PubMed Health⌕ Search

Biomedical subjects

T Friedrich

Publications and source records attributed to T Friedrich.

At least 19 recordsLinked to original sources
PubMed2005

Distribution of resonance strengths in microwave billiards of mixed and chaotic dynamics.

A new measure for statistical properties of the wave function components of quantum systems, the distribution of the product of two partial widths, is introduced. It is tested with data obtained in analog experiments with microwave billiards, where the product of two partial widths equals the resonance strengths in the microwave spectra. The billiards are from the family of the Limaçons, one with chaotic and two with mixed classical dynamics. For completely chaotic systems the partial widths generically obey a Porter-Thomas distribution. We show that in this case the distribution of their product equals a K0 distribution. While we find deviations of the experimental strength distribution from the K0 distribution for the billiards with mixed dynamics, the distributions agree perfectly for the chaotic billiard, when taking into account the experimental threshold of detection in the theoretical description. Hence, the strength distribution provides another stringent test for the connection between statistical properties of systems with classical chaotic dynamics and random matrix theory.

Journal Article↗
PubMed2005

Ion translocation by the Escherichia coli NADH:ubiquinone oxidoreductase (complex I).

The energy-converting NADH:ubiquinone oxidoreductase, also known as respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of ions across the membrane. It was assumed that the complex exclusively works as a proton pump. Recently, it has been proposed that complex I from Klebsiella pneumoniae and Escherichia coli work as Na+ pumps. We have used an E. coli complex I preparation to determine the type of ion(s) translocated by means of enzyme activity, generation of a membrane potential and redox-induced Fourier-transform infrared spectroscopy. We did not find any indications for Na+ translocation by the E. coli complex I.

Biological Transport↗
PubMed2004

First experimental evidence for quantum echoes in scattering systems.

A self-pulsing effect termed quantum echoes has been observed in experiments with an open superconducting and a normal conducting microwave billiard whose geometry provides soft chaos, i.e., a mixed phase space portrait with a large stable island. For such systems a periodic response to an incoming pulse has been predicted. Its period has been associated with the degree of development of a horseshoe describing the topology of the classical dynamics. The experiments confirm this picture and reveal the topological information.

Journal Article↗
PubMed2004

mBAND: a high resolution multicolor banding technique for the detection of complex intrachromosomal aberrations.

Precise breakpoint definition of chromosomal rearrangements using conventional banding techniques often fails, especially when more than two breakpoints are involved. The classic banding procedure results in a pattern of alternating light and dark bands. Hence, in banded chromosomes a specific chromosomal band is rather identified by the surrounding banding pattern than by its own specific morphology. In chromosomal rearrangements the original pattern is altered and therefore the unequivocal determination of breakpoints is not obvious. The multicolor banding technique (mBAND, see Chudoba et al., 1999) is able to identify breakpoints unambiguously, even in highly complex chromosomal aberrations. The mBAND technique is presented and illustrated in a case of intrachromosomal rearrangement with seven breakpoints all having occurred on one chromosome 16, emphasizing the unique analyzing power of mBAND as compared to conventional banding techniques.

Chromosome Aberrations↗
PubMed2002

Infestin, a thrombin inhibitor presents in Triatoma infestans midgut, a Chagas' disease vector: gene cloning, expression and characterization of the inhibitor.

This work describes the purification, gene cloning and expression of infestin, a thrombin inhibitor from midguts of Triatoma infestans. Infestin is located in the midgut and its purification was performed by anion-exchange and affinity chromatographies. The N-terminal sequence and the sequence of tryptic peptides were determined. Using RT-PCR, total RNA and infestin cDNA information, a DNA fragment was cloned which encodes a multi non-classical Kazal-type serine protease inhibitor. Isolated native infestin has two non-classical Kazal-type domains and shows an apparent molecular mass of 13 kDa, while its gene codes for a protein with four non-classical Kazal-type domains corresponding to an apparent molecular mass of 22 kDa. Two recombinant infestins, r-infestin 1-2 and r-infestin 1-4, were constructed using the vector pVT102U/alpha and expressed in S. cerevisiae. Native and r-infestin 1-2 showed very similar inhibitory activities towards thrombin and trypsin with dissociation constants of 43.5 and 25 pM for thrombin and 2.0 and 3.1 nM for trypsin, respectively. No other serine protease of the blood coagulation cascade was inhibited by the r-infestin 1-2. Surprisingly, r-infestin 1-4 inhibited not only thrombin and trypsin (K(i) of 0.8 and 5.2 nM, respectively), but also factor XIIa, factor Xa and plasmin (K(i) of 78 pM, 59.2 and 1.1 nM, respectively).

Amino Acid Sequence↗
PubMed2002

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease.

Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis.

Adult↗
PubMed2001

[Attitudes of students of medicine, sociology and jurisprudence towards autopsy].

UNLABELLED: Attitudes of students of medicine, sociology and jurisprudence towards autopsy. SUBJECT: The autopsy is an important instrument of quality control in medicine. Nevertheless, we observe a dramatic decrease of post-mortem examinations. Because physicians take a important role as mediators, we tried to examine the attitudes of medical students towards autopsy and possible differences to students of other faculties. PROBANDS AND METHODS: Data of medical students (n = 335), students of jurisprudence (n = 95), and of sociology (n = 26) at Leipzig University were collected with the help of a specially elaborated questionnaire >>Post-mortem Examination<< (Fragebogen zur Sektion, FBZS), and two questionnaires >>Death and Dying<< (Fragebogen zu Tod und Sterben, FIMEST) and >>Personality<< (Persönlichkeitsfragebogen, Giessen-Test). RESULTS: Referring to the attitudes towards post-mortem examination there is only a slight difference between students of the above-mentioned faculties. Even preclinical students showed no difference with their attitudes towards autopsy compared to the students of other faculties and they showed lack of knowledge and ethical doubts towards autopsy. CONCLUSION: Due to the significant lack of knowledge of the medical students of the University of Leipzig it seems questionable, if they will be able to convince relatives to give consent to an autopsy in later activity as physicians. More instructional work during study and further medical education should be done.

Attitude to Death↗
PubMed2001

Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.

This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.

Adult↗
PubMed2001

Identification of two tetranuclear FeS clusters on the ferredoxin-type subunit of NADH:ubiquinone oxidoreductase (complex I).

The proton-translocating NADH:ubiquinone oxidoreductase of respiratory chains (complex I) contains one flavin mononucleotide and five EPR-detectable iron-sulfur clusters as redox groups. Because of the number of conserved motifs typical for binding iron-sulfur clusters and the high content of iron and acid-labile sulfide of complex I preparations, it is predicted that complex I contains additional clusters which have not yet been detected by EPR spectroscopy. To search for such clusters, we used a combination of UV/vis and EPR spectroscopy to study complex I from Neurospora crassa and Escherichia coli adjusted to distinct redox states. We detected a UV/vis redox difference spectrum characterized by negative absorbances at 325 and 425 nm that could not be assigned to the known redox groups. Redox titration was used to determine the pH-independent midpoint potential to be -270 mV, being associated with the transfer of two electrons. Comparison with UV/vis difference spectra obtained from complex I fragments and related enzymes showed that this group is localized on subunit Nuo21.3c of the N. crassa or NuoI of the E. coli complex I, respectively. This subunit (the bovine TYKY) belongs to a family of 8Fe-ferredoxins which contain two tetranuclear iron-sulfur clusters as redox groups. We detected EPR signals in a fragment of complex I which we attribute to the novel FeS clusters of complex I.

Animals↗
PubMed2001

Two open states and rate-limiting gating steps revealed by intracellular Na+ block of human KCNQ1 and KCNQ1/KCNE1 K+ channels.

KCNQ1, the first member of a new K+ channel family, associates with the small KCNE1 subunit to form the slow cardiac delayed rectifier current, IKs. Mutations in both genes encoding these channels lead to cardiac arrhythmia. We studied the block by intracellular Na+ of human homomeric KCNQ1 (homomers) and heteromeric KCNQ1/KCNE1 (heteromers) expressed in CHO cells (Chinese hamster ovary cell line) using whole-cell patch recording. In the nominal absence of extracellular K+ and with 65 mM intracellular K+, the replacement of 65 mM intracellular N-methyl-D-glucamine (NMDG+) by 65 mM Na+ induced a decay of outward (K+) currents through homomers after maximal activation reminiscent of an inactivation process. The decay had a time constant in the hundreds of milliseconds range. The inactivation process of homomers was, however, not directly dependent on [Na+]i, as evidenced by unaltered biphasic deactivation at negative voltages. An instantaneous voltage-dependent Na+ block of homomers was revealed using tail current protocols with activating prepulses that saturated the gating processes of the channel. The instantaneous block was partially relieved at very large positive voltages (> or = 60 mV) and in 20 mM extracellular K+. The instantaneous block of homomers was much less pronounced if the tail currents were measured after short activating prepulses, demonstrating the presence of (at least) two open states: a first, relatively [Na+]i-insensitive and a subsequent [Na+]i-sensitive open state; the current decay reflects the transition between the two open states. Heteromers exhibited a very similar instantaneous block by Na+i independently of the prepulse duration. Heteromers did not show a Na+i-induced current decay. Our results demonstrate the presence of two open states of KCNQ1 channels with different [Na+]i sensitivities. The rate-limiting step of homomeric KCNQ1 gating at positive voltages is the transition between these two open states. The rate-limiting step of the gating of KCNQ1/KCNE1 channels appears to be the entry into the first open state.

Animals↗
PubMed2001

Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri.

Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through high-risk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle-regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase inhibitor gene p16(INK4a). Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16(INK4a). In line with this hypothesis, we observed marked overexpression of p16(INK4a) in all cervical intraepithelial neoplasm (CIN) I lesions (n = 47) except those associated with low-risk HPV types (n = 7), all CIN II lesions (n = 32), all CIN III lesions (n = 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16(INK4a) was observed in normal cervical epithelium (n = 42), inflammatory lesions (n = 48) and low-grade cervical lesions (CIN I) associated with low-risk HPV types (n = 7). Dysplastic cells could also be identified in cervical smears using a specific p16(INK4a) monoclonal antibody. These data demonstrate that p16(INK4a) is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears.

Biomarkers, Tumor↗
PubMed2001

Quinone-annonaceous acetogenins: synthesis and complex I inhibition studies of a new class of natural product hybrids.

The natural product hybrids quinone-mucocin and quinone- squamocin D were synthesized. In these hybrids, the butenolide unit of the annonaceous acetogenins mucocin and squamocin D is exchanged for the quinone moiety of the natural complex I substrate ubiquinone. For both syntheses, a modular, highly convergent approach was applied. Quinone-mucocin was constructed out of a tetrahydropyran (THP) component 1, a tetrahydrofuran (THF) unit 2, and a quinone precursor 3. A stereoselective, organometallic coupling reaction was chosen for the addition of the THP unit to the rest of the molecule. In the final step, the oxidation to the free quinone was achieved by using cerium(IV) ammonium nitrate (CAN) as the oxidizing agent. Quinone-squamocin D was assembled in a similar manner, from the chiral side chain bromide 16, the central bis-THF core 17, and the quinone precursor 18. Inhibition of complex I (isolated from bovine heart mitochondria) by the quinone acetogenins and several smaller building blocks was examined; quinone mucocin and quinone-squamocin D act as strong inhibitors of complex I. These results and the data from the smaller substructures indicate that other substructures of the acetogenins besides the butenolide group, such as the polyether component and the lipophilic left-hand side chain, are necessary for the strong binding of the acetogenins to complex I.

Animals↗
PubMed2001

[CT-guided marking of lung lesions before minimally invasive operation].

Video-assisted thoracoscopic surgery (VATS) is an established method for resection of suspicious pulmonary lesions. However, there are problems to detect small subpleural lesions. A procedure for localization of such lesions will be demonstrated. Since may 2000 our experience includes 5 patients (4m, 1f) suffering from solitary pulmonary lesions. In preparation of VATS a CT-guided marking was carried out using both a lasermarker system as well as a special marker system for lung lesions. All 5 procedures were successful. With the laser system the pulmonary nodule was exactly marked and the special wire was placed without any complications. Consequently, the pulmonary nodule was fixed. During video-assisted wedge resection the nodule can be tracted outside. Operating time was reduced in comparison to time consuming search of unmarked lesions. The combined application of CT-guided marking, transthoracic fixation of pulmonary nodule and VATS is recommended preoperatively. It should apply in lesions, which are located subpleural and thoracoscopically not visible.

Adult↗
PubMed2001

The voltage-dependent proton pumping in bacteriorhodopsin is characterized by optoelectric behavior.

The light-driven proton pump bacteriorhodopsin (bR) was functionally expressed in Xenopus laevis oocytes and in HEK-293 cells. The latter expression system allowed high time resolution of light-induced current signals. A detailed voltage clamp and patch clamp study was performed to investigate the DeltapH versus Deltapsi dependence of the pump current. The following results were obtained. The current voltage behavior of bR is linear in the measurable range between -160 mV and +60 mV. The pH dependence is less than expected from thermodynamic principles, i.e., one DeltapH unit produces a shift of the apparent reversal potential of 34 mV (and not 58 mV). The M(2)-BR decay shows a significant voltage dependence with time constants changing from 20 ms at +60 mV to 80 ms at -160 mV. The linear I-V curve can be reconstructed by this behavior. However, the slope of the decay rate shows a weaker voltage dependence than the stationary photocurrent, indicating that an additional process must be involved in the voltage dependence of the pump. A slowly decaying M intermediate (decay time > 100 ms) could already be detected at zero voltage by electrical and spectroscopic means. In effect, bR shows optoelectric behavior. The long-lived M can be transferred into the active photocycle by depolarizing voltage pulses. This is experimentally demonstrated by a distinct charge displacement. From the results we conclude that the transport cycle of bR branches via a long-lived M(1)* in a voltage-dependent manner into a nontransporting cycle, where the proton release and uptake occur on the extracellular side.

Animals↗
PubMed2001

Complex I: a chimaera of a redox and conformation-driven proton pump?

From phylogenetic sequence analysis, it can be concluded that the proton-pumping NADH:ubiquinone oxidoreductase (complex I) has evolved from preexisting modules for electron transfer and proton translocation. It is built up by a peripheral NADH dehydrogenase module, an amphipatic hydrogenase module, and a membrane-bound transporter module. These modules, or at least part of them, are also present in various other bacterial enzymes. It is assumed that they fulfill a similar function in complex I and related enzymes. Based on the function of the individual modules, it is possible to speculate about the mechanism of complex I. The hydrogenase module might work as a redox-driven proton pump, while the transporter module might act as a conformation-driven proton pump. This implies that complex I contains two energy-coupling sites. The NADH dehydrogenase module seems to be involved in electron transfer and not in proton translocation.

Electron Transport Complex I↗
PubMed2001

Understanding cytotoxic T-lymphocyte escape during simian immunodeficiency virus infection.

Infection of rhesus macaques with simian immunodeficiency virus (SIV) is an excellent model system for studying viral adaptation to immune responses. In this review, we discuss how the SIV-infected macaque has provided unequivocal evidence for cytotoxic T-lymphocyte (CTL) selection of viral escape variants. This improved understanding of CTL escape may influence human immunodeficiency virus (HIV) vaccine design as well as our understanding of HIV pathogenesis.

AIDS Vaccines↗