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Biomedical subjects

J Friedrich

Publications and source records attributed to J Friedrich.

At least 19 recordsLinked to original sources

Measurement of the beam-helicity asymmetry in the p((-->)e,e'p)pi(0) reaction at the energy of the Delta(1232) resonance.

In a p((-->)e,e'p)pi(0) out-of-plane coincidence experiment at the three-spectrometer setup of the Mainz Microtron MAMI, the beam-helicity asymmetry has been precisely measured around the energy of the Delta(1232) resonance and Q(2) = 0.2(GeV/c)(2). The results are in disagreement with three up-to-date model calculations. This is interpreted as a lack of understanding of the nonresonant background, which in dynamical models is related to the pion cloud.

Journal Article↗

Neutral pion threshold production at Q(2) = 0.05 GeV(2)/c(2) and chiral perturbation theory.

New data are presented on the p(e,e'p)pi(0) reaction at threshold at a four-momentum transfer of Q(2) = 0.05 GeV(2)/c(2). The data were taken with the three-spectrometer setup of the A1 Collaboration at the Mainz Microtron MAMI. The complete center of mass solid angle was covered up to a center of mass energy of 4 MeV above threshold. Combined with measurements at three different values of the virtual photon polarization epsilon, the structure functions sigma(T), sigma(L), sigma(TT), and sigma(TL) are determined. The results are compared with calculations in heavy baryon chiral perturbation theory and with a phenomenological model. The measured cross section is significantly smaller than both predictions.

Journal Article↗

Comparison of two hard keratinous substrates submitted to the action of a keratinase using an experimental design.

The influence of temperature, pH, keratinase concentration, substrate concentration and incubation time on the soluble proteins released by a new keratinase from Doratomyces microsporus was studied with a second-order experimental design. Only 15 or 18 spectrophotometric analyses were required to determine the optimal experimental conditions for this keratinase on nail and hoof. This study was carried out by measuring, according to Smith's method, the concentration of soluble proteins released by the enzyme on two substrates: nails and sheep hooves. Results give optimum conditions for the keratinase to release the soluble proteins: pH 8.2, keratinase concentration 0.14% (weight of keratinase lyophilisate/final volume) and substrate concentration 5% (weight of nail powder/final volume) for nails; temperature 38.8 degrees C, pH 9, substrate concentration 5% (weight of hoof powder/final volume) and a 5 h 55 min incubation time for hooves.

Animals↗

Measurement of the recoil polarization in the p(e-->, e'p-->)pi(0) reaction at the Delta(1232) resonance.

The recoil proton polarization has been measured in the p(e-->,e'p-->)pi(0) reaction in parallel kinematics around W = 1232 MeV, Q2 = 0.121 (GeV/c)2, and epsilon = 0.718 using the polarized cw electron beam of the Mainz Microtron. All three proton polarization components, Px/P(e) = (-11.4+/-1.3+/-1.4)%, P(y) = (-43.1+/-1.3+/-2.2)%, and P(z)/P(e) = (56.2+/-1.5+/-2.6)%, could be measured simultaneously. The Coulomb quadrupole to magnetic dipole ratio, CMR = (-6.4+/-0.7(stat)+/-0.8(syst))%, was determined from Px in the framework of the Mainz Unitary Isobar Model. The consistency among the reduced polarizations and the extraction of the ratio of longitudinal-to-transverse response is discussed.

Journal Article↗

Trehalose effect on low temperature protein dynamics: fluctuation and relaxation phenomena.

We performed spectral diffusion experiments in trehalose-enriched glycerol/buffer-glass on horseradish peroxidase where the heme was replaced by metal-free mesoporphyrin IX, and compared them with the respective behavior in a pure glycerol/buffer-glass (Schlichter et al., J. Chem. Phys. 2000, 112:3045-3050). Trehalose has a significant influence: spectral diffusion broadening speeds up compared to the trehalose-free glass. This speeding up is attributed to a shortening of the correlation time of the frequency fluctuations most probably by preventing water molecules from leaving the protein interior. Superimposed to the frequency fluctuation dynamics is a relaxation dynamics that manifests itself as an aging process in the spectral diffusion broadening. Although the trehalose environment speeds up the fluctuations, it does not have any influence on the relaxation. Both relaxation and fluctuations are governed by power laws in time. The respective exponents do not seem to change with the protein environment. From the spectral dynamics, the mean square displacement in conformation space can be determined. It is governed by anomalous diffusion. The associated frequency correlation time is incredibly long, demonstrating that proteins at low temperatures are truly nonergodic systems.

Biochemical Phenomena↗

Kinetic characterization of the changes in protein tyrosine phosphorylation of membranes, cytosolic Ca2+ concentration and viability in boar sperm populations selected by binding to oviductal epithelial cells.

On reaching the oviduct, spermatozoa are retained in the isthmic region of the oviduct until ovulation occurs. The essential steps of capacitation are co-ordinated in this region. In this study, a primary cell culture system of oviductal epithelial cells was established to investigate sperm binding to oviductal epithelium and modulation of sperm function during incubation under capacitating conditions in co-culture with oviductal epithelial cells. Epithelial cells were stripped from the oviducts of sows and cultivated for 5-7 days on Lab-Tek Chamber slides on Matrigel. The preparations on chamber slides and suspensions of control spermatozoa were incubated for 3 h in Tyrode's albumin lactate pyruvate (TALP) medium. At 3, 30, 60, 90 and 180 min the free-swimming spermatozoa were collected by washing, and membrane integrity, tyrosine phosphorylation patterns and [Ca(2+)](i) of bound, unbound and control spermatozoa were assessed with fluorescent probes (propidium iodide, Cy-3 and fluo-3-AM). The cells bound to oviductal epithelial cells showed reduced cytosolic Ca(2+) concentration, reduced and almost absent tyrosine phosphorylation of membrane proteins and higher viability at the time of the first sampling. Increases in Ca(2+) concentration and cell death occurred much more slowly during incubation in cells bound to oviductal epithelial cells compared with free-swimming spermatozoa, and no changes in tyrosine phosphorylation were observed. The preferential binding of viable, low-Ca(2+) cells with suppressed tyrosine phosphorylation and slower functional modulation of boar spermatozoa attached to oviductal epithelial cells might represent a mechanism for selecting functionally competent spermatozoa and prolonging their lifespan by delaying capacitation in the oviductal reservoir.

Animals↗

First determination of generalized polarizabilities of the proton by a virtual compton scattering experiment

Absolute differential cross sections for the reaction ep-->epgamma have been measured at a four-momentum transfer with virtuality Q2 = 0.33 GeV2 and polarization epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high-resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.

Journal Article↗

ATP synthesis during low-flow ischemia: influence of increased glycolytic substrate.

BACKGROUND: Our goals were to (1) simulate the degree of low-flow ischemia and mixed anaerobic and aerobic metabolism of an acutely infarcting region; (2) define changes in anaerobic glycolysis, oxidative phosphorylation, and the creatine kinase (CK) reaction velocity; and (3) determine whether and how increased glycolytic substrate alters the energetic profile, function, and recovery of the ischemic myocardium in the isolated blood-perfused rat heart. METHODS AND RESULTS: Hearts had 60 minutes of low-flow ischemia (10% of baseline coronary flow) and 30 minutes of reperfusion with either control or high glucose and insulin (G+I) as substrate. In controls, during ischemia, rate-pressure product and oxygen consumption decreased by 84%. CK velocity decreased by 64%; ATP and phosphocreatine (PCr) concentrations decreased by 51% and 63%, respectively; inorganic phosphate (P(i)) concentration increased by 300%; and free [ADP] did not increase. During ischemia, relative to controls, the G+I group had similar CK velocity, oxygen consumption, and tissue acidosis but increased glycolysis, higher [ATP] and [PCr], and lower [P(i)] and therefore had a greater free energy yield from ATP hydrolysis. Ischemic systolic and diastolic function and postischemic recovery were better. CONCLUSIONS: During low-flow ischemia simulating an acute myocardial infarction region, oxidative phosphorylation accounted for 90% of ATP synthesis. The CK velocity fell by 66%, and CK did not completely use available PCr to slow ATP depletion. G+I, by increasing glycolysis, slowed ATP depletion, maintained lower [P(i)], and maintained a higher free energy from ATP hydrolysis. This improved energetic profile resulted in better systolic and diastolic function during ischemia and reperfusion. These results support the clinical use of G+I in acute MI.

Adenosine Triphosphate↗

[Long-term follow up of bile duct injury by laparoscopic cholecystectomy and reconstruction with jejunum interposition].

The follow-up of patients with severe bile duct lesions after laparoscopic cholecystectomy often shows secondary complications. We report on a female patient suffering from long-lasting complications after bile duct injury and early reconstruction by end-to-end anastomosis via a T-tube drainage. More than 5 years later and after multiple dilatation and stenting of the bile duct stenosis the patient was treated with an expanding metal stent. The severe cholangitis persisted. So the patient was operated on: bile duct and connected stent were resected. The reconstruction was performed with an isoperistaltic jejunal conduit. More than 24 months later the patient is healthy and at work again.

Cholangitis↗

Keratinase of Doratomyces microsporus.

The fungus Doratomyces microsporus produced an extracellular keratinase during submerged aerobic cultivation in a medium containing a protein inducer for enzyme synthesis. The keratinase was purified to homogeneity using hydrophobic interaction chromatography followed by gel chromatography. The molecular weight was estimated to be 33 kDa (from SDS-PAGE analysis) or 30 kDa (by gel chromatography), suggesting a monomeric structure. The isoelectric point of the enzyme was determined to be around 9. The optimal pH and temperature for keratinolytic activity were pH 8-9 and 50 degrees C, respectively. The serine protease inhibitor PMSF totally inhibited the keratinase. The enzyme was not glycosylated. It was capable of hydrolysing different keratinous materials as well as some non-keratinous proteins. Hydrolysis of some synthetic substrates, specific for known proteinases, suggested that the keratinase of D. microsporus is close to proteinase K.

Animals↗

A first order experimental design to assess soluble proteins released by a new keratinase from Doratomyces microsporus on human substrates.

The influence of temperature, pH, keratinase concentration, substrate concentration and incubation time on the soluble proteins released by a new keratinase from Doratomyces microsporus was studied with an experimental design assisted by a simplex method. Only 16 spectrophotometric analyses were required. This study was carried out by measuring, according to Smith's method, the concentration of soluble proteins released by the enzyme on two human substrates: stratum corneum and nails. Results give optimum conditions for the keratinase to release the soluble proteins: Temperature, 28 degrees C; pH, 9.5; keratinase concentration, 0.94% (weight of keratinase lyophilisat/final volume), substrate concentration, 4.9% (weight of skin powder/final volume); and a 5 h 50 min incubation for the stratum corneum. Temperature, 37 degrees C; pH, 9.2, keratinase concentration, 0.11% (weight of keratinase lyophilisat/final volume); substrate concentration, 4.9% (weight of nail powder/final volume) and a 6 h 10 min incubation time for nails.

Algorithms↗

Ethambutol-sugar hybrids as potential inhibitors of mycobacterial cell-wall biosynthesis.

Ethambutol is an established front-line agent for the treatment of tuberculosis, and is also active against Mycobacterium avium infection. However, this agent exhibits toxicity, and is considered to have low potency. The action of ethambutol on the mycobacterial cell wall, particularly the arabinan, and comparison of the structure of ethambutol with several of the cell-wall saccharides, suggested that ethambutol-saccharide hybrids might lead to agents with a more selective mechanism of action. To this end, eight ethambutol-saccharide hybrids were synthesized and screened against M. tuberculosis and several clinical isolates of M. avium.

Antitubercular Agents↗

Sampling field heterogeneity at the heme of c-type cytochromes by spectral hole burning spectroscopy and electrostatic calculations.

We report on a comparative investigation of the heme pocket fields of two Zn-substituted c-type cytochromes-namely yeast and horse heart cytochromes c-using a combination of hole burning Stark spectroscopy and electrostatic calculations. The spectral hole burning experiments are consistent with different pocket fields experienced at the hemes of the respective cytochromes. In the case of horse heart Zn-cytochrome c, two distinguishable electronic origins with different electrostatic properties are observed. The yeast species, on the other hand, displays a single electronic origin. Electrostatic calculations and graphics modeling using the linearized finite-difference Poisson-Boltzmann equation performed at selected time intervals on nanosecond-molecular dynamics trajectories show that the hemes of the respective cytochromes sample different potentials as they explore conformational space. The electrostatic potentials generated by the protein matrix at the heme show different patterns in both cytochromes, and we suggest that the cytochromes differ by the number of "electrostatic substates" that they can sample, thus accounting for the different spectral populations observed in the two cytochromes.

Animals↗

Detection of circulating tumour cells in patients with breast or ovarian cancer by molecular cytogenetics.

Detection of micrometastases in patients with solid tumours may aid the establishment of prognosis and development of new therapeutic approaches. This study was designed to investigate the presence and frequency of tumour cells in the peripheral blood (PB) of patients with breast or ovarian cancer by using a combination of magnetic activated cell sorting (MACS) and fluorescence in situ hybridization (FISH). Separated tumour cell and PB-samples from 48 patients (35 breast cancers, 12 ovarian tumours, one uterine sarcoma) were analysed for the presence of numerical aberrations of chromosomes 7, 12, 17 and 17 q11.2-q12. Twenty-five patients had primary disease and 23 had relapsed. The technique allows the detection of one tumour cell in 106 normal cells. Circulating tumour cells were detected in 35/48 cases (17 patients had relapsed and 13 primary carcinoma with lymph node or solid metastases) by the expression of anti-cytokeratin and the presence of numerical chromosomal abnormalities. PB-tumour cells of patients with a primary carcinoma and without solid metastases had a significantly lower percentage of chromosomal aberrations, especially for chromosome 12 (P = 0.035; P = 0.038) compared to those with relapsed disease and solid metastases. Detection and quantification of minimal residual disease may monitor the response to cytotoxic or hormonal therapy and may identify women at risk of relapse.

Adult↗

Expression of mucosa-related integrin alphaEbeta7 on alveolar T cells in interstitial lung diseases.

The expression of alphaEbeta7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated alphaEbeta7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD), alphaE expression on CD4+ and CD8+ T cell subsets was evaluated by dual-colour flow cytometry in peripheral blood and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF; n = 18), hypersensitivity pneumonitis (HP; n = 20) and sarcoidosis (n = 44) in comparison with healthy controls (n = 15). In both healthy individuals and all patient groups the proportion of alphaE-bearing T cells in peripheral blood was < 2%, whereas the vast majority of alveolar CD8+ T cells consistently co-expressed alphaE. Absolute alveolar CD8+alphaE+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of alphaE-bearing CD4+ cells in BALF were significantly elevated in IPF (74.0 +/- 2.7%) and HP (70.0 +/- 2.4%) compared with normals (30.0 +/- 1.8%) (mean +/- s.e.m.; P < 0.01). In sarcoidosis, the alphaE expression on BALF CD4+ cells displayed subgroup dependency: proportions significantly lower than normal were noted in chest radiographic stage I (14.3 +/- 1.5%), but increased proportions in stages II (50.0 +/- 3.8%) and III (64.0 +/- 4.8%). Correlations between common markers of T cell activation or BALF transforming growth factor-beta (TGF-beta ) bioactivity and alphaE expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express alphaEbeta7 and that distinct patterns of alphaEbeta7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung.

Adolescent↗

[Assessing the quality of life after pancreas-kidney transplantation].

The pancreas-kidney transplantation strives for a reestablishment both of the physiological regulation of blood glucose levels without external insulin and of kidney function without the need of dialysis. Nevertheless, the postoperative morbidity of the combined transplantation is high. In long lasting diabetes type I, a strict selection of transplant candidates is necessary to minimize the risks of cardio-vascular complications. Between 1990 and 1997 only 17 of 44 patients really were accepted for transplantation in our unit. 13/17 patients are actually independent from external insulin and dialysis. Two other patients are free of dialysis, but the pancreas transplants had to be removed due to thrombosis or infection. In one case therapy-resistant acute rejection occurred and both organs had to be removed after two months. One women died four years after transplantation with a functioning kidney graft from myocardial infarction. 10 patients with stable transplant function are at work again. After normal pregnancy two women gave birth to healthy children, in one case twins. Drug regimen and outpatients visits are not seen as significant restrictions of the quality of life.

Adolescent↗

Detection of chromosomal aberrations in tumor cells and tumor infiltrating lymphocytes by molecular cytogenetics in patients with gynecological cancer.

Conventional cytogenetic studies of tumor cells from patients with breast or ovarian cancer have shown multiple chromosomal abnormalities including chromosomes 7, 12, and 17. This study was designed to analyze the cytogenetic features of tumor cells and tumor infiltrating lymphocytes (TILs) by using a combination of magnetic activated cell sorting (MACS) and fluorescence in situ hybridization (FISH). Tumor cell, peripheral blood (PB), and TIL samples from 37 patients (20 ovarian tumors, 13 breast cancers, 3 uterine sarcoma, 1 carcinoma of the filamentary tube) were analyzed for the presence of numerical aberrations of chromosomes 7, 12, and 17. All of the tumor cells showed a high frequency of numerical aberrations of chromosomes 7, 12, and 17, especially trisomies or tetrasomies. There was no statistically significant difference in the incidence of chromosomal abnormalities in tumor tissue and effusions, or between primary and relapsed disease in patients with breast or ovarian tumors. However, tumor cells from patients with solid metastatic disease had significantly higher numbers of aberrations of chromosome 7 in the primary tumor than in tumors from patients without metastases (P = 0.049), suggesting that chromosome 7 is frequently involved in the progression of disease. Monosomies and trisomies of chromosomes 7 and 12 also occurred at a low percentage of TILs without any statistically significant difference between primary and relapsed tumors. The presence of these aneuploidies might be responsible for treatment failures in the immunotherapy of gynecological cancer.

Adult↗