Biomedical subjects
E Braun
Publications and source records attributed to E Braun.
[Treatment interruption in HIV infected patients: clinical and biological evolution].
OBJECTIVE: The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment. PATIENTS AND METHODS: Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis. RESULTS: Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occurred for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P<0.001). The median values of viral load before and at the end of treatment interruption were <50 and 23749 copies/mL, respectively (P<0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS). CONCLUSIONS: Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption.
Macroscopic evidence of microscopic dynamics in the Fermi-Pasta-Ulam oscillator chain from nonlinear time-series analysis.
The problem of detecting specific features of microscopic dynamics in the macroscopic behavior of a many-degrees-of-freedom system is investigated by analyzing the position and momentum time series of a heavy impurity embedded in a chain of nearest-neighbor anharmonic Fermi-Pasta-Ulam oscillators. Results obtained in a previous work [M. Romero-Bastida, Phys. Rev. E 69, 056204 (2004)] suggest that the impurity does not contribute significantly to the dynamics of the chain and can be considered as a probe for the dynamics of the system to which the impurity is coupled. The (r,tau) entropy, which measures the amount of information generated by unit time at different scales tau of time and r of the observable, is numerically computed by methods of nonlinear time-series analysis using the position and momentum signals of the heavy impurity for various values of the energy density epsilon (energy per degree of freedom) of the system and some values of the impurity mass M. Results obtained from these two time series are compared and discussed.
Microscopics of complexation between long DNA molecules and positively charged colloids.
Extensive atomic force and electron microscopy reveal a new, generic DNA-colloid complex with a fixed number of DNA bases per colloid. The fiber shaped complex is stable in the presence of excess colloids in the solution. As more DNA is added to the solution and the ratio between colloids and DNA approaches the fiber's stoichiometry, the system undergoes a sharp coagulation transition. The system is restabilized at even higher DNA concentrations through localization of small colloid clusters on extensive DNA networks.
Microscopic chaos from Brownian motion in a one-dimensional anharmonic oscillator chain.
The problem of relating microscopic chaos to macroscopic behavior in a many-degrees-of-freedom system is numerically investigated by analyzing statistical properties associated to the position and momentum of a heavy impurity embedded in a chain of nearest-neighbor anharmonic Fermi-Pasta-Ulam oscillators. For this model we have found that the behavior of the relaxation time of the momentum autocorrelation function of the impurity is different depending on the dynamical regime (either regular or chaotic) of the lattice.
[Two cases of polyarteritis nodosa with a good prognosis?].
INTRODUCTION: Polyarteritis nodosa is a systemic necrotizing vasculitis that may become serious, even with no usual poor prognosis factors. EXEGESIS: We report two cases of polyarteritis nodosa with negative histology, starting only with an extensive necrosis of the extremities. The treatment, associating corticosteroids and, secondarily, immunosuppressors, did not prevent a bilateral half-leg amputation for the two patients. In the first case the disease stabilized, but in the second one, it worsened, leading to death within 2 years. CONCLUSION: This clinical aspect of the disease is unusual and should be identified because of its bad prognosis. It might benefit from a treatment from the outset associating corticosteroids and immunosuppressors, even with no usual bad prognosis factors.
Renal structure in neotropical bats: using stable isotopes to explore relationships between diet and morphology.
The relationship between kidney structure and diet was examined in several species of bats from the tropics. The trophic level of the bats was determined by their stable nitrogen isotopic composition (delta15 N). The results indicate that the relative thickness of the renal medulla is directly related to the trophic level of the bats. Additionally, we also determined the relationship between body mass and kidney structure. Relative medullary thickness was reciprocally related to body mass in animalivorous bats but no relationship was found in phytophagous bats. Stable isotope analysis provided a quantitative approximation of diet to test its relationship with kidney structure.
Rds and Rih mediate hypersensitive cell death independent of gene-for-gene resistance to the oat crown rust pathogen Puccinia coronata f. sp. avenae.
The Pca crown rust resistance cluster in the diploid Avena genus confers gene-for-gene specificity to numerous isolates of Puccinia coronata f. sp. avenae. Recombination breakpoint analysis indicates that specificities conferred by the Pca cluster are controlled by at least five distinct genes, designated Pc81, Pc82, Pc83, Pc84, and Pc85. Avena plants with the appropriate genotype frequently respond to P. coronata by undergoing hypersensitive cell death at the sites of fungal infection. Autofluorescence of host cells in response to P. coronata occurs in plants that develop visible necrotic lesions but not in plants that lack this phenotype. Two newly described, non-Pc loci were shown to control hypersensitive cell death. Rds (resistance-dependent suppressor of cell death) suppresses the hypersensitive response (HR), but not the resistance, mediated by the Pc82 resistance gene. In contrast, Rih (resistance-independent hypersensitive cell death) confers HR in both resistant and susceptible plants. Linkage analysis indicates that Rds is unlinked to the Pca cluster, whereas Rih is tightly linked to it. These results indicate that multiple synchronous pathways affect the development of hypersensitive cell death and that HR is not essential for resistance to crown rust. Further characterization of these genes will clarify the relationship between plant disease resistance and localized hypersensitive cell death.
Vitamin D and estrogen receptor gene polymorphisms in type 2 diabetes mellitus and in android type obesity.
OBJECTIVE: We studied the significance of BsmI restriction enzyme polymorphism of the vitamin D receptor (VDR) gene and the XbaI and PvuII polymorphisms of the estrogen receptor (ER) gene in patients with type 2 diabetes (n=49), android type obesity with normal carbohydrate metabolism (n=29) and healthy controls (n=138). METHODS: The distribution of genotypes in the study groups, as well as their relationship to fasting and 1 h postprandial serum C-peptide levels were analyzed. RESULTS: Postprandial serum C-peptide levels of BB genotypes were significantly higher in the diabetes and obese groups (6.18+/-5.09 ng/ml) compared with other genotypes (2.71+/-2.45 vs. 1.72+/-1.97 ng/ml, respectively, P=0.05). Among patients with type 2 diabetes and obese subjects, the XX allelic variant of the ER gene was more frequent (P=0.00015). Postprandial C-peptide levels of subjects exhibiting XX genotype were significantly lower compared with those with Xx genotype (1.67+/-2.16 vs. 3.8+/-3.72 ng/ml, P=0.021). The BBXx allelic combination of the VDR/ER receptor genes was less frequent in diabetic patients than in healthy subjects or in obese patients. The BBXx genotype was associated with significantly elevated postprandial C-peptide levels in all subjects compared with other combinations (9.65+/-3.14 vs. 1.35+/-2.82 ng/ml, P=0.003). No difference was found in the distribution of the PvuII polymorphism of the ER gene or in the association with the C-peptide levels among study groups. CONCLUSION: Polymorphisms of the VDR/ER receptor genes might play a role in the pathogenesis of type 2 diabetes by influencing the secretory capacity of beta-cells.
Differential expression of intracisternal A-particle transcripts in immunogenic versus tumorigenic S49 murine lymphoma cells.
Tumorigenic S49 mouse lymphoma cells (T-25) were compared to their nontumorigenic (immunogenic) substrate-adherent descendants (T-25-Adh), using the differential display technique. A 784-bp fragment with 92% sequence homology to the intracisternal A-particle (IAP) element family was isolated from the latter cells. IAP sequences are endogenous, noninfectious retroviral elements that can undergo transpositions and act as mutagens. Expression of IAP transcripts (as detected by the isolated fragment) was 5- to 10-fold higher in T-25-Adh cells than in T-25 cells. IAP RT-PCR cDNA clones derived from the immunogenic T-25-Adh cells, but not from T-25 cells, contain two distinctive motifs: (i) a motif characteristic of IAP elements expressed in lymphoid cells (lymphocyte specific, LS); (ii) a nonapeptide sequence known to stimulate cytotoxic T lymphocytes in a leukemia cell line expressing IAP sequences. In addition, expression of transcripts containing these motifs is enhanced in the immunogenic cells as opposed to the tumorigenic cells. Furthermore, one of the IAP elements (belonging to the LS1 subfamily) is specifically hypomethylated in the DNA of the immunogenic cells. The above-mentioned relationship was strengthened when tumorigenic revertants derived from T-25-Adh cells, as well as independently selected tumorigenic and immunogenic S49 sublines, were studied. In all cases, enhanced immunogenicity was linked to the up-regulation of specific IAP elements. No transpositions of LS1 elements were observed among the different sublines studied. These findings suggest that, in the S49 lymphoma, selectively expressed IAP retroviral elements may function in a tumor suppressive capacity by affecting the immunogenic potential of these cells.
Scale-invariant fluctuations at different levels of organization in developing heart cell networks.
In the last few years it has been realized that the intervals of spontaneous spiking events in the intact heart exhibit coexisting scale-invariant count fluctuations and anticorrelated interspike intervals fluctuations. Here, we show experimentally that this feature is an intrinsic property of single isolated heart cells, which is preserved when the cells couple into networks. We present a model explaining this behavior at both the single cell and network levels.
[It is a long way from Slagelse to Sebastopol].
Above I have told the story of Frederik Lov, who was the brother of my great-great-grandmother. He was born in 1802 as son of a watchmaker and graduated from the grammar school in Slagelse in 1822, the very year when the fairyteller Hans Christian Andersen was sent to the same school. Frederik Lov went to Copenhagen to study at >>The Royal Surgical Academy<<, but just before his final graduation he left for St. Petersburg in Russia as the Russian government had invited senior medical students and young doctors to come to work in Russia. True, it has been promised that the students could pass their exam in Russia in their native language. However, it turned out that Danish was not covered, so instead he was examined in Latin and passed his examination in 1828. He started his medical career at the naval hospital in Archangelsk, where he stayed for two years and learned to speak Russian. In 1830 he went with the frigate >>Smirna<< from Archangelsk towards Kronstadt, but was shipwrecked near Halmstad in Sweden. He was saved and could continue the journey one month later. In Kronstadt he was offered to join the Black Sea navy. He went to Sebastopol, where he stayed for the rest of his life. He participated in several military actions, especially in the Caucasian area. During the Crimean War he worked as a doctor in the fortifications of Sebastopol. At that time his family was evacuated and his house was destroyed by bombs. In 1874 he died as a highly decorated man. Frederik Lov's son Karl was also an officer. He was involved in battles in Caucasus like his father. After having left the army he became chief of the telegraph station of Sebastopol and later on the manager of the public bank of the town and elected member of the Duma. He lived at the house of Frederik Lov, which had been rebuilt after the Crimean War, and ever since descendents of Frederik Lov, lived in this house until it was destroyed by German bombs in 1942 and never rebuilt. A great-great-granddaughter of Frederik Lov, Olga Kulago, participated in the defense of Sebastopol in 1942 and was evacuated to Caucasus. After the war she studied medicine and graduated in 1950. She worked as an obstetrician until her retirement in 1977.
DNA-templated assembly and electrode attachment of a conducting silver wire.
Recent research in the field of nanometre-scale electronics has focused on two fundamental issues: the operating principles of small-scale devices, and schemes that lead to their realization and eventual integration into useful circuits. Experimental studies on molecular to submicrometre quantum dots and on the electrical transport in carbon nanotubes have confirmed theoretical predictions of an increasing role for charging effects as the device size diminishes. Nevertheless, the construction of nanometre-scale circuits from such devices remains problematic, largely owing to the difficulties of achieving inter-element wiring and electrical interfacing to macroscopic electrodes. The use of molecular recognition processes and the self-assembly of molecules into supramolecular structures might help overcome these difficulties. In this context, DNA has the appropriate molecular-recognition and mechanical properties, but poor electrical characteristics prevent its direct use in electrical circuits. Here we describe a two-step procedure that may allow the application of DNA to the construction of functional circuits. In our scheme, hybridization of the DNA molecule with surface-bound oligonucleotides is first used to stretch it between two gold electrodes; the DNA molecule is then used as a template for the vectorial growth of a 12 microm long, 100 nm wide conductive silver wire. The experiment confirms that the recognition capabilities of DNA can be exploited for the targeted attachment of functional wires.
Nonfluoroscopic endocardial catheter mapping of atrial fibrillation.
The treatment of drug-refractory atrial fibrillation (AF) remains one of the unsolved problems in cardiology. Surgical interventions have demonstrated that AF can be prevented by multiple incisions within both atria. Recently, this strategy has been translated into a catheter procedure. So far, the ablation approach is not based on individual electrophysiologic data, but constitutes only an anatomic approach. Further insight into the spatial and temporal distribution of the local electrograms during AF is needed. Electroanatomic maps acquired by sequential mapping over 45 seconds at each site during AF in six patients with paroxysmal AF were analyzed off-line. Electrograms were sampled at a mean of 36 +/- 12 sites in the left atrium of each patient. A total of 217 sites were sampled, of which 27.3% (59) represented type A (regular) AF, 9.7% (21) represented type B (totally irregular), and 63.1% (137) represented type C (mixture of type A and B) electrograms. The distribution was analyzed in 20 different segments of the left atrium, and a significantly higher incidence of type A electrograms was found in area 3 (upper lateral pulmonary vein) than at all other sites (P < 0.005). This observation needs further confirmation before any conclusion with regard to catheter ablation can be drawn, particularly because the analysis was based on bipolar recordings from a 4-mm tip electrode.
Preparative enantiomer separation of the inhalation anesthetics enflurane, isoflurane and desflurane by gas chromatography on a derivatized gamma-cyclodextrin stationary phase.
The preparative enantiomeric separation of the inhalation anesthetics enflurane (1) and isoflurane (2) in very high chemical (> 99.5%) and enantiomeric excess (ee > 99%) by gas chromatography (GC) on octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-gamma-cyclodextrin (4), dissolved in the apolar polysiloxane SE-54 and coated on Chromosorb P AW DMCS, is described. Up to 1 g of each enantiomer of 1-2 can been obtained per diem. The enantiomers of the highly volatile desflurane (3) can also be separated, albeit with diminished ee. The enantiomeric excess of 1-3 was checked by analytical GC on 4 and the absolute configuration of 2 and 3 has been determined via anomalous X-ray diffraction.
'Queenie railroad' touches our hearts.
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Voltage Fluctuations and Collective Effects in Ion-Channel Protein Ensembles.
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Effects of density and gating of delayed-rectifier potassium channels on resting membrane potential and its fluctuations.
The aim of this study is to evaluate directly, using a reduced experimental system, the nature of interactions between voltage-gated potassium channels and the resting membrane potential. Xenopus oocytes were injected with various concentrations of cRNA coding for a delayed-rectifier potassium channel Shaker-IR. The effects of the density and kinetics of the expressed channels on resting membrane potential is explored in isolated ("inside-out") patches. The channel density is given in terms of maximal conductance (Gmax), measured from the maximal slope of the I-V curve under voltage clamp conditions. The capacitance of the experimental setup is approximately 1 pF. At high channel densities (Gmax > 10 pA/mV) the mean membrane potential is stabilized at approximately -60 mV. This resting membrane potential is more than 35 mV positive to the reversal potential for potassium ions under the same experimental conditions. Analyses of voltage clamp experiments indicate that at high channel densities the mean membrane potential is determined by the rates of channel activation and deactivation, but is not affected by the rates involved in the process of slow (C-type) inactivation. In contrast, at lower channel densities membrane potential is very unstable, and its mean value and amplitude of fluctuations are strongly affected by the process of slow (C-type) inactivation.