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C Bauer

Publications and source records attributed to C Bauer.

At least 73 records · Page 4Linked to original sources
PubMed1999

Endothelin system-dependent cardiac remodeling in renovascular hypertension.

The aim of the present study was to analyze whether the cardiac endothelin system contributes to cardiac remodeling in rats with 2-kidney, 1 clip (2K1C) renovascular hypertension. The endothelin system seems to be a promising candidate for cardiac remodeling because endothelin (ET)-1 promotes growth of cardiomyocytes in vitro and induces cardiac collagen synthesis. The activity of the cardiac endothelin system was analyzed by measuring cardiac tissue big ET-1 and ET-1 concentrations as well as by estimating the cardiac expression of the ETA and ETB receptors 10 days, 4 weeks, and 12 weeks after the renal artery was clipped. The effects of long-term treatment with ETA, ETB, and combined ETA/ETB receptor antagonists on cardiac hypertrophy, media/lumen ratio of intracardiac arteries, and left ventricular fibrosis were also analyzed. This study demonstrated that the overall left ventricular cardiac endothelin system has a similar activity in the early, middle, and late stages of 2K1C renovascular hypertension compared with sham-operated controls. Fibrosis of the left ventricle and hypertrophy of intracardiac arteries, however, were markedly altered after long-term treatment with endothelin receptor antagonists in a blood pressure-independent manner. These 2 effects are mediated by different subtypes of endothelin receptors. ETA receptor blockade completely normalized the hypertrophy of intracardiac arteries (P<0. 01 compared with 2K1C without treatment) in renovascular hypertension, whereas the ETB antagonist reduced cardiac fibrosis of the left ventricle (P<0.001 compared with 2K1C without treatment) to baseline values. This study demonstrates that the cardiac endothelin system plays an important role in the development of cardiac fibrosis as well as in hypertrophy of intracardiac arteries in 2K1C renovascular hypertensive rats.

Animals↗
PubMed1999

Binding and selective detection of the secretory N-terminal domain of the alzheimer amyloid precursor protein on cell surfaces.

The secretory N-terminal domain of the Alzheimer amyloid precursor protein (sAPP) evokes specific responses in cells on binding to their surfaces. Because APP is expressed in a large variety of cell types, the localization of sAPP binding requires detection techniques that selectively recognize sAPP as a ligand. For this purpose, we prepared antibodies against recombinant sAPP695 (sAPPrec) previously expressed in E. coli. Such antibodies were found to distinguish between sAPPrec and cellular APP or sAPP, as shown by immunocytochemistry and by immunoblot. In addition, they allowed the selective localization of bound sAPPrec on cell surfaces without any signal from cellular APP or sAPP. Saturation of sAPPrec binding to cell surfaces, as determined radiometrically, was reached at 10 nM [125I]-sAPPrec. Binding was specific because it was almost completely inhibited by a 100-fold excess of unlabeled sAPPrec. This specificity of binding was confirmed by surface plasmon resonance spectroscopy. Binding of sAPPrec to cell surfaces occurred in patches and was dependent on the state of cell differentiation. The sAPPrec used in this study contains heparin binding sites, but enzymatic removal of cell surface associated heparin did not affect sAPPrec binding. Aldehyde fixation of cells strongly inhibited their ability to bind sAPPrec. The data point to a fixation-sensitive sAPPrec binding protein which is detectable in the form of patches and therefore is part of assembled cell surface microdomains.

Amyloid beta-Protein Precursor↗
PubMed1999

[Effects of the fenbendazole SR bolus on Trichostrongylus infections in young calves during two consecutive grazing periods].

A two-year study was conducted in northern Germany to investigate the effects of the fenbendazole slow release (SR) bolus on trichostrongyle infections in cattle. Two groups of dairy replacement calves were either given a bolus at their first turncut on pasture or treated with fenbendazole suspension twice in mid-summer and at housing. Bolus-treated and control animals were set stocked on separate pastures during their first grazing season (26 weeks) and grazed together during the second year (24 weeks). During the first season the bolus prevented substantially the output of strongyle eggs for more than four months resulting in a lower infection risk in late summer and autumn as compared to the control group. The plasma pepsinogen concentrations remained low in the bolus-treated cattle during their first grazing period but rose in the controls soon after turnout which indicated increasing trichostrongyle-caused damages of the abomasal mucosa. During the following housing period and the second grazing season the bolus-treated animals showed higher egg counts than the controls. No clinical sign of parasitic gastroenteritis and no patent lungworm infections were observed during the study. The bolus-treated cattle performed better than the control animals during both grazing seasons although the control group had compensated temporarily the group difference in weight gains during the housing period. In conclusion, the use of the fenbendazole SR bolus may impair the development of immunity to trichostrongyle infections to some extent but, under the present conditions, this does not seem of clinical or economic importance.

Abomasum↗
PubMed1998

Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage.

Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell-cell adhesion through desmosomal cadherins, which differ from classical cadherins in their attachments to intermediate filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin gene. Homozygous -/- mutant embryos proceeded through implantation, but did not survive beyond E6.5. Surprisingly, analysis of these embryos revealed a critical role for desmoplakin not only in anchoring IFs to desmosomes, but also in desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at least partially established in the DP (-/-) embryos, the paucity of desmosomal cell-cell junctions severely affected the modeling of tissue architecture and shaping of the early embryo.

Animals↗
PubMed1998

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies.

PURPOSE: This is a retrospective review to evaluate the role of surgery and intraoperative electron beam radiotherapy (IOERT) in the treatment of patients with previously irradiated advanced head and neck cancers. METHODS AND MATERIALS: Between January 1992 and March 1997, 38 patients (31 males, 7 females; median age of 62 years) with recurrent head and neck cancer were treated with maximal resection and IOERT at the Ohio State University (OSU). All had been previously treated with full-course radiotherapy (median 65.1 Gy, range 50-74.4 Gy). Twenty-nine patients (76%) had previously undergone one or more surgical procedures. After maximal surgery the tumor bed was treated with IOERT (single field in 36 patients and 2 fields in 2 patients), most commonly with 6 MeV electrons (87%). The dose administered (at 90% isodose line) was 15 Gy for close or microscopically positive margins in 34 patients and 20 Gy for gross disease in 1 patient. Further external beam radiation therapy (EBRT) was not given. RESULTS: After a median follow-up of 30 months (range 8-39 months), 24 of the 38 patients (66%) recurred within the IOERT field. Median time to IOERT failure was 6 months (95% CI: 4.3-7.7). The 6-month, 1-, and 2-year control rates within the IOERT volume were 41%, 19%, and 13%, respectively. Thirty of the 38 patients (79%) recurred in locoregional areas. Median time to locoregional failure was 4 months (95% CI: 3.3-4.7). The 6-month, 1-, and 2-year locoregional control rates were 33%, 11%, and 4%, respectively. Distant metastases occurred in 7 patients, 5 in association with IOERT failure and 2 with locoregional failure. Median overall survival was 7 months (95% CI: 4.7-9.3). The 6-month, 1-, 2-, and 3-year actuarial survival rates were 51%, 21%, 21%, and 8%, respectively. Major treatment-related complications occurred in 6 patients (16%). CONCLUSION: IOERT alone, at the dose used, is not sufficient for control of recurrent, previously irradiated head and neck cancers. Since higher IOERT doses are associated with high morbidity, we are currently evaluating the addition of limited EBRT dose and/or brachytherapy to improve the local control of these poor prognostic recurrent tumors, with acceptable morbidity.

Adenocarcinoma↗
PubMed1998

Efficacy of a 2 per cent moxidectin gel against gastrointestinal parasites of ponies.

The efficacy of moxidectin was evaluated in young ponies naturally infected with gastrointestinal parasites. Eight animals were treated orally with moxidectin at 0.4 mg/kg bodyweight and eight received only the vehicle. They were all necropsied two weeks later. Faecal samples were examined daily for egg counts and larval cultures. Parasites were recovered from total faecal samples collected daily and from the gastrointestinal tracts at necropsy. Moxidectin reduced the strongyle egg counts by > 99 per cent from three days after treatment but some individuals remained positive for 10 days. The drug had little or no ovicidal activity. As evaluated in the critical-controlled test, moxidectin was 99 to 100 per cent effective (P < 0.05) against luminal stages of parascaris equorum, Strongylus vulgaris, Triodontophorus species, Craterostomum acuticaudatum, 19 cyathostome species and Oxyuris equi. Adult S edentatus were also completely removed. Its efficacy against third stage larvae of Gasterophilus intestinalis was 95 per cent (P < 0.05). Luminal nematode stages were removed within a few days, and bots continued to be eliminated for at least two weeks after treatment. No activity was observed against Anoplocephala perforliata. As evaluated in the controlled test, moxidectin was 100 per cent effective against Habronema muscae (P < 0.05) and had a 76 per cent but not significant efficacy against encysted small strongyle larvae.

Administration, Oral↗
PubMed1998

Monofunctional platinum amine complexes destabilize DNA significantly.

Both cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+ bind DNA covalently at the N7 site of guanine residues forming mono-dentate adducts. However, like cisplatin and transplatin, only the cis isomer has anti-cancer activity, whereas the trans-isomer does not. In order to understand the molecular basis of the different activities associated with cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+, the interactions of these two platinum compounds with the DNA heptamer CCTG*TCC:GGACAGG duplex (G* is the platinated guanine) have been examined. The reaction rate of cis-[Pt(NH3)2(4-Me-Py)Cl]+ with the single-stranded CCTGTCC is significantly faster than that of the trans isomer. The solution structure of the platinum-DNA adducts has been studied by two-dimensional NMR spectroscopy. Both the cis-platinum adducts and the trans-platinum adducts destabilize the DNA duplex significantly. The melting temperature (Tm) of the platinated heptamer duplex is estimated to be 10 degrees C lower than for the unplatinated duplex by NMR. At 2 degrees C, the base pairs located on the 5' side of the oligonucleotide, beyond the platinum lesion site, are disrupted. Over time, the platinum-DNA complex decomposes and the cis-[Pt(NH3)2(4-Me-Py)] platinum complex is gradually detached from DNA. No interstrand crosslinking is observed. The biological implications of the structural studies are discussed.

Amines↗
PubMed1998

2'-Deoxyisoguanosine adopts more than one tautomer to form base pairs with thymidine observed by high-resolution crystal structure analysis.

The questions of whether different tautomeric forms of nucleic acid bases exist to any significant extent in DNA, or what their possible roles in mutation may be, are under intense scrutiny. 2'-Deoxyisoguanosine (iG) has been suggested to have a propensity to adopt the enol form. Isoguanine (also called 2-hydroxyadenine) can be found in oxidatively damaged DNA generated from treating DNA with a Fenton-type reactive oxygen-generating system and is known to cause mutation. We have analyzed the three-dimensional structure of the DNA dodecamer d(CGC[iG]AATTTGCG) (denoted iG-DODE) by X-ray crystallography and NMR. The crystal structure of the iG-DODE complexed with the minor groove binder Hoechst 33342, refined to 1.4 A resolution, showed that the two independent iG.T base pairs in the dodecamer duplex adopt different (one in Watson-Crick and the other in wobble) conformations. The high-resolution nature of the structure also affords unprecedented clear information about the conformation and interactions of the Hoechst drug. The Hoechst 33342 binds in the narrow minor groove at the iGAATT site, with the N-methylpiperazine ring near the iG4.T21 base pair. Three hydrogen bonds are found between the NH of the Hoechst ligand and T-O2 DNA atoms. In solution, the two iG.T base pairs in iG-DODE predominantly are in the wobble form at 2 degreesC. At higher temperatures, another duplex form (likely involving the enol form of iG) is in slow exchange with the keto form and becomes significantly populated, reaching approximately 40% at 40 degreesC. Our data support the conclusion that iG pairs with T in a Watson-Crick configuration to a significant extent at physiological temperature (37 degreesC), which may explain the facile incorporation rate of T across from an iG during in vitro DNA replication.

Adenosine↗
PubMed1998

From differentiation to proliferation: the secretory amyloid precursor protein as a local mediator of growth in thyroid epithelial cells.

In various species, thyrotropin (TSH) is known to stimulate both differentiation and proliferation of thyroid follicle cells. This cell type has also been shown to express members of the Alzheimer amyloid precursor (APP) protein family and to release the secretory N-terminal domain of APP (sAPP) in a TSH-dependent fashion. In this study on binding to the cell surfaces, exogenously added recombinant sAPP stimulated phosphorylation mediated by mitogen-activated protein kinase and effectively evoked proliferation in the rat thyroid epithelial cell line FRTL-5. To see whether this proliverative effect of sAPP is of physiological relevance, we used antisense techniques to selectively inhibit the expression of APP and the proteolytic release of sAPP by cells grown in the presence of TSH. The antisense-induced inhibition was detected by immunoblot, immunoprecipitation, and immunocytochemical analyses. After the reduced APP expression and sAPP secretion, we observed a strong suppression of the TSH-induced cell proliferation down to 35%. Recombinant sAPP but not TSH was able to overcome this antisense effect and to completely restore cell proliferation, indicating that sAPP acts downstream of TSH, in that it is released from thyroid epithelial cells during TSH-induced differentiation. We propose that sAPP operates as an autocrine growth factor mediating the proliferative effect of TSH on neighboring thyroid epithelial cells.

Amyloid beta-Protein Precursor↗
PubMed1998

Antigen-pulsed epidermal Langerhans cells protect susceptible mice from infection with the intracellular parasite Leishmania major.

Efficient vaccination against the parasite Leishmania major, the causative agent of human cutaneous leishmaniasis, requires the development of a resistance-promoting CD4+-mediated Th1 response. Epidermal Langerhans cells (LC) are critically involved in the induction of the primary immune response to Leishmania infection. They are able to ingest the parasites, to express MHC class II molecules with extraordinarily long half-life and to activate naive L. major-specific Th cells. Considering these unique properties, we studied the capacity of LC to mediate resistance to L. major in vivo. A single i.v. application of LC that had been pulsed with L. major antigen in vitro induced the protection in susceptible BALB/c mice against subsequent challenges with L. major parasites. Resistance could neither be induced by unpulsed LC, nor by L. major antigen alone or by L. major-pulsed macrophages. Development of resistance was paralleled by a reduced parasite burden and by a shift of the cytokine expression towards a Th1-like pattern. In contrast, control mice developed a Th2 response. In vitro exposure of LC to L. major antigen induced the expression of IL-12 (p40) mRNA. In conclusion, our data demonstrate that LC are able to serve as a natural adjuvant and to induce a protective immune response to L. major infection. This effect is based on the initiation of a Th1-like response that is likely to be mediated by IL-12.

Animals↗
PubMed1998

Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins.

Antineutrophil cytoplasmic antibodies (ANCA) are frequently associated with chronic inflammatory bowel diseases (IBD) and hepatobiliary disorders. However, their target antigens have not been identified yet. Recently, we observed an atypical perinuclear ANCA fluorescence (p-ANCA) together with an intranuclear staining using ANCA-positive sera from patients with IBD and hepatobiliary disorders. This observation suggests that the target antigens are localized within the nucleus of neutrophilic granulocytes. To further investigate this hypothesis, we examined sera from patients with ulcerative colitis, primary sclerosing cholangitis, autoimmune hepatitis or systemic vasculitis on ethanol or formaldehyde-fixed neutrophils using confocal laser scanning microscopy and immunoelectron microscopy. Counterstaining with propidium iodide, a DNA-specific dye, showed that ANCA-positive sera in IBD and heptobiliary disorders react with intranuclear antigens at the nuclear periphery of the neutrophils. Double immunolabeling techniques revealed that nuclear lamina proteins, lamins A, C and B1, and lamin B receptor were colocalized with the antigen(s) recognized by atypical p-ANCA. No colocalization was observed with classical p-ANCA and antibodies against histones (H1-H4). Our study showed that atypical p-ANCA are antinuclear antibodies reactive with granulocyte-specific antigens present in the nuclear lamina.

Adolescent↗
PubMed1998

Enzyme evolution and cancer: hypothesis why natural carcinogens are more potent than synthetic ones.

A great deal of evidence shows that carcinogen induced mutations in human cancers point towards natural rather than man-made agents. Here, we propose a model based on the premise that the evolutionary pressure of nature renders natural carcinogens more potent than artificial ones, present in equal concentration, by suitably modifying kinetic parameters of carcinogen metabolizing enzymes. Enzymes are evolved to bind the transition state of substrates more strongly than substrates themselves, thus obtaining more elevate values of the specificity constant kcat/Km (Ksp). Natural selection optimizing the catalytic power at the proper substrate concentration by suitable raising the Km values, reduce the Gibbs standard activation energy (G(0#)), accelerating the conversion of natural precarcinogens to potent carcinogens. Conversely, "man-made" carcinogens, since the last century in the biosphere, are converted to active metabolites at a lower rate than natural chemicals and the slower rate of activation would allow protective enzymes and DNA repair machinery more time to clean up the damage.

Carcinogens↗
PubMed1998

Cancer chemoprevention: some complications and limitations.

Chemopreventive strategies are very attractive and have earned serious consideration as a potential means of controlling cancer incidence. However, the use of some anti-initiating entities (enzyme inducers or inhibitors) devised to reduce tumor initiation is controversial. Indeed, considering the double-edged-sword (activating or detoxifying) nature of drug metabolizing enzymes, any attempt to modulate such catalysts by dietary components (including drugs) may lead to cancer risk.

Animals↗
PubMed1998

[Remifentanil in gynecologic laparoscopy. A comparison of consciousness and circulatory effects of a combination with desflurane and propofol].

OBJECTIVES: Rapid post-anaesthetic awakening and low hypnotic potency are two characteristic properties of the new opioid remifentanil. For clinical use remifentanil must be combined with another anaesthetic agent. Propofol is well-established for ambulatory anaesthesia, however, the properties of desflurane (low blood-gas solubility, rapid elimination) suggest this volatile anaesthetic to be a comparable alternative, particularly if rapid awakening is desired. The present study was designed to compare emergence times and haemodynamics for a combination of remifentanil wich hypnotic concentrations of either propofol or desflurane. METHODS: Gynaecological patients, scheduled for elective laparoscopy, were studied at random. After oral premedication with diazepam 0.08-0.12 mg/kg, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil infusion (0.5 microgram/kg/min), followed by propofol (approx. 2 mg/kg) and cisatracurium (0.1 mg/kg). For maintenance of anaesthesia remifentanil (0.25 microgram/kg/min) was combined with either desflurane (0.5 MAC = 3.0 vol%) or propofol (6 mg/kg/h). With termination of surgery anaesthetic delivery was discontinued simultaneously and recovery times were recorded. Heart rate and non-invasive blood pressure were recorded at defined points of interest. RESULTS: In total, 40 patients (desflurane n = 20, propofol n = 20) were studied in comparable groups. For both regimens, emergence after remifentanil-based anaesthesia was remarkably rapid between unconsciousness and complete recovery: In mean only 60 s elapsed from the onset of spontaneous breathing to the moment when patients could clearly state their name. In comparison, recovery times were significantly shorter after remifentanil-desflurane than after remifentanil-propofol: time to spontaneous ventilation 6.4 +/- 2.8 vs. 9.6 +/- 3.9 min (mean +/- SD, p = 0.01); extubation 6.7 +/- 2.8 vs. 9.8 +/- 4.0 min (p = 0.02) and arrival at PACU 11.1 +/- 3.4 vs. 14.7 +/- 4.2 min (p = 0.005). The courses of heart rate (HR) and mean arterial pressure (MAP) were mostly similar in both groups with only minimal or moderate cardiocirculatory reactions during intubation or start of surgery. CONCLUSIONS: Remifentanil in combination with either desflurane or propofol, used for general anaesthesia during gynaecological laparoscopy, will facilitate a smooth haemodynamic course as well as a rapid emergence thereafter. Recovery times after remifentanil-based anaesthesia are significantly shorter with 3.0 vol% of desflurane than with 6 mg/kg/h propofol. Thus, desflurane appears to be a well-suited adjunct to remifentanil and an ideal alternative to propofol, if rapid recovery is required. Differences are best explained by the pharmacological properties of both coanaesthetics and their applied dosages.

Adult↗