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P Leitner

Publications and source records attributed to P Leitner.

10 recordsLinked to original sources
PubMed2006

The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations.

BACKGROUND: Parkinson's disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson's disease in sibships from North America. OBJECTIVE: To make a thorough assessment of the SPR gene region in sporadic Parkinson's disease. METHODS: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson's disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. RESULTS: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson's disease affection status (p-value 0.004). CONCLUSIONS: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson's disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson's disease.

Age of Onset↗
PubMed1996

Natural-product inhibitors of human DNA ligase I.

Enzymatic activity mediated by recombinant human DNA ligase I (hLI), in conjunction with tannin removal procedures, has been applied to a natural-product screen involving approximately 1000 plant extracts and various pure compounds. The primary hLI activity assay involved the measurement of the amount of radiolabelled phosphate in a synthetic nucleic acid hybrid that becomes resistant to alkaline phosphatase as a result of ligation. A bioactivity-guided fractionation scheme resulted in the isolation of ursolic [IC50=100 micrograms/ml (216 microM)] and oleanolic [IC50=100 micrograms/ml (216 microM)] acids from Tricalysia niamniamensis Hiern (Rubiaceae), which demonstrated similar DNA ligase inhibition profiles to other triterpenes such as aleuritolic acid. Protolichesterinic acid [IC50=6 micrograms/ml (20 microM)], swertifrancheside [IC50 = 8 micrograms/ml(11)microM)] and fulvoplumierin [IC50=87 micrograms/ml (357 microM)] represent three additional natural-product structural classes that inhibit hLI. Fagaronine chloride [IC50=10 micrograms/ml (27 micronM] and certain flavonoids are also among the pure natural products that were found to disrupt the activity of the enzyme, consistent with their nucleic acid intercalative properties. Further analyses revealed that some of the hLI-inhibitory compounds interfered with the initial adenylation step of the ligation reaction, indicating a direct interaction with the enzyme protein. However, in all cases, this enzyme-inhibitor interaction did not disrupt the DNA relaxation activity mediated by hLI. These results indicate that, although the same enzyme active site may be involved in both enzyme adenylation and DNA relaxation, inhibitors may exert allosteric effects by inducing conformational changes that disrupt only one of these activities. Studies with inhibitors are important for the assignment of specific cellular functions to these enzymes, as well as for their development into clinically useful antitumour agents.

Adenosine Triphosphate↗
PubMed1995

Rigid analogs of camptothecin as DNA topoisomerase I inhibitors.

Substituted 8-ethyl-2-(2-oxo-1,2-dihydroindol-3-ylidene)-8-hydroxy-2,3,5,8- tetrahydro-6-oxa-3a-azacyclopenta[b]naphthalene-1,4,7-triones were synthesized and evaluated as topoisomerase I inhibitors in an in vitro cleavable complex assay. The activity of these compounds may be attributed to their rigid, planar geometry, and an attempt was made to correlate the SAR in this series to known attributes of camptothecin.

Alkaloids↗
PubMed1993

Plant antitumor agents. 30. Synthesis and structure activity of novel camptothecin analogs.

A large number of camptothecin (CPT) analogs have been prepared in the 20S, 20RS, and 20R configurations with a number of ring A substituents. Topoisomerase I (T-I) inhibition data (IC50) have been obtained by standard procedures. In general, substitution at the 9 or 10 positions with amino, halogeno, or hydroxyl groups in compounds with 20S configuration results in compounds with enhanced T-I inhibition. Compounds in the 20RS configuration were less active in vitro and in vivo and those in the 20R configuration were inactive. Compounds with 10,11-methylenedioxy substitution on ring A displayed a marked increase in potency in the T-I inhibition assay. The activities of some of the analogs as determined in a variety of in vivo assays including the L-1210 mouse leukemia assay were, in general, in accord with T-I inhibition. A number of water-soluble analogs such as 20-glycinate esters, 9-glycinamides, or hydrolyzed lactone salts were prepared and tested in in vitro and in vivo assays. In general, these compounds were less active than CPT both in terms of T-I inhibition and life prolongation in the L-1210 assay. However, certain 20-glycinate esters showed good in vivo activity after iv administration.

Animals↗
PubMed1993

[The value of psychopharmacotherapy in the treatment of borderline personality disorder].

The interest in the psychopharmacological treatment of the borderline personality disorder (BPS) has been steadily increased in the last years. There isn't, however, any investigation, which has proved the existence of a specific "Anti-Borderline-Drug" yet. There are, however, identifiable drug-responsive syndromes. The description by Coccaro and Karoussi (1991) of a syndrome of affective instability (abnormalities in the brain's adrenergic and cholinergic systems, respond to carbamazepine and lithium), transient psychotic phenomena (abnormalities in the central dopaminergic systems, respond to low-dose neuroleptics) and impulsive, aggressive behaviour (abnormalities in the central serotonergic systems, respond to serotonergic agents) seems to be very promising in this regard.

Anti-Anxiety Agents↗
PubMed1986

[Treatment of atypical and neurotic depression].

Hitherto it has not been usual to talk in the German language about the therapy-oriented concept of two forms of the progress of atypical depression (Type A and Type V). The characteristic symptom of Type A is angst, together with phobias, physical complaints, etc. In Type V there are vegetative symptoms, often towards evening (Hypersomnia, difficulty in getting to sleep, increased appetite, increased weight, increased libido), accompanied by hysterical extrovert personality traits, and of intermittent occurrence. These clinical pictures are amenable to psychopharmalogical therapy. In conformity with the assumption of "somatic accommodation" treatment with antidepressives is recommended in the case neurotic depression, too, at least in the initial stages of treatment.

Antidepressive Agents↗