Intermixing at Au-In and Pd-In interfaces at 90 K as observed by in situ Auger-electron and electron-energy-loss spectroscopy.
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Biomedical subjects
Publications and source records attributed to T Koch.
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The Alt gene product is a component of the T4 phage head. Upon infection of the host cell, approximately 40 copies of the Alt protein enter the cell together with the viral DNA molecule. The Alt protein then ADP-ribosylates one of the two alpha-subunits of host RNA polymerase. A restriction fragment harboring the ADP-ribosyltransferase gene of bacteriophage T4 was cloned into the plasmid vector pBluescript, the nucleotide sequence was determined, and the reading frame was identified. Two M13 clone libraries, established with DNA isolated from bacteriophages T2 and T6, then were screened for the corresponding genes. The nucleotide sequences of the three alt genes and the deduced amino acid sequences were compared. Secondary structure predictions and NAD-binding studies resulted in the location of the substrate-binding site in the NH2-terminal regions of the enzymes.
Whoever believes that the 'scientific' method should not be the sole approach to quality assurance and evaluation research may be attracted to fourth-generation evaluation. The first three generations of evaluation have been categorized as 'measurement-orientated', 'objective-orientated' and 'judgement-orientated', whereas fourth-generation evaluation is 'negotiation-orientated'. In the present paper the author embarks on a description of these generations and makes suggestions for the implementation of fourth-generation evaluation in the health care setting. The appeal of fourth-generation evaluation is that it argues for all 'stakeholders' to have a right to place their claims, concerns and issues on the negotiating table. The evaluator acts as a facilitator of the evaluation process. 'Stakeholders' refers to all people in the setting who are affected by the evaluation, including managers, evaluators, medical and nursing staff. Participation of patients/clients is central in the negotiation process.
The aim of this study was to evaluate the effect of an ultrapure bovine stroma-free hemoglobin (SFH) on pulmonary vascular resistance and mediator release and to analyze potential mechanisms of action in the isolated perfused rabbit lung model. Repetitive bolus applications of small amounts of bovine SFH were examined which resulted in a reproducible acute increase of pulmonary vascular resistance of approx. 9 mmHg (controls, n = 6). It was tested whether the platelet-activating factor (PAF) antagonist WEB 2086 (50 microM; n = 6), the cyclooxygenase blocker diclofenac (10 micrograms/ml; n = 6), the iron-chelating agent deferoxamine (500 micrograms/ml, n = 6) and the radical scavenger catalase (5000 U/ml; n = 6) exert a protective effect on vasoconstrictor response to SFH. The pressure increase was completely suppressed in the lungs pretreated with WEB 2086, whereas diclofenac, deferoxamine and catalase failed to inhibit the vasoconstriction due to SFH. No significant differences in either TXB2 generation or in histamine release were found in the WEB 2086 group compared with untreated lungs. The results point towards the crucial role of PAF in mediation of vasoconstrictor side effects due to SFH.
The aim of this paper is to show the way in which the decision trail of a qualitative research process can be maintained. It is argued that the trustworthiness (rigour) of a study may be established if the reader is able to audit the events, influences and actions of the researcher. The actual study containing the recording of this decision trail aimed to express the concerns of older patients who were admitted to the acute care sector. The study took place in two care of the elderly wards in a 1000-bed National Health Service hospital in the UK, in 1991. Eventually, 14 patients were interviewed, each on several occasions, and their concerns are expressed in themes, namely: routine geriatric style of care, depersonalization, care deprivation and geriatric segregation. I describe the preparations that were undertaken before patient interviews could commence. The literature recording the process of the interviewer's experience as data in qualitative research is scarce. I show the researcher's participation in making the data as part of an existential phenomenological research process. Existential phenomenology relies on recording influences while generating data such as significant literature, media reports, my value position and journal data.
Small volumes of hypertonic NaCl-solutions have been proven to restore haemodynamics in hypovolemic shock patients. Topic of this study was to investigate whether bolus application of 7.5% NaCl-6.5% starch-solution (HSS) apart from its relevance in shock might be an effective therapy in oedema. Considering differential therapeutic aspects, the volume effects of 7.2 ml HSS were tested in three types of oedema: hydrostatic oedema induced by venous congestion (n = 6), oedema caused by bradykinin injection (n = 6), and proteinase-induced oedema (n = 6). The arterial, venous pressure and weight changes indicating volume shifts between intra- and extravascular space were continuously monitored in 36 isolated perfused rabbit hindlimbs. Oedema formation was induced corresponding to a weight gain of 18-20 g. Subsequently 7.2 ml HSS were injected into the extracorporeal circulation system containing 200 ml cell free, isoosmotic perfusate. Six experiments of each oedema group without HSS-application served as controls. 75-100% of oedema formation could be remobilised via bolus application of HSS within 5 min in all types of oedema. A persisting weight reduction was detectable in the hydrostatic and bradykinin oedema, whereas in the elastase oedema the initial weight loss was followed by a regain of weight up to 180% of initial oedema formation at 120 min after HSS-application. The results show that, due to the osmotic gradient induced by bolus application of HSS, the hydrostatic and bradykinin oedema can be permanently remobilised, whereas the therapeutic effect during proteinase oedema is only short-lasting due to an irreversible damage of barrier function.
BACKGROUND: More than 300,000 pacemakers are implanted worldwide. During radiation therapy a damage of the pacemaker electronic is possible. METHODS: Twenty pacemakers have been irradiated with photons or electrons experimentally in three different situations: a) pacemaker and pacemaker electrode outside of the irradiation field: b) pacemaker outside, pacemaker electrode inside the irradiation field; c) all things inside the irradiation field. RESULTS: The voltage in the pacemaker electrode produced by the electric field of the accelerator did not exceed 0.8 mV if the electrode was outside the irradiation field. Induced voltage was up to 1.2 mV during irradiation with electrons (18 MeV) and the electrode being inside the treatment field with more than two thirds of its length. After delivering of not more than 10 Gy (photons) to the pacemaker, a decreasing amplitude of the pacemaker pulse occurred. The pulse frequency did not show any deviation. This seems to signal a severe early irreversible damage of the pacemaker that may cause sudden breakdown days or weeks after radiation. Two pacemakers showed a complete breakdown after irradiation with not more than 10 Gy. The others had a complete breakdown beyond doses of 50 Gy. CONCLUSIONS: It is recommended to keep CMOS pacemakers outside the treatment field and to explant if the dose to it was higher than 10 Gy.
One hundred and twenty (120) women, taking contraceptive pills, underwent a structured interview with a view elucidating their knowledge of the physiology of menstruation, the action and side effects of contraceptive pills and their compliance in the taking of contraceptive pills. The most important sources of information were the medical letters in magazines and the women's own doctors, while the teaching in the Folkeskole (primary and lower secondary school) had not had any major influence on the level of information. Well over one third of the interviewed women knew the most important action mechanism of the contraceptive pill, and half of the women could give a satisfactory explanation of the physiology of menstruation. Twenty-four percent (24%) thought that pregnancy could not occur until 1-2 months after the woman had ceased taking the pill. There was high compliance among the women i.e. that their behavior was correct when they had forgotten to take one or two contraceptive pills, when bleeding was irregular, and when beginning on a new package of pills. Eighty-three percent (83%) had experienced side effects that could be related to contraceptive pills. The investigation shows that there is a need for more efficient information about the effects of the Pill and about the physiology of menstruation.
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Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.
OBJECTIVE: This study was undertaken to discover if impaired blood clearance functions and killing capacity of the reticuloendothelial system contribute to the high occurrence rate of septic complications after shock, trauma, and thermal injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty-three standard-breed rabbits of either sex. INTERVENTIONS: Defined numbers of Escherichia coli (1.3 x 10(8)) colony-forming units were injected intravenously 60 min after induction of hypoxia, standardized by defined reduction of oxygen uptake (60% to 75% of baseline) induced by hypoventilation (n = 6) or hemorrhage (n = 6), after complete defibrination caused by the snake toxin, ancrod (n = 6), and after 60 mins without intervention (controls, n = 6). At 180 mins after bacterial injection, the animals were killed and tissue samples of liver, kidney, spleen, and lung were collected for microbiological examinations. MEASUREMENTS AND MAIN RESULTS: Bacterial elimination from the blood and distribution pattern of viable bacteria in liver, spleen, kidney, and lung were investigated in hemorrhagic, hypoxic, and defibrinated rabbits. Compared with controls, there was a distinct alteration of the elimination kinetics of bacteria from the circulating blood in the experimental groups. First, the initial counts of viable E. coli were up to 300% (p < .05) higher in the defibrination, hemorrhage, and hypoxia groups than in controls. Second, greater numbers of E. coli were found in the blood for a significantly (p < .001) longer period, coupled with up to four times higher counts in organ homogenates in the hemorrhagic and defibrinated groups (p < .01) and more than 100 times higher counts than control values in the hypoxic animals (p < .001). CONCLUSION: Hemorrhage, hypoxia, and intravascular coagulation induce impaired bacterial clearance from the blood that is associated with altered organ distribution patterns, thus reflecting dysfunction of the reticuloendothelial system.
Irradiation (350 nm) of air-saturated solutions of reagents containing an anthraquinone group linked to quaternary alkyl ammonium groups converts supercoiled DNA to circular and to linear DNA. Generation of linear DNA does not occur by accumulation of numerous single-strand cuts but by coincident-site double-strand cleavage of DNA. Irradiation forms the triplet state of the anthraquinone, which reacts either by hydrogen atom abstraction from a sugar of DNA or by electron transfer from a base of the DNA. Subsequent reactions result in chain scission. The quinone is apparently reformed after this sequence and reirradiation leads to double-strand cleavage.
The purpose of the study was to investigate the potential influence of endotoxin and tumor necrosis factor (TNF) on immune function in terms of systemic clearance and organ distribution of injected Escherichia coli in a rabbit model. To enable quantification of the clearance process, defined numbers of exogenous E. coli (1.3 x 10(8) CFU) were injected intravenously 60 min after bolus application of TNF (4 x 10(5) U, n = 6), after infusion of endotoxin (40 micrograms/kg of body weight) for 1 h (n = 6) or 4 h (n = 6), or after saline infusion (controls, n = 6). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. Endotoxin infusion produced a significant delay in blood clearance compared with saline and TNF pretreatment. The diminished systemic bacterial elimination was associated with significantly higher numbers of E. coli in the organs, thus reflecting reticuloendothelial system dysfunction. TNF had no major influence on the elimination kinetics of bacteria but affected the tissue distribution pattern with increased accumulation of E. coli in the lung (up to 100-fold of control values; P < 0.001).
BACKGROUND: The aim of this study was to investigate whether the pulmonary response to inflammatory stimulation, resulting in increased vascular resistance and permeability, could be attenuated by short-term infusion of triglycerides containing omega-3 fatty acids. With the concept of altering the composition of membrane phospholipids in such a manner that stimulation resulted in the release of less vasoconstrictive and permeability-enhancing metabolites of eicosapentaenoic acid instead of those of arachidonic acid (AA), the parenteral application of a lipid emulsion prepared from fish oil (Omegavenös) was tested in comparison with a soy oil preparation (Lipovenös). METHODS: Isolated lungs from anesthetized rabbits were ventilated and recirculatingly perfused (200 ml/min) with 200 ml cell-free buffer solution to which either 2 ml saline (controls, n = 6), 2 ml Lipovenös 10% (n = 6) or 2 ml Omegavenös 10% (n = 6) were added. To study the possible metabolic alterations in states of an enhanced AA turnover, lungs of each group were stimulated with smaller doses of A23187 (10(-8) M) during the 180-min lipid perfusion period, followed by a 10 times higher calcium ionophore A23187 (10(-7) M) challenge after washing out the lipids by exchange of perfusion fluid. Pulmonary artery pressure (PAP) and the lung weight gain indicating edema formation were monitored, and eicosanoids were analyzed in samples of the perfusate. RESULTS: Upon A23187 injection lung weight gain and PAP increase were significantly reduced (50%) in Omegavenös-perfused lungs in comparison with controls and Lipovenös treatment. The vascular reactions were accompanied by a shifting from LTC4 to LTC5 during and after Omegavenös perfusion. CONCLUSION: The data demonstrate that omega-3 fatty acids seem to be incorporated into the phospholipid pool of the pulmonary tissue, even after short-term infusion (3 h) resulting in an attenuated pressure reaction and edema formation due to an altered spectrum of metabolites in the case of inflammatory stimulation.
The influence of a novel pentoxifylline-analogue, HWA 138, on the polymorphonuclear neutrophil leukocyte (PMN)-mediated changes in pulmonary resistance and mediator release was investigated in the isolated perfused and ventilated rabbit lung model. Isolated, washed human granulocytes were injected into the pulmonary artery and stimulated by either 10(-6) mol/L N-formyl-L-leucin-methionyl-L-phenylalanine (FMP) or 3 x 10(-8) mol/L phorbol 12-myristate 13-acetate (PMA) in the presence or absence (controls) of HWA 138 (10(-4) mol/L). Shortly after granulocyte activation, there was a massive generation and release of thromboxane (> 110 pg/ml) and histamine (150-400 nmol/L), with an acute increase of pulmonary artery pressure (> 8 mmHg) in the control groups. Application of HWA 138 almost completely suppressed mediator formation and release as well as pulmonary vascular reaction in the FMP stimulated group. In contrast to this, HWA 138 was unable to influence either mediator release, the pulmonary pressure reaction or interstitial edema formation following PMA stimulation. In the present model, HWA 138 is supposed to be effective via granulocytes by decreasing mediator release, obviously due to burst reaction.
A sandwich-type enzyme reactor in which the enzymes are physically immobilized in a minimal dead space between two cellulose membranes, resulting in improved sensitivity, was developed for the electro-chemical detection of choline (Ch) and acetylcholine (ACh). The reactor contains the enzymes choline oxidase with or without acetylcholine esterase, for the detection of ACh and Ch, respectively. For the HPLC analysis of Ch and ACh the detection system was coupled post column. Levels of Ch and ACh of rat striatum tissue and human cerebrospinal fluid were found to be similar to those determined with published methods. Because of low back pressure--a further advantage of the reactor--the detection system could also be directly coupled to the outlet of a microdialysis device, allowing the on-line real-time measurement of extracellular brain Ch. The versatility of the enzyme reactor for the monitoring of analytes in HPLC eluates, flow injection analysis, with or without prepurification, is emphasized. The usefulness of the reactor-detector system in biomedical applications is illustrated by the measurement of increases of rat striatal extracellular Ch following cardiac arrest.
The adeno-associated virus (AAV) rep gene encodes a series of overlapping, multifunctional, nonstructural proteins (Rep proteins) which regulate the viral life cycle and which are also capable of trans-regulating nonviral gene expressions (reviewed in Berns, 1990, Microbiol. Rev. 54, 316-329). To investigate the expression of the AAV rep gene in a cellular chromosomal context, SV40-transformed Chinese hamster embryo (OD4) cells were infected with an AAV/neo hybrid virus and progeny resistant to the antibiotic G418 were selected and amplified. Chromosomal integration and RNA transcription of the AAV and neo DNA inserts were confirmed by Southern and Northern blotting procedures. One of the G418R cell lines stably expressed a protein which reacted specifically with AAV anti-Rep antiserum in Western immunoblots. The stable integration of AAV rep DNA, which did not interfere with cell proliferation under normal growth conditions, was associated with two changes in cellular phenotype: eight of nine lines were markedly more sensitive to UV light (254 nm) than were the parental OD4 cells; and seven of the nine lines had lost the capacity to promote SV40 origin DNA amplification in vitro, in contrast to the parental OD4 cells. OD4 cells transformed to G418R by AAV/neo DNA constructs with a deleted rep gene, or by a neo DNA construct lacking AAV DNA, did not display these phenotypic changes. It is suggested that stable integration of the AAV rep gene interferes with cellular processes connected with DNA repair and gene amplification.
The distribution of binding sites for atrial natriuretic peptide (ANP) has been examined in frozen sections of the guinea pig inner ear by means of autoradiography. The highest density was found in the stria vascularis of all cochlear turns. In membrane preparations of stria vascularis in vitro, the production of the second messenger cGMP was strongly stimulated by synthetic ANP in a dose dependent manner. Adenylate cyclase was neither stimulated nor inhibited by ANP, thus suggesting, that the binding sites coincide with an ANP receptor, which is coupled to guanylate cyclase but not negatively coupled to an adenylate cyclase molecule. The production of cyclic GMP could not be reduced by GDP-beta S, a strong inhibitor of the Gs protein. We conclude the existence of an ANP receptor-guanylate cyclase signal transfer system, similar to the beta 2 receptor-adenylate cyclase system in the inner ear, without coupling to a G protein. ANP might play a role in sodium and water regulation of the endolymph and might antagonize the action of vasopressin.