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Biomedical subjects

B Steffen

Publications and source records attributed to B Steffen.

14 recordsLinked to original sources
PubMed2005

A new mathematical procedure to evaluate peaks in complex chromatograms.

Automatic peak evaluation in chromatograms and subsequent quantification of compound concentrations is still a challenge in the analysis of complex samples containing hundreds or thousands of compounds. Although a number of software packages for peak evaluation exist, baseline definition and overlapping peaks of different shapes are the main reasons which prevent reliable automatic analysis of complex chromatograms. A new mathematical procedure is presented which uses peak shapes extracted from the chromatogram itself and modified by nonlinear (in fact, hyperbolic) stretching of the peak head and tail. With this approach, the peak parameters are position, height, scale of front, scale of tail, and smoothness of transition from front to tail scaling. This approach is found to give a substantially better fit than traditional analytically defined peak shapes. Together with a good peak finding heuristic and nonlinear optimization of parameters this allows a reliable automatic analysis of chromatograms with a large number of peaks, even with large groups of overlapping peaks. The analysis matches the quality of standard interactive methods, but still permits interactive refinement. This approach has been implemented and tested on a large set of data from chromatography of hydrocarbons in ambient air samples.

Chromatography↗
PubMed2004

Expression of the p14ARF tumor suppressor predicts survival in acute myeloid leukemia.

Cell cycle aberrations are associated with therapy outcome in many types of cancer. We analyzed mRNA expression levels of 18 cell cycle-related genes in bone marrow samples from 78 acute myeloid leukemia (AML) patients and six controls using high-throughput quantitative RT-PCR. Samples of AML patients contained significantly increased mRNA expression levels of the mdm2 and c-myc oncogenes. Also, the average expression levels of p14ARF and p16INK4A were higher in patient samples compared to controls. Leukemic blasts and control bone marrow samples did not differ significantly in the expression levels of proliferation-associated genes such as cyclin A2 and pcna. When single genes were analyzed for prognostic significance in Kaplan-Meier and Cox regression analyses, a low p14ARF level emerged as a strong and independent predictor for poor survival (P=0.04 and 0.029). Subsequently, p14ARF mRNA levels were analyzed in a second, independent patient population (n=57). Again, low p14ARF levels were associated with a worse outcome. Finally, immunohistochemistry analysis of AML tissue arrays confirmed the widespread expression of c-myc and p14ARF in AML on the protein level. Taken together, the expression of the p53 regulators mdm2 and p14ARF are altered in AML, and low p14ARF levels indicate a poor prognosis.

Acute Disease↗
PubMed2000

Investigation of mathematical methods for efficient optimisation of aqueous two-phase extraction.

Mathematical strategies were applied to optimise the extraction of recombinant leucine dehydrogenase from E. coli homogenates and endoglucanase 1 from culture filtrates of Trichoderma reesei in polyethylene glycol-phosphate systems. The goal was to test mathematical tools which could facilitate the optimisation procedure in aqueous two-phase systems. A modified simplex approach, the method of steepest ascent and a genetic algorithm were successfully applied and compared. The methods differ in the height of the optimum found, the number of experiments and the time required. The genetic algorithm proved to be an optimisation procedure which can be used well in aqueous two-phase systems. The simplex procedure has to be further improved.

Algorithms↗
PubMed1999

The effects of garlic preparations against human tumor cell proliferation.

Epidemiological studies in China provide reason to suspect that a rich garlic content in the diet might reduce the proliferation of tumors in humans. We conducted experiments on human tumor cell lines and determined the influence of a garlic powder preparation, a garlic extract (reported as 8-10% L(+)-alliin enriched), and a combination thereof, on cellular proliferation in cell cultures, employing the widely used indirect neutral red procedure. Garlic powder failed to inhibit the growth of human hepatoma HepG2 or human colorectal carcinoma Caco2 cells at concentrations of up to 1000 micrograms/ml. Garlic extract, in which the alliin content was highly enriched was also unable to inhibit the growth of these cells. However, when the garlic extract was supplemented with garlic powder (to 10% final concentration) there was a concentration-dependent clear inhibition of tumor cell growth (IC50 values of 330 micrograms/ml for HepG2 and 480 micrograms/ml for Caco-2 cells). The growth of the human lymphatic leukemia cell line CCRF CEM was significantly inhibited in a dose-dependent manner by both garlic powder and garlic extract at concentrations as low as 30 micrograms/ml. However, no potentiation of this effect occurred upon mixing of the two preparations. Our results suggest that the antiproliferative effects of garlic may be due to breakdown products of alliin, such as allicin or polysulfides, rather than alliin itself, since the addition of an alliinase system (garlic powder) to an alliin enriched preparation without alliinase (garlic extract) potentiated the effects observed with the two preparations alone.

Animals↗
PubMed1998

Antitumor-activities of coumarin, 7-hydroxy-coumarin and its glucuronide in several human tumor cell lines.

Coumarin is found in many medicinal plants and therefore also used in phytomedicine for the treatment of venous diseases. The metabolic pathways of coumarin in the human body lead to the intermediate 7-hydroxy-coumarin and consequent glucuronidation in the intestine and liver. The antitumor activities of coumarin (C) and its known metabolite 7-hydroxy-coumarin (7-OH-C) were tested in several human tumor cell lines. C as well as 7-OH-C inhibited cell proliferation of a gastric carcinoma cell line, a colon-carcinoma cell line (Caco-2), a hepatoma-derived cell line (HepG2) and a lymphoblastic cell line (CCRF CEM) in a concentration-dependent way, the IC50-values were 1.59-3.57 mM for C and 0.68-2.69 mM for 7-OH-C. The glucuronide of 7-OH-C was ineffective in this respect.

Antineoplastic Agents↗
PubMed1997

[Frozen section diagnosis using telepathology].

DEFINITION: Since 1992 we transfer digitalized frozen section images by means of videomicroscope and a personal computer through the public telephone network (ISDN) to the Institut of Pathology at the University Hospital in Basel. The aim of this study is to determine whether the quality of frozen section diagnosis obtained by telepathology is comparable to the conventional one. METHOD: The frozen section diagnoses by telepathology from Oct. 1992 to May 1996 (n = 94) are compared to the paraffin sections performed in each case after the primary examination. The result is then compared to the well documented data of conventional frozen section diagnosis in the literature. RESULTS: From Oct. 1992 to May 1996 we performed 94 frozen sections. In 84 cases the diagnosis was correct compared to the paraffin section (89%). The sensitivity to detect a malignant tumor was 92%, the specifity 100%. Four examinations were not conclusive and one examination had to be canceled because of technical problems. DISCUSSION: In the literature, 92% of malignancy is diagnosed by conventional frozen section [1]. Telepathology gives the same result.

Frozen Sections↗
PubMed1996

Identification and treatment of women with hyperglycaemia diagnosed during pregnancy can significantly reduce perinatal mortality rates.

We wished to determine whether gestational diabetes was associated with an increased perinatal mortality rate, and to investigate the cause for the observed increase in the incidence of gestational diabetes. We therefore reviewed the results of glucose tolerance tests and pregnancy outcome in 116,303 pregnancies, 1971-1994, at the Mercy Hospital for Women. The main outcome measurements were the presence or absence of gestational diabetes, and perinatal mortality. Over the entire period of the study, gestational diabetes was associated with an increased risk of perinatal mortality (Mantel-Haenszel adjusted odds ratio 1.53, 95% CI 1.13-2.06, p = 0.0069). Women with gestational diabetes that was only diagnosed retrospectively had a higher perinatal mortality rate than their contemporaries with normal glucose tolerance (OR 2.31, 95% CI 1.37-3.91, p = 0.0025). Women in whom a glucose tolerance test was not performed continued to have a higher perinatal mortality rate than women who were tested (adjusted OR 2.21, 95% CI 1.56-3.12, p < 0.00001). There has been an increase in the prevalence of gestational diabetes from 2.9% to 8.8%. Some of this is due to changes in population characteristics (increases in maternal age, obesity and proportion from South-East Asia), but there was still an independent increase over time. We conclude that identification and treatment of women with gestational diabetes can reduce perinatal mortality rates. Similarly to diabetes mellitus in the total population, the prevalence of gestational diabetes has increased over time.

Diabetes, Gestational↗
PubMed1994

Cytotoxicity of heavy metals in the human small intestinal epithelial cell line I-407: the role of glutathione.

Cytotoxicities of metal salts were determined in the intestinal epithelial cell line I-407 in microwell culture plates over 48 h using the widely utilized and accepted neutral red uptake procedure. Rank order cytotoxicities induced by the metal salts (in terms of LC50 values) were found to be HgCl2 (32 microM) > CdCl2 (53 microM) > CuCl2 (156 microM) > T12SO4 (377 microM) > Pb(NO3)2 (1.99 mM). Combined administration of the two most toxic metals at their LC50's showed that their toxicities were not additive or synergistic. The role of glutathione in determining toxicity induced by the metal salts in these cells was assessed by inhibition of its synthesis. Buthionine sulfoximine pretreatment at 1 mM, which was not toxic to the cells, caused sustained reduction in cellular glutathione content (to 13.8% after 48 h) and increased toxicities induced by HgCl2 (5.7-fold) and CuCl2 (1.44-fold) as shown by reductions in the LC50 values. Toxicity induced by the other metals remained unaffected. Administration of glutathione with either HgCl2 or CdCl2 did not protect the cells against their toxicity, and in the case of cadmium its toxicity was exacerbated. N-Acetylcysteine diminished toxicity induced by mercury but not cadmium.

Cadmium↗
PubMed1989

[The effect of dimetindene on liver and kidney function in the cholestatic rat].

Dimetindene (active principle of Fenistil) belongs to the group of H1-antihistamines which are used in the treatment of allergic disorders. An experimental approach was made to clarify the risk of dimetindene application during the conditions of an impaired liver function as a consequence of extrahepatic cholestasis (bile-duct ligation). Acute and subchronic treatment with dimetindene (1 and 10 mg/kg p.o., respectively) did not enhance the effect of cholestasis on the parameters of liver function (plasma bile acids, glutamate pyruvate transaminase (GPT), alkaline phosphatase) or kidney function (creatinine, urea retention in plasma). It is concluded that the use of dimetindene in the treatment of pruritus during cholestasis is without notable risk.

Alanine Transaminase↗
PubMed1988

Modulation of rat gastric mucosal prostaglandin E2 release by dietary linoleic acid: effects on gastric acid secretion and stress-induced mucosal damage.

We studied chronic intake of diets deficient in or supplemented with linoleic acid to determine whether it affects gastric acid secretion, release of prostaglandin E2, and stress-induced lesions. For 8-10 wk rats were fed three dietary regimens supplying 3.5% (control group), 0.3%, and 10% of total calories as linoleic acid. We found that diets deficient in linoleic acid (0.3%) reduced release of prostaglandin E2 into the gastric lumen (-77%) and increased basal (+133%) and pentagastrin-stimulated acid secretion (+93%) and the area of cold restraint-induced gastric mucosal lesions (+280%), when compared with the control group. Diets supplemented with linoleic acid (10%) increased prostaglandin E2 release into the gastric lumen (+106%) and reduced basal (-44%) and pentagastrin-stimulated acid secretion (-78%) and the area of cold restraint-induced mucosal.lesions (-80%). Prevention of these lesions by the 10% linoleic acid diet was confirmed by quantitative histology. Pretreatment with indomethacin (8 mg/kg intraperitoneally) abolished the effects of the 10% linoleic acid diet on prostaglandin formation, acid secretion, and mucosal injury. We conclude that in rats chronic intake of dietary linoleic acid reduces acid secretion and prevents cold restraint-induced mucosal lesions, possibly because of augmented synthesis of endogenous prostaglandins in the gastric mucosa.

Animals↗
PubMed1988

Antidotal effects of deferrioxamine in experimental liver injury--role of lipid peroxidation.

Pretreatment with deferrioxamine (DFO, 125-500 mg/kg i.p.) protected male mice against CCl4- or CBrCl3-induced hepatotoxicity which is closely related to an inhibition of iron-dependent lipid peroxidation monitored by ethane exhalation. For allyl alcohol, 1,1-dichloroethylene, dimethylnitrosamine, thioacetamide, bromobenzene and paracetamol no hepatoprotection was achieved with DFO indicating that lipid peroxidation is not involved as a primary mechanism of toxicity. In the case of bromobenzene a marked in vivo lipid peroxidation was observed, which was unaffected by DFO and appears therefore to be iron-dependent.

Animals↗
PubMed1986

Calcium, calmodulin, and cyclic adenosine monophosphate modulate prostaglandin E2 release from isolated human gastric mucosal cells.

We studied prostaglandin E2 (PGE2) release from isolated cells of the human gastric mucosa. Mucosal cells were enzymatically isolated from biopsy specimens of human fundic mucosa. The results from these crude cell preparations were compared to those obtained in fractions with enriched (65-80%) or depleted parietal cell content (3-7%) which were prepared from gastric mucosa obtained at surgery. PGE2 release in the enriched parietal cell fractions exceeded that from crude or parietal cell depleted preparations 3- and 13-fold, respectively. However, despite this quantitative difference, all preparations responded similarly to the test agents. Newly synthesized PGE2 was not stored intracellularly but was released into the incubation medium. Release increased linearly for 30 min. Addition of the calcium ionophore A23187 enhanced PGE2 release 4- to 5-fold. The effect of A23187 required the presence of extracellular Ca2+ (10(-3) mol/liter). Assuming that A23187 alters Ca2+ flux in gastric cells as it does in other cell systems our data indicate that increased Ca2+ influx enhances PGE2 release. Since calmodulin is of importance for intracellular Ca2+ action, the calmodulin antagonists trifluoperazine and W7 were tested. Both antagonists inhibited PGE2 release by 65-85%, trifluoperazine being slightly more effective. Activation of the adenylate cyclase system by forskolin or direct addition of (Bu)2cAMP, a stable cAMP-analog, also inhibited PGE2 release. We conclude that PGE2 is released from parietal and from nonparietal cells of the human gastric mucosa, although the major quantity is released from the light density fraction that is enriched in parietal cells. In parietal and nonparietal cells Ca2+ is of importance in the regulation of gastric mucosal PGE2 release and calmodulin seems to mediate this intracellular action of Ca2+. cAMP inhibits PGE2-release from gastric cells.

Bucladesine↗
PubMedDate not supplied

Biotransformation enzymes in two renal epithelial cell lines (LLC-PK1 and RK-L).

The activities of smooth endoplasmic reticulum (SER) and cytosolic xenobiotic-metabolizing enzymes were studied in two established renal tubular cell lines, LLC-PK1 and RK-L (rat kidney, Lübeck). The glutathione content in both cell lines was about 20-fold higher than in rat kidney homogenates; this is explained by a 20- to 50-fold lower activity of gamma-glutamyl transpeptidase in the cell lines. Among SER enzymes, the cytochrome P-450-dependent dimethylhydrazine demethylase was in the same range in both cell lines as compared with rat kidney S9 fraction. Pretreatment with phenobarbital (0.1 mM in the culture medium for 3 d) did not induce SER or cytosolic enzyme activities. The glutathione content in both epithelial cell lines can be modified by an inhibitor of GSH synthesis (buthionine sulfoximine, BSO), whereas inhibition of gamma-glutamyl transpeptidase (acivicin) did not significantly increase the GSH-concentration. Despite these biochemical characteristics, the utility of the new RK-L-line needs to be evaluated in experimental studies on renal transport processes and metabolism as well as cytotoxicity and genotoxicity of xenobiotics.

Animals↗