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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 55 records · Page 3Linked to original sources
PubMed2000

Plutonium(IV) sequestration: structural and thermodynamic evaluation of the extraordinarily stable cerium(IV) hydroxypyridinonate complexes.

Ligands containing the 1-methyl-3-hydroxy-2(1H)-pyridinone group (Me-3,2-HOPO) are powerful plutonium(IV) sequestering agents. The Ce(IV) complexes of bidentate and tetradentate HOPO ligands have been quantitatively studied as models for this sequestration. The complexes Ce(L1)4, Ce(L2)4, Ce(L3)2, and Ce(L4)2 (L1 = Me-3,2-HOPO; L2 = PR-Me-3,2-HOPO; L3 = 5LI-Me-3,2-HOPO; L4 = 5LIO-Me-3,2-HOPO) were prepared in THF solution from Ce(acac)4 and the corresponding ligand. The complex Ce(L4)2 was also prepared in aqueous solution by air oxidation of the Ce(III) complex [Ce(L4)2]-. Single-crystal X-ray diffraction analyses are reported for Ce(L1)(4)x2CHCl3 [P1 (no. 2), Z = 2, a = 9.2604(2) A, b = 12.1992(2) A, c = 15.9400(2) A, alpha = 73.732(1) degrees, beta = 85.041(1) degrees, gamma = 74.454(1) degrees], Ce(L3)2x2CH3OH [P2(1)/c (no. 14), Z = 4, a = 11.7002(2) A, b = 23.0033(4) A, c = 15.7155(2) A, beta = 96.149(1) degrees], Ce(L4)(2).2CH3OH [P1 (no. 2), Z = 2, a = 11.4347(2) A, b = 13.8008(2) A, c = 15.2844(3) A, alpha = 101.554(1) degrees, beta = 105.691(1) degrees, gamma = 106.746(1) degrees], and Ce(L4)2x4H2O [P2(1)/c (no. 14), Z = 4, a = 11.8782(1) A, b = 22.6860(3) A, c = 15.2638(1) A, beta = 96.956(1) degrees]. A new criterion, the shape measure S, has been introduced to describe and compare the geometry of such complexes. It is defined as [formula: see text], where m is the number of edges, delta i is the observed dihedral angle along the ith edge of delta (angle between normals of adjacent faces), theta i is the same angle of the corresponding ideal polytopal shape theta, and min is the minimum of all possible values. For these complexes the shape measure shows that the coordination geometry is strongly influenced by small changes in the ligand backbone or solvent. Solution thermodynamic studies determined overall formation constants (log beta) for Ce(L2)4, Ce(L3)2, and Ce(L4)2 of 40.9, 41.9, and 41.6, respectively. A thermodynamic cycle has been used to calculate these values from the corresponding formation constants of Ce(III) complexes and standard electrode potentials. From the formation constants and from the protonation constants of the ligands, extraordinarily high pM values for Ce(IV) are generated by these tetradentate ligands (37.5 for Ce(L3)2 and 37.0 for Ce(L4)2). The corresponding constants for Pu(IV) are expected to be substantially the same.

Crystallography, X-Ray↗
PubMed2000

ATP for the DNA ligation step in base excision repair is generated from poly(ADP-ribose).

In mammalian cells, the base excision repair (BER) pathway is the main route to counteract the mutagenic effects of DNA lesions. DNA nicks induce, among others, DNA polymerase activities and the synthesis of poly(ADP-ribose). It is shown here that poly(ADP-ribose) serves as an energy source for the final and rate-limiting step of BER, DNA ligation. This conclusion was drawn from experiments in which the fate of [(32)P]poly(ADP-ribose) or [(32)P]NAD added to HeLa nuclear extracts was systematically followed. ATP was synthesized from poly(ADP-ribose) in a pathway that strictly depended on nick-induced DNA synthesis. NAD was used for the synthesis of poly(ADP-ribose), which, in turn, was converted to ATP by pyrophosphorylytic cleavage utilizing the pyrophosphate generated from dNTPs during DNA synthesis. The adenylyl moiety was then preferentially used to adenylate DNA ligase III, from which it was transferred to the 5'-phosphoryl end of the nicked DNA. Finally, ligation to the 3'-OH end resulted in the release of AMP. When using NAD, but not poly(ADP-ribose), in the presence of 3-aminobenzamide, the entire process was blocked, confirming poly(ADP-ribosyl)ation to be the essential initial step. Thus, poly(ADP-ribose) polymerase-1, DNA polymerase beta, and ligase III interact with x-ray repair cross-complementing protein-1 within the BER complex, which ensures that ATP is generated and specifically used for DNA ligation.

Adenosine Triphosphate↗
PubMed2000

[Postpartum risk factors in the development of children born to opiate-addicted mothers; comparison between mothers with and without methadone substitution].

In a retrospective case control study at the University of Frankfurt, Germany, 101 babies born to opiate-addicted mothers were identified from birth charts from 1988 to 1995. After birth, they developed a withdrawal syndrome (neonatal abstinence syndrome). Fifty control infants and their mothers were selected from neonatal wards. The group of opiate-exposed babies was subdivided into a group born to mothers without methadone treatment (n = 48) and a group born to mothers who were enrolled in a methadone program (n = 51). The methadone infants had a significantly higher mean birth weight (2822 g) than children in the group without methadone (2471 g). The abstinence syndrome was much more intense in the methadone group (convulsions 47.1%) than in heroin-exposed babies without methadone treatment (convulsions 27.1%). Women in methadone maintenance programs lived in more stable socioeconomic conditions than opiate-addicted women without methadone substitution. Moreover, they cared significantly better for their babies: 81.3% of the methadone mothers visited their children on a regular basis and 90.9% cared adequately. The data emphasize the need in future research to look more closely at the role of methadone treatment programs in the development of opiate-exposed babies.

Adult↗
PubMed2000

[Value of ultrasound in early diagnosis of renal cell carcinoma].

The importance of ultrasonography in early detection of renal cell carcinoma was analyzed for 1854 patients, who were operated from 1975 to 1997. The 5-year survival rate of all patients amounts to 75%, the 10- and 20-year survival rate was 68% and 64%. While from 1975 to 1986 tumor symptoms like hematuria (30%), abdominal pain (19%) and palpable mass (3%) lead to diagnosis of renal cell carcinoma in 56% of all cases, there were only 26% from 1987 to 1997. 83% of asymptomatical tumors from 1987 to 1997 were accidentally detected by means of ultrasonography in a kidney independent examination. These tumors are significantly smaller (5.5 cm) than the tumors of symptomatical patients (7.8 cm) and show often a significantly lower local tumor stage, a better tumor grade, frequently lymph nodes, which are free of tumor infiltration and more rarely distant metastasis. The 5-year survival rate of patients with incidental tumors, detected by ultrasonography (82%) was significantly better (log rank < 0.001) in comparison with the symptomatical patients (72%). These results verify 1. The effectivity of ultrasonography in early diagnosis of renal cell carcinoma and 2. The advantage of survival on patients with early tumor detection. That's why asymptomatic patients, who selected under risk factors should be examinated by ultrasonography consistently too.

Adolescent↗
PubMed2000

[Pathogenetic and clinical aspects of low estradiol level in the man].

To elucidate a possible role of low estradiol (E2) levels in blood serum of men, normal values were determined in 91 healthy men (age 20-75 years), classified as high or low complaint-index due to a psychological questionnaire. Statistical analysis gave no correlation of estradiol levels to age or complaint index in normal men whereas testosterone (T) could be significantly correlated to complaint-index (p < 0.01) and free testosterone (fT) could be significantly correlated to age (p < 0.001) and complaint-index (p < 0.01). T and E2 were determined in 1370 clinical patients with various urological diseases, T, fT and E2 in 1261 ambulant patients. In 72/1370 (5.2%) and 76/1261 (6%) patients, low E2-levels (< 10 pg/ml) were found in blood serum. In 56/76 (74%) patients with low E2-levels, T or fT was simultaneously low. Isolated low E2-levels were found in 20/1261 (1.6%) patients. In clinical patients, no special urological disease correlated to low E2-levels. Due to these results, low E2 levels in men are in most cases the result of low testosteron levels. The adequate hormonal treatment in men is therefore the replacement of testosteron. Substitution of E2 in men is at that time an experimental therapy, that is limited on selected cases.

Adult↗
PubMed2000

Regulation of renal artery smooth muscle tone by alpha1-adrenoceptors: role of voltage-gated calcium channels and intracellular calcium stores.

The ischemia induced vasospasm of the renal arterial blood vessels mediated by alpha1-adrenoceptors is of importance for the loss of kidney function. This is based on reduced perfusion of the kidney cortex occurring in kidney transplant and organ preserving surgery. The present study considered the intracellular mechanism of the norepinephrine (NE) induced renal artery vasospasm by using swine renal artery smooth muscle ring. Norepinephrine and phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM (n = 7) and 10 nM (n = 4), and an EC50 of 0.3 microM and 1 microM, respectively. The receptor was identified as alpha1A-subtype. The contraction was completely inhibited by verapamil (IC50 = 1.51 microM; n = 11) and diltiazem (IC50 = 9.49 microM; n = 8) and 85% by nifedipine (IC50 = 0.13 microM; n = 21). Blockade of the intracellular inositol- 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store by thapsigargin (1 microM, n = 7) or suppression of Ca2+ release from the intracellular Ca2+-sensitive Ca2+ store by ryanodine (100 microM, n = 4) inhibited the PE induced contraction by 39.5% and 47.6%, respectively. The results suggest a key role of voltage-dependent Ca2+ channels and intracellular Ca2+ stores in the alpha1A-adrenoceptor induced contraction of the renal artery.

Adrenergic alpha-Agonists↗
PubMed2000

New functions of a long-known molecule. Emerging roles of NAD in cellular signaling.

Over the past decades, the pyridine nucleotides have been established as important molecules in signaling pathways, besides their well known function in energy transduction. Similarly to another molecule carrying such dual functions, ATP, NAD(P)+ may serve as substrate for covalent protein modification or as precursor of biologically active compounds. Protein modification is catalyzed by ADP-ribosyl transferases that attach the ADP-ribose moiety of NAD+ to specific amino-acid residues of the acceptor proteins. For a number of ADP ribosylation reactions the specific transferases and their target proteins have been identified. As a result of the modification, the biological activity of the acceptor proteins may be severely changed. The cell nucleus contains enzymes catalyzing the transfer of ADP-ribose polymers (polyADP-ribose) onto the acceptor proteins. The best known enzyme of this type is poly(ADP-ribose) polymerase 1 (PARP1), which has been implicated in the regulation of several important processes including DNA repair, transcription, apoptosis, neoplastic transformation and others. The second group of reactions leads to the synthesis of an unusual cyclic nucleotide, cyclic ADP-ribose (cADPR). Moreover, the enzymes catalyzing this reaction may also replace the nicotinamide of NADP+ by nicotinic acid resulting in the synthesis of nicotinic acid adenine dinucleotide phosphate (NAADP+). Both cADPR and NAADP+ have been reported to be potent intracellular calcium-mobilizing agents. In concert with inositol 1,4,5-trisphosphate, they participate in cytosolic calcium regulation by releasing calcium from intracellular stores.

Adenosine Diphosphate↗
PubMed2000

Diagnosis of nonpalpable testes in childhood: comparison of magnetic resonance imaging and laparoscopy in a prospective study.

In a prospective study, the accuracy of magnetic resonance imaging (MRI) and laparoscopy in the diagnosis of nonpalpable testes was evaluated. Advantages and disadvantages of the two procedures were compared. 29 boys with unilateral nonpalpable testis underwent MRI. When MRI failed to demonstrate a testis, laparoscopy with a 1.9 mm mini-laparoscope was performed. All cases were verified by operative exploration of the inguinal region. MRI demonstrated 10 inguinal and 7 abdominal testes. MRI revealed no testis in 12 boys. The false positive rate was 32%, correct negative findings were confirmed in four patients. When laparoscopy was performed, preservable testis could be demonstrated in 8 of 12 patients (1 abdominal, 7 inguinal) which otherwise were not visible on MRI. The correct positive rate was 100%. We encountered no complications with laparoscopy. In summary, laparoscopic evaluation is recommended as the preferable method in pediatric cases of nonpalpable testes.

Adolescent↗
PubMed2000

Reliability of nocturnal blood pressure dipping.

BACKGROUND: Increasing evidence documents the fact that individuals whose blood pressure drops or 'dips' relatively little at night have a higher risk of numerous cardiovascular illnesses. OBJECTIVE: To examine the reliability of various measures of nocturnal blood pressure dipping. METHODS: This study examined 17 individuals with ambulatory blood pressure monitoring on three 24 h recordings while they pursued a schedule similar to that of in-patients on a clinical research unit. Nocturnal dipping of blood pressure was scored three ways: as the drop in blood pressure between 10 p.m. and 6 a.m. ('clocktime'), as the drop in blood pressure tailored to each individual's reported bedtime ('bedtime'), and as the drop in blood pressure accompanying polysomnographically verified sleep ('sleeptime'). RESULTS: Adequate reliability was obtained for all three measures of dipping. There was, in general, a significant correlation across testing occasions (P<0.05). The correlation coefficient ranged from 0.5 to 0.8, depending on which criterion of dipping was selected and whether the endpoint was systolic blood pressure, diastolic blood pressure, or mean arterial blood pressure. CONCLUSIONS: The reliability of systolic blood pressure dipping was somewhat lower than that of diastolic or mean arterial blood pressure dipping. Dipping appears to be a reliable construct. While no one definition of dipping was demonstrably better than another, the most sensible definition of dipping would allow some adjustment for defining 'night' on the basis of each individual's idiosyncratic bed time.

Adult↗
PubMed2000

[Retrospect and prospects of surgical quality assurance in Germany].

Quality in health can not be reached by sanctions or checks--as experiences show also in other fields. Improvement can be achieved only by a quality philosophy. Qualified and international used tools are the ISO 9000 and EFQM model, even if the application in the health sector requires adaptations.

Forecasting↗
PubMed1999

Insect immune activation by recombinant Galleria mellonella apolipophorin III(1).

Apolipophorin III (apoLp-III) is an exchangeable insect apolipoprotein. Its function, as currently understood, lies in the stabilization of low-density lipophorin particles (LDLp) crossing the hemocoel in phases of high energy consumption to deliver lipids from the fat body to the flight muscle cells. Recent studies with native Galleria mellonella-apoLp-III gave first indications of an unexpected role of that protein in insect immune activation. Here we report the immune activation by the recombinant protein, documenting a newly discovered correlation between lipid physiology and immune defense in insects. The complete cDNA sequence of G. mellonella-apoLp-III was identified by mixed oligonucleotide-primed amplification of cDNA (MOPAC), 3'-RACE-PCR, and cRACE-PCR. The sequence coding for the native protein was ligated into a pET-vector; this construct was transfected into Escherichia coli and overexpressed in the bacteria. Photometric turbidity assays with human low density lipoprotein (LDL) and transmission electron microscopy studies on apoLp-III-stabilized lipid discs revealed the full functionality of the isolated recombinant apoLp-III with regard to its lipid-association ability. For proving its immune-stimulating capacity, apoLp-III was injected into the hemocoel of last instar G. mellonella larvae and the antibacterial activity in cell-free hemolymph was determined 24 h later. As a result, the hemolymph samples of injected insects contained strongly increased antibacterial activities against E. coli as well as clearly enhanced lysozyme-like activities. From Northern blot analysis of total RNA from insects injected with apoLp-III or the bacterial immune provocator lipopolysaccharide, it could be concluded that the transcription rate of apoLp-III mRNA does not vary in comparison to untreated last instar larvae.

Amino Acid Sequence↗
PubMed1999

Functional interaction of poly(ADP-ribose) with the 20S proteasome in vitro.

The nuclear enzyme poly(ADP-ribosyl) transferase (pADPRT) catalyzes the formation of poly(ADP-ribose) from NAD+. Several nuclear proteins and pADPRT itself are targets for the modification by poly(ADP-ribosyl)ation. It is demonstrated here that poly(ADP-ribose) or pADPRT automodified with poly(ADP-ribose) interacts noncovalently with the 20S proteasome in vitro. The interaction of pADPRT with the 20S proteasome requires the long ADP-ribose polymers formed by automodification of the pADPRT with poly(ADP-ribose). As a result pADPRT automodified with short ADP-ribose oligomers is unable to associate with the 20S proteasome. The interaction with poly(ADP-ribose) causes a specific stimulation of the peptidase activity of the 20S proteasome. Modified pADPRT does not serve as a substrate for the degradation by the 20S proteasome. No covalent modification of the 20S proteasome by ADP-ribosylation was observed. The results may point to a functional relationship between pADPRT and the 20S proteasome in a pathway protecting the cell from oxidative damage.

Cysteine Endopeptidases↗
PubMed1999

Stimulation of the catalytic activity of poly(ADP-ribosyl) transferase by transcription factor Yin Yang 1.

The transcriptional regulator Yin Yang 1 (YY1) has previously been demonstrated to physically interact with poly(ADP-ribosyl) transferase (ADPRT). This nuclear enzyme catalyzes the synthesis of ADP-ribose polymers and their attachment to target proteins. It is reported here that YY1 associates preferably with the extensively auto(ADP-ribosyl)ated form of ADPRT, but not with deproteinized ADP-ribose polymers. In the presence of YY1 the catalytic rate of ADPRT is enhanced about 10-fold. This stimulation is in part due to modification of YY1, thus serving as a substrate of the reaction. In addition, automodification of ADPRT is also substantially increased. The activation by YY1 is most pronounced at low concentrations of ADPRT suggesting that the presence of YY1 may either facilitate the formation of catalytically active dimers of ADPRT or lead to the occurrence of active heterooligomers. The potential significance of these observations was verified by analyzing the activity of ADPRT in HeLa nuclear extracts. The endogenous enzyme exhibited an about 10-fold higher activity as compared to the isolated recombinant protein. It is likely that the heat-stable transcription factor YY1 contributed to the increased activity of ADPRT detected in the nuclear extracts, because heated extracts had a similar stimulatory effect on isolated ADPRT as isolated YY1 used at comparable concentrations. It is concluded that YY1 may be an important regulator of ADPRT and, therefore, could support the function of ADPRT to facilitate DNA repair.

Cell Nucleus↗
PubMed1999

A randomized, double-blind study of a skin patch of a dopaminergic agonist, piribedil, in Parkinson's disease.

This randomized, double-blind trial was designed to evaluate the efficacy of a transdermal system of piribedil on the motor symptoms of Parkinson's disease during 3 weeks of treatment administered to three different groups: placebo, one piribedil patch (1 PP), and two (2 PP) piribedil patches. Twenty-seven patients with idiopathic Parkinson's disease, treated with L-dopa but not sufficiently controlled, were included in this trial. The test treatment did not demonstrate any clinical efficacy on either the main end point (Unified Parkinson's Disease Rating Scale motor score) or the secondary end points (rigidity, bradykinesia, postural, and resting tremor scores). The main adverse events were nausea (11%), vomiting (7.4%), and malaise (7.4%) mainly observed in the placebo group (four of seven patients). The local acceptability of the transdermal system was good. Plasma piribedil concentrations at the end of treatment were 6.74+/-1.10 and 9.31+/-3.33 ng/mL in the 1 PP and 2 PP groups, respectively. These plasma levels could account for the lack of clinical efficacy, because a previous pharmacokinetics-PD study conducted in parkinsonian patients and treated with the intravenous route demonstrated that the critical limits of activity on tremor were between 10 and 30 ng/mL.

Administration, Cutaneous↗
PubMed1999

Karlsburg Type I diabetes risk study of a general population: frequencies and interactions of the four major Type I diabetes-associated autoantibodies studied in 9419 schoolchildren.

AIMS/HYPOTHESIS: The Karlsburg Type I (insulin-dependent) diabetes risk study on schoolchildren aims to evaluate the predictive diagnostic value of diabetes-associated autoantibodies in the general population. METHODS: We took capillary serum from 9419 schoolchildren, aged 6-17 years, for testing of autoantibodies (AAbs) to glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA2A) and insulin (IAA) by 125I-antigen binding. We also tested for autoantibodies to cytoplasmic islet cell antigens (ICA) immunohistochemically. RESULTS: By testing of 9419 sera for the four AAbs at cut-off at or greater than the 98th centile for the radioassayed AAbs and at or greater than 10 Juvenile Diabetes Foundation (JDF) units for ICA, 8.1% of schoolchildren had at least one AAb. We found that 3.04, 2.97, 2.35, and 0.86% had IAA, GADA, IA2A or ICA, respectively. 7.3% had only one AAb and 0.8% (75) had two or more AAbs, reflecting a risk to develop diabetes. Thus, by primary screening by combined testing of GADA and IA2A, 98.7% (74/75) would be identified. At high AAb levels, cut-off at or greater than the 99.8th centile and at or greater than 40 JDF units for ICA, 0.23% (22/9419) of schoolchildren, similar to the disease prevalence of 0.3%, had two or more AAbs. Ten of 17 children tested had reduced (p < 0.001) first-phase insulin secretion by intravenous glucose tolerance test. Six of 22 subjects developed Type I diabetes within a follow-up of 19 +/- 10 months. CONCLUSION/INTERPRETATION: For children older than 5 years the combined anti-GAD/IA2 test with cut-off at or greater than the 98th centile should be used for primary screening followed by testing for IAA and ICA. Subjects at risk for diabetes have two or more AAbs at or greater than the 98th centile. Subjects at risk for rapid progression to Type I diabetes have two or more AAbs at or greater than the 99.8th centile.

Adolescent↗
PubMed1999

Treatment of erectile dysfunction with external vacuum devices.

In a retrospective study, the medical and psychological outcome of the use of external vacuum devices in the treatment of erectile dysfunction in 190 patients was evaluated, using a questionnaire and a clinical examination. 110/190 patients (57.8%) answered the questionnaire. 22/110 patients (20%) rejected the device primarily and 34/110 (30.9%) after a period of up to 16 weeks (primary rejection rate 50.9%). A secondary drop-out rate of 8/110 (7.3%) was observed after an intermediate time of 10.5 months. 46/110 (41.8%) patients were long-term users (median 27.6 months, range 7-70 months). Long-term users were mainly patients who did not respond to intracavernosal pharmacotherapy. In the group of long-term users, 98% of patients and 85% of their partners were satisfied with the vacuum therapy. Complications were minor (hematoma 9.8%; skin injury 2.2%), 69.8% of long-term users never had problems with the device. 74% of users reported regular orgasm. Vacuum therapy is a safe and effective non-invasive treatment of erectile dysfunction with a limited primary acceptance and low drop-out rates in long-term follow-ups.

Adult↗