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Biomedical subjects

M Wenzel

Publications and source records attributed to M Wenzel.

At least 19 recordsLinked to original sources
PubMed2003

TRAIL-beta and TRAIL-gamma: two novel splice variants of the human TNF-related apoptosis-inducing ligand (TRAIL) without apoptotic potential.

Tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a recently identified member of the TNF family, which induces programmed cell death in a variety of neoplastic cell types, but not in most nonneoplastic cells. In this study, we report on the identification of two novel alternative splice variants of TRAIL in neoplastic and non-neoplastic human cells lacking either exon 3 (TRAIL-beta) or exons 2 and 3 (TRAIL-gamma). In both splice variants, loss of exon 3 resulted in a frame shift generating a stop codon with consecutive extensive truncation in the extracellular domain. Ectopic expression revealed a loss of proapoptotic potential for both alternative splice variants. In contrast to the predominantly cytoplasmatic localisation of GFP-tagged TRAIL-alpha and TRAIL-beta, TRAIL-gamma showed an additional association with the cell surface and nuclear membrane. In conclusion, alternative splicing might be involved in fine tuning of TRAIL-induced apoptosis and underlines the complexity of the TRAIL system.

Alternative Splicing↗
PubMed2002

Differential subcellular localization of functionally divergent survivin splice variants.

Survivin is an inhibitor of apoptosis protein (IAP) that is markedly overexpressed in most cancers. We identified two novel functionally divergent splice variants, i.e. non-antiapoptotic survivin-2B and antiapoptotic survivin-deltaEx3. Because survivin-2B might be a naturally occurring antagonist of antiapoptotic survivin variants, we analyzed the subcellular distribution of these proteins. PSORT II analysis predicted a preferential cytoplasmic localization of survivin and survivin-2B, but a preferential nuclear localization of survivin-deltaEx3. GFP-tagged survivin variants confirmed the predicted subcellular localization and additionally revealed a cell cycle-dependent nuclear accumulation of survivin-deltaEx3. Moreover, a bipartite nuclear localization signal found exclusively in survivin-deltaEx3 may support cytoplasmic clearance of survivin-deltaEx3. In contrast to the known association between survivin and microtubules or centromeres during mitosis, no corresponding co-localization became evident for survivin-deltaEx3 or survivin-2B. In conclusion, our study provided data on a differential subcellular localization of functionally divergent survivin variants, suggesting that survivin isoforms may perform different functions in distinct subcellular compartments and distinct phases of the cell cycle.

Alternative Splicing↗
PubMed2002

Aerobic and facultatively anaerobic cellulolytic bacteria from the gut of the termite Zootermopsis angusticollis.

AIMS: To demonstrate the occurrence of cellulolytic bacteria in the termite Zootermopsis angusticollis. METHODS AND RESULTS: Applying aerobic cultivation conditions we isolated 119 cellulolytic strains from the gut of Z. angusticollis, which were assigned to 23 groups of aerobic, facultatively anaerobic or microaerophilic cellulolytic bacteria. 16S rDNA restriction fragment pattern and partial 16S rDNA sequence analysis, as well as numerical taxonomy, were used for the assignment of the isolates. The Gram-positive bacteria of the actinomycetes branch could be assigned to the order Actinomycetales including the genera Cellulomonas/Oerskovia, Microbacterium and Kocuria. The Gram-positive bacteria from the order Bacillales belonged to the genera Bacillus, Brevibacillus and Paenibacillus. Isolates related to the genera Afipia, Agrobacterium/Rhizobium, Brucella/Ochrobactrum, Pseudomonas and Sphingomonas/Zymomonas from the alpha-proteobacteria and Spirosoma-like from the "Flexibacteriaceae" represented the Gram-negative bacteria. CONCLUSIONS: A cell titre of up to 10(7) cellulolytic bacteria per ml, determined for some isolates, indicated that they may play a role in cellulose digestion in the termite gut in addition to the cellulolytic flagellates and termite's own cellulases. SIGNIFICANCE AND IMPACT OF THE STUDY: The impact of bacteria on cellulose degradation in the termite gut has always been a matter of debate. In the present survey we investigated the aerobic and facultatively anaerobic cellulolytic bacteria in the termite gut.

Aerobiosis↗
PubMed2001

Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels.

ATP-sensitive potassium channels (K-ATP channels) directly couple the energy state of a cell to its excitability, are activated by hypoxia, and have been suggested to protect neurons during disturbances of energy metabolism such as transient ischemic attacks or stroke. Molecular studies have demonstrated that functional K-ATP channels are octameric protein complexes, consisting of four sulfonylurea receptor proteins and four pore-forming subunits which are members of the Kir6 family of inwardly rectifying potassium channels. Here we show, using specific antibodies against the two known pore-forming subunits (Kir6.1 and Kir6.2) of K-ATP channels, that only Kir6.1 and not Kir6.2 subunits are expressed in astrocytes. In addition to a minority of neurons, Kir6.1 protein is present on hippocampal, cortical, and cerebellar astrocytes, tanycytes, and Bergmann glial cells. We also provide ultrastructural evidence that Kir6.1 immunoreactivity is primarily localized to distal perisynaptic and peridendritic astrocyte plasma membrane processes, and we confirm the presence of functional K-ATP channels in Bergmann glial cells by slice-patch-clamp experiments. The identification of Kir6.1 as the principal pore-forming subunit of plasma membrane K-ATP channels in astrocytes suggests that these glial K-ATP channels act in synergy with neuronal Kir6.2-mediated K-ATP channels during metabolic challenges in the brain.

Adenosine Triphosphate↗
PubMed2001

Long term effects of non-invasive mechanical ventilation on pulmonary haemodynamics in patients with chronic respiratory failure.

BACKGROUND: It is not known whether long term nocturnal mechanical ventilation (NMV) reduces pulmonary hypertension in patients with chronic respiratory failure (CRF). METHODS: Pulmonary haemodynamics, spirometric values, and gas exchange were studied in 33 patients requiring NMV due to CRF (20 with thoracic restriction, 13 with chronic obstructive pulmonary disease (COPD)) at baseline and after 1 year of NMV given in the volume cycled mode. Patients with COPD also received supplemental oxygen. RESULTS: Long term NMV improved gas exchange while lung function remained unchanged. Mean pulmonary artery pressure at rest before NMV was higher in patients with thoracic restriction than in those with COPD (33 (10) mm Hg v 25 (6) mm Hg). After 1 year of NMV mean pulmonary artery pressure decreased in patients with thoracic restriction to 25 (6) mm Hg (mean change -8.5 mm Hg (95% CI -12.6 to -4.3), p<0.01) but did not change significantly in patients with COPD (mean change 2.2 mm Hg (95% CI -0.3 to 4.8)). CONCLUSIONS: Long term NMV in CRF improves pulmonary haemodynamics in patients with thoracic restriction but not in patients with COPD.

Chronic Disease↗
PubMed2001

A social categorization approach to distributive justice: social identity as the link between relevance of inputs and need for justice.

What are relevant inputs or criteria for judging entitlements in a given situation? As will be argued, an answer to this central problem of distributive justice must consider the perceiver's self-definition and structuring of the social context, in terms of social categorizations. The construal of the primary category of potential recipients is particularly important as its prototypical dimensions are likely criteria for entitlement judgments. Its representation depends on the perceiver's salient identity. Two studies yielded support for this perspective. In Study 1, students regarded their psychology department's distinctive quality as more important for psychologists than an out-group's quality. When highly identified, they perceived a psychologist who outperformed another on the in-group quality to have a higher entitlement to a job. In Study 2, German participants regarded the European Union's (EU) denial of EU membership to Turkey as more just the more prototypically European they thought Germany was, in contrast to Turkey; and, in turn, they did so the more strongly they identified as Germans. The findings suggest that relevance of inputs and, thus, the justice motive are based on identity concerns.

Adult↗
PubMed2001

Tailor-made dyes for fluorescence correlation spectroscopy (FCS).

Two new fluorescent labels are presented that are optimized for excitation with He/Ne laser and red diode lasers. Application in FCS and labeling of proteins and oligomers are demonstrated. A strong rise of quantum yield and emission life time upon binding to biomolecules are characteristic features of the dyes.

Benzopyrans↗
PubMed2000

Silicone oil removal from a silicone intraocular lens with perfluorohexyloctane.

Silicone oil can be easily dissolved in vivo from silicone intraocular lenses by perfluorohexyloctane. Using specular microscopy, we examined the corneal endothelium in a patient with silicone lens implantation immediately after cataract surgery and 5 weeks postoperatively. There were no signs of acute or chronic toxicity to the endothelium.

Cataract Extraction↗
PubMed2000

Amphotericin B severely affects expression and activity of the endothelial constitutive nitric oxide synthase involving altered mRNA stability.

The therapeutic use of the antifungal drug amphotericin B (AmB) is limited due to severe side effects like glomerular vasoconstriction and risk of renal failure during AmB administration. As nitric oxide (NO) has substantial functions in renal autoregulation, we have determined the effects of AmB on endothelial constitutive NO synthase (ecNOS) expression and activity in human and rat endothelial cell cultures. AmB used at concentrations of 0.6 to 1.25 microg ml(-1) led to increases in ecNOS mRNA and protein expression as well as NO production. This was the result of an increased ecNOS mRNA half-life. In contrast, incubation of cells with higher albeit subtoxic concentrations of AmB (2.5 - 5.0 microg ml(-1)) resulted in a decrease or respectively in completely abolished ecNOS mRNA and protein expression with a strongly reduced or inhibited ecNOS activity, due to a decrease of ecNOS mRNA half-life. None of the AmB concentrations affected promoter activity as found with a reporter gene construct stably transfected into ECV304 cells. Thus, our experiments show a concentration-dependent biphasic effect of AmB on expression and activity of ecNOS, an effect best explained by AmB influencing ecNOS mRNA stability. In view of the known renal accumulation of this drug the results reported here could help to elucidate its renal toxicity.

Amphotericin B↗
PubMed2000

Deficient activation of CD95 (APO-1/Fas)-mediated apoptosis: a potential factor of multidrug resistance in human renal cell carcinoma.

The pronounced resistance of human renal cell carcinoma (RCC) to anticancer-induced apoptosis has primarily been related to the expression of P-glycoprotein and effective drug detoxification mechanisms. Because the CD95 system has recently been identified as a key mediator of anticancer drug-induced apoptosis, we analysed the contribution of the CD95 system to chemotherapy-induced apoptosis in four newly established RCC cell lines. Here, we demonstrate that all RCC cell lines expressed CD95-receptor and -ligand. Exposure to agonistic anti-CD95 antibodies resulted in induction of apoptosis and significant (P < 0.05) reduction of cell number in three out of four cell lines, indicating that the essential components for CD95-mediated apoptosis were present and functionally intact in the majority of these RCC cell lines. Moreover, treatment of cultures with bleomycin or topotecan, a novel topoisomerase I inhibitor with little substrate affinity for P-glycoprotein, led to induction of apoptosis and significant (P < 0.05) dose-dependent reduction of cell number in all RCC cell lines. Both anticancer drugs also induced upregulation of CD95 ligand expression in all cell lines. Additionally, augmentation of CD95 receptor expression was found in three RCC cell lines, including one p53-mutated cell line, whereas another p53-mutated cell line showed no or only a weak CD95 receptor upregulation after exposure to topotecan or bleomycin, respectively. Despite this upregulation of CD95 receptor and ligand, antagonistic antibodies directed against CD95 receptors or ligands could not inhibit induction of apoptosis by topotecan and bleomycin in any cell line. Thus, although a functionally intact CD95 signalling cascade is present in most RCC cell lines, the anticancer drugs topotecan and bleomycin that induce upregulation of CD95 receptor and ligand fail to effectively activate CD95-mediated apoptosis. This deficient activation of CD95-mediated apoptosis might be an important additional factor for the multidrug resistance phenotype of human RCCs.

Antineoplastic Agents↗
PubMed2000

[Specular microscopy follow-up of endophthalmitis after cataract operation].

INTRODUCTION: Since the first reports of specular microscopic photographs in vivo of the corneal endothelium, endophthalmitis is said to damage endothelial cells irreversibly. PATIENTS AND METHOD: We controlled 29 eyes 1 to 10 years after endophthalmitis following cataract surgery using specular microscopy. We tried to find out, if endophthalmitis leads to significant endothelial damage and we wanted to describe the in-vivo-cytological follow-up of the implanted lenses. RESULTS: Endothelial cell-density of the eyes with endophthalmitis (n = 29) was 2733/mm2 (+/- 680). In those eyes receiving cataract-surgery without endophthalmitis in the fellow eye (n = 14), the endothelial density was 2851/mm2 (+/- 360). If the fellow eye has had no cataract surgery (n = 13), cell density was 3110/mm2 (+/- 750). Hypopyon-iritis after cataract-surgery did not decrease endothelial cell count significantly more than cataract-surgery without hypopyon-iritis (p > 0.05). At the last control at least one year after surgery, 36% of all IOLs were free of any cellular deposits. There was no case of a foreign-body-reaction. CONCLUSION: In our patients, postoperative endophthalmitis has not led to significant endothelial damage. In none of our patients, endophthalmitis has led to chronic foreign-body reaction against the implant or to granulomatous uveitis. Specular microscopy of the corneal endothelium and of the implanted lens may help to differentiate in the case of postoperative inflammation between an infection and a foreign-body-reaction. In the case of a sterile foreign-body-reaction, there are no inflammatory cells on the endothelium or in the anterior chamber.

Cataract Extraction↗
PubMed1999

Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties.

Recently, a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer. Therefore, we analyzed the expression of survivin in human renal cell carcinomas (RCCs), known to be largely resistant to chemotherapy. Northern blot analysis and RT-PCR revealed survivin expression in newly established RCC cell lines (n = 11) of all major histological types. Moreover, we identified two novel splice variants of survivin, lacking exon 3 (survivin-deltaEx3) or retaining a part of intron 2 as a cryptic exon (survivin-2B). Both sequence alterations cause marked changes in the structure of the corresponding proteins, including structural modifications of the baculovirus inhibitor of apoptosis protein repeat domain. The role of the novel isoforms in the regulation of apoptosis was assessed in transfection experiments, showing conservation of antiapoptotic properties for survivin-deltaEx3 and a markedly reduced antiapoptotic potential for survivin-2B. In conclusion, our observations suggest a complex regulatory balance between the different isoforms of survivin, which might determine the response to proapoptotic stimuli, not only in human RCCs but also in fetal tissues and other types of cancer.

Alternative Splicing↗
PubMed1999

[Biocompatibility of flexible intraocular lenses in vivo].

PURPOSE: One aspect of biocompatibility of IOLs can be tested using specular microscopy of the anterior and posterior surface of the lens in vivo. METHODS: We examined 45 patients after implantation of a "Memory lens" and 31 patients after the implantation of an "Acrysof" lens 3-6 months after surgery. RESULTS: Typical deposits (Lens epithelial cells, spindle-shaped macrophages, giant cells, pigment, Wolter membrane) were rarely seen on both types of lenses. There were fewer lens epithelial cells on the posterior capsule and less secondary cataract after implantation of the "Acrysof" lens. CONCLUSIONS: We did not find any indication of reduced biocompatibility in any of the lenses examined. The reduced rate of secondary cataract after implantation of the "memory lens" may be explained by the fact that this lens type sticks to the posterior capsule better.

Aged↗
PubMed1999

[Retinal hemodynamics in patients with normal pressure glaucoma. Quantification with digital laser scanning fluorescein angiography].

UNLABELLED: Chronic ischemia of the retina and the optic nerve head seems of importance especially in patients with normal-tension glaucoma (NTG). The purpose of this study was to examine the retinal hemodynamics in patients with NTG. PATIENTS: Twenty-five patients with NTG were examined (3 weeks washout period) in this study (age 58 +/- 16 years). The arteriovenous passage (AVP) time and arterial and venous diameters from scanning laser fluorescein angiograms were evaluated by means of digital image analysis. RESULTS: The AVP time in patients with NTG (2.78 +/- 1.1 s) was significantly prolonged (P < 0.0001) compared with healthy subjects (1.58 +/- 0.4 s). No significant correlation was found between arterial and venous diameters, intraocular pressure, blood pressure or calculated perfusion pressure and retinal arteriovenous passage time. CONCLUSION: Patients with NTG showed prolonged retinal passage, which could cause chronic hypoxia. This prolongation of circulation is not correlated with any of the clinical parameters. Thus, a circulatory defect might be a primary factor in the pathogenesis of NTG.

Angiography, Digital Subtraction↗
PubMed1999

[Effect of intermittent ventilation on pulmonary hypertension in chronic respiratory failure].

Intermittent non-invasive (or nocturnal mechanical ventilation) eliminates symptoms of hypoventilation and improves gas exchange in patients with chronic respiratory failure. Performing right heart catheterisation we studied the influence of nocturnal mechanical ventilation on pulmonary hemodynamics. We investigated 20 patients with restrictive thoracic diseases (Post-TBC: n = 9, scoliosis: n = 11, PaCO2: 59.8 +/- 7.6 mmHg) and 13 patients with COPD (n = 13, PaCO2: 58.5 +/- 7.8 mmHg). All patients were mechanically ventilated in controlled mode. During the study the medication was not changed; COPD patients with long-term oxygen maintained this therapy. Right-heart catheterisation was performed immediately before and after 1 year nocturnal mechanical ventilation. In patients with thoracic restriction NMV induced a marked reduction of pulmonary artery pressure (PAP) from 33.2 +/- 10.0 mmHg before to 24.8 +/- 6.2 mmHg after 1 year nocturnal mechanical ventilation. In the COPD group PAP increased from 25.3 +/- 6.0 mmHg before to 27.5 +/- 6.0 mmHg after 1 year nocturnal mechanical ventilation. In contrast to the COPD group in patients with chronic respiratory failure due to thoracic restriction nocturnal mechanical ventilation causes substantial reduction in pulmonary artery pressure after a one year application.

Carbon Dioxide↗
PubMed1999

[Scintigraphic demonstration of aspiration in long-term ventilation patients with tracheotomy].

The main complication of enteral feeding in prolonged mechanical ventilation via tracheostomy is the subsequent aspiration pneumonia. We used a scintigraphic method for the detection of enteral feeding aspiration and compared the results with clinical evidence of aspiration. The study population consisted of 62 consecutive tracheotomised patients (16 females, age: 64.1 +/- 11.1 years). The swallowing test was done in an upright or semirecumbent body position with the patients spontaneously breathing. The standard feed consisted of a liquid, semiliquid and solid meal which was labelled by 100 MBQ 99 TC. Scintigraphic aspiration (SA) was defined as positive if radioactivity was detected in the bronchial system. Clinical aspiration (CA) was defined as positive if there was cough, choking and distress after swallowing; furthermore, when receiving enteral feeding during suctioning or bronchoscopy. Both clinically significant aspiration (CA) and scintigraphic aspiration (SA) were found to be identical in 10 of 62 (16%) patients. CA, but not SA: 4/62 (6.5%). SA, but not CA (Subclinical aspiration): 4/62 (6.5%). Nor CA neither SA: 44/62 (71%) patients. Radiolabelled feed can be used as a feasible marker to detect aspiration. The test is a useful screening test and strategy to minimize aspiration. The scintigraphic method failed to identify all tracheotomised patients with clinically significant aspiration. However, scintiscanning did suggest that some patients had subclinical aspiration.

Deglutition↗