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J Lehmann

Publications and source records attributed to J Lehmann.

At least 19 recordsLinked to original sources
PubMed1999

The combined effect of interferon beta and radiation on five human tumor cell lines and embryonal lung fibroblasts.

PURPOSE: The combined effect of natural Interferon-beta (n-IFN-beta) and ionizing radiation was tested in vitro on 5 different tumor cell lines and 1 embryonal lung fibroblast cell line. MATERIALS AND METHODS: The following cell lines were used: A549 (lung cancer), MCF-7 (breast cancer), CaSki (cervical cancer), WiDr (colon cancer), ZMK-1 (head and neck cancer), and MRC-5 (embryonal lung fibroblast line). Cells were incubated with n-IFN-beta (30 I.U./ml to 3000 I.U./ml) 24 h before irradiation. Irradiation was given as single dose between 1 and 6 Gy. Cell survival was evaluated using a standard colony-forming assay. RESULTS: Incubation with n-IFN-beta enhanced the effect of radiation in all tumor cell lines tested. The maximum sensitizing enhancement ratios (SER) at the 37% survival level were: 1.66 for A549 cells, 1.47 for CaSki cells, 1.56 for MCF-7 cells, 1.40 for WiDr cells, and 1.57 for ZMK-1 cells. In the nonneoplastic MRC-5 cell line, no radiosensitizing effect of n-IFN-beta could be demonstrated. The linear quadratic fit of the survival curves showed an increase of the alpha-component for all tumor cell lines treated with n-IFN-beta. CONCLUSIONS: IFN-beta enhanced the effect of radiation in the tumor cell lines, but not in the nonmalignant lung fibroblasts. The increase of the alpha component in the survival curves indicates that impaired radiation repair or the accumulation of sublethal damage might play a role for the radiosensitizing effect of n-IFN-beta.

Humans↗
PubMed1999

Effects of paclitaxel in combination with radiation on human head and neck cancer cells (ZMK-1), cervical squamous cell carcinoma (CaSki), and breast adenocarcinoma cells (MCF-7).

BACKGROUND AND PURPOSE: The anticancer drug paclitaxel, a natural product from Taxus brevifolia, is a microtubule-stabilising agent, which has been shown to block different cells in the G2/M phase of the cell cycle and so modulate their radioresponsiveness. We investigated the radiosensitizing potential of paclitaxel in human head and neck cancer cells (ZMK-1), in cervical squamous cell carcinoma cells (CaSki) and in breast adenocarcinoma cells (MCF-7). METHODS: ZMK-1 cells were incubated with paclitaxel for 3, 9, or 24 h before irradiation. ZMK-1-, CaSki- and MCF-7 cells were incubated with paclitaxel for 24 h after irradiation. The paclitaxel concentration (70 nM, 7 nM, 0.7 nM) was chosen to obtain equivalent toxicity at the different incubation times (3 h, 9 h, 24 h respectively). Radiation doses were from 0 to 8 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of paclitaxel to cause accumulation of cells in the G2/M phase of the cell cycle. RESULTS: Paclitaxel alone was cytotoxic in a time- and concentration-dependent manner. Up to 36% of the ZMK-1 cells accumulated in G2/M after treatment for 24-36 h. If the cells were incubated with paclitaxel before irradiation the isoeffect enhancement ratios for ZMK-1 cells, determined at the 37% survival level, were 0.81, 1.48 and 1.15 for 3-h, 9-h, and 24-h pre-incubations respectively. For a paclitaxel incubation of 24 h after irradiation, the isoeffect enhancement ratios, determined at the 37% survival level, were 0.72, 0.76 and 1.2 for the ZMK-1. CaSki, and MCF-7 cells respectively. CONCLUSION: In the three cell lines no radiosensitizing effect of paclitaxel could be demonstrated unambiguously. The use of asynchronized cells or the support of cellular repair mechanisms while the cells are blocked in G2/M could partly explain the results.

Adenocarcinoma↗
PubMed1998

Differential mucin MUC7 gene expression in invasive bladder carcinoma in contrast to uniform MUC1 and MUC2 gene expression in both normal urothelium and bladder carcinoma.

Mucins (MUCs) are high molecular weight membrane glycoproteins. The gene expression of MUCs (MUC1-MUC8) may change characteristically during malignant transformation of epithelial tissues. Total RNA was isolated from the four bladder cancer cell lines RT4, 647V, HT1376, and 486P (pathological gradings between G1 and G4) and 17 samples of transitional cell carcinomas, as well as 16 samples of normal human urothelium of the bladder from surgically removed specimens. The RNA samples were studied with MUC1-, MUC2- and MUC7-specific nested reverse transcription-PCRs. Gene expression of MUC1 and MUC2 was found positive in all normal, as well as in malignant, tissue samples and in the tumor cell lines. In contrast, gene expression of MUC7 was only detected in bladder cancer cell lines and samples of invasive transitional cell carcinomas, but neither in superficial, noninvasive bladder tumors nor normal bladder urothelium. Only one of the samples of normal urothelium obtained from 16 different tumor-bearing bladders was positive for MUC7 gene expression. These results suggest a differential MUC7 gene expression with the onset of malignant transformation of the bladder urothelium.

Carcinoma, Transitional Cell↗
PubMed1998

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 2. Structure-activity relationship and optimization of the phenyl alkyl ether moiety.

We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propanoic acid (2) (PPARgamma pKi = 8.94, PPARgamma pEC50 = 9.47) as a potent and selective PPARgamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPARgamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-pyridin-4-yloxazol+ ++- 4-yl)ethoxy]phenyl¿propionic acid (16) (PPARgamma pKi = 8.85, PPARgamma pEC50 = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-¿2-[5-methyl-2-(4-methylpiperazin+ ++- 1-yl)thiazol-4-yl]ethoxy¿phenyl)propionic acid (24) (PPARgamma pKi = 8.66, PPARgamma pEC50 = 8.89) provided two potent and selective PPARgamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPARgamma ligands (PPARgamma pKi's 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPARgamma binding, functional activity, selectivity, and aqueous solubility.

Adipocytes↗
PubMed1998

[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia].

BACKGROUND: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin). METHODS: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients. CONCLUSIONS: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.

Adult↗
PubMed1998

Long-term effects of repeated maternal separation on three different latent inhibition paradigms.

In the present study we investigated the effect of repeated maternal separation on postnatal days 12, 14, 16, and 18 for 6 h/day on Wistar rats on three latent inhibition (LI) paradigms: two-way active avoidance, conditioned emotional response (CER), and conditioned taste aversion (CTA). In addition, hyperactivity induced by d-amphetamine and stereotypies induced by apomorphine were evaluated. In all three LI experiments, the control animals showed only marginal LI, whereas the maternally separated animals showed enhanced LI (only males in CTA). In two-way active avoidance within the nonpreexposed condition maternally separated animals showed improved acquisition of avoidance learning compared with the control animals. Sensitivity in response to amphetamine and apomorphine was not altered by the maternal separation procedure. Thus, maternal separation in this study, contrary to previous reports, but in line with results obtained following early handling before weaning, led to enhancement of the LI phenomenon as assessed in each of the three procedures. As our maternal separation procedure (6 h on days 12, 14, 16, and 18) led to behavioral outcomes that differed from those reported by Ellenbroek and Cools (24 h on day 10), it is suggested that maternal separation regimens that are dissimilar may lead to different and sometimes opposite behavioral effects.

Amphetamine↗
PubMed1998

Kinetics of DNA strand breaks and protection by antioxidants in UVA- or UVB-irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay.

The aim of this study was to characterize the genotoxic action of UVA and UVB in human keratinocytes by application of the single cell gel electrophoresis assay (SCGE assay). Dose dependence of DNA damage, the time course of its repair, and the influence of cellular antioxidant status were assessed. Irradiation with UVA or UVB both resulted in a dose-dependent increase in the level of DNA damage. A time course study to evaluate the repair kinetics in keratinocytes irradiated with 5 J/cm2 UVA revealed an immediate occurrence of DNA effects which subsequently disappeared within about 1 h, indicating removal of DNA lesions. This rapid repair of DNA damage is consistent with the observation that 5 J/cm2 UVA did not impair cellular viability. In contrast, exposure to 15 mJ/cm2 UVB resulted in a prolonged repair of DNA damage which lasted about 25 h. Thus, the repair kinetics of UVA- and UVB-induced DNA damage clearly differed from each other, implicating the induction of different types of DNA lesions by UVA and UVB. Neither a pretreatment with Mg-ascorbyl phosphate or D,L-alpha-tocopherol, nor depletion of endogenous glutathione altered cellular sensitivity to UVB. In contrast, the DNA damaging effects of UVA could be counteracted by a pretreatment with these antioxidants. These observations confirm that the UVA-induced effects on DNA are related to radical mediated strand breaks and DNA lesions forming alkali-labile sites. The UVB-induced effects mainly occur as a consequence of excision repair-related strand breaks. The observed repair kinetics of DNA lesions and the influence of cellular antioxidant status may help to elucidate protective mechanisms against the carcinogenic effects of UV radiation present in sunlight.

Antioxidants↗
PubMed1998

Murine leishmaniosis: a paradigm for the importance of T helper 1 and T helper 2 cells.

The murine model of leishmaniosis is a prototypic example for the critical role played by T helper cells in immunity to pathogens. Cytokines, such as interleukin-12 and interleukin-4, are the major regulatory factors for differentiation of naive T helper cells into T helper 1 and T helper 2 cells, respectively. T helper 1 cells, which are cellular immune mechanisms involving gamma interferon production, are associated with protection against murine leishmaniosis. Loss of T helper 1 activity (i.e., reduced gamma interferon production and lack of macrophage activation) leads to a fatal progressive course of murine leishmaniosis. Knowledge of the murine model of leishmaniosis is now contributing to studies of infectious diseases in humans, livestock and companion animals. Greater insight into the pathogenesis, diagnosis and therapy of infectious diseases will be gained from the analysis of cytokine-dependent regulation of T helper responses during infection. In particular, the development of prophylactic and therapeutic vaccines will benefit significantly from these studies.

Animals↗
PubMed1997

The biochip. A new membrane bioreactor system for the cultivation of animal cells in defined tissue-like cell densities.

Based on the laminar structure of the human liver tissue, a high cell density membrane bioreactor was developed that emulates a cell layer thickness of 40 microns. The "biochip" consists of a platinum-coated metal cell grid covered with two microfiltration membranes to form separate cell chambers of defined volume. Starting with a continuous chemostat process, the viability of a model suspension cell culture could be stabilized at 98%. In a second step these cells were transferred into the biochip system and were cultivated successfully for several days under tissue-like cell densities in a modified membrane holder under cross-flow conditions.

Animals↗
PubMed1997

About a symmetry of the genetic code.

Considering the three codonic positions as independent, it is possible to explain the grouping of the 64 trinucleotides (without AAA, TTT, CCC and GGG) into three equal sets T0, T1 and T2 according to their preferable reading frame (0, 1 or 2) in coding sequences. Supposing that the two complementarity strands of DNA are coding, it is demonstrated that the complementary of a codon is classified in to the same set, which has been observed statistically (with a few exceptions) in the coding sequences by Arquès & Michel [(1996) J. theor. Biol. 182, 45-58] and Arquès et al. [(1997) J. theor. Biol. 185, 241-253]. Finally, the circular property of the code pointed out by these authors is demonstrated, and a direct consequence to biological considerations of these properties is discussed.

Animals↗
PubMed1997

Organic nitrates. II. Synthesis and biological activities of 4-nitrooxymethylphenyl-1,4-dihydropyridines.

Both 2-nitrooxymethyl-4-phenyl- (2) and 4-nitrooxymethylphenyl-1,4-dihydropyridines (3) represent new combinations of two different vasodilating structures. 2 could not be isolated due to its spontaneous lactonization. Derivatives of 3 were obtained via Hantzsch synthesis using nitrooxymethylated benzaldehydes. The inotropic potency in isolated porcine trabecular muscles and the vasodilator activity in isolated porcine coronary arteries of four nitrooxyphenyl-dihydropyridines were determined. Nitrendipine (NTD) and glyceryl trinitrate (GTN) were used for reference. 3 were negative inotropic, however, less than NTD and--except for the dicyano derivative 3d--more than GTN. Vasodilator properties were less pronounced than that of both nitrendipine and GTN. Vascular selectivity was low.

Animals↗
PubMed1997

Young Investigator Award presentation at the 13th annual meeting of the ESMRMB, September 1996, Prague. Quantification of pulmonary water compartments by magnetic resonance.

The purpose of this study was to quantify pulmonary water compartments of total, intravascular, and extravascular lung water in excised and perfused sheep lungs with the use of magnetic resonance imaging techniques. Total lung water was measured by proton density maps calculated from multi-spin-echo images. Intravascular lung water was evaluated by magnetic resonance angiography before and after injection of gadolinium diethylenetriamine penta-acetic acid polylysine, a macromolecular paramagnetic contrast agent. Intravascular lung water was calculated from signal intensity histogram changes comparing pre- and postcontrast angiograms. Extravascular water was calculated as the difference between total and intravascular lung water. Quantities of total and intravascular lung water measured by magnetic resonance techniques were compared to reference results obtained from wet/dry weight gravimetry and Evans blue dilution performed after imaging. Magnetic resonance and reference results correlated significantly (total lung water: r = 0.93, p < 0.001; intravascular lung water: r = 0.80, p < 0.001; extravascular lung water: r = 0.89, p < 0.001). Therefore, we conclude that quantitative magnetic resonance techniques are potentially useful for the clinical evaluation of pulmonary water compartments.

Animals↗
PubMed1997

Capillary blood glucose monitoring. Are you putting yourself and your patients/clients at risk?

The performance of portable capillary blood glucose monitoring is now a widely accepted skill performed by nurses in a variety of settings. A person may have their blood glucose level taken by a nurse in the acute care setting, home environment, community health setting, doctor's surgery, work place or in community blood glucose screening program. This article aims to highlight the precautions necessary for the safe delivery of this component of care.

Blood Glucose Self-Monitoring↗
PubMed1997

[Magnetic resonance imaging of the degree of pulmonary edema using a macromolecular contrast medium].

PURPOSE: Development and experimental validation of a method tor the quantification of pulmonary oedema by measurement of total lung water and intravascular lung water and by calculation of extravascular lung water. MATERIAL AND METHODS: Isolated sheep lung preparations with unilateral pulmonary oedema were perfused (pulsatile pump) and examined under ventilatory arrest and during ventilation. Total lung water was calculated from proton density obtained from a multi-spin echo sequence and gravimetrically (reference method). Pulmonary intravascular volume was calculated from signal intensity histograms obtained from 3D-TOF MR-angiograms before and after application of the macromolecular contrast medium gadolinium-DTPA-polylysine. The reference method was a dye-dilution technique. Extravascular lung water was calculated as the difference between total lung water and pulmonary intravascular volume. RESULTS: Under ventilatory arrest, the magnetic resonance technique for the measurement of extravascular lung water correlated well with the reference technique (r = 0.89, n = 42 lungs). In 10 lungs the correlation coefficients were r = 0.95 (ventilatory arrest) and r = 0.92 (ventilated lungs). CONCLUSION: The results demonstrate that magnetic resonance imaging enhanced by a macromolecular contrast medium may be applicable for quantification of pulmonary oedema.

Animals↗
PubMed1997

[MR imaging of experimental pulmonary embolism using a macromolecular contrast medium].

PURPOSE: To evaluate macromolecular contrast-enhanced MR-angiography for the detection of experimentally induced pulmonary artery embolism and to determine the size of the smallest detectable embolised vessel. METHODS: Pulmonary artery embolism was artificially induced in eight isolated perfused sheep lungs by injecting room air into the main pulmonary artery. The pulmonary vascular system enhanced by macromolecular gadolinium-DTPA-polylysine was imaged with a flow-sensitive gradient-echo technique. RESULTS: Pulmonary artery embolism was demonstrated in all eight lungs by an obvious cut-off phenomenon in the contrast-enhanced arteries proximal to the pulmonary air emboli. The smallest detectable embolised artery measured 1.6 mm in diameter and was located in the 6th generation of the pulmonary vascular system. CONCLUSIONS: In this experimental study MR angiography enhanced by a macromolecular contrast agent allowed noninvasive diagnosis of pulmonary artery embolism.

Animals↗