in the investigated series of astrocytoma compared with normal brain. HBGTII, HBGTIIC, and EAAT2/3 were amplified from seven and four tumours and one sample, respectively. EAAT2/31 was expressed in none of the tumour specimens studied. In conclusion, in astrocytic tumours of different histopathological grades there was a substantial reduction of RNA splicing events in EAAT2. The impairment of EAAT2 splicing indicates an altered expression which is not primarily involved in the tumorigenesis but may contribute to some biological properties of astrocytoma such as oedema, necrosis, and tumour related seizures.

Alternative Splicing↗