Search PubMed⌕ Search

Biomedical subjects

P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Influences on fermentation and thiamine metabolism in bovine rumen fluid (in vitro)--part 3: Effects of artificially contaminated hay with Cladosporium herbarum and Fusarium graminearum, respectively].

The influence of contaminated hay [Cladosporium herbarum (CL) and Fusarium graminearum (FU), respectively] on fermentation and thiamine metabolism of bovine rumen content was investigated using the longterm rumen simulation technique (RUSITEC). Six investigation periods 25 days long each were carried out. A nine days feeding period with normal hay was followed by the testphase I (five days) with a mixture of normal and mouldy hay and testphase II (five days) with additive an 0.3 mg thiamine per reaction vessel. The last four days served as regeneration time with normal hay. The following marginal effects of mouldy hay on rumen fermentation patterns could be noted. A) During testphase I: cellulase activity: +10.0% (FU); alternation of the thiamine derivate pattern, but no effect on total thiamine content (CL, FU). B) During testphase II the results were more obvious: bacterial protein synthesis: -22.6% (CL), -24.4% (FU). Alternation of the fatty acid pattern: propionate (-7.30% FU), n-butyrate (-3.90% CL, +3.49% FU), n-valerate (-8.5% CH, FU). Cellulase activity: -17.0% (CL, FU). But no effect on total thiamine (CL, FU); alternation of the thiamine derivate pattern: more non phosphorylate thiamine. The noted effects on rumen fermentation and thiamine metabolism were not severe enough to be responsible for the development of a CCN.

Animal Feed↗
PubMed2003

Erectile dysfunction is associated with a high prevalence of hyperlipidemia and coronary heart disease risk.

OBJECTIVES: Erectile dysfunction (ED) is frequently of vascular origin. An association between ED and ischemic heart disease has been suggested as a consequence of endothelial disease of penile and coronary arteries. The role of serum lipid levels has been demonstrated in coronary heart disease (CHD), but the relationship with ED is poorly documented. We evaluated undiagnosed hyperlipidemia in ED patients and their coronary heart disease risk. METHODS: We prospectively compared a group of patients with ED to matched non-ED patients. Risk factors for ED and CHD were noticed and a serum lipid work up (total cholesterol [TC], triglycerides [TG], HDL-cholesterol [HDL-C], LDL-cholesterol [LDL-C] and TC/HDL-C ratio) was measured. We compared the prevalence of hyperlipidemia in the two groups and its impact as predictor of ED. We calculated the risk to develop CHD in patients with or without ED based upon commonly accepted variables of the Framingham Heart study. RESULTS: 215 patients had ED (mean age 57.6+/-9.6 years) and 100 no ED (mean age 59.7+/-8.3 years). The prevalence of hypercholesterolemia (TC >200 mg/dl or 5.17 mmol/l) was 70.6% vs. 52% in ED and non-ED groups respectively (p=0.06). After exclusion of confounding factors, logistic regression analyses showed HDL-C and TC/HDL-C ratio as significant predictors of ED (p=0.011 and 0.000 respectively). Increased 10-year CHD risk was found in 56.6% in the ED group compared to 32.6% in the control group (p<0.05). The median risk was 12.18% vs. 9.07% respectively with a significant age-related risk (p<001). CONCLUSIONS: Hyperlipidemia is common in ED patients. HDL-C and TC/HDL-C ratio are predictors of ED. These patients have a high risk of later developing CHD. Erectile dysfunction might therefore serve as sentinel event for coronary heart disease.

Adult↗
PubMed2003

Persistently altered visceral perception after resection of an esophageal granular cell myoblastoma: a therapeutic concept revisited.

Granular cell tumors (GCTs) are rare and usually benign gastrointestinal tumors. Their most frequent symptoms are dysphagia and epigastric or retrosternal discomfort. We here report a case of esophageal GCT with continued symptoms of retrosternal discomfort, postprandial feeling of fullness, and early satiety despite complete thoracoscopic resection of the tumor. In contrast, all functional tests were in the normal range. We thus suggest that, due to their neuroectodermal origin, GCTs may affect neuronal alterations leading to a persistently disturbed visceral mechanosensory perception. Consequently, this case also cautions the therapeutic concept to solely relieve GCT symptoms by resection if the tumor is less than 20 mm in diameter.

Adult↗
PubMed2003

Effects of L-arginine and sodium nitroprusside on the spontaneous contractility of human non-pregnant uterus.

BACKGROUND: The aim of this study was to investigate, in isolated human non-gravid myometrium, the involvement of the cyclic guanosine monophosphate (cGMP) pathway in nitric oxide (NO) induced relaxation. METHODS: Strips of human myometrium from hysterectomized women were suspended in organ baths for recording of isometric tension. Cumulative concentration-response curves for L-arginine and sodium nitroprusside were performed in the presence of methylene blue (10 micromol/l) or vehicle (control). The effect of increasing concentrations of 8-bromo-cGMP on uterine spontaneous contraction was also studied. RESULTS: L-arginine and sodium nitroprusside induced a concentration-dependent decrease in the amplitude of the myometrial spontaneous contractions. Pre-treatment with methylene blue enhanced the inhibitory effect of L-arginine and sodium nitroprusside on myometrial spontaneous contractions. In addition, 8-bromo-cGMP had no effect on spontaneous contractions in human myometrium. CONCLUSIONS: These data provide evidence that L-arginine and sodium nitroprusside inhibit the spontaneous contractions of the non-pregnant human uterus through a cGMP independent pathway.

Arginine↗
PubMed2002

Capsaicin-sensitive nerve fibres induce epithelial cell proliferation, inflammatory cell immigration and transforming growth factor-alpha expression in the rat colonic mucosa in vivo.

BACKGROUND: Capsaicin-sensitive nerve fibres protect gastrointestinal mucosa in animal models of mucosal injury by modulation of mucosal blood flow and mucus secretion. The aim of our study was to evaluate the effects of capsaicin-sensitive nerve fibres in rat colonic mucosa on epithelial cell proliferation and transforming growth factor-alpha (TGFalpha) expression, which is important in mucosal defence, protection and repair. METHODS: Male Wistar rats received either a capsaicin enema with or without giving antagonists to calcitonin-gene-related-peptide (CGRP) or substance P (SP) i.v. immediately prior to the capsaicin enemas; a capsaicin enema after sensory desensitization as described previously; or a vehicle enema. In all experiments, animals received 50 mg/kg BrdU i.v. and were killed at 2, 4, 8, 12, 24 and 48 h after the various treatments. Colonic mucosal specimens were evaluated microscopically for mucosal damage, changes in the numbers of inflammatory cells and BrdU-immunoreactive epithelial cell nuclei. In the same specimens, TGFalpha-mRNA and -protein expression were evaluated by RT-PCR and Western blot analysis using standardized procedures. RESULTS: A significant increase in the number of mucosal inflammatory cells and an increase in BrdU-immunoreactive nuclei were detected following mucosal exposure to capsaicin. A 2-fold increase of TGFalpha mRNA and a 10-fold increase of TGFalpha protein expression were obtained 2-12 h after capsaicin enemas. The effects on the invading number of inflammatory cells and on the increase in BrdU immunoreactive epithelial cell nuclei were significantly reduced by both CGRP and SP antagonists and were abolished in rats previously sensory-desensitized. CONCLUSION: Capsaicin-sensitive nerve fibres modulate epithelial cell proliferation and TGFalpha expression in colonic mucosa as well as a migration of inflammatory cells into the colonic mucosa. These effects are mediated by the neurotransmitters CGRP and SP.

Animals↗
PubMed2001

Peroxynitrite-induced nitration of tyrosine-34 does not inhibit Escherichia coli iron superoxide dismutase.

The peroxynitrite anion is a potent oxidizing agent, formed by the diffusion-limited combination of nitric oxide and superoxide, and its production under physiological conditions is associated with the pathologies of a number of inflammatory and neurodegenerative diseases. Nitration of Escherichia coli iron superoxide dismutase (Fe-SOD) by peroxynitrite was investigated, and demonstrated by spectral changes and electrospray mass spectroscopic analysis. HPLC and mass studies of the tryptic digests of the mono-nitrated Fe-SOD indicated that tyrosine-34 was the residue most susceptible to nitration by peroxynitrite. Exclusive nitration of this residue occurred when Fe-SOD was exposed to a cumulative dose of 0.4 mM peroxynitrite. Unlike with human Mn-SOD, this single modification did not inactivate E. coli Fe-SOD at pH 7.4. When Fe-SOD was exposed to higher concentrations of peroxynitrite (7 mM), eight tyrosine residues per subunit of the protein, of the nine available, were nitrated without loss of catalytic activity of the enzyme. The pK(a) of nitrated tyrosine-34 was determined to be 7.95+/-0.15, indicating that the peroxynitrite-modified enzyme appreciably maintains its protonation state under physiological conditions.

Amino Acid Sequence↗
PubMed2001

Fusion proteins of B7.1 and a carcinoembryonic antigen (CEA)-specific antibody fragment opsonize CEA-expressing tumor cells and coactivate T-cell immunity.

Genetic engineering can be used to generate antigen-specific molecules for improved tumor immunotherapy. We have constructed genes coding for fusion proteins consisting of a high-affinity antibody single-chain antibody fragment (scFv) specific for the human carcinoembryonic antigen (CEA) and the costimulation domain of the murine B7.1 molecule (mB7.1) linked to the antibody moiety by an IgG3 peptide linker. The hybrid genes were constructed in 2 orientations, one with the scFv located N-terminal to mB7.1 and one vice versa. Soluble proteins were expressed by CHO cells, purified using anti-idiotype-affinity chromatography and characterized by tumor-cell binding and costimulation activity. When tumor cells expressing CEA on the cell membrane were opsonized with the CEA-specific costimulators, both fusion proteins specifically stimulated murine T-cell preparations to proliferate in a similar manner. Our data suggest that "costimulation coating" of tumor cells may be a suitable approach for activation of a sustained cellular antitumor response. It also provides the opportunity to increase tumor immunogenicity using easily generated soluble fusion proteins that advantageously link biological functions of both the humoral and the cellular arm of the specific immune system.

Animals↗
PubMed2001

Electroosmotic flow in composite microchannels and implications in microcapillary electrophoresis systems.

The electroosmotic flow in laminated excimer laser-ablated microchannels has been studied as a function of the depth of the rectangular channels, and particular emphasis has been given to the difference in the zeta-potentials between the lamination layer and the ablated substrate. Experimental electroosmotic flow follows the tendency predicted by a recently published model. The zeta-potentials of lamination and ablated surfaces were determined for poly(ethylene terephthalate) and poly(carbonate) substrates by fitting the experimental data with a numerical implementation of this model. In the experimentally investigated range of channel cross sections, a linear fit to the data gives a good approximation of the zeta-potentials for both materials. Moreover, a flow injection analysis of fluorescein dye has been performed to show the severe loss in numbers of theoretical plates, caused by Taylor dispersion, when such microchannels, dedicated to microcapillary electrophoresis, are used.

Journal Article↗
PubMed2001

Lipopeptide adjuvants: generation of lactate dehydrogenase isoenzyme-specific antibodies for immunochemical diagnosis.

Lactate dehydrogenase catalyzes the final step in glycolysis, the interconversion of pyruvate and lactate. The tetrameric enzyme is composed of one or two subunits (H and/or M) resulting in five isoenzyme forms: LDH-H4, -H3M1, -H2M2, -H1M3, and -M4. The relative distribution of the LDH isoenzymes is tissue dependent and a significant marker for the diagnosis of hepatoma of the liver, myocardial infarction, muscular dystrophy, and a wide variety of other acute and chronic diseases to be detected by alterations of the LDH isoenzyme pattern in serum. Immunochemical approaches to the routine determination of LDH depend on isoenzyme specific antibodies. Since the H- and M-subunits for human LDH are highly homologous, LDH isoenzyme specific antibodies for immunochemical monitoring are hard to generate. Here we present data on the generation and characterization of LDH isoenzyme-specific mono- and polyclonal antibodies in different species in the presence of lipopeptide adjuvants. Western-Blot and ELISA analysis showed that antisera and monoclonal antibodies recognize their homologous antigens with high specificity and are therefore suitable for immunochemical monitoring of the LDH isoenzymes H4 and M4. In addition, they can be used for the determination of LDH isoenzyme specific activity which is an essential prerequisite for online amperometric immunosensor monitoring.

Adjuvants, Immunologic↗
PubMed2001

Continuous free-flow electrophoresis separation of cytosolic proteins from the human colon carcinoma cell line LIM 1215: a non two-dimensional gel electrophoresis-based proteome analysis strategy.

The conventional approach for analyzing the protein complement of a genome involves the combination of two-dimensional gel electrophoresis (2-DE) and mass spectrometric based protein identification technologies. While 2-DE is a powerful separation technique, it is severely limited by the insolubility of certain classes of proteins (e.g. hydrophobic membrane proteins), as well as the amount of protein that can be processed. Here, we describe a simple procedure for resolving complex mixtures of proteins that involves a combination of free flow electrophoresis (FFE), a liquid-based isoelectric focussing (IEF) method, and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Resolved proteins were identified by peptide fragment sequencing using capillary column reversed-phase high performance liquid chromatography (RP-HPLC)/mass spectrometry (MS). An initial demonstration of the method was performed using digitonin/ethylenediaminetetraacetic acid EDTA extracted cytosolic proteins from the human colon carcinoma cell line, LIM 1215. Cytosolic proteins were separated by liquid-based IEF (pH range 3-10) into 96 fractions, and each FFE fraction was further fractionated by SDS-PAGE. Selected protein bands were excised from the SDS-PAGE gel, digested in situ with trypsin, and subsequently identified by on-line RP-HPLC/electrospray-ionization ion trap MS. Our results indicate that FFE is: (i) an extremely powerful liquid-based IEF method for resolving proteins; (ii) not limited by the amount of sample that can be loaded onto the instrument; and (iii) capable of fractionating intact protein complexes (a potentially powerful tool for cell-mapping proteomics). An up-to-date list of cytosolic proteins from the human colorectal carcinoma cell line LIM 1215 can be found in the Joint Protein Structure Laboratory (JPSL) proteome database. This information will provide an invaluable resource for future proteomics-based biological studies of colon cancer. The JPSL proteome database can be accessed through the World Wide Web (WWW) network (http://www.ludwig.edu.au/jpsl/jpslhome.html).

Chromatography, High Pressure Liquid↗
PubMed2001

A new spectrophotometric method for the determination of total and ferric iron in rain water at the ppb level.

A new, simple, selective and sensitive spectrophotometric procedure for the on-site quantification of iron at nano-gram levels in atmospheric precipitations, i.e. rain as sample source is described. It is based on the color reaction of Fe3+ with SCN- ions in the presence of a cationic surfactant, i.e. cetylpyridinium chloride (CPC), in strong HCl solution, and subsequent extraction of the complex with N-octylacetamide into toluene or chloroform. The apparent molar absorptivity of the complex is 2.60 x 10(5) L mol(-1) cm(-1) at lambdamax = 480 nm at an enrichment factor (EF) of 10. The detection limit (causing higher absorbance than the sum of the blank absorbance (0.009) and 3 SD) is 5 ng mL(-1) Fe. Ions commonly associated with iron did not interfere in the present method. The effect of analytical variables, i.e. amount and type of the reagents, acidity, solvent, temperature, dilution, etc., in the determination of iron are discussed. The validity of the present method is checked with GF-AAS. The method has been applied to the determination of iron at the ppb level in rain water samples.

Journal Article↗
PubMed2001

Fluorine determination in human and animal bones by particle-induced gamma-ray emission.

Fluorine was determined in the iliac crest bones of patients and in ribs collected from post-mortem investigations by particle-induced gamma-ray emission based on the 19F(p,p'gamma)19F reaction, using 2.0/2.5 MeV protons. The results indicate that for 68% of the human samples the F concentration is in the range 500-1999 microg g(-1). For comparison purposes fluorine was also determined in some animal bones; in some animal tissues lateral profiles of fluorine were measured.

Adolescent↗
PubMed2001

Quantification of corrosion phenomena in plastic processing machines.

In a model platelet system the corrosion of metallic materials was studied by processing polyethylene, polyphenylene sulfide, and glass-fibre-reinforced polyphenylene sulfide. The measurement methods used were scanning electron microscopy (images), electron-probe microanalysis (lateral element maps), secondary-ion mass spectrometry (depth profiles), X-ray photoelectron spectroscopy (chemical bonding), and grazing-incidence X-ray diffraction (structures of crystalline compounds). As nondestructive measure of corrosive attack, grazing-incidence X-ray diffraction, using the intensity ratio (IFe-O/IFe), was found to be the method of choice. The reproducibility for the total procedure was found to range between 6 and 13% (rel.). The intensity ratio was examined as function of depth, of the time of stress, of material composition, and of the surrounding atmosphere. Oxides were identified as main corrosion products. The extent of oxide formation is proportional to the time elapsed after processing.

Journal Article↗
PubMed2001

Immunostimulation by the synthetic lipopeptide P3CSK4: TLR4-independent activation of the ERK1/2 signal transduction pathway in macrophages.

Synthetic lipopeptides based on bacterial lipoprotein are efficient activators for monocytes/macrophages inducing the release of interleukin (IL)-1, IL-6, tumour necrosis factor-alpha (TNF-alpha), reactive oxygen/nitrogen intermediates, and the translocation of nuclear factor kappaB (NFkappaB). In this report we investigate the signal transduction pathways involved in leucocyte activation by the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)3-lysine (P3CSK4). We show that P3CSK4 activates mitogen-activated protein (MAP)-kinases ERK1/2 and MAP kinase (MAPK)-kinases MEK1/2 in bone-marrow-derived macrophages (BMDM) and in the macrophage cell line RAW 264.7. Additionally, we could detect differences between the P3CSK4 and lipopolysaccharide (LPS)-induced phosphorylation of MAP kinases: Different levels in phosphorylation were found both in kinetics and dose-response using RAW 264.7 cells or BMDM from BALB/c and LPS responder mice (C57BL/10ScSn) or LPS non-responder mice (C57BL/10ScCr). The lipopeptide activated the MAPK-signalling cascade in both LPS responder and non-responder macrophages, whereas LPS induced the MAPK signalling pathway only in macrophages derived from LPS responder mice. An approximately 70% decrease of lipopeptide induced NFkappaB translocation and an about 50% reduction of nitric oxide (NO) release was observed in the presence of anti-CD14. These data correspond to the reduction of phosphorylation of ERK1/2 after stimulation with P3CSK4 in the presence of anti-CD14 antibodies. Inhibition of MEK1/2 by PD98059 completely reduced the lipopeptide-induced phosphorylation of ERK1/2 indicating that MEK1/2 are solely responsible for the phosphorylation of the downstream-located MAP kinases ERK1/2.

Animals↗
PubMed2001

Pressure support noninvasive positive pressure ventilation treatment of acute cardiogenic pulmonary edema.

We assessed cardiogenic pulmonary edema (CPE) patient response to full mask pressure support noninvasive positive pressure ventilation (NPPV). Adult patients presenting to the emergency department (ED) in acute respiratory failure who clinically required endotracheal intubation (ETI) were studied. In addition to routine therapy consisting of oxygen, nitrates, and diuretics, patients were started on full mask NPPV using a Puritan Bennett 7200 ventilator delivering pressure support 10 cm H(2)O, PEEP 5 cm H(2)O, FiO(2) 100%. Pressure support was titrated to achieve tidal volumes of 5 to 7 mL/kg, and PEEP titrated to achieve oxygen saturation (SaO(2)) > 90%. Outcome measures included arterial blood gas (ABG), Borg dyspnea score, vital signs, and need for ETI. Twenty patients mean age 74.7 +/- 14.3 years were entered on the study. Initial mean values on FiO(2) 100% by nonrebreather mask: pH 7.17 +/-.13, paCO(2) 65.5 +/- 19.4 mmHg, paO(2) 73.8 +/- 27.3 mm Hg, SaO(2) 89.7 +/- 10.0%, Borg score 8.1 +/- 1.4, and respiratory rate(RR) 38 +/- 6.3. At 60 minutes of NPPV, improvement was statistically significant: pH 7.28 (difference.11; 95% CI.04-.19), paCO(2) 45 (difference 20.5; 95% CI 8-33), Borg score 4.1 (difference 4.0; 95% CI 3-5), and RR 28.2 (difference 9.8; 95% CI 5-14). NPPV duration ranged from 30 minutes to 36 hours (median 2 hours, 45 minutes). Eighteen patients (90%) improved allowing cessation of NPPV. Two patients with concomitant severe chronic obstructive pulmonary disease (COPD) required ETI. There were no complications of NPPV. NPPV using full face mask and pressure support provided by a conventional volume ventilator is an effective treatment for CPE and may help prevent ETI.

Acute Disease↗
PubMed2001

Mycophenolate mofetil reduces tissue damage and inflammation in an experimental model of colitis in rats.

BACKGROUND: Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats. METHODS: Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. RESULTS: Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P = 0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes. CONCLUSION: Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.

Animals↗
PubMed2001

Expression of insulin-like growth factor binding proteins and collagen in experimental colitis in rats.

OBJECTIVES AND DESIGN: Crohn's disease is complicated by smooth muscle hyperplasia and stricture formation. Insulin-like growth factor (IGF)-1 and insulin-like growth factor binding proteins (IGFBPs) may be involved in stimulating intestinal smooth muscle growth and collagen synthesis. Therefore, we investigated the expression of IGFBPs, collagen and collagenase activity in rat colitis and the effects of IGF-1 on IGFBP and collagen expression in rat colonic smooth muscle cells. METHODS: Animals were sacrificed during a 4-week time course of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. RNA from the animals' colons was blotted and hybridized with collagen-1 and IGFBP mRNA probes. Tissue proteins were screened for IGFBPs by Western ligand blotting. Collagenase activity was measured by zymography. Rat colonic smooth muscle cells in primary culture were incubated with IGF-1 then collagen-1, and IGFBP mRNAs and proteins were measured. RESULTS: In the rat tissue, IGFBP-3 mRNA and protein were increased 2 h after induction of colitis. IGFBP-4 mRNA was elevated after 2 h and IGFBP-4 protein after 4 h. IGFBP-5 mRNA was upregulated after 2 h with a peak at 12 h. IGFBP-5 protein was upregulated after 1 h and reached a peak at 3 days. Collagen-1 mRNA was increased after 5 days. Collagenase levels were decreased after 1 h and returned to normal by 28 days. In rat colonic smooth muscle cells, IGF-1 increased collagen-1 and IGFBP-5 expression. CONCLUSION: We demonstrated an upregulation of IGFBP and collagen expression and a downregulation of collagenase in rat colitis. In colonic smooth muscle cells, we found an upregulation of collagen-1 and IGFBP-5 following IGF-1 incubation. These results suggest an important role of IGF-1 in the collagen synthesis in colitis, mediated by IGFBPs.

Animals↗