Biomedical subjects

M Baur

Publications and source records attributed to M Baur.

At least 37 records · Page 2Linked to original sources

PubMed1997

Mismatch repair in Schizosaccharomyces pombe requires the mutL homologous gene pms1: molecular cloning and functional analysis.

Homologues of the bacterial mutS and mutL genes involved in DNA mismatch repair have been found in organisms from bacteria to humans. Here, we describe the structure and function of a newly identified Schizosaccharomyces pombe that encodes a predicted amino acid sequence of 794 residues with a high degree of homology to MutL related proteins. On the basis of its closer relationship to the eukaryotic "PMS" genes than to the "MLH" genes, we have designated the S. pombe homologue pms1. Disruption of the pms1 gene causes a significant increase of spontaneous mutagenesis as documented by reversion rate measurements. Tetrad analyses of crosses homozygous for the pms1 mutation reveal a reduction of spore viability from > 92% to 80% associated with a low proportion (approximately 50%) of meioses producing four viable spores and a significant, allele-dependent increase of the level of post-meiotic segregation of genetic marker allele pairs. The mutant phenotypes are consistent with a general function of pms1 in correction of mismatched base pairs arising as a consequence of DNA polymerase errors during DNA synthesis, or of hybrid DNA formation between homologous but not perfectly complementary DNA strands during meiotic recombination.

Adenosine Triphosphatases↗

PubMed1997

Cooperative binding interactions required for function of the Ty1 sterile responsive element.

The Ste12p transcription factor controls the expression of Ty1 transposable element insertion mutations and genes whose products are required for mating in Saccharomyces cerevisiae. The binding site for Ste12p is a consensus DNA sequence known as a pheromone response element (PRE). Upstream activating sequences (UASs) derived from known Ste12p-dependent genes have previously been characterized to require either multiple PREs or a single PRE coupled to a binding site for a second protein. The Ste12p-dependent UAS from Ty1, called a sterile response element (SRE), is of the second type and is comprised of a PRE and an adjacent TEA (TEF-1, Tec1, and AbaA motif) DNA consensus sequence (TCS). In this report, we show by UV cross-linking analysis that two proteins, Ste12p and a protein with an apparent size of 72 kDa, directly contact the Ty1 SRE. Other experiments show that Tec1p is required for formation of the Ty1 SRE protein-DNA complex and is physically present in the complex. These results establish a direct role for Tec1p in the Ty1 SRE and yet another set of combinatorial interactions that achieve a qualitatively distinct mode of transcriptional regulation with Ste12p.

Base Sequence↗

PubMed1997

Prevention of thromboembolism with use of recombinant hirudin. Results of a double-blind, multicenter trial comparing the efficacy of desirudin (Revasc) with that of unfractionated heparin in patients having a total hip replacement.

Specific inhibition of thrombin is a new method for the prevention of postoperative deep-vein thrombosis. The objective of this multicenter, randomized, double-blind study was to compare the efficacy and safety of desirudin (Revasc, CGP 39393; fifteen milligrams two times a day) with that of unfractionated heparin (5000 international units three times a day) in patients having a primary elective total hip replacement. The medications were administered subcutaneously, starting preoperatively and continuing for eight to eleven days. The primary end point was a confirmed thromboembolic event during the treatment period. The presence of deep-vein thrombosis was evaluated with bilateral venograms, which were centrally assessed by two independent radiologists. A total of 445 eligible patients were randomized: 220, to management with heparin, and 225, to management with desirudin. A per-protocol analysis of efficacy was performed for the 351 patients (79 per cent) for whom an adequate bilateral venogram had been made within eight to eleven days after the operation or who had had a proved thromboembolic event. The prevalence of confirmed deep-vein thrombosis was thirteen (7 per cent) of 174 patients who had received desirudin and forty-one (23 per cent) of 177 patients who had received heparin, a significant difference (p < 0.0001). The prevalence of proximal deep-vein thrombosis was also significantly reduced (p < 0.0001), by 79 per cent, in the group that had received desirudin (six [3 per cent] of 174 patients) compared with in the group that had received heparin (twenty-nine [16 per cent] of 177). There were no confirmed pulmonary embolisms or deaths during the period of prophylaxis. During a six-week follow-up period, pulmonary embolism was confirmed in four patients, all of whom had received heparin. There was no significant difference between the treatment groups with respect to bleeding variables or bleeding complications. These data demonstrate that a fixed dose of fifteen milligrams of desirudin, started preoperatively and administered subcutaneously twice daily for at least eight days, provided effective, safe prevention of thromboembolic complications, with no specific requirements for laboratory monitoring, in patients who had a total hip replacement.

Aged↗

PubMed1997

Valsartan: long-term efficacy and tolerability compared to lisinopril in elderly patients with essential hypertension.

A total of 501 elderly patients with essential hypertension were randomized to receive valsartan or lisinopril in this one year multi-center, double-blind, parallel group trial. Patients received valsartan 40 mg (n = 334) or lisinopril 2.5 mg (n = 167) daily for 2 weeks with subsequent titration (alone or in combination with hydroclorothiazide), depending on response to treatment. The primary efficacy variable was the percentage of patients with a response, defined as sitting diastolic blood pressure < 90 mmHg or drop of > or = 10 mmHg from baseline. A high percentage of patients responded to treatment in both valsartan and lisinopril groups: 80% for both groups at 12 weeks and 81% and 87%, respectively, at 52 weeks with no statistically significant difference between treatments (12 weeks, p = 0.925; 52 weeks, p = 0.148). More patients on lisinopril experienced drug-related cough (7.5% on valsartan, 17.4% on lisinopril). In 5.4% of lisinopril treated patients, cough led to discontinuation of therapy compared to 0.6% on valsartan. Valsartan 80 mg daily provides comparable short and long-term antihypertensive efficacy to lisinopril in elderly patients with a lower incidence of drug-related cough.

Aged↗

PubMed1995

Pharmacokinetics of 4'-O-tetrahydropyranyladriamycin given on a weekly schedule in patients with advanced breast cancer.

Improved quality of life has gained importance over shortly lasting remissions in yet incurable metastatic breast cancer. Fractionation of drug administration is one of the possible approaches to reduce the concentration-dependent toxicity of anthracyclines. We evaluated the pharmacokinetics of 4'-O-tetrahydropyranyladriamycin (THP-ADM) under weekly administration in patients with advanced breast cancer (dose escalation, from 20 to 27 mg/m2 THP-ADM). The concentration-time curves of THP-ADM in plasma were best described by an open three-compartment model [half-life of the first disposition phase (t1/2 alpha), 3.15 min; terminal elimination half-life (t1/2 gamma), 13.9 h] with a mean area under the curve (AUC) of 12.2 ng h ml-1mg-1 m-2, resulting in a mean plasma clearance of 86.9 1h-1 m-2. Metabolism included the formation of Adriamycin (ADM), Adriamycinol (ADM-OH), 13-dihydro-4'-O-tetrahydropyranyladriamycin (THP-OH), 7-deoxyadriamycinone (7H-ADn), and 7-deoxy-13-dihydroadriamycinone (7H-ADn-OH), with maximal plasma concentrations ranging from 2.8 to 5.5 ng/ml. The mean total amount of cytotoxic anthracyclines excreted into urine, mainly as the parent drug, was 5% of the delivered dose. ADM and ADM-OH, but not the parent drug, were observed in urine at up to 4 weeks after the last therapeutic cycle. There was a significant correlation between the leukocyte nadir under therapy and the AUC of ADM-OH (r = 0.800, P < 0.05). Since no shift in the plasma kinetics was observed from the first to the sixth cycle, the favorable ratio of the AUCs of THP-ADM and ADM after fractionation of THP-ADM suggests lower toxic side effects attributable to ADM. This hypothesis was confirmed in a clinical study, where no severe cardiotoxicity and only mild alopecia were observed in 19 patients. Thus, pharmacokinetics studies might be helpful in both individualization of therapy with THP-ADM and optimization of the administration schedule.

Adult↗

PubMed1995

[Managing of an innovation in health care: the case of polyvalent intravenous immunoglobulins at the Assistance-Publique-Hôpitaux de Paris].

Managing new innovations in medicine is a particularly timely subject. There is an abundant history concerning over expectations resulting from the development of new treatments or diagnostic procedures, some shown to be less effective than promised, others even found to be dangerous. A new aspect to the question is the importance of economic pressures which require rational investment decisions when diffusing innovating technologies. In 1991, the Commission for the evaluation and diffusion of innovating technologies (CEDIT) at the University Hospitals of Paris (Assistance Publique-Hôpitaux de Paris) developed a programme aimed at better managing the distribution and use of polyvalent intravenous immunoglobulins (IgIV), a new promising therapeutic tool with both a high cost and a certain number of risks. The programme was designed to assist prescribers in elaborating better therapeutic strategies and to help hospital managers rationalize expenditures for IgIV. The results of this experience are presented here together with certain conclusions concerning the way management decisions can be applied to the diffusion of an innovation in health care.

Diffusion of Innovation↗

PubMed1994

Recombination fractions in the HLA system based on the data set 'provinces Françaises': indications of haplotype-specific recombination rates.

In the large genetic survey "Provinces Françaises' the recombination fractions in the HLA system have been estimated by a family analysis programme (FAP). A total of 1332 families were analysed and in general the findings were in agreement with recombination fractions reported previously. The maternal recombination rates were on average 1.8 times higher than the corresponding ones for males. The comparison of the recombination fractions with the corresponding physical distances suggests the existence of hot spots of recombination. The analysis did not show deviations from expected values for HLA-A and B alleles on HLA-A/B recombinant haplotypes. However, analysis of HLA-B/DR recombinant haplotypes showed a skewed distribution of B and DR alleles. The significance of the findings is difficult to evaluate as all results are estimated numbers and frequencies but a manual analysis of the recombinant families confirmed the observations. HLA-B/DR recombinant haplotypes carried often HLA-DR3 and DR11 whereas DR2 and DR7 were more rarely present on recombinant haplotypes. DR4 had an increased incidence on BF/DR recombinant haplotypes but not on A/B or B/BF recombinant haplotypes. Some of the haplotypes with the strongest linkage disequilibria as A1,B8,DR3 and A3,B7,DR2 seem to be less frequently involved in recombinations than other haplotypes. Variations of recombination rates depending on certain alleles or haplotypes might partially explain the conservation of some haplotypes or part of haplotypes in Caucasoids.

Alleles↗

PubMed1993

In vitro and in vivo evaluation of the combination of cisplatin and its analogue carboplatin for platinum dose intensification in ovarian carcinoma.

BACKGROUND: Cisplatin and its analogue carboplatin have been shown to cause dose-dependent growth inhibition throughout a wide dose range in the ovarian cancer cell lines OVCAR-3, 2780, HTB-77, and CRL-1572 tested. Cisplatin was 30 times more effective than carboplatin. The combination of both substances led to a less-than-synergistic effect, as was revealed by an isobologram in the OVCAR-3 cell line. Because of the different toxicity pattern, cisplatin and carboplatin theoretically are ideal candidates for combination chemotherapy in platinum-sensitive tumors. METHODS: In a Phase II study, the efficacy, the toxicity profile, and the feasibility of combining both substances were assessed in 20 previously untreated patients with ovarian cancer. The regimen consisted of carboplatin (300 mg/m2) on day 1, followed by cisplatin (100 mg/m2) on day 2 every 4 weeks. RESULTS: A total of 81 cycles were administered (median, 4 cycles; range, 1-6 cycles); four patients experienced complete remission and three experienced clinical partial remissions. Limiting toxicities were thrombocytopenia, leukopenia, and ototoxicity. The mean (+/- standard deviation [SD]) carboplatin and cisplatin dose intensities (DI) reached during the first four cycles of therapy were 58 mg/m2/week (+/- 18 mg/m2/week) and 21 mg/m2/week (+/- 7 mg/m2/week), respectively, which corresponded closely to the projected DI of 75 and 25 mg/m2/week, respectively. Based on the equivalence ratio of 4:1, the DI of carboplatin has been converted into the respective cisplatin DI, resulting in a total DI estimate. The overall DI of 37 mg/m2/week (+/- 14 mg/m2/week) was close to the projected one of 44 mg/m2/week. CONCLUSIONS: Combining cisplatin with carboplatin was found to represent a feasible and efficacious therapeutic strategy for increasing platinum dose intensity.

Anemia↗

PubMed1993

Gastric emptying of solids and liquids in obesity.

The purpose of this study was to determine whether obese patients have different rates of solid and liquid gastric emptying compared to healthy controls. Twenty-four obese patients (7 males, 17 females) were investigated prior to dietary restriction. The patients had a weight excess above ideal weight ranging from 25% to 216% (mean weight 118.1 +/- 6.5 kg). The control group consisted of 8 healthy subjects (4 males, 4 females), within 10% of the ideal weight. The solid phase of the test meal consisted of 40 g bread, 30 g ham, 10 g margarine, and two scrambled eggs labeled with 99mTc. For the liquid phase, 200 ml orange juice was labeled with 201Tl. Three-minute counts of both tracers were taken for 106 min using a large field-of-view gamma camera. In obese patients, a significantly shortened lag phase for the emptying of solids was observed (27.0 +/- 3.3 versus 38.4 +/- 4.1 min; P < 0.05). Half-emptying time (105.9 +/- 6.7 versus 100.7 +/- 5.7 min), emptying rate (0.60 +/- 0.04 versus 0.71 +/- 0.07%/min), and total emptying of solids (49.4 +/- 3.6 versus 50.5 +/- 5.0%) were not different from controls. Obese subjects had a trend to slowed liquid emptying (half-time 82.7 +/- 4.8 versus 69.9 +/- 6.9 min; emptying rate 0.59 +/- 0.03 versus 0.65 +/- 0.03%/min; total emptying 59.8 +/- 2.9 versus 66.0 +/- 3.3%), but this was not statistically significant. There was no correlation between weight or body surface area and rate of solid or liquid gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Etoposide and carboplatin as salvage and first-line therapy in ovarian cancer patients.

BACKGROUND: The agents etoposide and carboplatin are active against ovarian cancer and display synergistic anti-tumor activity in animal tumor models. The objective of these two phase II trials was to determine the efficacy and toxicity of the combination of etoposide with carboplatin in previously treated and untreated patients with ovarian cancer. PATIENTS AND METHODS: Etoposide (100 mg/m2) was administered as a one-hour infusion on three consecutive days and carboplatin (400 mg/m2) as a 30-minute infusion on day 2 of each monthly scheduled cycle. In 20 patients, previously treated with cisplatin-containing regimens, a total of 102 cycles was applied as salvage therapy (ST) and in 27 patients, a total of 168 cycles as first-line therapy (FLT). RESULTS: ST yielded 2 complete remissions (CR) and one partial remission (PR); in 7 patients, no evidence of disease (NED) and in 6 patients, no change (NC) were observed. The progression-free intervals (PFI) lasted a median 7.0 months (range < 2-14 months). FLT resulted in 7 CR (4 of them pathologically (p) verified), 11 NED (1 pNED), 3 PR (1 pPR) and 6 NC. The objective response rate was 63% (95% confidence interval: 36-89%). PFI lasted a median 8.0 months (range 3-25+ months); median survival had not been reached at the time of evaluation. Thrombocytopenia (WHO grade 4) was the limiting toxicity. CONCLUSIONS: Although not fulfilling the expectations of synergistic activity as shown in preclinical models, the combination of etoposide with carboplatin is an active and feasible therapy regimen in the out-patient management of ovarian cancer.

Adult↗

PubMed1993

Differential modulation of epidermal keratinization in immortalized (HaCaT) and tumorigenic human skin keratinocytes (HaCaT-ras) by retinoic acid and extracellular Ca2+.

The growth and differentiation response to retinoic acid (RA) was studied in the human keratinocyte line HaCaT and tumorigenic clones transfected with c-Ha-ras oncogene (HaCaT-ras). Differentiation (mainly keratin synthesis) was evaluated and correlated to cell proliferation in vitro but also growth behaviour in vivo (tumorigenicity). Comparable to normal keratinocytes, HaCaT cells and ras clones showed increased expression of the epidermal suprabasal keratins K1 and K10 upon RA depletion of the media (delipidized serum), while simple epithelial type keratins K7, K8 and K18 as well as K19 and K13 (typical of internal stratified epithelia) were almost completely suppressed. The cell density-dependent increase of K1 and K10 at intermediate RA levels (as in regular media with untreated serum) was also observed at Ca2+ levels below 0.1 mM, thus being clearly unrelated to stratification, whereas K13 synthesis was Ca(2+)-dependent and initiated with stratification. The effects on keratins were fully reversed by increasing RA concentrations. There was only mild stimulation of proliferation at RA doses (10(-10) to 10(-8) M) not directly corresponding to suppression of keratinization. Thus, the negative RA influence on K1 and K10, opposed to the effect on simple keratins, substantiates the preserved regulatory capacity rendering these cells appropriate models for biological testing. Among the various tumorigenic HaCaT-ras clones highly and moderately differentiating ones could be distinguished, accordingly induction in vitro led to a comparable spectrum of differentiation markers (K1 and K10 appearing early, and filaggrin late) as growth in vivo. These in vitro results demonstrate that, in spite of some differences in RA sensitivity, virtually all clones possess the epidermal differentiation repertoir which is regulated according to the same principles. Finally, this confirms our in vivo data that differentiation potential is not inversely related to the state of transformation or tumorigenicity.

Calcium↗

PubMed1993

Primary leiomyosarcoma of the liver--a case report.

This is the 17th report on primary leiomyosarcoma of the liver in world literature. In 1980, a 69-year old white female patient was admitted with pain in the right upper abdomen and loss of weight of 12 kg. Increased blood sedimentation rate, elevated serum markers of the liver and ultrasound evolved a big tumor of the right liver without extrahepatic tumor nodules. Right hemihepatectomy was undertaken, the tumor was completely resected. After histologic examinations, leiomyosarcoma of the liver with 1 mitosis per 10 high power fields was diagnosed. 10 years later, the patient was readmitted with symptoms of pain, tiredness and night sweat. At this time, 3 intrahepatic and 1 retroperitoneal tumor nodules were detected. A sure-cut needle biopsy revealed the recurrent leiomyosarcoma with 4 mitoses per 10 high power fields. The survival period of 10+ years is the longest of all 17 patients with primary hepatic leiomyosarcoma reported so far. The low rate of mitoses per high power field and primary surgical resection are considered the reasons for the long survival period.

Aged↗

PubMed1993

Identification of Azospirillum species by RFLP and pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) was applied to analyse the restriction fragment length polymorphism of Azospirillum brasilense and Azospirillum lipoferum strains. Genomic DNA was digested by rarely cutting restriction enzymes and subjected to PFGE using the Rotaphor system. The restrictions with SpeI produced 10-20 fragments with sizes from about 10 kb to 900 kb. The separation resulted in a strain-specific banding pattern in almost every case. After Southern blotting and hybridization with 23S rRNA gene probes, the species could be determined. With the combination of both methods, identification of re-isolates from soil at the species and strain level is possible.

Azospirillum↗

PubMed1992

Prevalence of antibodies to hepatitis C virus in patients with hepatocellular carcinoma in Austria.

In 12 of 54 (22%) patients with histologically verified hepatocellular carcinoma, antibodies to hepatitis C virus were found. In patients with hepatocellular carcinoma the frequency of anti-hepatitis C virus positivity was similar whether cirrhosis (6 of 22 patients (27%)) was present or not (2 of 15 (13%)). Out of 54, 23 patients (43%) were negative both for hepatitis B or C markers. Out of 53, 22 (42%) had positive hepatitis B markers, 8 of 22 were HBsAg positive. Patients with hepatocellular carcinoma and cirrhosis had a higher percentage of hepatitis B virus markers than patients with cirrhosis without hepatocellular carcinoma. Our of 70 patients with cirrhosis but without hepatocellular carcinoma, 24 (34%) had antibodies to hepatitis C virus. Our data of similar frequencies of antibodies to hepatitis C virus in patients with hepatocellular carcinoma or with liver cirrhosis but without hepatocellular carcinoma indicate that at least in Austrian patients, hepatitis C virus infections are not an important factor for development of hepatocellular carcinoma.

Adolescent↗

PubMed1992

The REV2 gene of Saccharomyces cerevisiae: cloning and DNA sequence.

The REV2 gene of Saccharomyces cerevisiae was cloned and sequenced; it contains an open reading frame of 1986 bp with a coding potential of 662 amino acids. Interruption of the chromosomal REV2 gene by integrating the URA3 gene coupled with partial deletion of the 3' terminal region produced viable haploid rev2 delta mutants. This indicates that the REV2 gene is non-essential for growth. The rev2 delta mutant is slightly more UV-sensitive than strains carrying various rev2 alleles (rev2-1, rev2x, rad5-1, rad5-8). The putative Rev2 protein is probably a globular protein containing a highly conserved nucleotide-binding site and two zinc-finger domains.

Amino Acid Sequence↗

PubMed1992

MACOP-B treatment in patients with Ki-1-positive large-cell anaplastic lymphoma.

Nine adult patients with Ki-1-positive large-cell anaplastic lymphoma were treated with MACOP-B. Two suffered from relapsed disease and had previously received chemotherapy; a third patient had received a single dose of 100 mg/m2 cisplatin before initiation of MACOP-B. The stage of lymphoma was determined according to the Ann Arbor Conference criteria and was II in one, III in two and IV in six patients. All patients had constitutional symptoms. Five patients had achieved complete remission 4 weeks after termination of the protocol and there were two partial remissions. One patient died of massive pulmonary embolism during the 4th week of treatment; another patient, who had received MACOP-B as salvage therapy, died of progressive lymphoma 1 month after completion of the regimen. Maximal observed toxicities according to WHO were mucositis grade 3 (n = 3) and there were three cases with thromboembolic complications, including a fatal pulmonary embolism in a young patient. However, MACOP-B appears an effective, fairly well-tolerated and feasible therapy for patients with Ki-1-positive large-cell anaplastic lymphoma.

Adult↗

PubMed1992

[Differential prognosis of patients with breast cancer with pleuritis carcinomatosa and with pulmonary lymphangiosis carcinomatosa].

The retrospective analysis of 672 consecutive patients with breast cancer revealed malignant pleural effusion and lymphangitic carcinomatosis of the lung to be the sites of first relapse of the disease in only 2% and 1%, respectively. In half of the 10 patients with malignant pleural effusions evaluable for survival, generalization of the disease was recorded at 51 months (range 0-197 months); the corresponding data for patients with lymphangitic carcinomatosis of the lung (n = 7) were 19 months (range 9-44 months). This difference was statistically significant (p < 0.05). The median survival of patients with pleural effusions and with lymphangitic carcinomatosis of the lung was 22 and 8 months, respectively (n.s.).

Adult↗

PubMed1991

[5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma].

17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗