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Biomedical subjects

M Husmann

Publications and source records attributed to M Husmann.

At least 19 recordsLinked to original sources
PubMed2006

[Guidance of interventions in subintimal recanalization and fenestration of dissection membranes using a novel dual-lumen intravascular ultrasound catheter].

PURPOSE: To evaluate the feasibility and effectiveness of IVUS-guided puncture for gaining controlled target lumen reentry in subintimal recanalization of chronic iliac/femoral artery occlusions and in fenestration of aortic dissections. MATERIALS AND METHODS: Between 5/2004 and 12/2005 12 consecutive patients (7 male, 5 female; mean age 64.6 +/- 12.0 years) with chronic critical limb ischemia and ischemic complications of aortic dissection were treated using the Pioneer catheter. This 6.2-F dual-lumen catheter combines a 20-MHz IVUS transducer with a pre-shaped extendable, hollow 24-gauge nitinol needle. This coaxial needle allows real-time IVUS-guided puncture of the target lumen and after successful reentry a 0.014" guidewire may be advanced through the needle into the target lumen. 7 patients were treated for aortic dissection and 5 patients (with failed previous attempts at subintimal recanalization) for chronic arterial occlusion. Patients with aortic dissection (5 type A dissections, 2 type B dissections) had developed renal ischemia (n = 2), renal and mesenteric ischemia (n = 2), or low extremity ischemia (n = 3). Patients with chronic arterial occlusions (2 common iliac artery occlusions, 3 superficial femoral artery occlusions) experienced ischemic rest pain (n = 4), and a non-healing foot ulcer (n = 1). RESULTS: The technical success rate using the Pioneer catheter was 100%. The recanalization/fenestration time was 37 +/- 12 min. Procedure-related complications did not occur. In 10 cases a significant improvement of clinical symptoms was evident. One patient with aortic dissection and ischemic paraplegia required subsequent surgical intervention. One patient had persistent ischemic rest pain despite successful recanalization of a superficial femoral artery occlusion. CONCLUSION: The Pioneer catheter is a reliable device which may be helpful for achieving target lumen reentry in subintimal recanalization of chronic occlusions and in fenestration of aortic dissections.

Aged↗
PubMed2005

Deformation and bursting of nonspherical polysiloxane microcapsules in a spinning-drop apparatus.

We analyze the deformation and bursting process of nonspherical organosiloxane capsules in centrifugal fields. Measurements were performed in a commercial spinning-drop tensiometer at different values of tube rotation. A theoretical analysis of the mechanics of initially ellipsoidal elastic shells subjected to centrifugal forces is developed where the deformation of the capsule is predicted as a function of the initial geometry and membrane elastic properties. For different types of organosiloxane membranes the Poisson number varies between 0 and 0.9. This phenomenon points to a considerable reduction of the membrane thickness at the onset of mechanical stress. Membrane-breaking processes always initiated at one of the pole ends of the capsules. Such rupture processes can be interpreted in terms of the derived theoretical model.

Capsules↗
PubMed2005

Fatty acids liberated from low-density lipoprotein trigger endothelial apoptosis via mitogen-activated protein kinases.

Enzymatic modification of low-density lipoprotein (LDL) as it probably occurs in the arterial intima drastically increases its cytotoxicity, which could be relevant for the progression of atherosclerotic lesions. LDL was treated with a protease and cholesterylesterase to generate a derivative similar to lesional LDL, with a high content of free cholesterol and fatty acids. Exposure of endothelial cells to the enzymatically modified lipoprotein (E-LDL), but not to native or oxidized LDL, resulted in programmed cell death. Apoptosis was triggered by apoptosis signal-regulating kinase 1 dependent phosphorylation of p38. Depletion and reconstitution experiments identified free fatty acids (FFA) as the triggers of this pathway. Levels of FFA in native LDL are low and the lipoprotein is therefore not cytotoxic; enzymatic cleavage of cholesterylesters liberates FFA that can rapidly trigger an apoptosis signaling cascade in neighboring cells. Blockade of this pathway can rescue cells from death.

Apoptosis↗
PubMed2002

Polymer erosion in PLGA microparticles produced by phase separation method.

This article deals with polymer erosion in biodegradable microparticles produced using the phase separation method. Poly(lactic-co-glycolic acid) copolymers with different compositions and molecular weights were employed. The microparticles were stored in phosphate buffer for 6 months. The molecular weight of the polymers was determined by size exclusion chromatography, and the weight loss was monitored gravimetrically. No weight loss was measured in the first weeks, although the molecular weight decreased significantly already from the start. After a certain storage period which was found to be specific for the type of polymer, the weight of the microparticles decreased rapidly. The start of this weight loss occurred when the molecular weight of the polymer in the degrading microparticles reached a threshold of approximately 15,000. This critical molecular weight was found to be identical for all investigated polymers, i.e. it was independent of the initial molecular weight of the polymer and of the lactic-glycolic ratio.

Chromatography, Gel↗
PubMed2001

In situ hemodynamics of perforating veins in chronic venous insufficiency.

PURPOSE: The prevalence of incompetent perforators increases linearly with the clinical severity of chronic venous insufficiency (CVI) and the presence of deep vein incompetence. Putative transmission of deep vein pressure to skin may cause dermal hypoxia and ulceration. Despite extensive prospective interest in the contribution of perforators toward CVI, their hemodynamic role remains controversial. The aim of this prospective study was to determine the in situ hemodynamic performance of incompetent perforating veins across the clinical spectrum of CVI, by means of duplex ultrasonography. METHODS: A total of 265 perforating veins of 90 legs that had clinical signs and symptoms consistent with CVI in 67 patients referred consecutively to the blood flow laboratory were studied. The clinical distribution of the examined limbs was CEAP(0), 10 limbs; CEAP(1-2), 39 limbs; CEAP(3-4), 21 limbs; and CEAP(5-6), 20 limbs. With the use of gated-Doppler ultrasonography on real-time B-mode imaging, the flow velocity waveforms were obtained from the lumen of perforators on release of manual distal leg compression in the sitting position and analyzed for peak and mean velocities, time to peak velocity, volume flow, venous volume displaced outward, and flow pulsatility. The diameter and duration of outward flow (abnormal reflux > 0.5 seconds) were also measured. RESULTS: Incompetent perforators had bigger diameters, higher peak and mean velocities and volume flow, longer time to peak velocity, and bigger venous volume displaced outward (VV(outward)) than competent perforators (all, P <.0001). The diameter of incompetent perforators did not change significantly with CEAP class (all, P >.1). Incompetent thigh and lower-third calf perforators had a significantly bigger diameter than perforators in the upper and middle calf combined (both, P <.05), in incompetent perforators: reflux duration was unaffected by CEAP class or site (P >.3); peak velocity was higher in those in CEAP(3-4) than those in CEAP(1-2) (P =.024); mean velocity in those in CEAP(3-6) during the first second of reflux was twice that of those in CEAP(1-2) (P <.0001); both higher volume flow and VV(outward) were found in the thigh perforators than those in the upper and middle calf thirds (P <.03); CEAP(3-6) volume flow and VV(outward), both in the first second, were twice that in those in CEAP(1-2) (P <.002); flow pulsatility in those in CEAP(5-6) was lower than in those in CEAP(1-2) (P =.014); in deep vein incompetence, higher peak velocity, volume flow, VV(outward), and diameter occurred than in its absence (P <.01). CEAP designation correlated significantly with mean velocity and flow pulsatility, both in the first second (r = 0.3, P <.01). The flow direction pattern in perforator incompetence was uniform across the CVI spectrum: inward on distal manual limb compression, and outward on its release; competent perforators had a smaller percentage of outward flow on limb compression (P <.01). CONCLUSION: In addition to an increase in diameter, perforator incompetence is characterized by significantly higher mean and peak flow velocities, volume flow, and venous volume displaced outward, and a lower flow pulsatility. Differences in early reflux enable a better hemodynamic stratification of incompetent perforators in CVI classes. In the presence of deep reflux, incompetent perforators sustain further hemodynamic impairment. In situ hemodynamics enable quantification of the function of perforators and can be used in the identification of the clinically relevant perforators and the impact of surgery.

Adolescent↗
PubMed2001

Subcytocidal attack by staphylococcal alpha-toxin activates NF-kappaB and induces interleukin-8 production.

Formation of transmembrane pores by staphylococcal alpha-toxin can provoke a spectrum of events depending on target cell species and toxin dose, and in certain cases, repair of the lesions has been observed. Here, we report that transcriptional processes are activated as a response of cells to low toxin doses. Exposure of monocytic (THP-1) or epithelial (ECV304) cells to 40 to 160 ng/ml alpha-toxin provoked a drop in cellular ATP level that was followed by secretion of substantial amounts of interleukin-8 (IL-8). Cells transfected with constructs comprising the proximal IL-8 promoter fused to luciferase or to green fluorescent protein cDNA exhibited enhanced reporter gene expression following toxin treatment. Electrophoretic mobility shift and immunofluorescence assays demonstrated that IL-8 secretion was preceded by activation of NF-kappaB. Transfection experiments conducted with p65/p50 double-deficient cells showed that activation of the IL-8 promoter/reporter by toxin was absolutely dependent on NF-kappaB. In contrast, this transcription factor was not required for lesion repair. Attack of cells by low doses of a pore-forming toxin can lead to transcriptional gene activation, which is followed by production of mediators that may contribute to the initiation and propagation of inflammatory lesions.

Adenosine Triphosphate↗
PubMed2000

Nuclear receptors modulate the interaction of Sp1 and GC-rich DNA via ternary complex formation.

Binding sites for transcription factor Sp1 have been implicated in the transcriptional regulation of several genes by hormones or vitamins, and here we show that a GC-rich element contributes to the retinoic acid response of the interleukin 1beta promoter. To explain such observations, it has been proposed that nuclear receptors can interact with Sp1 bound to GC-rich DNA. However, evidence supporting this model has remained indirect. So far, nuclear receptors have not been detected in a complex with Sp1 and GC-rich DNA, and the expected ternary complexes in non-denaturing gels were not seen. In search for these missing links we found that nuclear receptors [retinoic acid receptor (RAR), thyroid hormone receptor (TR), vitamin D(3) receptor, peroxisome-proliferator-activated receptor and retinoic X receptor] induce an electrophoretic mobility increase of Sp1-GC-rich DNA complexes. Concomitantly, binding of Sp1 to the GC-box is enhanced. It is proposed that nuclear receptors may partially replace Sp1 in homo-oligomers at the GC-box. RARs and Sp1 can also combine into a complex with a retinoic acid-response element. The presence of RAR and Sp1 in complexes with either cognate site was revealed in supershift experiments. The C-terminus of Sp1 interacts with nuclear receptors. Both the ligand- and DNA-binding domains of the receptor are important for complex formation with Sp1 and GC-rich DNA. In spite of similar capacity to form ternary complexes, RAR but not TR up-regulated an Sp1-driven reporter in a ligand-dependent way. Thus additional factors limit the transcriptional response mediated by nuclear receptors and Sp1.

Animals↗
PubMed2000

Potassium regulates IL-1 beta processing via calcium-independent phospholipase A2.

We report that potassium leakage from cells leads to activation of the Ca2+-independent phospholipase A2 (iPLA2), and the latter plays a pivotal role in regulating the cleavage of pro-IL-1 beta by the IL-converting enzyme caspase-1 in human monocytes. K+ efflux led to increases of cellular levels of glycerophosphocholine, an unambiguous indicator of phospholipase A2 activation. Both maturation of IL-1 beta and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA2 inhibitor. Bromoenol lactone-dependent inhibition of IL-1 beta processing was not due to perturbation of the export machinery for pro-IL-1 beta and IL-1 beta or to caspase-1 suppression. Conspicuously, activation of Ca2+-dependent phospholipase A2 did not support but rather suppressed IL-1 beta processing. Thus, our findings reveal a specific role for iPLA2 activation in the sequence of events underlying IL-1 beta maturation.

Biological Transport↗
PubMed2000

GyrA sequence-based typing of Legionella.

Comparative sequence analysis of a 423-bp segment of the gyrA gene including a region homologous to the quinolone resistance-determining region (QRDR) of other species was evaluated as a novel typing method for Legionella strains. The study was performed with 29 reference strains representing 11 different Legionella species, with various serogroups, and with 13 clinical isolates of L. pneumophila. Pulsed-field gel electrophoresis and serotyping were employed for comparison of the clinical isolates. QRDR sequencing proved to be a highly discriminative tool for typing Legionellae, and permitted identification of species, serogroups and even different strains within serogroup 1. None of the isolates were resistant to quinolones in vitro and this correlated with dissence of mutations in the QRDR region. The data show that comparative sequence analysis of a short fragment of the gyrA gene is a potentially useful tool for typing of Legionella beyond the serogroup level. It is anticipated that mutations of the QRDR may arise in Legionella as a consequence of the introduction of quinolones as the agents of choice for the treatment of infections with this agent in immunocompromised patients. The employment of QRDR-typing maybe helpful in uncovering such mutations.

4-Quinolones↗
PubMed1999

Isolation of Abiotrophia adiacens from a brain abscess which developed in a patient after neurosurgery.

We report the case of a patient who developed a large brain abscess after neurosurgery. Cerebrospinal fluid from the abscess drainage yielded Abiotrophia adiacens-specific PCR products and microorganisms that were identified by conventional microbiological methods and by 16S ribosomal DNA analysis as Abiotrophia adiacens, which was formerly classified as a member of nutritionally variant streptococci.

Astrocytoma↗
PubMed1998

Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis.

Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe complications of secondary dengue virus (DV) infection. Vascular leakage, hemorrhagic diathesis and complement activation are the hallmarks of the disease. The short-lived nature of the plasma leakage syndrome has led to the conclusion that altered permeability is most likely effected by a soluble mediator. In the present study, we show that infection of human endothelial cells with DV induces the transcriptional up-regulation and secretion of RANTES and IL-8 and, in the presence of anti-dengue Abs, the formation of nonlytic complement complexes. Extremely high levels of IL-8 were detected in plasma and pleural fluid samples from patients with DSS. Furthermore, DV infection of endothelial cells in vitro caused apoptosis. Complement activation, chemokine induction, and apoptotic cell death may act in concert to cause the fulminant but short-lived vascular leakage that is characteristic of DHF/DSS.

Apoptosis↗
PubMed1998

Atherogenic properties of enzymatically degraded LDL: selective induction of MCP-1 and cytotoxic effects on human macrophages.

The mechanisms underlying the selective accumulation of macrophages in early atherosclerotic lesions are poorly understood but are likely to be related to specific properties of altered low density lipoprotein (LDL) deposited in the subendothelium. Enzymatic, nonoxidative degradation of LDL converts the lipoprotein to a potentially atherogenic moiety, enzymatically altered LDL (E-LDL), which activates complement and is rapidly taken up by human macrophages via a scavenger receptor-dependent pathway. Immunohistological evidence indicates that E-LDL is present in an extracellular location in the early lesion. We report that E-LDL causes massive release of monocyte chemotactic protein 1 (MCP-1) from macrophages and that expression of interleukin 8 or RANTES remains unchanged. Release of MCP-1 was preceded by a rapid expression of MCP-1 mRNA, which was detectable after 15 minutes, reached maximum levels after 1 hour, and remained detectable for 12 hours after exposure to concentrations as low as 10 microg/mL E-LDL. MCP-1 mRNA induction and protein release by E-LDL exceeded that evoked by oxidized LDL. Release of MCP-1 was dependent on de novo protein synthesis and on the activity of tyrosine kinases. At higher concentrations, E-LDL, but not oxidized LDL, exerted toxic effects on macrophages that in part appeared to be due to apoptosis. The results show that E-LDL possesses major properties of an atherogenic lipoprotein.

Arteriosclerosis↗
PubMed1996

A novel SP-1 site in the human interleukin-1 beta promoter confers preferential transcriptional activity in keratinocytes.

To investigate the mechanisms of transcriptional activation of interleukin-1beta (IL-1beta) in non-monocytic cells, we constructed a series of reporter plasmids with the bacterial chloramphenicol acetyltransferase gene linked to various parts of the human IL-1beta promoter and performed transient transfection experiments. We identified a promoter segment that activates transcription most efficiently in keratinocytes. Electrophoretic mobility shift assays (EMSA) with a 43-mer oligonucleotide derived from the functionally identified cis-acting element revealed specific complexes. By competition analysis with transcription factor consensus sequence oligonucleotides and by immunosupershift, transcription factor SP-1 or a closely related protein was shown to bind to this regulatory element. The closest match to the known SP-1 consensus sequence within the respective region is a TCCCCTCCCCT motif. Mutation of this motif almost completely, and specifically, abolished the binding of two low-mobility complexes and led to a 95% decrease of constitutive transcriptional activation of a reporter construct IL-1beta (-170/+108). Likewise, activation of this reporter construct by tumor necrosis factor-alpha depended on the SP-1 site. These observations suggest that a so-far-unrecognized SP-1 site in the human IL-1beta promoter may participate in the transcriptional regulation of this gene in keratinocytes.

Cell Line, Transformed↗
PubMed1996

Case of fatal systemic infection with an Aureobacterium sp.: identification of isolate by 16S rRNA gene analysis.

The case of a 75-year-old man who succumbed to a disseminated infection most likely caused by a species of the genus Aureobacterium is reported. Identification of the isolate was achieved by comparative 16S rRNA gene analysis. Aureobacteria are commonly found in the environment. However, only recently have they been recognized as a cause of infections including septicemia and soft tissue infections. To our knowledge, this is the first documentation of a fatal infection caused by an Aureobacterium sp.

Aged↗
PubMed1995

Relevance of immunologic reactions for tissue failure of bioprosthetic heart valves.

The use of biologic heart valve prostheses is decreasing because of the high incidence of failure of these bioprostheses resulting from tissue degeneration or tearing. Immunologic reactions might play a decisive role in this process. The present experimental and clinical studies were conducted to investigate the relevance of immunologic reactions to the tissue failure of glutaraldehydetanned bovine pericardial and porcine valves. Specimens of the two different types of valve material were implanted in the abdominal muscles of rats. Enzyme-linked immunosorbent assays and tritiated thymidine incorporation tests were performed to detect specific antibodies and activated T cells. All specimens were studied histologically. Identical enzyme-linked immunosorbent assays and tritiated thymidine incorporation tests were performed in 29 patients with bioimplants and in 48 controls. Twenty explanted bioprostheses were investigated using histologic and immune histologic methods. The results of the enzyme-linked immunosorbent assays and lymphocyte proliferation tests showed that glutaraldehyde-tanned bovine pericardial valves can provoke cellular and humoral immunologic reactions in rats and human beings. In explanted bovine valves, macrophages were found invading and degrading implant collagen, starting from surface lesions. The combination of the formation of mechanical lesions, the development of cellular infiltrates, and collagen disruption strongly indicates that initial surface lesions initiate the immunologic reactions in bovine pericardial valves as the result of the exposure of incompletely tanned collagen. These immune responses might accelerate tissue degeneration. Porcine valves do not provoke immunologic reactions.

Animals↗
PubMed1994

Recovery of human fibroblasts from attack by the pore-forming alpha-toxin of Staphylococcus aureus.

When applied at low concentrations (< 10 micrograms/ml), staphylococcal alpha-toxin generates a small channel in keratinocyte and lymphocyte membranes that permits selective transmembrane flux of monovalent ions. Here we show that a moderate concentration (1-50 micrograms/ml) of alpha-toxin similarly produces a small pore in membranes of human fibroblasts. This process leads to rapid leakage of K+ and to a drop in cellular ATP to 10-20% of normal levels in 2 h. In the presence of medium supplemented with serum and at pH 7.4, the cells are able to recover from toxin attack, so that normal levels of K+ and ATP are reached after 6-8 h at 37 degrees C. The repair process is dependent on the presence of serum in the medium and is very sensitive towards pH. Decreases of pH in the medium to < or = 7.0 as well as increases to > or = 7.8 causes the repair mechanism to fail. The fate of cell-bound toxin molecules was investigated by using a radiolabelled tracer and by immunological detection of toxin exposed at the cell surface. The results indicated that 50-70% of the toxin was shed from cell membranes. However, there was no clear correlation between shedding and recovery, and shedding was also observed in cells that died at pH 7.8. Shedding was not decisive for repair, since cells that had recovered from toxin attack continued to carry 30-40% of initially bound toxin on their cell surface. Blockade of Na+/K(+)-ATPases with ouabain evoked similar kinetics of K(+)-depletion in control cells, compared with cells that had just recuperated from toxin attack and that still carried 30-40% alpha-toxin on their surface. We therefore tentatively concluded that repair of alpha-toxin lesions was due to closure of small pores, rather than from compensation of membrane leaks by up-regulation of Na+/K(+)-ATPase activity. We speculate that repair of small membrane lesions may extend to other agents that produce channels of similar nature in nucleated cells. Larger pores created by E. coli hemolysin or streptolysin O, both of which form larger functional transmembrane lesions, could not be repaired by fibroblasts.

Adenosine Triphosphate↗