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Biomedical subjects

T Pfeiffer

Publications and source records attributed to T Pfeiffer.

At least 19 recordsLinked to original sources

[Interdisciplinary operative procedure-pelvis and abdomen].

Surgery for tumors in the abdomen, retroperitoneum, and pelvis requires technical skills and expertise sometimes beyond the capability of a single surgeon. This holds especially true if curative tumor resection involves replacement of arteries and veins, which needs careful planning to avoid long periods of ischemia, and the selection and provision of vascular substitutes according to anatomical position, postsurgical therapy, and adjuncts to avoid thrombosis and infection of vascular grafts. Since the works of Fortner, the value of close collaboration between general and vascular surgeons has been demonstrated, but many of the former even today continue to attempt the operation alone, although the result is not always a masterpiece. The authors refer to their experience in major tumor surgery in either the single management of vascular complications or collaboration. The potential value of close collaboration is presented by negative examples, and a plea is made for a less "eminence"-based management of these sometimes difficult cases, which is based on vast positive experience with vascular diseases of the aorta and the visceral and iliac arteries and veins, including safety measures and adjuncts.

Abdominal Neoplasms↗

The incidence of iliac aneurysms in patients with abdominal aortic aneurysms: comparison of four centers in Europe and the USA.

BACKGROUND: The purpose of this study was to compare the anatomy of the aortoiliac vessels in patients scheduled for infrarenal abdominal aortic aneurysm (AAA) repair in four different countries. MATERIAL AND METHODS: Consecutives series of 100 preoperative CT-scans were evaluated at each center. Diameters of the suprarenal aorta, maximal diameter of the aneurysm, right and left common and external iliac artery as well as the hypogastric arteries were recorded and compared between each center. RESULTS: Configuration of the AAA above bifurcation was similar at each center. The dimensions of the aortic bifurcation and the common iliac arteries were different among the centers. Common iliac arteries with diameters over 25 mm were significantly more common at center 1 (p < 0.001, p = 0.002 and p < 0.001). Among centers 2, 3 and 4 there was no significant difference in common iliac diameters. CONCLUSIONS: Configuration of the iliac arteries in AAA was significantly different for Swiss patients compared to American, Austrian and German patients. Reasons for these differences are unclear, epidemiological or genetic factors may be responsible.

Adult↗

Hemodynamically relevant hematuria several months after biopsy of a kidney graft: an unusual cause.

We report the case of a 52-year-old female patient, who after a complicated living donor kidney transplantation, underwent kidney biopsy for suspected rejection. Duplex scanning revealed a small, asymptomatic arteriovenous (AV) fistula which was assessed as being hemodynamically unimportant. During follow-up, several urinary tract infections occurred and recurrent short episodes of hematuria were attributed to cystitis, urethritis and urosepsis. Eight months later, the patient developed suddenly massive hematuria, tamponade of the urinary bladder and hemorrhagic shock as well as urosepsis. Duplex sonography showed a massive pseudoaneurysm in addition to the AV fistula. Arteriography confirmed the Duplex sonographic findings and embolization was performed after treatment of concomitant urosepsis. The fistula was closed completely and bleeding ceased. Although AV fistulas are rare complications of kidney biopsies and in most cases they remain asymptomatic, life-threatening hematuria can present several months after a biopsy due to the development of a pseudoaneurysm. Concomitant infectious complications of the urinary tract, bleeding disorders and other factors can be misleading during the assessment of the cause of gross hematuria. Regular Duplex sonographic follow-up examinations in patients with AV fistulas are advisable.

Aneurysm, False↗

[Aortoiliac reconstruction after kidney transplantation. Strategies to avoid ischemic damage of the transplant].

INTRODUCTION: The rising life expectancy of patients undergoing kidney transplantation and the improvement in the function rate of the allografts have led to an increasing number of patients suffering from arteriosclerosis-related diseases of the aortoiliac arteries. In these particular cases, an interruption of the blood supply of the allograft is always necessary for operative repair of the aortic and iliac arteries. This means a high risk of ischemic damage to the transplanted kidney. PATIENTS AND METHODS: Between 1987 and 2000, 1,076 kidney transplantations were performed in our department. During this time, 14 reconstructive operations of the aortoiliac arteries were performed in 12 patients (6 women, 6 men, average age 55.2 (45-71) years). Operations were indicated in patients suffering from occlusive disease with imminent extremity or allograft loss, and symptomatic or asymptomatic aneurysms with a maximum diameter of more than 4 cm. In patients presenting with thoracoabdominal (1) and abdominal aortic aneurysms (3), protection of the transplanted kidney was performed by axilloiliac or axillofemoral bypass. Hypothermic flush-perfusion of the allograft containing PGE1 and heparin was performed in seven of nine operations for occlusive disease. RESULTS: None of the patients presented with a permanent decrease in kidney function, six patients showed temporary creatinine elevation, and in nine patients creatinine levels at discharge were lower than they were preoperatively. None of the patients died. CONCLUSION: Reviewing all reported methods of allograft protection, we recommend a three-step strategy including sequential clamp technique (ischemia < 30 min.), hypothermic flush-perfusion (ischemia < or = 60 min.), and temporary axilloiliac/femoral shunt (ischemia > 60 min), depending on the expected renal ischemia time.

Aged↗

Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae.

MOTIVATION: Reconstructing and analyzing the metabolic map of microorganisms is an important challenge in bioinformatics. Pathway analysis of large metabolic networks meets with the problem of combinatorial explosion of pathways. Therefore, appropriate algorithms for an automated decomposition of these networks into smaller subsystems are needed. RESULTS: A decomposition algorithm for metabolic networks based on the local connectivity of metabolites is presented. Interrelations of this algorithm with alternative methods proposed in the literature and the theory of small world networks are discussed. The applicability of our method is illustrated by an analysis of the metabolism of Mycoplasma pneumoniae, which is an organism of considerable medical interest. The decomposition gives rise to 19 subnetworks. Three of these are here discussed in biochemical terms: arginine degradation, the tetrahydrofolate system, and nucleotide metabolism. The interrelations of pathway analysis of biochemical networks with Petri net theory are outlined.

Algorithms↗

Cooperation and competition in the evolution of ATP-producing pathways.

Heterotrophic organisms generally face a trade-off between rate and yield of adenosine triphosphate (ATP) production. This trade-off may result in an evolutionary dilemma, because cells with a higher rate but lower yield of ATP production may gain a selective advantage when competing for shared energy resources. Using an analysis of model simulations and biochemical observations, we show that ATP production with a low rate and high yield can be viewed as a form of cooperative resource use and may evolve in spatially structured environments. Furthermore, we argue that the high ATP yield of respiration may have facilitated the evolutionary transition from unicellular to undifferentiated multicellular organisms.

Adenosine Triphosphate↗

Correlation between processing efficiency for ribonuclease P minimal substrates and conformation of the nucleotide -1 at the cleavage position.

It is demonstrated that acceptor stem duplexes derived from native tRNAs which contain a three-nucleotide extension at the 5'-terminus of mature tRNA are minimal substrates for ribonuclease P from both Escherichia coli and Bacillus subtilis. Variants with a cytidine at position -1 are most efficiently processed whereas the G -1 variant represents a comparatively poor substrate. An A -1 acceptor stem variant is a slightly better substrate than the G -1 variant though generally distinctly less efficient than the C -1 duplex. This is in qualitative agreement with the frequency of the occurrence of the corresponding nucleotides at position -1 in natural substrates, which is highest for pyrimidines and least for G. NMR analyses of the corresponding acceptor stems reveal that the conformation of the nucleotides at position -1 correlates with the substrate preferences of Ribonuclease P: Whereas C -1 adopts a conformation characterized by a glycosidic angle in the anti range (close to high-anti), the G -1 is clearly in syn conformation, and that of A -1 is intermediate between high-anti and syn. The riboses of nucleotides -1 are in all cases predominantly 2'-endo puckered.

Adenosine↗

Generation of a flexible cell line with regulatable, high-level expression of HIV Gag/Pol particles capable of packaging HIV-derived vectors.

HIV-derived vectors are of potential clinical relevance due to their ability to transduce nondividing cells in vitro and in vivo. However, the generation of cell lines stably and reproducibly expressing high amounts of defined subviral particles, capable of packaging and transducing HIV-derived vectors, has been hampered by the cytotoxicity of some of the required gene products, in particular of the HIV-1 protease. The successful use of regulatable gene expression systems to overcome this problem requires that the remaining basally expressed gene product activity is below the threshold for cytotoxicity. To try to achieve this, we have consecutively introduced appropriate plasmids, encoding HIV rev and HIV gag/pol gene products, each under the control of separate ecdysone-inducible promoters, into human 293 cells. Using a protocol in which a specific HIV protease inhibitor, Saquinavir, was continuously present in the culture medium during selection, we could generate stable cell lines inducibly expressing high amounts of subviral particles. A cell line, termed 293-Rev/Gag/Pol(i), which has been characterized in more detail, inducibly releases, within 48 h postinduction, high amounts of HIV Gag/Pol particles (about 10 microg CA/ml). These HIV Gag/Pol particles can package and transduce third-generation HIV vectors to high titers. Thus, in addition to other applications, the 293-Rev/Gag/Pol(i) cell line represents a "founder" packaging cell line which, depending on the requirement, can be further modified to include specific transgene-encoding vector and targeting glycoprotein genes.

Cell Line↗

Working memory limitation as a source of confusion in the abstract THOG task.

Limitations of working memory are proposed as a major determinant of problem difficulty in the THOG task. This task is a logical reasoning task which uses an exclusive disjunction and requires hypothetico-deductive reasoning. Four experiments with students of mathematics or psychology were used to test the hypotheses that, first, guiding participants' attention facilitates the task and, second, the use of paper and pencil as external problem representation reliefs working memory load. Focusing participants' attention upon a critical aspect of the task does not improve solution rates. Students of mathematics were better than students of psychology, but only if they were allowed to use paper and pencil or to work on the task repeatedly. These results partially support the working memory hypothesis. They point toward the importance of training and practice in relatively simple meta-cognitive skills in logical reasoning.

Attention↗

Exploring the minimal substrate requirements for trans-cleavage by RNase P holoenzymes from Escherichia coli and Bacillus subtilis.

We analysed the processing of small bipartite model substrates by Escherichia coli and Bacillus subtilis RNase P and corresponding hybrid enzymes. We demonstrate specific trans-cleavage of a model substrate with a 4 bp stem and a 1 nucleotide (nt) 5' flank, representing to date the smallest mimic of a natural RNase P substrate that could be processed in trans at the canonical RNase P cleavage site. Processing efficiencies decreased up to 5000-fold when the 5' flank was shortened from 3 to 1 nt. Reduction of the 5' flank to 1 nt was more deleterious than reducing the stem from 7 to 4 bp, although the 4 bp duplex formed only transiently, in contrast to the stable 7 bp duplex. These results indicate that the crucial contribution of nt -2 in the single-stranded 5' flank to productive interaction is a general feature of A- and B-type bacterial RNase P enzymes. We also showed that an Rp-phosphorothioate modification at nt -2 interferes with processing. Bacterial RNase P holoenzymes are also capable of cleaving single-stranded RNA oligonucleotides as short as 5 nt, yielding RNase P-specific 5'-phosphate and 3'-OH termini, with measured turnover rates of up to 0.7 min-1. All cleavage sites were at least 2 nt away from the 5' and 3' ends of the oligonucleotides. Some cleavage site preferences were observed dependent on the identity of the RNase P RNA subunit.

Bacillus subtilis↗

Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.

A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.

AIDS-Related Opportunistic Infections↗

Membrane fusion between retroviral particles: host-range extension and vaccine prospects.

We have analyzed if different populations of retroviral particles carrying the viral and cellular receptors of membrane viruses, respectively, are able to specifically fuse with each other. Using the glycoprotein of human immunodeficiency virus type 1 and its cellular receptor complex, we demonstrate that interviral membrane fusion can, indeed, occur and that the resultant fused viral structures are able to infect cells and transduce a marker gene. On the one hand, these results have relevance for the development of vaccine strategies based on fusion-induced conformational epitopes on the viral glycoprotein. However, in addition to this potential practical application, the results obtained (which were extended to include analyses with the vesicular stomatitis virus G protein and its cellular receptor) have far-reaching implications for in vivo situations in which simultaneous infections with different membrane viruses can occur.

AIDS Vaccines↗

Effects of phosphorothioate modifications on precursor tRNA processing by eukaryotic RNase P enzymes.

The cleavage mechanism has been studied for nuclear RNase P from Saccharomyces cerevisiae, Homo sapiens sapiens and Dictyostelium discoideum, representing distantly related branches of the Eukarya. This was accomplished by using precursor tRNAs (ptRNAs) carrying a single Rp or Sp-phosphorothioate modification at the normal RNase P cleavage site (position -1/+1). All three eukaryotic RNase P enzymes cleaved the Sp-diastereomeric ptRNA exclusively one nucleotide upstream (position -2/-1) of the modified canonical cleavage site. Rp-diastereomeric ptRNA was cleaved with low efficiency at the modified -1/+1 site by human RNase P, at both the -2/-1 and -1/+1 site by yeast RNase P, and exclusively at the -2/-1 site by D. discoideum RNase P. The presence of Mn(2+ )and particularly Cd(2+) inhibited the activity of all three enzymes. Nevertheless, a Mn(2+ )rescue of cleavage at the modified -1/+1 site was observed with yeast RNase P and the Rp-diastereomeric ptRNA, consistent with direct metal ion coordination to the (pro)-Rp substituent during catalysis as observed for bacterial RNase P enzymes. In summary, our results have revealed common active-site constraints for eukaryotic and bacterial RNase P enzymes. In all cases, an Rp as well as an Sp-phosphorothioate modification at the RNase P cleavage site strongly interfered with the catalytic process, whereas substantial functional interference is essentially restricted to one of the two diastereomers in other RNA and protein-catalyzed hydrolysis reactions, such as those catalyzed by the Tetrahymena ribozyme and nuclease P1.

Animals↗

Export and transport of tRNA are coupled to a multi-protein complex.

Vigilin is a ubiquitous multi heterogeneous nuclear ribonucleoprotein (hnRNP) K homologous (KH)-domain protein. Here we demonstrate that purified recombinant human vigilin binds tRNA molecules with high affinity, although with limited specificity. Nuclear microinjection experiments revealed for the first time that the immuno-affinity-purified nuclear vigilin core complex (VCC(N)) as well as recombinant vigilin accelerate tRNA export from the nucleus in human cells. The nuclear tRNA receptor exportin-t is part of the VCC(N). Elongation factor (EF)-1alpha is enriched in VCC(N) and its cytoplasmic counterpart VCC(C), whereas EF-1beta, EF-1gamma and EF-1delta are basically confined to the VCC(C). Our results suggest further that vigilin and exportin-t might interact during tRNA export, provide evidence that the channeled tRNA cycle is already initiated in the nucleus, and illustrate that intracellular tRNA trafficking is associated with discrete changes in the composition of cellular cytoplasmic multi-protein complexes containing tRNA.

Animals↗

[Results of conventional surgical therapy of abdominal aortic aneurysms since the beginning of the "endovascular era"].

INTRODUCTION: In 1990 the new method of endovascular graft treatment of abdominal aortic aneurysms (AAA) emerged. For this reason we analyzed the results of open surgery for AAA in our department to consider the question of standard therapy. METHODS: In a retrospective study the medical data of 941 consecutive patients treated by open surgery in a single center from 1990 to 1997 (mean age 67 years, 14.5 % female, 3.2 % suprarenal AAA) were analyzed. Operations were performed electively in 778 asymptomatic patients, urgently in 104 symptomatic patients, and as emergency operations (immediately after admission) in 59 symptomatic patients (45 patients presenting with rupture). RESULTS: Mortality was 1.54 % (elective operations), 8.65 % (urgent operations), and 35.6 % (emergency operations, rupture). Morbidity was 15.9 % (elective operations), 28.8 % (urgent operations), and 66.7 % (emergency operations, rupture). Mortality was not increased in patients undergoing additional procedures of the renal, iliac, femoral, or crural arteries. CONCLUSION: Because of its low mortality and morbidity today open surgical repair remains the standard therapy for AAA.

Adolescent↗