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Biomedical subjects

A Schultz

Publications and source records attributed to A Schultz.

At least 37 records · Page 2Linked to original sources

Reconstructive urology in the nordic countries--a hospital questionnaire survey.

A hospital survey of adult reconstructive urologic surgery in the Nordic countries is presented. The response rate was 80% and included most general hospitals and university clinics. Despite similarities between the healthcare systems of the various countries several differences were found. Cystectomy was performed in a large number of institutions in all countries except Denmark. The annual number of orthotopic bladder substitutions per institution was calculated as three to four (range of medians for each country) and the number of continent cutaneous diversions as two to seven. Open urethral procedures were performed more frequently in Sweden than in the other countries. Surgery for penile curvature and implantation of three-component prostheses for erectile dysfunction was more commonly performed in Denmark and Iceland compared to Sweden.

Denmark↗

Impact of plasmapheresis on platelet hemostatic capacity in healthy voluntary blood donors detected by the platelet function analyzer PFA-100.

Previous flow cytometry studies showed that platelet activation may occur during cytapheresis, cardiopulmonary bypass and hemodialysis. The aim of this pilot study was to determine if the impact of plasmapheresis leads to alterations in platelet hemostatic capacity. Plasmapheresis was carried out in 30 volunteers using an Autopherese C (Baxter) and an MCS3p (Haemonetics). Blood samples were collected and analyzed immediately before and after plasmapheresis. As a result of the plasmapheresis on the Autopherese C, the mean closure time (CT) for collagen/epinephrine (Col/Epi) increased from 118.2 +/- 25.1 to 149.9 +/- 35.0 s and from 88.7 +/- 16.9 to 98.5 +/- 26.3 s for collagen/ADP (Col/ADP), respectively. Seven subjects showed impaired CTs after plasmapheresis for Col/Epi. For Col/ADP, five subjects showed impaired CTs after apheresis. Statistical analysis (McNemar test) showed a significant difference before and after apheresis for Col/Epi (P = 0.024) but not for Col/ADP (P = 0.088). Similar results were shown for plasmapheresis carried out with the MCS3p. These findings show that plasmapheresis can cause an impairment of platelet function in healthy volunteers as measured by the PFA-100, an effect of so far unknown clinical significance.

Adult↗

Dehalogenation of chlorinated hydroxybiphenyls by fungal laccase.

We have investigated the transformation of chlorinated hydroxybiphenyls by laccase produced by Pycnoporus cinnabarinus. The compounds used were transformed to sparingly water-soluble colored precipitates which were identified by gas chromatography-mass spectrometry as oligomerization products of the chlorinated hydroxybiphenyls. During oligomerization of 2-hydroxy-5-chlorobiphenyl and 3-chloro-4-hydroxybiphenyl, dechlorinated C---C-linked dimers were formed, demonstrating the dehalogenation ability of laccase. In addition to these nonhalogenated dimers, both monohalogenated and dihalogenated dimers were identified.

Basidiomycota↗

Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease.

Thymomas are the only tumors that are proven to generate mature T cells from immature precursors. It is unknown, however, whether intratumorous thymopoiesis has an impact on the peripheral T-cell pool and might thus be related to the high frequency of thymoma-associated myasthenia gravis. This study shows, using fluorescence-activated cell sorting-based analyses and T-cell proliferation assays, that thymopoiesis and T-cell function in thymomas correspond with immunologic alterations in the blood. Specifically, the proportion of circulating CD45RA(+)CD8(+) T cells is significantly increased in patients with thymoma compared with normal controls, in accordance with intratumorous T-cell development that is abnormally skewed toward the CD8(+) phenotype. Moreover, it is primarily the proportion of circulating CD45RA(+)CD8(+) T cells that decreases after thymectomy. The results also demonstrate that T cells reactive toward recombinant autoantigens are distributed equally between thymomas and blood, whereas T-cell responses to foreign antigen (ie, tetanus toxoid) are seen only among circulating T cells and not among thymoma-derived T cells. These functional studies support the hypothesis that thymopoiesis occurring within thymomas alters the peripheral T-cell repertoire. Because many thymomas are enriched with autoantigen-specific T cells, a disturbance of circulating T-cell subset composition by export of intratumorous T cells may contribute to paraneoplastic autoimmune disease arising in patients with thymoma. (Blood. 2000;96:3872-3879)

Adolescent↗

A thermodynamic explanation for black smoker temperatures

There is a remarkable difference between the maximum temperature of black smoker effluent (350 degrees C-400 degrees C) and the temperature of the solidifying magma which heats it (approximately 1,200 degrees C). It has been suspected for some time that the nonlinear thermodynamic properties of water might be responsible for this discrepancy. Here, we translate this hypothesis into a physical model, by examining the internal temperature structure of convection cells in a porous medium. We demonstrate that, at pressures appropriate to seafloor crust, plumes of pure water form naturally at approximately 400 degrees C for any heat source with temperature greater than approximately 500 degrees C. Higher temperatures are confined to a boundary layer at the base of the convection cell, where the flow is horizontal. The phenomenon is explained analytically using the thermodynamic properties of water, and is illustrated by numerical simulations. Our model predicts the existence of the high-temperature 'reaction zone' found in ophiolites and suggests that vent temperatures will remain steady as magma chambers solidify and cool.

Journal Article↗

Rings in the Planetesimal Disk of beta Pictoris.

The nearby main-sequence star beta Pictoris is surrounded by an edge-on disk of dust produced by the collisional erosion of larger planetesimals. Here we report the discovery of substructure within the northeast extension of the disk midplane that may represent an asymmetric ring system around beta Pic. We present a dynamical model showing that a close stellar flyby with a quiescent disk of planetesimals can create such rings, along with previously unexplained disk asymmetries. Thus we infer that beta Pic's planetesimal disk was highly disrupted by a stellar encounter in the last hundred thousand years.

Journal Article↗

Genetic aberrations common in gastric high-grade large B-cell lymphoma.

Genetic aberrations associated with the development of extranodal high-grade large B-cell lymphoma originating in the stomach have not been fully identified yet. We analyzed 31 such lymphomas using 73 microsatellite markers for allelic imbalance and microsatellite instability. The highest frequency (42%) of loss of heterozygosity (LOH) was found on the long arm of chromosome 6. We identified 2 LOH hot spots on 6q21-22.1 and 6q23.3-25, flanked by markers D6S246-D6S261 and D6S310-D6S441, respectively, containing putative tumor suppressor genes (TSGs). These 6q aberrations were found to be the sole allelic imbalance in 1 patient only; they were mostly accompanied by additional abnormalities. Several known TSGs, namely, the APC, p15/p16, p53, and DCC genes, were found to suffer frequent LOH during lymphomagenesis. LOH was also detected in regions containing putative TSGs on 7q and 13q14. Frequent amplification of genomic material was found in the 2p, 3q27 at the BCL-6 gene locus, 6p, 7q, 11q23-24 at the MLL gene locus, and 18q regions. Analysis of the pattern of occurrence of these aberrations revealed an association of the amplification of the MLL gene region with LOH at the p53 locus (P =.02). Only low frequency of microsatellite instability (MSI) was detected in these lymphomas and MSI incidence increased with age (P =.01). Karyotypic instability thus plays the main role in the development of gastric high-grade large B-cell lymphoma. Common genetic aberrations responsible for lymphomagenesis are deletions of 6q, loss of p53, and amplification of the 3q27 and the MLL gene regions. (Blood. 2000;95:1180-1187)

Age Factors↗

Tumor biology of mucosa-associated lymphoid tissue lymphomas.

Extranodal lymphomas arising at mucosal sites exhibit clinicopathological features that suggest a closer relationship of these tumors to the structure and function of mucosa-associated lymphoid tissue (MALT) than to lymph nodes. The factors that induce MALT in these tissues are operative in early MALT lymphoma development and the progressive independence on T-cell help defines late stages of MALT lymphoma genesis.

Antigens↗

The role of microsatellite instability in gastric low- and high-grade lymphoma development.

DNA mismatch repair genes and their dysfunction as evidenced by microsatellite instability (MSI) play an important role in the pathogenesis of a variety of tumors, most prominently hereditary nonpolyposis colorectal cancer (HNPCC). However, their role in development of extranodal lymphomas has not been established yet. We therefore evaluated for MSI 25 gastric low-grade marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type and 31 gastric high-grade diffuse large B-cell lymphomas (DLBCLs) with 29 and 118 microsatellites, respectively. Compared with HNPCC, the overall level of MSI was much lower with a mean of 2.6% MSI-positive repeats in the DLBCLs; the frequency of MSI showed a tendency to increase with age (P = 0.01), as did MSI variability (P = 0.02). Low-grade mucosa-associated lymphoid tissue lymphomas displayed even less MSI (sevenfold) than DLBCLs (P = 0.009). MSI frequency thus increases with the transition from low- to high-grade disease and with age; it does not seem to initiate lymphomagenesis. Other microsatellites than those typically mutated in HNPCC frequently revealed MSI in these lymphomas, especially dinucleotide repeats on chromosomes 3, 5, and 18. To facilitate rapid screening of lymphomas for MSI and to establish a tool for future MSI frequency comparisons, we recommend to use repeats D3S1261, D3S1530, D5S346, D17S250, D18S474, and DCC.

Adult↗

Epileptiform activity in the EEGs of two nonepileptic children under sevoflurane anaesthesia.

Two case reports of nonepileptic children are presented, who developed paroxysmal EEG potentials in routinely performed EEG recordings during inhalation of sevoflurane, 7 and 8% by volume respectively. Taking into account several reports from the literature about epileptiform potentials or convulsive movements under similar conditions, it seems to be important to investigate carefully the circumstances under which these phenomena appear as well as possible clinical consequences.

Anesthetics, Inhalation↗

Protein kinase C beta1 is implicated in the regulation of neuroblastoma cell growth and proliferation.

To investigate a putative involvement of protein kinase C (PKC) isoforms in supporting neuroblastoma cell proliferation, SK-N-BE(2) neuroblastoma cells were transfected with expression vectors coding for the C2 and V5 regions from different PKC isoforms. These structures have been suggested to inhibit the activity of their corresponding PKC isoform. The PKC fragments were fused to enhanced green fluorescent protein to facilitate the detection of transfected cells. Expression of the C2 domain from a classical PKC isoform (PKCalpha), but not of C2 domains from novel PKCdelta or PKCepsilon, suppressed the number of neuroblastoma cells positive for cyclin A and bromodeoxyuridine incorporation. This indicates a role for a classical isoform in regulating proliferation of these cells. Among the V5 fragments from PKCalpha, PKCbetaI, and PKCbetaII, the PKCbetaI V5 had the most suppressive effect on proliferation markers, and this fragment also displaced PKCbetaI from the nucleus. Furthermore, a PKCbeta-specific inhibitor, LY379196, suppressed the phorbol ester- and serum-supported growth of neuroblastoma cells. There was a marked enhancement by LY379196 of the growth-suppressive and/or cytotoxic effects of paclitaxel and vincristine. These results indicate that PKCbetaI has a positive effect on the growth and proliferation of neuroblastoma cells and demonstrate that inhibition of PKCbeta may be used to enhance the effect of microtubule-interacting anticancer agents on neuroblastoma cells.

Antineoplastic Agents, Phytogenic↗

H+ -PPases: a tightly membrane-bound family.

The earliest known H+-PPase (proton-pumping inorganic pyrophosphatase), the integrally membrane-bound H+-PPi synthase (proton-pumping inorganic pyrophosphate synthase) from Rhodospirillum rubrum, is still the only alternative to H+-ATP synthase in biological electron transport phosphorylation. Cloning of several higher plant vacuolar H+-PPase genes has led to the recognition that the corresponding proteins form a family of extremely similar proton-pumping enzymes. The bacterial H+-PPi synthase and two algal vacuolar H+-PPases are homologous with this family, as deduced from their cloned genes. The prokaryotic and algal homologues differ more than the H+-PPases from higher plants, facilitating recognition of functionally significant entities. Primary structures of H+-PPases are reviewed and compared with H+-ATPases and soluble PPases.

Amino Acid Sequence↗

Interindividual heterogeneity in the hypoxic regulation of VEGF: significance for the development of the coronary artery collateral circulation.

BACKGROUND: The coronary artery collateral circulation may be beneficial in protecting against myocardial ischemia and necrosis. However, there is a tremendous interindividual variability in the degree of new collateral formation in patients with coronary artery disease. The basis for this interindividual heterogeneity is not understood. In this study we test the hypothesis that failure to generate collateral vessels is associated with a failure to appropriately induce with hypoxia or ischemia the angiogenic factor, vascular endothelial growth factor (VEGF). METHODS AND RESULTS: We correlated the VEGF response to hypoxia in the monocytes harvested from patients with coronary artery disease with the presence of collaterals visualized during routine angiography. We found that there was a highly significant difference in the hypoxic induction of VEGF in patients with no collaterals compared with patients with some collaterals (mean fold induction 1.9+/-0.2 versus 3.2+/-0.3, P<0.0001). After subjecting the data to ANCOVA, using as covariates a number of factors that might influence the amount of collateral formation (ie, age, sex, diabetes, smoking, hypercholesterolemia), patients with no collaterals still have a significantly lower hypoxic induction of VEGF than patients with collaterals. CONCLUSIONS: This study provides evidence in support of the hypothesis that the ability to respond to progressive coronary artery stenosis is strongly associated with the ability to induce VEGF in response to hypoxia. The observed interindividual heterogeneity in this response may be due to environmental, epigenetic, or genetic causes. This interindividual heterogeneity may also help to explain the variable angiogenic responses seen in other conditions such as diabetic retinopathy and solid tumors.

Cell Hypoxia↗

Guanylyl cyclases with the topology of mammalian adenylyl cyclases and an N-terminal P-type ATPase-like domain in Paramecium, Tetrahymena and Plasmodium.

We cloned a guanylyl cyclase of 280 kDa from the ciliate Paramecium which has an N-terminus similar to that of a P-type ATPase and a C-terminus with a topology identical to mammalian adenylyl cyclases. Respective signature sequence motifs are conserved in both domains. The cytosolic catalytic C1a and C2a segments of the cyclase are inverted. Genes coding for topologically identical proteins with substantial sequence similarities have been cloned from Tetrahymena and were detected in sequences from Plasmodium deposited by the Malaria Genome Project. After 99 point mutations to convert the Paramecium TAA/TAG-Gln triplets to CAA/CAG, together with partial gene synthesis, the gene from Paramecium was heterologously expressed. In Sf9 cells, the holoenzyme is proteolytically processed into the two domains. Immunocytochemistry demonstrates expression of the protein in Paramecium and localizes it to cell surface membranes. The data provide a novel structural link between class III adenylyl and guanylyl cyclases and imply that the protozoan guanylyl cyclases evolved from an ancestral adenylyl cyclase independently of the mammalian guanylyl cyclase isoforms. Further, signal transmission in Ciliophora (Paramecium, Tetrahymena) and in the most important endoparasitic phylum Apicomplexa (Plasmodium) is, quite unexpectedly, closely related.

Amino Acid Sequence↗

H+-proton-pumping inorganic pyrophosphatase: a tightly membrane-bound family.

The earliest known H+-proton-pumping inorganic pyrophosphatase, the integrally membrane-bound H+-proton-pumping inorganic pyrophosphate synthase from Rhodospirillum rubrum, is still the only alternative to H+-ATP synthase in biological electron transport phosphorylation. Cloning of several higher plant vacuolar H+-proton-pumping inorganic pyrophosphatase genes has led to the recognition that the corresponding proteins form a family of extremely similar proton-pumping enzymes. The bacterial H+-proton-pumping inorganic pyrophosphate synthase and two algal vacuolar H+-proton-pumping inorganic pyrophosphatases are homologous with this family, as deduced from their cloned genes. The prokaryotic and algal homologues differ more than the H+-proton-pumping inorganic pyrophosphatases from higher plants, facilitating recognition of functionally significant entities. Primary structures of H+-proton-pumping inorganic pyrophosphatases are reviewed and compared with H+-ATPases and soluble proton-pumping inorganic pyrophosphatases.

Amino Acid Sequence↗

Association of acetylcholine receptor alpha-subunit gene expression in mixed thymoma with myasthenia gravis.

OBJECTIVE: To investigate the association of MG with the transcription of muscular or neuronal acetylcholine receptor (AChR) subunit genes in thymomas. BACKGROUND: Many steps in the pathogenesis of MG have been elucidated but, with rare exceptions, its etiology is unknown. In patients with MG with thymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmatic why MG develops in some patients but not in others. METHODS: Reverse transcriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies were carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between thymoma subtypes. RESULTS: Considering all thymomas (n = 35), no correlation was found between MG status and AChR gene expression as detected by RT-PCR. However, when histologically defined thymoma subtypes were studied separately, transcription of the muscular AChR P3A- alpha-subunit gene was significantly associated (alpha < 0.01) with the occurrence of MG in mixed thymomas (n = 17), but not in thymomas of the cortical type. For the other muscular AChR subunits (P3A+ alpha isoform, beta, gamma, delta, and epsilon) and the alpha2 and beta4 neuronal AChR subunits, no such correlation was detected. CONCLUSIONS: Expression of the P3A AChR alpha-subunit gene might be important for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically different thymoma subtypes.

Adult↗