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T Fleischmann

Publications and source records attributed to T Fleischmann.

At least 19 recordsLinked to original sources
PubMed2006

Detection of lysergic acid in ruminal fluid, urine, and in endophyte-infected tall fescue using high-performance liquid chromatography.

Ergot alkaloids present in endophyte-infected tall fescue induce fescue toxicosis in livestock consuming the plant. The lysergic acid (LA) ring structure is a common moiety among the ergot alkaloids. Little is known about the bioavailability of LA because of limitations in available analytical protocols. Thus, a high-performance liquid chromatography procedure was developed to analyze biological matrices for LA. The biological matrices of interest were tall fescue straw and seed, and ruminant feces, urine, and ruminal fluid. Lysergic acid was added to each matrix at a high (150 ng/ml) or low (30 ng/ml) level. Using the high-level addition, the greatest recovery of LA was obtained from ruminal fluid, feces, and urine (P < 0.05), with an average 85.1% recovered. At the low level, a greater recovery of added LA was observed in the ruminal fluid, urine, and feces (82.1%; P < 0.05) than that in the other 2 matrices (62.6%). The limit of quantitation (LOQ) in ruminal fluid and urine was 5.5 and 18.4 ng/ml, respectively. Seed, straw, and feces had higher LOQ (24.2, 14.5, and 36.0 ng/g, respectively). Limit of detection (LOD) was 1.64, 10.80, 4.35, 5.52, and 7.26 ng/g for ruminal fluid, feces, urine, seed, and straw, respectively. To test the assay in vivo, samples of ruminal fluid and urine were collected from steers consuming a diet containing 400 ng of ergovaline/g and 30 ng of LA/g. All matrices sampled resulted in levels above the LOD and LOQ for the assay, indicating that this assay is sufficiently sensitive for use in assessing the bioavailability of LA.

Animals↗
PubMed2005

Growth and hepatic in vitro metabolism of ergotamine in mice divergently selected for response to endophyte toxicity.

This study investigated if genetic differences exhibited in endophyte-resistant and -susceptible mouse lines had persisted after 13 generations in which the integrity of lines was maintained yet selection ceased. Experimental groups were mouse lines fed an endophyte-free (E-) or -infected (E+) diet. The in vitro metabolism of the ergot alkaloid ergotamine in mouse liver microsomes was characterized by LC-MS/MS and compared between both lines before and after exposure to E+ feed. No difference in the average daily weight gain of pups between resistant and susceptible mice was observed on the E+ diet. Thus, for the weight gain selection criterion under study, the difference established between the two lines appears not to have persisted over the extended period of relaxed selection. Microsomal incubations produced nine predominate peaks in the HPLC assay. The peaks were confirmed by LC-MS/MS to be ergotamine, ergotamine epimer, monohydroxylated metabolites (M1, M2, M1e, M2e) and dihydroxylated metabolites (M3--5). A gender difference for metabolite formation was observed on the E- diet, in that females produced a greater amount of M1, M1e and M3--5 than males. When challenged with the E+ diet, mice showed differences in concentration of M3 for line (resistant > susceptible) and gender (female > male) and of M4 and M5 for gender (female > male). Gender differences in the metabolism of ergotamine have not been shown before in these lines of mice or other species used to study ergot alkaloid metabolism. This adds a potential source of variation in the susceptibility to fescue toxicity not explored previously and would be of value to investigate further.

Animal Feed↗
PubMed2001

Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis.

Intra-abdominal infection in patients following major visceral surgery is associated with high mortality. Using a macrophage depletion technique, we demonstrate that in murine septic peritonitis, Kupffer cells are a major source of systemic IL-10 levels. Kupffer cell-depleted mice were highly susceptible to the lethal effects of septic peritonitis and exhibited an increased bacterial load. Kupffer cell-depleted mice were protected by the administration of an IL-10-Fc fusion protein. Loss of Kupffer cell-derived IL-10 was associated with a weak increase in serum IL-12 levels, whereas TNF, IL-1alpha, and IL-18 levels were not significantly elevated, suggesting that the loss of Kupffer cell-derived IL-10 did not result in a toxic cytokine release syndrome. Instead, loss of Kupffer cell-derived IL-10 was associated with a reduced splenocyte production of IFN-gamma that is required for immune protection in murine septic peritonitis. Therefore, the results suggest that the protective function of IL-10 in septic peritonitis may not be restricted to the anti-inflammatory activities of IL-10.

Animals↗
PubMed1999

Determination of polyhydroxyalkanoates in activated sludge by ion chromatographic and enzymatic methods.

Two new detection methods for the determination of poly-beta-hydroxybutyrate (PHB) and -valerate (PHV) are described. Both methods are based on depolymerization of PHB/PHV to 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV). Depolymerization was achieved by either propanolic or hydrolytic digestion. Propanolic digestion transformed commercial PHB/PHV stoichiometrically into 3HB/3HV and yielded apparently complete recoveries of bacterial PHB/PHV from activated sludge. Hydrolytic digestion was suitable only for PHB determination. For quantification of 3HB and 3HV directly from digested sludge, a method based on ion-exchange chromatography and conductivity detection was developed (IC-method). Alternatively, the total of 3HB and 3HV was quantified using a commercial enzymatic test kit and colorimetric detection (enzyme method). Both detection methods are easier to perform than previous methods and are suitable for complex matrices such as activated sludge. The IC-method is recommended for high sample throughputs or if distinction between PHB and PHV is essential. Enzymatic detection is recommended if a few samples per day have to be measured immediately or if an ion chromatograph is unavailable.

1-Propanol↗
PubMed1999

Fate of the herbicides mecoprop, dichlorprop, and 2,4-D in aerobic and anaerobic sewage sludge as determined by laboratory batch studies and enantiomer-specific analysis.

Aerobic degradation experiments with the racemic mixtures of mecoprop and dichlorprop revealed that activated sludge collected from the aeration tank of a municipal waste water treatment plant degraded both enantiomers of mecoprop and dichlorprop within 7 days, albeit in an enantioselective manner; the (S) enantiomers were preferentially degraded. Mecoprop, dichlorprop, and 2,4-D were completely metabolized under aerobic conditions, as shown by the 86-98% elimination of dissolved organic carbon. Under anaerobic conditions, the concentration of 2,4-D decreased exponentially with a first-order reaction rate constant of 0.24 per day and without a lag-phase. After an incubation time of 17 days, 2,4-D was completely removed. 2,4-Dichlorophenol was the main metabolite of anaerobic 2,4-D degradation; only traces of 4-chlorophenol were detected. In contrast, the chiral phenoxypropionic acid herbicides mecoprop and dichlorprop persisted under anaerobic conditions during 49 days of incubation.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1999

cis-chlorobenzene dihydrodiol dehydrogenase (TcbB) from Pseudomonas sp. strain P51, expressed in Escherichia coli DH5alpha(pTCB149), catalyzes enantioselective dehydrogenase reactions.

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5alpha(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (-)-cis-(S,2R) enantiomer remained unchanged. CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3, 4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (-)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enantiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1, 2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols.

Biotransformation↗
PubMed1997

Purification and characterization of 2-hydroxybiphenyl 3-monooxygenase, a novel NADH-dependent, FAD-containing aromatic hydroxylase from Pseudomonas azelaica HBP1.

2-Hydroxybiphenyl 3-monooxygenase (HbpA), the first enzyme of 2-hydroxybiphenyl degradation in Pseudomonas azelaica HBP1, was purified 26-fold with a yield of 8% from strain HBP1 grown on 2-hydroxybiphenyl. The enzyme was also purified from a recombinant of Escherichia coli JM109, which efficiently expressed the hbpA gene. Computer densitometry of scanned slab gels revealed a purity of over 99% for both enzyme preparations. Gel filtration, subunit cross-linking, and SDS-polyacrylamide gel electrophoresis showed that the enzyme was a homotetramer with a molecular mass of 256 kDa. Each subunit had a molecular mass of 60 kDa containing one molecule of noncovalently bound FAD. The monooxygenase had a pI of 6.3. It catalyzed the NADH-dependent ortho-hydroxylation of 2-hydroxybiphenyl to 2,3-dihydroxybiphenyl. Molecular oxygen was the source of the additional oxygen of the product. The enzyme hydroxylated various phenols with a hydrophobic side chain adjacent to the hydroxy group. All substrates effected partial uncoupling of NADH oxidation from hydroxylation with the concomitant formation of hydrogen peroxide. 2,3-Dihydroxybiphenyl, the product of the reaction with 2-hydroxybiphenyl, was a non-substrate effector that strongly facilitated NADH oxidation and hydrogen peroxide formation without being hydroxylated and also was an inhibitor. The apparent Km values (30 degrees C, pH 7.5) were 2.8 microM for 2-hydroxybiphenyl, 26.8 microM for NADH, and 29.2 microM for oxygen. The enzyme was inactivated by p-hydroxymercuribenzoate, a cysteine-blocking reagent. In the presence of 2-hydroxybiphenyl, the enzyme was partly protected against the inactivation, which was reversed by the addition of an excess of dithiothreitol. The NH2-terminal amino acid sequence of the enzyme contained the consensus sequence GXGXXG, indicative of the betaalphabeta-fold of the flavin binding site and shared homologies with that of phenol 2-hydroxylase from Pseudomonas strain EST1001 as well as with that of 2,4-dichlorophenol 6-hydroxylase from Ralstonia eutropha.

Amino Acid Sequence↗
PubMed1997

ABVD chemotherapy of Hodgkin's disease.

The authors report on their results in ABVD therapy, which was given by 91 patients with Hodgkin's disease as first-line treatment. 78 patients (85% achieved complete, 10 (11%) partial remission, 3 (4%) did not respond to therapy. In the follow-up period (36-223 months) 6 patients (7%) died because of the progression of Hodgkin's disease. Serious side effects or treatment-related death did not occur. Based on their results of ABVD, the authors find ABVD chemotherapy effective as first-line treatment of Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Influence of the pathological psychological state of cancer patients on their decisions.

The diagnosis of cancer in many cases provokes a crisis, resulting in an increase of regression and defence mechanisms (splitting, projective identification, projection, denial, repression). This article reviews the increased sensitivity, the partial and temporary narrowing of consciousness, and the weakening of reality control. In many cases fluctuating depersonalisation and derealisation develop. At our Institute we performed a complex psychological examination of 41 patients, suffering from malignant lymphoma, immediately after informing them of the diagnosis but prior to their first treatment. The psychological examination of volunteering patients involved an initial interview, Rorschach and Szondi projective tests, a Wechsler intelligence test and a discussion of the results with the patient. The relatively frequent temporary pathological psychic conditions exert an influence on the decisions of patients make about their treatment and interventions, and may also influence the doctor patient relationship.

Adolescent↗
PubMed1995

[Second malignant disease in patients under treatment for malignant lymphoma].

Between 1978 and 1993, 1013 patients 529 with Hodgkin's disease and 484 with non-Hodgkin's lymphomas--were treated in our department. Out of 1013 patients secondary neoplasms developed in 23 cases: 3 acute nonlymphocytic leukemia, 19 solid tumors and 1 secondary non-Hodgkin's lymphoma. The median time from diagnosis of malignant lymphoma was 7 years and their median age was 49 years. 11 patients with secondary tumor were treated with chemotherapy and 12 received combined (radio- and chemo-) therapy. Since alkylating agents increase the risk of leukemia and radiation contributes mainly to other cancer, future treatment protocols should attempt to reduce the most serious consequences of therapy without compromising the survival. Careful lifelong observation is indicated for patients with malignant lymphomas, with special attention given to new clinical signs or symptoms.

Adult↗
PubMed1994

[CHOP-Bleo therapy in high-malignancy non-Hodgkin lymphoma].

The records of 85 patients were reviewed in order to study the efficacy of CHOP-Bleo combination chemotherapy and to determine factors influencing prognosis. The patients were treated between 1978 and 1989, the median age was 44.4 (range, 15-68) years, the majority of them were in advanced clinical stages (92.9%). Systemic (B) symptoms were present in half of the patients and a quarter of them had bulky disease. Complete response was achieved in 36 patients (42.5%), partial response in 26 patients (30.5%), and primary treatment failure occurred in 23 patients (27.0%). The median survival was 92.6 months and 36.5% of the patients remained relapse-free at 10 years. The expected 5-year and 10-year survival rates were 47% and 39%, respectively. Using multivariate analysis B symptoms, involvation of two or more extralymphatic sites and lymphoblastic histologic subtype proved to be unfavourable prognostic factors. The most frequently observed side-effects were myelosuppression, neurotoxicity and gastrointestinal symptoms. No treatment-related death have occurred.

Adolescent↗
PubMed1992

[Initial results of hybrid chemotherapy of Hodgkin's disease using COPP/VBA].

19 patients with advanced, previously untreated Hodgkin's disease were treated with COPP/ABV (cyclophosphamide, vincristine, procarbasine, prednisolone, adriamycin, bleomycine, vinblastine) hybrid regimen. Complete response was achieved in 8 patients, partial response in 9 patients and primary treatment failure occurred in 2 patients. Two patients received involved field irradiation for the residual disease. 17 months after finishing the therapy one of the complete responders suffered a relapse. Of the 8 partial responders, 5 patients relapsed. 2 relapses occurred during the treatment and 3 relapses were observed in the first 7 months of follow-up. 2 of the partial responders and both nonresponders succumbed to their disease. There were no serious side effects and treatment-related death did not occur.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Comparative study of advanced-stage Hodgkin's lymphoma patients treated with either COPP or ABVD drug combinations].

Between January 1985 and March 1988, 45 patients with advanced Hodgkin's disease were randomly assigned to receive either COPP (22 patients) or ABVD (23 patients). 9 and 16 patients achieved complete remission in the COPP and ABVD groups, respectively. One of the complete responders (COPP) relapsed during the follow-up. Patients treated with COPP experienced myelosuppression and neurotoxicity more frequently whereas alopecia and gastrointestinal symptoms were observed among those receiving ABVD. Present data confirm the favorable impact of primary ABVD treatment in advanced Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Treatment of resistant Hodgkin's disease with CCNU, etoposide and prednimustine (CEP).

Starting in January 1984, 63 patients with resistant Hodgkin's disease received CEP as salvage-usually third-line-chemotherapy. Complete response (CR) was achieved in 3%, partial response (PR) in 51%. The median duration of remission (CR + PR) was greater than 15 months. Treatment was generally well tolerated. Our results confirm that CEP is an effective therapeutic regimen in resistant Hodgkin's disease.

Adolescent↗
PubMed1989

Prednimustine treatment in malignant lymphomas.

Prednimustine (Stereocyt, Leo 1031) is a chlorambucil ester of prednisolone. Results from clinical trials confirm that prednimustine is active in malignant lymphomas. The efficacy of Stereocyt was evaluated in 25 patients, who were divided into three subgroups: 10 patients with refractory Hodgkin's disease and 7 with refractory non-Hodgkin lymphoma (NHL), while 8 patients received prednimustine as primary therapy for low-grade NHL. Totally 17 partial remissions were observed in all three groups of patients. Leukopenia and thrombopenia were induced in 3 patients, but were mild and reversible after withdrawal of the drug.

Adult↗