Futility-futilis-the leaky vessel.
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Adult↗
Biomedical subjects
T Schmidt
Publications and source records attributed to T Schmidt.
Effect of white wine on esophageal peristalsis and acid clearance.
BACKGROUND: In a previous study it was demonstrated that white wine reduces the lower esophageal sphincter pressure and induces gastroesophageal reflux characterized by reflux episodes of long duration. In the present study, it was evaluated whether wine disturbs esophageal peristalsis and acid clearance. METHODS: Twelve healthy volunteers (7F, 23-37 years) received 300 ml white wine (8% vol/vol; WW), an ethanol solution (8% vol/vol; ET) or tap water (WA) together with a standardized meal in a random order. Acid clearance was tested by instillation of 15 ml 0.1 N HCI into the distal esophagus. The number of swallows (dry swallow every 30 sec) were counted until pH rose again above 5. Five wet swallows (5 ml) were applied to test primary peristalsis and five insufflations of 20 ml of air were performed to test secondary peristalsis. Each test was done immediately after and 60 min after ingestion of the beverages. RESULTS: A significantly higher number of swallows were needed to clear the esophagus immediately after ingestion of wine (P < 0.01; median number: WW 12; ET 8; WA 7) due to an increase in the frequency of failed, simultaneous, and low-amplitude contractions. The frequency of triggered secondary contractions was decreased (P < 0.02; WW 70%; ET 100%; WA 100%) and the latency between air injection and onset of secondary peristalsis was prolonged (P < 0.05; WW 9 sec; ET 7 sec; WA 6 sec) immediately after ingestion of white wine. Wet swallow induced primary peristalsis was not influenced by wine. No significant differences in the measured parameters were seen 60 min after ingestion of the three beverages. CONCLUSION: White wine disturbs temporarily esophageal clearance due to a disturbance of triggering secondary peristalsis and due to an increase in ineffective contractions. The ethanol content alone is not responsible for the effects of white wine on esophageal peristalsis and acid clearance.
Adult↗
The Pim-1 kinase stimulates maturation of TCRbeta-deficient T cell progenitors: implications for the mechanism of Pim-1 action.
We demonstrate that overexpression of Pim-1, a cytoplasmic serine/threonine kinase of poorly defined function, results in the development of substantial numbers of CD4(+)CD8(+) double-positive thymocytes in two independent knock-out mouse models (i.e. the RAG-1-deficient and TCRbeta gene enhancer-deleted mice) in which production of a functionally rearranged TCRbeta gene (hence the pre-TCR) is impaired. This activity of Pim-1, however, does not affect signaling through the Ras/Raf/MAP kinase cascade nor signaling which mediates suppression of TCRbeta gene recombination (i.e. allelic exclusion). While overexpression of Pim-1 positively affects cell cycle progression in selected CD4(-)CD8(-) double-negative precursors, it did not affect expression of components of the cell cycle machinery, with the exception of the G(1)-specific phosphatase Cdc25A upon antigen receptor stimulation. We propose that Pim-1 acts downstream, or in parallel, to pre-TCR-mediated selection as one factor involved in the proliferative expansion of beta-selected pre-T cells.
Alleles↗
Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart-Treves syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity assay.
We report on a 72-year-old patient developing Stewart-Treves syndrome (STS) of the right arm 9 years after curative irradiation for ipsilateral stage III breast cancer. Facing the poor track record of both irradiation and chemotherapy in this highly malignant lymphangiosarcoma, amputation was recommended but refused by the patient. Therefore, limb conserving-therapy using three courses of intra-arterial mitoxantrone (MX) and paclitaxel (PTX) was attempted. This novel chemotherapy protocol was selected by pretherapeutic ex vivo ATP-based chemosensitivity testing of autologous tumor tissue. The patient experienced complete response, which was subsequent histologically confirmed by compartment resection. When developing recurrent STS outside of the perfused area 6 months after primary therapy, the patient was retested and reinduced with three other courses of intraarterial MX/PTX which again produced durable complete remission. This case demonstrates the benefit of indivdualized therapy in this prognostically desperate disease allowing both limb conservation and maintained quality of life.
Adenosine Triphosphate↗
Evaluation of protocols allowing emergency medical technicians to determine need for treatment and transport.
OBJECTIVE: To determine whether emergency medical technicians (EMTs) can safely apply protocols to assign transport options and to assess agreement between groups of providers on application of the protocols. METHODS: Developed protocols categorized patients as: 1) needs ambulance; 2) go to the emergency department (ED) by alternative means; 3) contact primary care provider (PCP); or 4) treat and release. After education on the application of the protocols, first responders and ambulance EMTs categorized patients at the scene prior to transport but did not change current practice. Ambulance reports were reviewed using a predetermined list of critical events that signified the need for an ambulance. RESULTS: The EMTs categorized 1,300 study patients as follows: 1,023 (79%) needed ambulance transport, 200 (15%) could go to the ED by alternative means, 63 (5%) could contact a PCP, 14 (1%) could be treated and released. Categorizations by a first responder and the transporting EMT were compared for 209 patients. Collapsing categories to "need ambulance/do not need ambulance" showed fair concordance (kappa = 0.51). Initially, 30 of 277 (11%) patients determined not to need an ambulance appeared to experience a critical event. After review, 23 patients had events that may not warrant advanced life support transport. Seven (3%) had critical events in the ambulance warranting ambulance transport. Most were miscategorized by the EMT. Overall sensitivity and specificity for identifying patients needing ambulance transport were 94.5% and 32.8%, respectively. CONCLUSIONS: From 3% to 11% of patients determined on scene not to need an ambulance had a critical event. Emergency medical services systems need to determine an acceptable rate of undertriage. Further study is needed to determine whether better adherence to the protocols might increase safety.
Adult↗
The complicated meaning of placebo and placebo effect.
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Ethics, Medical↗
Structural fingerprinting: subgrouping of comoviruses by structural studies of red clover mottle virus to 2.4-A resolution and comparisons with other comoviruses.
Red clover mottle virus (RCMV) is a member of the comoviruses, a group of picornavirus-like plant viruses. The X-ray structure of RCMV strain S has been determined and refined to 2.4 A. The overall structure of RCMV is similar to that of two other comoviruses, Cowpea mosaic virus (CPMV) and Bean pod mottle virus (BPMV). The sequence of the coat proteins of RCMV strain O were modeled into the capsid structure of strain S without causing any distortion, confirming the close resemblance between the two strains. By comparing the RCMV structure with that of other comoviruses, a structural fingerprint at the N terminus of the small subunit was identified which allowed subgrouping of comoviruses into CPMV-like and BPMV-like viruses.
Amino Acid Sequence↗
The structure of cucumber mosaic virus and comparison to cowpea chlorotic mottle virus.
The structure of cucumber mosaic virus (CMV; strain Fny) has been determined to a 3.2-A resolution using X-ray crystallography. Despite the fact that CMV has only 19% capsid protein sequence identity (34% similarity) to cowpea chlorotic mottle virus (CCMV), the core structures of these two members of the Bromoviridae family are highly homologous. As suggested by a previous low-resolution structural study, the 305-A diameter (maximum) of CMV is approximately 12 A larger than that of CCMV. In CCMV, the structures of the A, B, and C subunits are nearly identical except in their N termini. In contrast, the structures of two loops in subunit A of CMV differ from those in B and C. These loops are 6 and 7 residues longer than the analogous regions in CCMV. Unlike that of CCMV, the capsid of CMV does not undergo swelling at pH 7.0 and is stable at pH 9.0. This may be partly due to the fact that the N termini of the B and C subunits form a unique bundle of six amphipathic helices oriented down into the virion core at the threefold axes. In addition, while CCMV has a cluster of aspartic acid residues at the quasi-threefold axis that are proposed to bind metal in a pH-dependent manner, this cluster is replaced by complementing acids and bases in CMV. Finally, this structure clearly demonstrates that the residues important for aphid transmission lie at the outermost portion of the betaH-betaI loop and yields details of the portions of the virus that are hypothesized to mediate binding to aphid mouthparts.
Amino Acid Sequence↗
Molecular characterization and chromosomal distribution of species-specific repetitive DNA sequences from Beta corolliflora, a wild relative of sugar beet.
Repetitive DNA sequences have been isolated from a Sau3AI plasmid library of tetraploid Beta corolliflora (2n = 4x = 36), a wild relative of sugar beet (B. vulgaris). The library was screened by differential hybridization with genomic DNA of B. corolliflora and B. vulgaris. When used as probes for Southern hybridization of genomic DNA, six clones were determined to represent highly repetitive DNA families present only in the B. corolliflora genome. Five other sequences were highly repetitive in B. corolliflora and low or single copy in B. vulgaris. The insert size varied between 43 bp and 448 bp. Two sequences pBC1279 and pBC1944 displayed strong homology to a previously cloned satellite DNA from B. nana. With one exception, sequences are tandemly arranged as revealed by a typical ladder pattern after genomic Southern hybridization. The chromosomal distribution of five probes was determined by fluorescence in situ hybridization (FISH) of mitotic metaphases from B. corolliflora and a triploid hybrid between B. vulgaris and B. corolliflora. Three sequences were spread along all chromosome arms of B. corolliflora while one sequence was present on only six chromosomes. The chromosome-specific sequence pBC216 was found in close vicinity to the 5S rDNA located on B. corolliflora chromosome IV. This set of species-specific sequences has the potential to be used as probes for the identification of monosomic alien addition lines and for marker-assisted gene transfer from wild beet to cultivated beet.
Base Sequence↗
Pre- and postoperative hormonal treatment in patients with hysteroscopic surgery.
Hysteroscopic surgery is widely used for the treatment of patients suffering from infertility and menorrhagia. Preoperative and postoperative treatment plays an important role in this kind of surgery. The indications for hormonal pre- and postoperative treatment are very different and depend on the type of surgery and the condition of the patient. For a septum dissection, preoperative treatment is not necessary. Postoperative estrogen therapy can be helpful especially after dissection of a large septum. For intrauterine adhesiolysis, preoperative treatment is without benefit. In cases of adhesions of grades 3 and 4, postoperative treatment entailing insertion of an IUD and application of estrogens for about 3 months is recommended. A higher amenorrhea rate after endometrium ablation can be reached by pretreatment with a GnRH analogue or danazol. For resection methods, pretreatment is not necessary in any case. The success rate of endometrium ablation (reduction of blood loss) is not influenced by pretreatment. Pretreatment can be useful in coagulation techniques in patients suffering from secondary anemia and in high-risk patient. In patients who need hormone replacement therapy after endometrium ablation, gestagen application is necessary. For prevention of bleedings, a continuous combined hormone replacement therapy should be used and so a bleeding-free treatment is possible. The residual endometrium will so be protected against hyperplasia. Another alternative postoperative method after endometrial ablation is insertion of a levonorgestrel IUS. Our studies show advantages for protection of the endometrium, for contraception and a high amenorrhea rate. Prior to a hysteroscopic myoma resection, pretreatment with GnRH analogues is indicated for all myomas with a diameter of more than 3 cm and/or an intramural portion or for patients suffering from secondary anemia. The aim of the pretreatment is not only to obtain a thin endometrium but also to reduce the size and vascularization of the myomas. The failure rate in patients not treated with GnRH analogues is higher especially in large intramural myomas. Pre- and postoperative hormonal treatment can be effective, especially in the treatment of patients suffering from menorrhagia. The indications for hormonal pre- and postoperative treatment should be very strong. A hysteroscopic surgeon should be also have some experience in hormonal treatment.
Danazol↗
[The pathophysiology of chronic constipation].
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Chronic Disease↗
Differential diagnosis and non-surgical treatment of pelvic actinomycosis.
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Actinomycosis↗
Plasmid DNA for pharmaceutical applications.
With the advent and progress of recombinant DNA technology into a variety of fields such as medical therapy, preventive or curative vaccination or the induction of regeneration, the demand for large quantities of highly purified DNA is increasing. Traditional methods of purifying plasmids usually require sophisticated methodology if the DNA is to be separated from RNA and other contaminating organic components. In particular, methods for obtaining supercoiled covalently closed circular (CCC) plasmid DNA in pure form, cope with the requirement that other plasmid topologies also produced have to be separated from the final product. The innovative technology of capillary gel electrophoresis (CGE) contributes a sensitive tool to the short list of applicable quality control assays for clinical grade plasmid DNA.
Biotechnology↗
Oncogenic potential of cyclin E in T-cell lymphomagenesis in transgenic mice: evidence for cooperation between cyclin E and Ras but not Myc.
To study the oncogenic activity of cyclin E in an in vivo system we generated transgenic mice expressing high levels of cyclin E in T-lymphocytes by using a construct containing the CD2 locus control region. These animals were neither predisposed to develop any tumors spontaneously nor showed an increased incidence when crossbred with Emu L-myc transgenic mice but developed hyperplasia in peripheral lymphoid organs at later age with an incidence of 27%. When treated with the DNA methylating carcinogen N-methylnitrosourea (MNU) that provokes the development of T-cell lymphomas, CD2-cyclin E transgenic animals came down with T-cell neoplasia showing a significant higher incidence (54%) than normal non transgenic controls (31%). In one of eight tumors that arose in normal MNU treated mice we could find an expected activating point mutation in the Ki-ras gene (12.5%). In contrast, the same mutation occurred in five of 16 tumors from CD2-cyclin E transgenic mice (31.2%). Whereas cyclin E overexpression alone did not lead to an increased CDK2 activity we observed in all tumors that emerged from either MNU treated normal mice or treated CD2-cyclin E transgenics a downregulation of p27KIP1 and a higher histone H1 kinase activity in CDK2 immunoprecipitates compared to normal tissue. These findings demonstrate that high level expression of cyclin E can predispose T-cells for hyperplasia and malignant transformation. However, the results also suggest that this activity of cyclin E is manifest only when other cooperating oncogenes in particular ras genes are present and activated. This would be consistent with our previous finding that cyclin E and Ha-Ras cooperate in focus formation assays in rat embryo fibroblasts.
Animals↗
Induction of micronuclei by CsCl in vivo and in vitro.
In the present study, we report the results of an investigation of the potential of nonradioactive CsCl for the induction of micronuclei in polychromatic erythrocytes of mouse bone marrow and in human lymphocytes cultured and blocked with cytochalasin-B. No significant increase in micronucleus frequency was observed in the polychromatic erythrocytes of mice which received 500 mg/kg of CsCl. In vitro experiments with human lymphocytes cultured in medium containing 250 and 500 micrograms/ml CsCl also showed no increase in micronucleus frequency compared to untreated controls. These same experiments, however, demonstrated a reduction in mitotic activity with increasing CsCl concentration in the culture medium. This report is the first to describe studies on the possible induction of micronuclei in vitro and in vivo by nonradioactive CsCl.
Adult↗
The refined crystal structure of cowpea mosaic virus at 2.8 A resolution.
Comoviruses are a group of plant viruses in the picornavirus superfamily. The type member of comoviruses, cowpea mosaic virus (CPMV), was crystallized in the cubic space group I23, a = 317 A and the hexagonal space group P6(1)22, a = 451 A, c = 1038 A. Structures of three closely similar nucleoprotein particles were determined in the cubic form. The roughly 300-A capsid was similar to the picornavirus capsid displaying a pseudo T = 3 (P = 3) surface lattice. The three beta-sandwich domains adopt two orientations, one with the long axis radial and the other two with the long axes tangential in reference to the capsid sphere. T = 3 viruses display one or the other of these two orientations. The CPMV capsid was permeable to cesium ions, leading to a disturbance of the beta-annulus inside a channel-like structure, suggesting an ion channel. The hexagonal crystal form diffracted X rays to 3 A resolution, despite the large unit cell. The large ( approximately 200 A) solvent channels in the lattice allow exchange of CPMV cognate Fab fragments. As an initial step in the structure determination of the CPMV/Fab complex, the P6(1)22 crystal structure was solved by molecular replacement with the CPMV model determined in the cubic cell.
Amino Acid Sequence↗
Quantitative analysis of plasmid forms by agarose and capillary gel electrophoresis.
Plasmids may appear in different forms: circular with different degrees of coiling, partially cleaved or linear, and multimeric as concatamers or catenates. Capillary gel electrophoresis (CGE) of plasmid samples allows the determination of plasmid form distribution. Monomeric and dimeric plasmid DNA forms were separated by both CGE and agarose gel electrophoresis (AGE). The pattern of isoform bands from AGE was compared to the corresponding peak pattern from CGE, and differences in the relative mobility of the plasmid forms between the two methods were found. The comparison of AGE and CGE allows the assignment of AGE bands to CGE peaks. Additionally, the different isoforms can now be quantified by CGE. Routine plasmid form analysis by CGE may be automated, allowing easy, fast, and highly reliable quantification. CGE also offers high resolution and the amount of DNA required is very low. Therefore this method is very useful for the analysis of therapeutics based on plasmid DNA during their production, isolation, and formulation.
Chromatography, High Pressure Liquid↗
Protection against hydrogen peroxide cytotoxicity in rat-1 fibroblasts provided by the oncoprotein Bcl-2: maintenance of calcium homoeostasis is secondary to the effect of Bcl-2 on cellular glutathione.
The oncoprotein Bcl-2 protects cells against apoptosis, but the exact molecular mechanism that underlies this function has not yet been identified. Studying H2O2-induced cell injury in Rat-1 fibroblast cells, we observed that Bcl-2 had a protective effect against the increase in cytosolic calcium concentration and subsequent cell death. Furthermore, overexpression of Bcl-2 resulted in an alteration of cellular glutathione status: the total amount of cellular glutathione was increased by about 60% and the redox potential of the cellular glutathione pool was maintained in a more reduced state during H2O2 exposure compared with non-Bcl-2-expressing controls. In our cytotoxicity model, disruption of cellular glutathione homoeostasis closely correlated with the pathological elevation of cytosolic calcium concentration. Stabilization of the glutathione pool by Bcl-2, N-acetylcysteine or glucose delayed the cytosolic calcium increase and subsequent cell death, whereas depletion of glutathione by dl-buthionine-(S, R)-sulphoximine, sensitized Bcl-2-transfected cells towards cytosolic calcium increase and cell death. We therefore suggest that the protection exerted by Bcl-2 against H2O2-induced cytosolic calcium elevation and subsequent cell death is secondary to its effect on the cellular glutathione metabolism.
Acetylcysteine↗