Search PubMed⌕ Search

Biomedical subjects

A Mayer

Publications and source records attributed to A Mayer.

At least 37 records · Page 2Linked to original sources

Soluble Fas may be a proinflammatory marker after cardiopulmonary bypass in children.

OBJECTIVES: Ischemia-reperfusion injury after cardiopulmonary bypass is known to provoke an inflammatory response, which can be attenuated with steroid pretreatment. Cardiopulmonary bypass is also known to stimulate apoptosis. Induction of the cellular apoptotic cascade occurs via interaction between two membrane receptors: Fas and Fas ligand. Both molecules also exist in soluble forms, whose significance remains undetermined; however, both may have a proinflammatory role. We aimed to document the temporal profile of soluble Fas and soluble Fas ligand after cardiopulmonary bypass and to investigate whether steroid pretreatment alters this response. METHODS: The study was of a non-randomized, non-blinded, prospective nature. Twenty-seven infants were monitored prospectively, of whom 13 received dexamethasone at induction of anesthesia. Soluble Fas, soluble Fas ligand, and interleukin 6 were measured from induction of anesthesia until 24 hours after admission to the intensive care unit. Data on clinical and laboratory variables were also collected at the same time intervals. RESULTS: As expected, dexamethasone pretreatment attenuated interleukin 6 release and the clinical systemic inflammatory response after bypass. Soluble Fas showed a remarkably similar profile to interleukin 6, in terms of temporal release and attenuation with steroids. There was also a correlation between maximum soluble Fas and markers of capillary leak (colloid requirement and drain loss). Conversely, soluble Fas ligand release was unchanged by cardiopulmonary bypass and steroid administration. However, patients with higher soluble Fas ligand levels exhibited a more dramatic drop and delayed recovery in monocyte count, consistent with the role of this molecule in apoptosis. CONCLUSIONS: Release of soluble Fas and soluble Fas ligand follows a markedly different temporal profile after cardiopulmonary bypass. The similarity between soluble Fas and interleukin 6, together with the attenuation of both with steroids, may suggest a role for soluble Fas as a proinflammatory marker.

Anti-Inflammatory Agents↗

Primary thyroid lymphoma is a heterogeneous disease.

We retrospectively analyzed 26 patients with thyroid lymphoma (TL). Patients were mostly females, with a median age of 59 yr, presenting a rapidly growing nodular goiter with or without cervical adenopathy, without symptoms related to lymphoma for 81% and hypothyroidism in 61%. A previous history of Hashimoto thyroiditis was observed in 11 patients. Six different subtypes of lymphoma were observed: 13 of 26 (50%) had diffuse large B cell lymphoma, 6 (23%) mucosa- associated lymphoid tissue (MALT) lymphoma, 3 (12%) had follicular lymphoma, 2 (7%) had Hodgkin's disease, 1 (4%) had small lymphocytic lymphoma, and 1 (4%) had Burkitt's lymphoma. Diffuse large B cell lymphoma patients presented a compressive multinodular goiter, cervical adenopathy (66%), disseminated disease (50%), and poor performance status, with a poor prognosis (5-yr survival at 44%) despite a treatment based on a multidrug regimen. MALT lymphoma arose in patients with previous history of Hashimoto disease, was localized in all but 1, and was biologically associated with hypothyroidism and a high level of serum antithyroid antibodies. With total thyroidectomy, prognosis was good (5-yr survival at 100%). We did not find any routine clinical or biological parameters that could predict the evolution from Hashimoto's thyroiditis to MALT lymphoma. In conclusion, we confirmed the histological heterogeneity of TL corresponding to different clinical presentations and different prognoses.

Antineoplastic Combined Chemotherapy Protocols↗

(22)Ne(alpha,n)(25)Mg: the key neutron source in massive stars.

The excitation function of the reaction (22)Ne(alpha,n)(25)Mg, the key neutron source in the astrophysical s process in massive stars, has been determined from threshold at E(alpha) = 570 up to 1450 keV with an experimental sensitivity of 10(-11) b. For all resonances in this energy range new resonance parameters have been measured. For a possible resonance at about 635 keV a new upper limit omega gamma < 60 neV for the strength was obtained. Based on the new data, improved reaction rates were calculated as a function of temperature. The new uncertainty limits are considerably smaller than in previous determinations, ruling out the large enhancement factors, up to 500, assumed in some stellar model calculations.

Journal Article↗

Cdc42p functions at the docking stage of yeast vacuole membrane fusion.

Membrane fusion reactions have been considered to be primarily regulated by Rab GTPases. In the model system of homotypic vacuole fusion in the yeast Saccharomyces cerevisiae, we show that Cdc42p, a member of the Rho family of GTPases, has a direct role in membrane fusion. Genetic evidence suggested a relationship between Cdc42p and Vtc1p/Nrf1p, a central part of the vacuolar membrane fusion machinery. Vacuoles from cdc42 temperature-sensitive mutants are deficient for fusion at the restrictive temperature. Specific amino acid changes on the Cdc42p protein surface in these mutants define the putative interaction domain that is crucial for its function in membrane fusion. Affinity-purified antibodies to this domain inhibited the in vitro fusion reaction. Using these antibodies in kinetic analyses and assays for subreactions of the priming, docking and post-docking phase of the reaction, we show that Cdc42p action follows Ypt7p-dependent tethering, but precedes the formation of trans-SNARE complexes. Thus, our data define an effector binding domain of Cdc42p by which it regulates the docking reaction of vacuole fusion.

Adenosine Triphosphatases↗

12C(alpha,gamma)16O: the key reaction in stellar nucleosynthesis.

The angular distributions of gamma rays from the 12C(alpha,gamma)16O reaction have been measured at 20 energy points in the energy range E(cm) = 0.95 to 2.8 MeV. The sensitivity of the present experiment compared to previous direct investigations was raised by 1-2 orders of magnitude, by using an array of highly efficient ( 100%) Ge detectors shielded actively with BGOs, as well as high beam currents of up to 500 microA that were provided by the Stuttgart Dynamitron accelerator. The S(E1) and S(E2) factors deduced from the gamma angular distributions have been extrapolated to the range of helium burning temperatures applying the R-matrix method, which yielded S(300)(E1) = (76+/-20) keV b and S(300)(E2) = (85+/-30) keV b.

Journal Article↗

Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion.

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans-complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2+/calmodulin-dependent fashion. V0 trans-complexes may therefore form a continuous, proteolipid-lined channel at the fusion site. We propose that radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion.

Calmodulin↗

Antibodies to PECAM-1 and glucocorticoids reduce leukocyte adhesion in adjuvant arthritis of the rat knee synovium in vivo.

OBJECTIVE AND DESIGN: To demonstrate the effect of monoclonal antibodies to the adhesion-molecule PECAM-1 (CD31) and of prednisolone on leukocyte adhesion in rat adjuvant arthritis. MATERIAL: Adjuvant arthritis was induced in male CD-rats (five groups of n = 6) 18 days prior to measurements. TREATMENT: Mouse-monoclonal antibody to rat CD-31 at 200 microg/kg or prednisolone at 24 mg/kg were administered i.v. 15 minutes prior to measurements. METHODS: Venules within the intact rat-knee synovium were focused by confocal laser scanning microscopy. Numbers of rolling and adherent leukocytes were assessed in vivo. RESULTS: Induction of arthritis significantly increased rolling and adherent leukocytes compared to healthy controls. Both monoclonal antibodies to PECAM-1 and prednisolone significantly reduced adherent, but not rolling leukocytes in arthritic animals. CONCLUSIONS: The method used is well suited for in vivo quantification of leukocyte adhesion under the influence of antiadhesive therapies. PECAM-1 might be an interesting target for novel therapies in rheumatoid arthritis.

Animals↗

The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis.

OBJECTIVE: Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. PATIENTS: Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. INTERVENTIONS: We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate < 22 mmol/l) either with or without increased UMA (> 3 mEq/l). MEASUREMENTS AND RESULTS: Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P < 0.0001) but not a lower absolute Cl (P = 0.5) in the acidotic subgroup with raised UMA, and by the inverse relationship between TA and the Cl:Na ratio. (coefficient of determination (r2) = 0.37, P < 0.0001). The best discriminator for the presence of raised TA was the albumin-corrected anion gap (AGcorr), however, this could not track changes in TA with clinical accuracy. The Cl:Na ratio discriminated reasonably well, a ratio of < 0.75 identified TA (positive predictive value (PPV) 88%) with a likelihood ratio (LR) similar to the AG (7.8 vs7.4). Conversely, a high ratio (> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. CONCLUSION: In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.

Acidosis↗

Immunology and growth characteristics of ocular basal cell carcinoma.

BACKGROUND: Knowledge about immunological features and growth characteristics of palpebral (ocular) basal cell carcinomas (BCCs) is limited. In particular, it is unclear whether ocular BCC represents in this regard a special BCC entity or not. METHODS: Twenty BCCs of the lid area (ocular BCCs) were investigated immunohistologically using monoclonal antibodies against CD4, CD8, CD45Ro, CD50, CD68, HECA-452, Ki67 (MIB1), and the p53 epitope. For comparison, nine BCCs excised distant from the eye (non-ocular BCCs) were evaluated. RESULTS: In BCCs the distribution of the immunocompetent cells investigated is markedly irregular. These cells are localized mainly around BCC islands. Only a few of them invade tumour cell aggregates. The CD4:CD8 ratio as detected by immunohistochemistry is >1 in 82% of ocular BCCs and in 88% of nonocular BCCs. Often there are dense infiltrations of CD68+ cells (macrophages) and HECA-452+ cells adjacent to tumour cell aggregates. The growth fraction [percentage of proliferating (Ki67+/MIB 1+) cells] varies from 0% to more than 30%. Proliferative activity is enhanced at the invasion front. Additionally, the amount of p53+ cells differs considerably among the BCCs. CONCLUSIONS: CD4+ T cells seem to be the most important cell population for BCC immunosurveillance, offering the chance for conservative interferon therapy. The role of CD68+ and HECA-452+ cells has to be further elucidated. In many tumours the large amount of proliferating cells contrasts to the usually slow growth of BCCs, indicating strong apoptotic processes. The results can be regarded only as semiquantitative. So far, ocular and nonocular BCCs exhibit no essential differences regarding immunocompetent cell infiltration and growth characteristics. According to this, palpebral BCCs are "normal" BCCs and not a special BCC variant. Therefore, results from dermatological research concerning BCC can be extended without limitations to their counterparts in the lid area.

Adult↗

Inverse electronic scattering by singular values decomposition within the Fresnel-Kirchhoff formalism.

The inverse scattering technique we presented previously to enable a sample reconstruction from the diffraction figures obtained by electronic projection microscopy is reforrmulated within the Fresnel-Kirchhoff formalism, which describes the sample as a two-dimensional mask. The method relies on the use of singular values decomposition techniques, thus providing the best least-squares solutions and enabling a reduction of noise. The technique is applied to the analysis of a two-dimensional nanometric sample that is observed in Fresnel conditions with an electronic energy of 40 eV. The algorithm turns out to provide results with a mean relative error around 1% and to be very stable against random noise.

Journal Article↗

Comparison between experimental and computer simulations of current-voltage (I-V) characteristics of dielectric-coated photon-stimulated field emitters.

For the purpose of simulating photon-stimulated field emission by taking account of three-dimensional aspects, a transfer-matrix formulation of electronic scattering was combined with a Floquet expansion of the wave function for taking account of quanta exchanges between the electrons and the external radiation. With specific techniques to preserve numerical stability, this transfer-matrix formalism is well suited to compute the transmission of the field-emitted/photon-stimulated electrons between two electrodes. This theory is applied to the computation of Fowler-Nordheim curves describing the photon-stimulated field emission of a tungsten plane emitter (described by z< or =0), which supports a nanometric protrusion and a dielectric coating. The extraction bias ranges from 12 to 24V, for an inter-electrode distance of 4nm. The electromagnetic radiation has a wavelength of 0.67 microm and a power flux density ranging from 5.96 x 10(10) to 5.96 x 10(12) W/m2. The effects due to the protrusion and the dielectric coating are studied. These theoretical results are compared with the experimental data.

Journal Article↗

Real-space formulation of the quantum-mechanical electronic scattering under static n-fold axially symmetric electric and magnetic fields in a projection microscope.

A numerical technique is developed to compute electronic propagation in three-dimensional potential-energy and vector-potential distributions, as required for the quantum-mechanical modelization of scattering in static electric and magnetic fields in a projection microscope. The technique is implemented in a transfer-matrix and Green's functions general procedure to simulate field-emission and electronic projection microscopy. In particular, simulated observations of a transverse magnetic field confirms the occurrence of diffraction fringes that are oriented in the direction of the field. These diffraction fringes are mainly associated with the detection of a magnetic flux and tend to be more pronounced as this quantity increases. In the conditions of this paper, the smallest magnetic flux that was detected could be associated with a phase shift of around 2pi/8 rad.

Journal Article↗

What drives membrane fusion in eukaryotes?

The fusion of biological membranes is the terminal step of all vesicular trafficking reactions in eukaryotic cells. Therefore, this fusion is fundamental for the transfer of proteins and lipids between different compartments, for exocytosis and for the structural integrity of organelles. In the past decade, many parts of the molecular machinery involved in fusion have been uncovered. Although the mechanisms responsible for mutual recognition and binding of membranes inside eukaryotes are becoming reasonably well known, there is considerable uncertainty as to what causes the actual merging of the lipid bilayer. Two classes of mechanisms have been proposed. Proximity models postulate that very close apposition of membranes suffices to induce fusion. By contrast, pore models propose that continuous proteinaceous pores between apposed membranes could be the basis for fusion.

Animals↗

Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia.

OBJECTIVE: Inflammatory bowel disease (IBD)-associated anemia responds to i.v. iron therapy. However, because of concurrent chronic inflammation, some patients do not respond adequately. Erythropoietin therapy has been shown to be effective in the latter cohort. Our goal was to find parameters that can predict the effectiveness of iron sucrose in IBD-associated anemia. METHODS: One hundred three patients with severe IBD-associated anemia (Hb < or = 10.5 g/dl) were treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an open label, multicenter trial. Treatment response was defined as an increase in Hb of > or =2.0 g/dl. A logistic regression analysis was performed with treatment response as the dependent variable and the following independent variables: serum erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity. RESULTS: Sixty-seven of 103 patients (65%) responded to iron sucrose. From the variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were significantly associated with treatment response. The R2 values showed that erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6 (1.3%), contribute a relevant amount of information to the model. An estimated 80% probability of treatment response was found at erythropoietin levels of >166 U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L. CONCLUSIONS: Serum erythropoietin, sTfR, and transferrin concentrations have the potential to predict the response to iron sucrose therapy in IBD-associated anemia. These parameters may help to identify individuals who benefit the most from additional erythropoietin treatment.

Anemia, Iron-Deficiency↗

[Radio-chemotherapy of locally advanced head and neck cancer, providing tissue and organ protection]

PURPOSE: the study of the effect of Amifostine in reducing acute mucositis, xerostomia and late xerostomia emerging in the course of locally advanced head and neck cancer radio-chemotherapy. METHODS: Starting in 1999 we have conducted radio-chemotherapy treatment on 7 patients with or without Amifostine protection, each receiving 60 Gy (2 Gy a day/5 fractions a week) loco-regional irradiation. From the first to the fifth day and from the twenty-first to the twenty-fifth day prior to irradiation they were given a 70 mg/m(2) Carboplatin treatment. In the Amifostine group, on days 1-5 and 21-25 300 mg/m(2) and on days 6-20 and 26-30 200 mg/m(2) Amifostine therapy was given prior to the radio- and chemotherapy. RESULTS: In the course of the trial we did not find any haematologic side effects, or side effects directly connected to the Amifostine, which would have required suspension of the therapy. In the active phase, mucositis of Grade 1-2 was detected 1-2 weeks later than in the control group, in contrast to the mucositis of Grade 2-3 in the other arm. Global oral discomfort associated with acute xerostomia was of Grade 4-6 on a linear scale of ten, compared with Grade 7-8 on the active line. We had similar results when testing the symptoms directly connected with late xerostomia. Unstimulated and stimulated saliva production doubled following the Amifostine treatment. CONCLUSION: Despite the small pool of patients we have the impression that Amifostine can effectively reduce the severity of acute mucositis, xerostomia and late xerostomia.

Journal Article↗

[Radiochemotherapy of bladder cancer with/without tissue-organ protection]

The authors report the results of radiochemotherapy for bladder cancer, both advanced and early with a poor prognosis, on the basis of their own material as well as based on the literature. More than half of the patients received radioprotective madication at the same time. The short follow-up does not allow for far-reaching conclusions, but early results and limited complications appear hopeful. The authors emphasise that, if indicated, radiochemotherapy can serve as an alternative to cystectomy.

Journal Article↗

[Electronic portal imaging (EPI) on linear accelerator]

The EPI has become available recently in the Oncoradiological Centre of Budapest. The purpose of this paper is to review the construction and operation of the electronic portal imaging devices (EPIDs). The different EPID systems as well the EPID technique vs. portal films are compared. The advantages in patient set-up and the detection of the set-up errors are discussed. The use of the EPID technique in the clinical everyday practice is detailed. Recommendations of the set-up error correction for the most often occurring failures is given.

Journal Article↗

[Preoperative radiation therapy for rectal cancer. personal experience]

PURPOSE: Comparison of the effectiveness of preoperative and "sandwich" (preoperative and postoperative) radiation therapy in the treatment of midrectum and lower rectum carcinoma, based on a prospective clinical trial. MATERIAL AND METHOD: Over the period between 1990 and 1997, we treated 115 patients suffering from mid-rectum and lower rectum carcinoma at the Budapest Oncoradiological Centre, using sandwich therapy (22.5 Gy preoperative-27.5 Gy postoperative) in the case of 36 patients and 36 Gy preoperative radiation therapy in the case of 79 patients with external-beam megavoltage therapy with mostly telecobalt radiation and to a smaller number of cases 6 MV energy. The external-beam radiation therapy was nearly always applied with a 4-field box technique, and radical surgery was performed within 10 days following the preoperative radiation treatment. Effectiveness was evaluated in terms of a Log-Rank and Peto-Wilcoxon tests and the Kaplan-Meier survival curve. RESULTS: The effectiveness of the different therapies was compared in terms of the percentage of local failure and the rate of disease-free survival. The results show that when using the "sandwich" radiation therapy local failure is expected to occur in 13.8% of all cases, compared with 17.7%, when only preoperative radiation therapy is used. In terms of five-year disease-free survival, the sandwich therapy seems to be better, but for a higher number of years, namely 7.5, the preoperative radiation therapy yielded better results. CONCLUSION: In terms of local failure, the effectiveness of the preoperative and the "sandwich" radiation therapies for the treatment of mid-rectum and lower rectum carcinoma was nearly identical, while preoperative radiation therapy provided longer disease-free survival. Further trials using multivariation analysis need to be performed to evaluate the two types of radiation treatments, taking into account other parameters, such as grading, age and lymphatic spread.

Journal Article↗