Determination of the enzyme telomerase in needle biopsies and fine needle aspiration cytology samples of the prostate in the diagnosis of prostate cancer.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
M Müller
Publications and source records attributed to M Müller.
Biological ultrastructure as revealed by high resolution cryo-SEM of block faces after cryo-sectioning.
Ultrastructural information was obtained by imaging the block face of high-pressure-frozen cryo-sectioned biological samples in a high-resolution cryo-SEM. Cryo-sectioning leads to a well-defined flat artificial surface in contrast to cryo-fracturing. Typical artefacts of cryo-sections such as compression and crevasses were not visible on the block face. The ultrastructural features known from resin sections and from freeze-fractures could also be found on the block faces. The cytoplasms show particles of different size which most likely represent proteins. The effects of radiation damage could be reduced considerably by applying the double layer coating technique and backscattered electron imaging. High quality cryo-sections are only obtained from vitrified material. Reasonably flat block faces were, however, also obtained from adequately frozen microcrystalline samples, thereby facilitating ultrastructural studies in the frozen hydrated state.
Animals↗
Affinity of the periplasmic chaperone Skp of Escherichia coli for phospholipids, lipopolysaccharides and non-native outer membrane proteins. Role of Skp in the biogenesis of outer membrane protein.
The Skp protein of Escherichia coli has been proposed to be a periplasmic molecular chaperone involved in the biogenesis of outer membrane proteins. In this study, evidence is obtained that Skp exists in two different states characterized by their different sensitivity to proteases. The conversion between these states can be modulated in vitro by phospholipids, lipopolysaccharides and bivalent cations. Skp is able to associate with and insert into phospholipid membranes in vitro, indicating that it may associate with phospholipids in the inner and/or outer membrane in vivo. In addition, it interacts specifically with outer membrane proteins that are in their non-native state. We propose that Skp is required in vivo for the efficient targeting of unfolded outer membrane proteins to the membrane.
Bacterial Outer Membrane Proteins↗
Long-term survival after surgery for recurrent advanced sarcomatoid renal carcinoma.
Explore the source record for details and available documents.
Aged↗
Combined analysis of polymorphisms of the tumor necrosis factor-alpha and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis.
Environmental and genetic factors are thought to interact in the manifestation of psoriasis, but knowledge about the involved genes and antigens is incomplete. This study has focused on the association between psoriasis and inherited variations in xenobiotic metabolism and cytokine production as two components that may influence cutaneous immune responses to foreign substances. Polymorphisms of N-acetyltransferase 2, glutathione S-transferases T1 and M1, and promoter polymorphisms of the genes encoding for tumor necrosis factor-alpha and interleukin-10 were investigated in 151 Caucasian patients with psoriasis (100 with type I and 51 with type II psoriasis) and in 123 healthy controls. Polymorphisms were detected by polymerase chain reaction-based methods, restriction enzyme analysis, and direct sequencing. There were no significant differences in the distribution of enzyme polymorphisms or point mutations at position -1082 of the interleukin-10 promoter between the psoriasis groups and the control group. The G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter (TNF alpha-238*A allele) was more common in type I psoriasis (27%) than in the controls [9.8%; odds ratio 3.4 (95% confidence interval 1.6-7.2); p = 0.0012; pcorr = 0.018]. Surprisingly, this overrepresentation of the tumor necrosis factor alpha-238*A allele was observed in male patients [4.1 (1.5-11.0); p = 0.0046; pcorr = 0.064] but not in female patients [1.8 (0.5-6.5); p = 0.5]. The G-->A polymorphism at position -308 of the tumor necrosis factor-alpha promoter was less frequent in type I psoriasis (23%) compared with controls (35.7%), although the negative association was weak [0.54 (0.3-0.97); p = 0.041; pcorr = not significant]. The distribution of the TNF alpha-238*A and TNF alpha-238*A alleles was similar in type II patients and controls. Our results suggest that male carriers of the G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter are at an increased risk to develop early-onset psoriasis.
Adolescent↗
Effects of an oxidizing agent (hydrogen peroxide) on the glutathione system in epidermal cells of Allium cepa L. investigated by histochemical staining.
The glutathione system in epidermal cells of Allium cepa L. was measured by a quantitative image analysis method, using histochemical staining by monochlorobimane. Blockage of thiol groups with N-ethylmaleimide decreased fluorescence to a small rest fluorescence of maximum 5%. Pre-treatment with dithiothreitol increased fluorescence yield in all cells compared to the monochlorobimane treatment alone. These results correspond to the blockage or the reduction of the total pool of glutathione in the cells. After treatment with N-ethylmaleimide and subsequent incubation with dithiothreitol followed by labelling with bimane a low fluorescence yield was observed which correspond to the proportion of GSSG. Specimens that were incubated in H2O2 prior to the treatments described above exhibited a decrease in total glutathione and in reduced glutathione and an increase in the proportion of GSSG compared to the control.
Allium↗
Foreign body reaction to meshes used for the repair of abdominal wall hernias.
OBJECTIVE: To investigate the local tissue reactions to meshes that had been removed from humans. DESIGN: Open study SETTING: Surgical department of the technical University, Aachen, Germany. MATERIAL: Samples of 17 non-absorbable meshes (1 polyester, 10 polypropylene, 2 reduced polypropylene, and 4 polytetrafluorethylene, PTFE) and 1 absorbable mesh (polyglactin 910) that had been implanted for repair of abdominal wall defects. INTERVENTIONS: Light and transmission electron microscopy, immunohistochemistry, and histological examination. MAIN OUTCOME MEASURES: Signs of inflammatory response. RESULTS: Light microscopy showed chronic inflammatory tissue reaction, even after years, with pronounced differences among materials. Partial volume of inflammatory cells (%) varied from 32 in polypropylene, to 12 in expanded PTFE, 8 in polyester, and 7 in reduced polypropylene. Formation of connective tissue correlated significantly with the extent of the inflammatory reaction (p<0.01). In meshes implanted for long periods there were still numerous macrophages at the interface between tissue and polypropylene (45%), polyester (45%), expanded PTFE (25%), and reduced polypropylene (22%). There was no difference in time dependent tissue reactions (p = 0.19). CONCLUSION: Inflammation around alloplastic materials used to repair defects in the abdominal wall persists for many years. There was evidence of long term wound complications as a result of persistent foreign body reactions. Further studies are required to evaluate the long term tissue response to these materials.
Abdominal Muscles↗
Influence of cyclodextrins on the in vitro corneal permeability and in vivo ocular distribution of thalidomide.
The aim of the present study has been to develop aqueous Thalidomide (THA) eye drops in order to minimize systemic side effects and to improve bioavailability following topical application. Cyclodextrins (CDs), suitable vehicles to improve aqueous solubility of THA, were evaluated with regard to their ability to influence in vitro corneal permeability of THA. Additionally, rabbit eyes received either THA-suspension (0.04%) (THA-SP) or THA (0.04%)/hydroxypropyl-beta-cyclodextrin (HP-beta-CD) (12.5%) solution (THA-CD). In vitro corneal permeation studies demonstrated that the absolute amount of THA permeated could not be increased by means of CDs. The percentile release of THA was extensively decreased using saturated THA/CD solutions. Following loading doses of either THA-CD or THA-SP onto the rabbit eye, significantly increased aqueous humor levels were obtained for THA-CD 30 min (THA-CD:THA-SP=4.6:1) and 60 min (THA-CD:THA-SP=3.1:1) post instillation (p<0.05). In the iris-ciliary body, significantly increased THA levels were obtained using THA suspension (THA-CD(60 min):THA-SP(60 min)=1:6.1) (p<0.05). In the cornea, conjunctiva, vitreous and sclera, differences between the THA tissue levels were not statistically significant. Cyclodextrins might be a useful tool to formulate aqueous THA eye drop solutions and modify intraocular drug bioavailability.
Angiogenesis Inhibitors↗
In vitro studies with purified components reveal signal recognition particle (SRP) and SecA/SecB as constituents of two independent protein-targeting pathways of Escherichia coli.
The molecular requirements for the translocation of secretory proteins across, and the integration of membrane proteins into, the plasma membrane of Escherichia coli were compared. This was achieved in a novel cell-free system from E. coli which, by extensive subfractionation, was simultaneously rendered deficient in SecA/SecB and the signal recognition particle (SRP) components, Ffh (P48), 4. 5S RNA, and FtsY. The integration of two membrane proteins into inside-out plasma membrane vesicles of E. coli required all three SRP components and could not be driven by SecA, SecB, and DeltamicroH+. In contrast, these were the only components required for the translocation of secretory proteins into membrane vesicles, a process in which the SRP components were completely inactive. Our results, while confirming previous in vivo studies, provide the first in vitro evidence for the dependence of the integration of polytopic inner membrane proteins on SRP in E. coli. Furthermore, they suggest that SRP and SecA/SecB have different substrate specificities resulting in two separate targeting mechanisms for membrane and secretory proteins in E. coli. Both targeting pathways intersect at the translocation pore because they are equally affected by a blocked translocation channel.
Adenosine Triphosphatases↗
Effects of low-dose dopexamine on splanchnic oxygenation during major abdominal surgery.
OBJECTIVE: To study the influence of low-dose dopexamine on splanchnic oxygenation during major abdominal surgery. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: University hospital. PATIENTS: Eighteen adult patients undergoing elective major abdominal surgery. INTERVENTIONS: The patients received either dopexamine at 1 microg/kg/min (group A, n = 9) or 0.90% saline as control (group B, n = 9). MEASUREMENTS AND RESULTS: To assess the splanchnic oxygenation, intestinal tissue PO2 (PtissO2) and gastric intramucosal Pco2 (PmucCO2) were measured, and the PCO2 gap (PmucCO2 - PaCO2) was calculated at baseline (T1) and after an infusion period of 60 mins (T2). There was no difference between the groups in the global oxygen transport parameters. Low-dose dopexamine increases PtissO2 on the serosal side of the small bowel (deltaPtissO2, 17+/-24 mm Hg in group A vs. -5+/-10 in group B). The changes in PtissO2 at the serosal side of the colon after dopexamine demonstrated a nonsignificant increase (deltaPtissO2, 7+/-11 mm Hg in group A vs. -11+/-23 mm Hg in group B). In both groups, the Pco2 gap (group A, 6+/-7 mm Hg [T1] and 5+/-6 mm Hg [T2], vs. group B, 9+/-10 mm Hg [T1] and 12+/-10 mm Hg [T2]) remained unchanged compared with the baseline. CONCLUSION: It is concluded that low-dose dopexamine improves PtissO2 at the serosal side of the gut, preferably at the small bowel. However, low-dose dopexamine did not improve gastric PmucCO2.
Abdomen↗
Radiologic and mechanical properties of inactivated ossicle homografts.
OBJECTIVE: This study examined the effects of old and new inactivation (sterilization) techniques on the radiologic and mechanical properties of ossicle homografts. MATERIALS AND METHODS: Ninety normal incuses and malleuses received either treatment with 1) 5% formaldehyde/cialit, 2) 1N NaOH, 3) 0.9% LpH, or 4) autoclaving at 134'C, or no treatment. All ossicles were assessed radiologically by high-resolution computed tomography. After imaging, all ossicles underwent mechanical testing by destructive axial compression in a mechanical testing machine measuring force and displacement. RESULTS: Ossicles treated with cialit, NaOH, or autoclaving showed a significant decrease of ultimate force and stiffness compared with controls. LpH treatment caused no such changes in these structural properties. Material properties of yield strength, ultimate strength, and elastic modulus were also altered by cialit, NaOH, and autoclaving, but were much more difficult to assess because of uncertainty in parameter estimates. There was a significant increase in radiologic density in autoclaved ossicles, a reduction in cialit- and LpH-treated ossicles, and no change in NaOH-treated ossicles. CONCLUSIONS: All tested inactivation procedures changed the biomechanical and/or radiologic properties of ossicle homografts. However, the new procedures used to inactivate infectious agents produced changes similar to the older treatments with formaldehyde/cialit. Human allografts are able to withstand harsh but safe sterilization procedures. The NaOH treatment seems to be the most suitable method for the future. The biologic (osteogenic) potentials of ossicle homografts treated with these new preservation/inactivation methods are still unknown. Further investigations are necessary to re-evaluate the clinical use of ossicle homografts in middle ear reconstructive surgery.
Adult↗
Improved labelling of no-carrier-added 123I-MIBG and preliminary clinical evaluation in patients with ventricular arrhythmias.
Meta-[123I]iodobenzylguanidine (123I-MIBG) is currently used to assess myocardial sympathetic innervation by single photon emission tomography (SPET). In recent studies, an enhanced cardiac uptake of 123I-MIBG with high specific activity has been reported, suggesting the clinical potential of no-carrier-added (n.c.a.) 123I-MIBG in the assessment of abnormalities in cardiac sympathetic function. This paper describes the preparation of n.c.a. 123I-MIBG by non-isotopic Cu(I)-assisted [123I]iododebromination and by [123I]iododestannylation, both resulting in n.c.a. 123I-MIBG with radiochemical yields of 88 +/- 6% and high specific activity (> or = 6.3 TBq.mumol-1) in a total synthesis time of less than 50 min. The diagnostic potential of n.c.a. 123I-MIBG (> 6.3 TBq.mumol-1) was studied in 13 patients (nine patients with malignant ventricular arrhythmias and four patients suspected of phaeochromocytoma) and compared to commercial 123I-MIBG (approximately 75 MBq.mumol-1) using a dual-headed SPET camera (MULTISPECT II). High specific activity results in higher 123I-MIBG uptake in the heart and in the liver in all patients. The calculated heart-to-lung and heart-to-liver count ratios 4.5 h post-injection increased by 22 +/- 6% and 10 +/- 5% with n.c.a. 123I-MIBG compared to commercial 123I-MIBG respectively. In contrast, no significant correlation between the specific activity of 123I-MIBG and lung uptake could be established in this study. Analysis of radioactivity in blood after the intravenous injection of n.c.a. and commercially available 123I-MIBG showed an initial rapid clearance of radioactivity from blood, followed by a plateau from 60 min onwards. Within the first 24 h, more than 85% of the plasma activity was unchanged 123I-MIBG. The free 123I-iodide concentration determined 24 h post-injection was 2 +/- 1% with commercial 123I-MIBG and 3 +/- 2% with n.c.a. 123I-MIBG. In conclusion, the results of this investigation indicate that n.c.a. 123I-MIBG is a promising clinical tool for imaging myocardial sympathetic dysfunction by SPET. High specific activity n.c.a. 123I-MIBG can now be prepared by simple one-step methods giving high radiochemical yields and high purity suitable for clinical application. This encourages the further clinical validation of n.c.a. 123I-MIBG on a large scale.
3-Iodobenzylguanidine↗
Phase transitions in open quantum systems.
We consider the behavior of open quantum systems through the dependence of the coupling to one decay channel by introducing the coupling parameter alpha, which is proportional to the average degree of overlapping. Under critical conditions, a reorganization of the spectrum takes place that creates a bifurcation of the time scales with respect to the lifetimes of the resonance states. We derive analytically the conditions under which the reorganization process can be understood as a second-order phase transition and illustrate our results by numerical investigations. The conditions are fulfilled, e.g., for a uniform picket-fence level distribution with equal coupling of the states to the continuum. Energy dependencies within the system are included. We consider also the case of an unfolded Gaussian orthogonal ensemble and of a spectrum bounded from below. In all these cases, the reorganization of the spectrum occurs at the critical value alpha(crit) of the control parameter globally over the whole energy range of the spectrum. All states act cooperatively.
Journal Article↗
Intermolecular structure factors of macromolecules in solution: integral equation results.
The intermolecular structure of semidilute polymer solutions is studied theoretically. The low-density limit of a generalized Ornstein-Zernicke integral equation approach to polymeric liquids is considered. Scaling laws for the dilute-to-semidilute crossover of the random-phase approximation (RPA)-like structure are derived for the intermolecular structure factor on large distances when intermolecular excluded volume is incorporated at the microscopic level. This leads to a nonlinear equation for the excluded volume interaction parameter. For macromolecular size-mass scaling exponents nu above a spatial-dimension dependent value, nu(c)=2/d, mean-field-like density scaling is recovered, but for nu<nu(c) the density scaling becomes nontrivial in agreement with field-theoretic results and justifying phenomenological extensions of the RPA. The structure of the polymer mesh in semidilute solutions is discussed in detail and comparisons with large-scale Monte Carlo simulations are added. Finally, a possibility to determine the correction to scaling exponent omega(12) is suggested.
Journal Article↗
Penetration of moxifloxacin into peripheral compartments in humans.
To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min. An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)(interstitial fluid)/AUC(total-plasma) ratios ranging from 0.38 to 0.55 and mean AUC(interstitial fluid)/AUC(free-plasma) ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant Streptococcus pneumoniae. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans.
4-Quinolones↗
Distribution and antimicrobial activity of ciprofloxacin in human soft tissues.
Interstitial ciprofloxacin concentrations in soft tissues were measured by microdialysis following intravenous administration of 200 mg to each of eight healthy volunteers. Interstitial ciprofloxacin concentrations were significantly lower than corresponding total serum drug concentrations; the interstitium-to-serum concentration ratios ranged from 0.55 to 0.73. An in vitro simulation based on interstitial pharmacokinetics showed a substantially lower antimicrobial activity than did the simulation based on serum pharmacokinetics. Thus, ciprofloxacin concentrations at the site of effect may be subinhibitory although effective concentrations are attained in serum.
Adult↗
Penetration of ciprofloxacin into the interstitial space of inflamed foot lesions in non-insulin-dependent diabetes mellitus patients.
Interstitial ciprofloxacin concentrations were measured by microdialysis in inflamed foot lesions of non-insulin-dependent diabetes mellitus patients following intravenous administration of 0. 2 g of ciprofloxacin. Interstitial ciprofloxacin concentrations were significantly lower than corresponding serum concentrations. There was no significant difference in the penetration of ciprofloxacin into inflamed and unaffected tissue (area under the concentration-time curve(infection)/area under the concentration-time curve(unaffected tissue) = 0.99 +/- 0.15 [mean +/- standard error], n = 6). Thus, inflammation appears to have little or no effect on the penetration of ciprofloxacin into tissue.
Aged↗
Intrinsic optical signals in rat hippocampal slices during hypoxia-induced spreading depression-like depolarization.
In interfaced rat hippocampal slices spreading depression (SD) and hypoxia-induced SD-like depolarization are associated with increased light reflectance and decreased light transmittance, indicating increased light scattering. By contrast, mild hypotonicity or electrical stimulation decrease light scattering, which is usually taken to be caused by cell swelling. This difference has been attributed to experimental conditions, but in our laboratory moderate osmotic challenge and SD produced opposite intrinsic optical signals (IOSs) in the same slice under identical conditions. To decide whether the SD-induced IOS is related to cell swelling, we investigated the effects of Cl(-) transport inhibitors and Cl(-) withdrawal on both light reflectance and transmittance, as well as on changes in interstitial volume and tissue electrical resistance. In normal [Cl(-)](o), early during hypoxia, there was a slight decrease in light reflectance paired with increase in transmittance. At the onset of hypoxic SD, coincident with the onset of cell swelling (restriction of TMA(+) space), the IOS signals suddenly inverted, indicating sharply increased scattering. The SD-related IOSs started in a single spot and spread out over the entire CA1 region without invading CA3. Application of 2 mM furosemide decreased IOS intensity. When [Cl(-)](o) was substituted by methylsulfate or gluconate, the SD-related reflectance increase and transmittance decrease were suppressed and replaced by opposite signals, indicating scattering decrease. Yet Cl(-) withdrawal did not prevent cell swelling measured as shrinkage of TMA(+) space. The SD-related increase of tissue electrical resistance was reduced when bath Cl(-) was replaced by methylsulfate and almost eliminated when replaced by gluconate. The TMA(+) signal is judged to be a more reliable indicator of interstitial space than tissue resistance. Neither application of cyclosporin A nor raising [Mg(2+)](o) depressed the SD-related reflectance increase, suggesting that Cl(-) flux through mitochondrial "megachannels" may not be a major factor in its generation. Fluoroacetate poisoning of glial cells (5 mM) accelerated SD onset and enhanced the SD-induced reflectance increase threefold. This suggests, first, that glial cells normally moderate the SD process and, second, that neurons are the predominant generators of the light-scattering increase. We conclude that light scattering by cerebral tissue can be changed by at least two different physical processes. Cell swelling decreases light scattering, whereas a second process increases scattering. During hypoxic SD the scattering increase masks the swelling-induced scattering decrease, but the latter is revealed when Cl(-) is removed. The scattering increase is Cl(-) dependent, nevertheless it is apparently not related to cell volume changes. Its underlying mechanism is as yet not clear; possible factors are discussed.
Animals↗