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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Efficiency of a portable B-scan ultrasound device in comparison to a high-end machine in abdominal ultrasound. Results of a pilot study].

AIM: To determine the comparative performance of a portable sonography device in abdominal ultrasound. METHOD: In the daily routine of abdominal ultrasound scanning, the portable device SonoSite was tested against the high-end machine ATL 5000 HDI by two examiners with more than 5 years of ultrasound experience. The examination was restricted to the B-scan with a hands-on scanning time of 10 minutes. Patients with unknown diagnoses were first examined with the SonoSite, and the findings and diagnoses documented. Consecutively, the examination was repeated using the ATL HDI 5000. Differing findings and diagnoses were documented in a written form. RESULTS: There were 62 identical results in 60 patients. The high-end device yielded 23 additional findings. Examination with the portable device did not allow a definite diagnosis in 4 more cases. This difference is statistically significant with a confidence interval of 95 %. CONCLUSION: Portable ultrasound devices are surprisingly effective in the hands of experienced examiners. Imaging quality is predictably inferior to so-called high-end devices. Nearly all acute and therapeutically relevant diagnoses and findings were registered, even though nearly a quarter of the findings diagnosed with the high-end device were overlooked. These findings were mostly clinically irrelevant or very small in size. As could be expected, problems arose with pathological findings requiring high resolution, i.e., liver metastases, tiny gallstones, appendicitis, Crohn's disease etc. These form a clear indication for a high-end ultrasound examination.

Abdomen↗
PubMed2003

De novo 9-break-event in one chromosome 21 combined with a microdeletion in 21q22.11 in a mentally retarded boy with short stature.

We report on a moderately mentally retarded 12-year-old boy of short stature showing the most complex chromosomal rearrangement (CCR) within a single chromosome ever described. A de novo derivative chromosome 21 was recognized in GTG-banding shortly after birth. However, the nature of the rearrangement remained obscure up to the application of the chromosome 21-specific centromere-near multicolor-FISH (subcenM-FISH) probe set and of six selected locus-specific probes along chromosome 21. An unbalanced 9-break-event was uncovered with breakpoints in 21p13, 21p13-->12, 21q11.2, 21q21.1, 21q22.11, 21q22.11, 21q22.12, 21q22.22 and 21q22.3. A deletion of 21q22.11 was detected by application of the BAC probe bk249H10. The karyotype can be described as 46,XY,der(21)(:p13-->p1213::q22.3-->q22.22:: q11.2-->p1213::q11.2-->q21.1::q22.11-->q21.1::q22.12--> q22.22::p13-->p13). The clinical signs can either be due to gene inactivation in connection with structural changes at the break and fusion regions, to the building of new fusion genes within the CCR and/or to the deletion of genes in 21q22.11.

Abnormalities, Multiple↗
PubMed2002

Involvement of cyclic nucleotides in renal artery smooth muscle relaxation.

The elevation of vascular smooth muscle tone in the renal arteries during kidney transplantation and nephron-sparing surgery plays a major role in postsurgical organ dysfunction. Therefore, a better understanding of the intracellular mechanisms of contraction and relaxation is of fundamental interest to improve urological treatment. The present study was designed to investigate the complex intracellular system of cyclic nucleotides involved in the regulation of smooth muscle relaxation by using swine renal artery rings in the Schuler organ bath. Phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM and an EC(50) of 804 nM. The receptor was identified as alpha(1A)-subtype by the selective antagonist WB4101. Increasing the intracellular concentration of cyclic 3':5'-adenosine monophosphate (cAMP) by dibutyryl-cAMP (5 mM) and forskolin (5 micro M) resulted in a decreased contractiltity of 48.0% and 76.3%, respectively. Elevation of the cytosolic content of cyclic 3':5'-guanosine monophosphate (cGMP) using dibutyryl-cGMP (1 mM), sodium nitroprusside (100 micro M) and SIN-1 (100 micro M) decreased the average PE-induced contraction by 16.4%, 41.9% and 62.4%, respectively. The unselective phosphodiesterase inhibitors theophylline (1 mM), papaverine (100 micro M) and IBMX (5 mM) reduced the PE-induced contraction by 37.3%, 93.1% and 95.5%, respectively. Furthermore, selective inhibition of phosphodiesterases by milrinone (PDE(3)-selective) resulted in a decreased contractility by 1.3% (50 micro M), 29.5% (100 micro M) and 93.5% (5 mM), and using rolipram (PDE(4) selective), the PE-induced contraction was inhibited by 57.9% (50 micro M) and 81.9% (100 micro M). The results suggest the involvement of cAMP and cGMP in the relaxation of renal artery smooth muscle cells. Moreover, phosphodiesterases, especially PDE(3) and PDE(4), seem to play a critical role in the regulation of renal artery smooth muscle tone.

Animals↗
PubMed2002

Immunogenicity of polymeric implants: long-term antibody response against polyester (Dacron) following the implantation of vascular prostheses into LEW.1A rats.

Implanted biomaterials trigger acute and chronic inflammatory responses directly correlated to the central role of phagocytic cells at the host-implant interface. This study was designed to evaluate specific humoral immune responses following repeated intraperitoneal implantations of collagen-impregnated polyester (Dacron) prosthetic segments into LEWIS rats. Serum antibody detection was performed by enzyme immunoassay with the prosthetic segments as a target. Cutoff values for antibody positivity were greater than or equal to the 99th percentile for control rats. Polymer immunoglobiulin G (IgG) antibodies were significantly increased (p < 0.05) by repeated implantation and were subsequently followed until experimental day 293. Antibody formation was significantly enhanced through the application of complete Freund's adjuvant in combination with the first implantation. All rats within this group were antibody-positive on day 53, but only 6 of 10 animals that received the prosthesis without the adjuvant were. After preincubation of sera with bovine collagen type I (solid phase adsorbed or in solution), polymer antibody binding was discovered not to be diminished, indicating that the IgG antibodies detected were not directed against the prosthesis impregnation. Furthermore, a significant correlation was obtained between polymer antibody binding to collagen-impregnated and nonimpregnated prostheses (r(s) = 0.797, p < 0.001). There was no substantiated correlation between antibody binding to polyester and to an irrelevant polymer (Tecoflex EG 80). We conclude that specific polymer antibodies may indeed provide an additional parameter for biocompatibility testing as well as a possible serological marker of an inflammatory response to implants.

Animals↗
PubMed2002

[Long-term outcome of conservative surgery for kidney cancer: survival, blood pressure, and renal function].

PURPOSE: Nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) remains controversial for elective indications (low stage RCC in the presence of a normal contralateral kidney). In this single center study survival rate and, as novel aspects, the frequency of postoperative arterial hypertension and renal function parameters were investigated to evaluate safety and efficacy of NSS. PATIENTS AND METHODS: The complete data of 248 patients operated nephron-sparing for RCC between 1975 and 1995 were evaluated. One hundred and seventy-five patients were treated for elective indication (95% with tumor stage T1 or T2), 73 patients for mandatory indication (bilateral tumors, solitary kidney, renal insufficiency). The mean follow-up was 75 months (maximum 23 years). RESULTS: Mean tumor-size was lower under elective (3.8 cm) than under mandatory (4.7 cm) indication. Overall tumor-specific survival after 5 years for both indications was 88%. Comparing preoperative vs. follow-up values, arterial blood pressure and serum-creatinine values remained unchanged for both indications. The incidence of postoperative proteinuria (19% imperative, 11% elective indication) was strongly related to hypertension. CONCLUSIONS: NSS for RCC under elective indication achieves patient survival comparable to the results of radical nephrectomy. The presented data do not indicate significant longterm complications such as arterial hypertension, proteinuria or deterioration of renal function as a result of glomerulosclerosis or hyperfiltration. This gives further argument for the concept of NSS in RCC as an alternative to radical nephrectomy in the presence of a healthy contralateral kidney.

Blood Pressure↗
PubMed2002

[Validation of the French language version of the Parkinson's Disease Questionnaire - PDQ-39].

After Alzheimer's disease, Parkinson's disease (PD) is the second most frequent degenerative disease of the central nervous system. The consequences of PD at the functional, social and emotional levels warrant a better understanding the patient's perceptions as measured using a specific instrument rather than restricting the medical approach to the clinical evaluation of the motor component. In 1996, we began implementation of a project to transculturally validate the single specific instrument that had been published and was available at that time: PDQ-39. The scale consists in a 39-item questionnaire enabling determination of an overall quality-of-life score and scores for 8 specific dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort. Eighty-nine patients taking part in an open-label study of the safety of a combination of pergolide and dopa therapy were included and followed up on D15 and after 8 weeks. The process of "Forward-Backward" translation, conducted in close liaison with the authors, enabled semantic and linguistic validation of the French language version. The content was validated by PD experts. At baseline, the patients presented quality-of-life scores that were particularly impaired for the dimensions exploring Mobility, Emotional well-being and Bodily discomfort. The main metric properties of the scale were confirmed. The PDQ-39 scores were closely correlated with the related concepts investigated by generic scale, SF-36. The PDQ-39 scores were correlated with the "Mental and Mood Status", "Everyday Activities" and "Motor Status" dimensions determined by the UPDRS. The reliability, expressed by Cronbach coefficients alpha, showed strong consistency of the instrument, very similar to the data for the original version. In contrast to what was observed with SF-36, the scale was particularly sensitive to clinical changes. The initial results make PDQ-39 a precious tool for the optimization of management of patients presenting with PD.

Female↗
PubMed2001

Structural and functional characterization of human NAD kinase.

NADP is essential for biosynthetic pathways, energy, and signal transduction. Its synthesis is catalyzed by NAD kinase. Very little is known about the structure, function, and regulation of this enzyme from multicellular organisms. We identified a human NAD kinase cDNA and the corresponding gene using available database information. A cDNA was amplified from a human fibroblast cDNA library and functionally overexpressed in Escherichia coli. The obtained cDNA, slightly different from that deposited in the database, encodes a protein of 49 kDa. The gene is expressed in most human tissues, but not in skeletal muscle. Human NAD kinase differs considerably from that of prokaryotes by subunit molecular mass (49 kDa vs 30-35 kDa). The catalytically active homotetramer is highly selective for its substrates, NAD and ATP. It did not phosphorylate the nicotinic acid derivative of NAD (NAAD) suggesting that the potent calcium-mobilizing pyridine nucleotide NAADP is synthesized by an alternative route.

Animals↗
PubMed2001

Insect immune activation by apolipophorin III is correlated with the lipid-binding properties of this protein.

Apolipophorin III (apoLp-III) is an exchangeable insect apolipoprotein consisting of five amphipathic alpha-helices. The protein is able to open reversibly on associating with hydrophobic surfaces and plays a role both in lipid transport and induction of immune responses. Point mutations were introduced at positions 66 (N-->D) and/or 68 (K-->E) between helices 2 and 3, a region possibly serving as a hinge for the opening of the molecule when associating with lipids. The lipid-binding properties of the mutant proteins were analyzed and compared with their immune inducing activities. Structural properties of the proteins were studied by far UV circular dichroism spectroscopy and their abilities to form discoidal complexes of dimyristoyl phosphatidylcholine (DMPC) vesicles were investigated. In comparison to wild-type apoLp-III, apoLp-III(N66D/K68E), and apoLp-III(K68E) displayed significantly decreased lipid-binding abilities and immune stimulating activities, while these effects were less noticeable with apoLp-III(N66D). The secondary structure of the double mutant apoLp-III(N66D/K68E) was similar to that of wild-type apoLp-III. A noticeable reduction of alpha-helical content could be observed for the single mutants apoLp-III(N66D) and apoLp-III(K68E), which was accompanied by an increase in percentage amount of beta-turns. The stability of the secondary structure determined by heat denaturation was not affected by mutagenesis. Furthermore, the ability of all proteins to form discoidal complexes of equal size and shape in the presence of dimyristoyl phosphatidylcholine indicated that the mutagenesis did not affect the molecular architecture in the lipid-associated conformation. The relationship between reduced lipid association and reduced immune stimulating activity supports the hypothesis that apoLp-III-induced immune activation is triggered by the conformational change of the protein.

Amino Acid Substitution↗
PubMed2001

Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria.

Mitochondrial ADP-ribosylation leads to modification of two proteins of approximately 26 and 53 kDA: The nature of these proteins and, hence, the physiological consequences of their modification have remained unknown. Here, a 55 kDa protein, glutamate dehydrogenase (GDH), was established as a specific acceptor for enzymatic, cysteine-specific ADP-ribosylation in mitochondria. The modified protein was isolated from the mitochondrial preparation and identified as GDH by N-terminal sequencing and mass spectrometric analyses of tryptic digests. Incubation of human hepatoma cells with [14C]adenine demonstrated the occurrence of the modification in vivo. Purified GDH was ADP-ribosylated in a cysteine residue in the presence of the mitochondrial activity that transferred the ADP-ribose from NAD+ onto the acceptor site. ADP- ribosylation of GDH led to substantial inhibition of its catalytic activity. The stoichiometry between incorporated ADP-ribose and GDH subunits suggests that modification of one subunit per catalytically active homohexamer causes the inactivation of the enzyme. Isolated, ADP-ribosylated GDH was reactivated by an Mg2+-dependent mitochondrial ADP-ribosylcysteine hydrolase. GDH, a highly regulated enzyme, is the first mitochondrial protein identified whose activity may be modulated by ADP-ribosylation.

Adenosine Diphosphate↗
PubMed2001

Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis.

Nicotinamide mononucleotide adenylyl transferase (NMNAT) is an essential enzyme in all organisms, because it catalyzes a key step of NAD synthesis. However, little is known about the structure and regulation of this enzyme. In this study we established the primary structure of human NMNAT. The human sequence represents the first report of the primary structure of this enzyme for an organism higher than yeast. The enzyme was purified from human placenta and internal peptide sequences determined. Analysis of human DNA sequence data then permitted the cloning of a cDNA encoding this enzyme. Recombinant NMNAT exhibited catalytic properties similar to the originally purified enzyme. Human NMNAT (molecular weight 31932) consists of 279 amino acids and exhibits substantial structural differences to the enzymes from lower organisms. A putative nuclear localization signal was confirmed by immunofluorescence studies. NMNAT strongly inhibited recombinant human poly(ADP-ribose) polymerase 1, however, NMNAT was not modified by poly(ADP-ribose). NMNAT appears to be a substrate of nuclear kinases and contains at least three potential phosphorylation sites. Endogenous and recombinant NMNAT were phosphorylated in nuclear extracts in the presence of [gamma-(32)P]ATP. We propose that NMNAT's activity or interaction with nuclear proteins are likely to be modulated by phosphorylation.

Amino Acid Sequence↗
PubMed2001

Pathophysiological relevance of mitochondria in NAD(+) metabolism.

Pyridine nucleotides are mostly stored within mitochondria where they are involved in different functions ranging from energy metabolism to cellular signaling. Here we discuss the mechanisms of mitochondrial NAD(+) metabolism and release that may contribute to the crucial roles played by these organelles as triggers or amplifiers of physiological and pathological events.

Apoptosis↗
PubMed2001

A cellular survival switch: poly(ADP-ribosyl)ation stimulates DNA repair and silences transcription.

Poly(ADP-ribosyl)ation is a post-translational modification occurring in the nucleus. The most abundant and best-characterized enzyme catalyzing this reaction, poly(ADP-ribose) polymerase 1 (PARP1), participates in fundamental nuclear events. The enzyme functions as molecular "nick sensor". It binds with high affinity to DNA single-strand breaks resulting in the initiation of its catalytic activity. Activated PARP1 promotes base excision repair. In addition, PARP1 modifies several transcription factors and thereby precludes their binding to DNA. We propose that a major function of PARP1 includes the silencing of transcription preventing expression of damaged genes. Concomitant stimulation of DNA repair suggests that PARP1 acts as a switch between transcription and DNA repair. Another PARP-type enzyme, tankyrase, is involved in the regulation of telomere elongation. Tankyrase modifies a telomere-associated protein and thereby prevents it masking telomeric repeats providing access of telomerase for telomere elongation. Therefore, poly(ADP-ribosyl)ation reactions may act as molecular switches in DNA metabolism.

Animals↗
PubMed2001

[Bilateral kidney tumor. Therapy management and histopathological results with long-term follow-up of 66 patients].

Bilateral renal cell carcinoma is detected at an incidence rate of 1.6-6% of all renal tumors. The management, histopathological results and the long-term follow-up of 66 patients with bilateral renal cell carcinoma (29 synchronous, 37 asynchronous tumors) are presented in this issue. The incidence rate of bilateral renal cell carcinoma (RCC) at our hospital was 3.5%. Nephron-sparing surgery should be used first for the smaller and favourably located tumor when radical nephrectomy of the contralateral tumor is necessary. Thus, the patients can be spared dialysis. The histopathological results showed a significantly higher incidence rate of chromophil RCCs in cases of synchronous bilateral renal tumors (36%). The 5-year survival rate was 82%. Patients with asynchronous renal cell carcinomas were significantly younger than those with synchronous RCCs (median age: 60.2 years). The histopathological results were similar to unilateral renal cell carcinomas. Clear cell carcinoma was detected in 70% of cases. The 5-year survival rate was 61% and lower than that of synchronous tumors (82%). There was no significant difference because of the small number of cases. Current standardised techniques of nephron-sparing surgery achieve good survival rates, therefore making bilateral nephrectomy only necessary in very poor cases. In cases of chromophil renal cell carcinomas, the contralateral kidney should always be carefully examined, because these tumors were significantly more often detected to be bilateral. The risk of also developing a tumor in the contralateral kidney increases with decreasing age at first manifestation (< 55 years, 6%). Especially in those younger than 55 years, partial nephrectomy seems to be recommended for unilateral renal tumors in patients with a normal contralateral kidney (tumor size < 4 cm in diameter).

Adenocarcinoma, Clear Cell↗
PubMed2001

Mus cervicolor murine leukemia virus isolate M813 belongs to a unique receptor interference group.

Murine leukemia virus (MuLV) M813 was originally isolated from the Southeast Asian rodent Mus cervicolor. As with the ecotropic MuLVs derived from Mus musculus, its host range is limited to rodent cells. Earlier studies have mapped its receptor to chromosome 2, but it has not been established whether M813 shares a common receptor with any other MuLVs. In this study, we have performed interference assays with M813 and viruses from four interference groups of MuLV. The infection efficiency of M813 was not compromised in cells expressing any one of the other MuLVs, demonstrating that M813 must use a distinct receptor for cell entry. The entire M813 env coding region was molecularly cloned. Sequence analysis revealed high similarity with other MuLVs but with a unique receptor-binding domain. Substitution of M813 env sequences in Moloney MuLV resulted in a replication-competent virus with a host range and interference profile similar to those of the biological clone M813. M813 thus defines a novel receptor interference group of type C MuLVs.

3T3 Cells↗
PubMed2000

Stabilization of a Reactive Cationic Species by Supramolecular Encapsulation Coordination Number Incommensurate Cluster Formation, Part 15. This research was supported by NSF grant CHE-9709621. We gratefully acknowledge Prof. Julie A. Leary and Dr. Ulla Andersen for their assistance with mass spectrometry. We also thank the Miller Foundation for a postdoctoral fellowship to M.Z. and the NIH for a postdoctoral fellowship to J.L.B. Part 14: J. Xide, K. N. Raymond, Angew. Chem. 2000, 112, 2857-2859; Angew. Chem. Int. Ed. 2000, 39, 2745-2747.

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Journal Article↗