[In vitro fertilization. Life situation and expectations of couples waiting for treatment show the need of supportive discussion].
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Counseling↗
Biomedical subjects
A Möller
Publications and source records attributed to A Möller.
Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis.
Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine that is produced by monocytes and keratinocytes upon stimulation. Because psoriasis is a skin disease characterized by a hyperproliferative activity of keratinocytes and an inflammatory infiltrate, in the present study IL-6 production of monocytes and keratinocytes of patients with psoriasis was investigated. Peripheral blood mononuclear cells (PBMC) derived from psoriatics, atopics, and healthy controls were incubated for 24 h and, subsequently, supernatant IL-6 activity was measured using an IL-6-dependent hybridoma cell line (B9). Compared to controls and atopics, PBMC of psoriatics produced significantly increased amounts of biologically active IL-6. These findings were also confirmed by Western blot analysis using a specific antiserum directed against IL-6. Moreover, when the sera of the same patients were tested for IL-6 activity, sera of psoriatics contained significantly elevated amounts of circulating IL-6 in comparison to samples from atopics and healthy controls. In contrast to normal or uninvolved skin, keratinocytes in psoriatic lesions were remarkably positive for IL-6 as detected by immunohistochemistry and in situ hybridization. In addition, IL-6 also was found to induce its own synthesis and release by monocytes. These findings indicate that keratinocytes and monocytes in psoriasis are activated to produce increased amounts of IL-6, which may be one of the mediators involved in the regulation of both local and systemic inflammatory reactions occurring in skin diseases such as psoriasis.
Adult↗
Radiography transculcitam: technique and devices to simplify bedside radiography.
Bedside chest radiography may be simplified by placement of the cassette under the mattress instead of directly under the patient. With the cassette pressed down into the mattress, a horizontal lateral view can be obtained without having to lift the patient. One technician can use two simple devices to obtain anteroposterior and lateral views, even of a heavy, unconscious patient. A cassette holder for cross-table views of small subjects is also described.
Beds↗
Low incidence of transplant-related complications in patients with chronic release of tumor necrosis factor-alpha before admission to bone marrow transplantation: a clinical correlate of cytokine desensitization?
To investigate the role of tumor necrosis factor-alpha (TNF-alpha) released by activated macrophages, sequential serum samples of 120 patients undergoing bone marrow transplantation (BMT) were analyzed by enzyme-linked immunosorbent assay. De novo increases in serum TNF-alpha levels were correlated with the development of acute endothelial complications as well as acute graft-versus-host disease. In addition, the analysis of time courses revealed a different capacity of TNF-alpha regulation at various phases of BMT. While patients with acute TNF-alpha release in the first 2 weeks of BMT had a significantly enhanced incidence of complications, a subgroup of 9 patients with chronic asymptomatic release of TNF-alpha before admission to BMT was observed. These patients were protected from complications in the course of the first 6 months of BMT. Our observations indicate the occurrence of desensitization for TNF-alpha, as it is also reported after repeated injections of TNF-alpha or endotoxin in experimental models.
Adolescent↗
In vitro generation of smooth muscle-contracting leukotrienes from isolated epidermal cells.
Single-cell suspensions of murine and human epidermal cells were studied for the presence of peptidoleukotrienes (LTs), using in vitro guinea pig ileum contraction as bioassay and a commercial radioimmunoassay. The calcium ionophore A23187 at 5 x 10(-6) M alone or in combination with arachidonic acid at 10(-4) M caused release of LTC4/D4 within 10-30 min and for up to 18 h. LTB4, as was measured in the chemotaxis assay, was released at different levels and with different kinetics from the same cells. Epidermal cells may thus regulate cutaneous inflammation by secreting potent vasoactive and muscle-contracting in addition to chemotactic lipid mediators.
Animals↗
Mast cells and their mediators in immediate and delayed immune reactions.
Tissue mast cells and the closely related blood basophils are distinguished by their special mediators and their high-affinity IgE membrane receptors. These properties have made the cells be viewed traditionally as effector cells of immediate-type hypersensitivity reactions. More recently, mast cells have been shown to develop from the myeloid series of the bone marrow under the influence of interleukins 3, 4, 6, 9, 10 and 11. Mast cell and basophil lines of murine and human origin have also been shown to express and release interleukins 1, 3, 4, 5, 6, 8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulizing factor and interferon-gamma. Certain cytokines are also able to induce mediator release from mast cells. Furthermore, mast cells have in the past been shown to be modestly phagocytic and to express major histocompatibility complex class II membrane markers after appropriate stimulation. These findings show that mast cells are intricately associated with immune reactions and suggest that they may not only sustain and modulate but possibly also initiate immune responses.
Animals↗
Evaluation of measurement of human TNF in plasma by ELISA.
The performance of a sandwich-ELISA for TNF measurement in plasma and serum was studied. The ELISA was first statistically analyzed. Interassay coefficient of variance and the intraassay coefficient of variance for the concentration range between 0.5 and 5 ng/ml was less than 10%. The sensitivity of the sandwich-ELISA for TNF in culture medium was 10 pg/ml. The ELISA was shown to be specific for biologically active TNF, since a good correlation between the ELISA and the WEHI bioassay was observed when partially inactive, denatured TNF was measured. The effect of various anticoagulation systems on the reliability of human TNF measurement has been evaluated. The oxalate/NaF and EDTA systems were both appropriate, as appeared from the observed blockade of the production of TNF in the tube, either in the cell-glycolysis-blocked or in the calcium-depleted situation, respectively. An eventual decrease in the recovery of rTNF after collection of blood was prevented in the oxalate/NaF tubes. Recovery of TNF in the ELISA was diminished in the presence of plasma or serum. Techniques to enhance the efficiency of the measurement of TNF in plasma by ELISA were compared. The data indicate that in the presence of 1.1 M NaCl, the TNF masking effect of normal plasma was largely abrogated. The presence and role of inhibiting plasma components in plasma of healthy and diseased individuals are discussed.
Biological Assay↗
Treatment of aGVHD with OKT3: clinical outcome and side-effects associated with release of TNF alpha.
Monoclonal antibodies are increasingly used for treatment of acute graft-versus-host disease (aGVHD) in bone marrow transplantation. We treated seven patients with steroid resistant aGVHD with the monoclonal anti-T cell antibody OKT3. Though five patients showed improvement of aGVHD, only two became long-term survivors. OKT3 treatment was accompanied by deterioration of microangiopathy and prolonged increase of tumor-necrosis-factor alpha serum levels indicating activation of monocytes/macrophages in vivo, as this was not observed in a control group of patients receiving anti-T cell globulin. These findings may be related to immunostimulatory activity reported for OKT3 in vitro. Strategies interfering with cytokine release should improve clinical results of OKT3 treatment.
Acute Disease↗
Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation.
Acute graft-versus-host disease, interstitial pneumonitis, endothelial leakage syndrome, and veno-occlusive disease are major complications of bone marrow transplantation. Though several new regimens for prophylaxis and treatment of these syndromes have been introduced, the overall incidence has been only slightly reduced over the last few years. We retrospectively analyzed tumor necrosis factor alpha (TNF alpha) serum levels between day -8 and day 100 after bone marrow transplantation in 56 patients transplanted in our unit for a variety of hematological diseases. In 34 patients with uneventful courses, mean TNF alpha levels rose to a maximum of 76 +/- 29 pg/mL. In contrast, 22 patients with major transplant related complications showed mean increases of TNF alpha of 492 +/- 235 pg/mL (P less than .0001). Increases of TNF alpha occurred before interstitial pneumonitis and severe acute graft-versus-host disease with a latency of 25 to 54 days. Early complications such as endothelial leakage syndrome and veno-occlusive disease were closely associated with increases of TNF alpha serum levels. Our study suggests two pathways of TNF alpha release: activation of host macrophages and stimulation of donor cells in the course of acute graft-versus-host disease. Cytokine monitoring should be helpful for prediction and earlier treatment of major transplant related complications.
Adolescent↗
Monoclonal antibodies to human tumor necrosis factor alpha: in vitro and in vivo application.
Three stable murine hybridoma cell lines, which secrete monoclonal antibodies (mAb) to human tumor necrosis factor alpha (TNF alpha), were established. None of the monoclonal antibodies cross-reacted with lymphotoxin, interleukin 2 (IL 2) or Interferon gamma (IFN gamma). The highly species-specific monoclonal antibody, designated as mAb 195, neutralizes the cytotoxic activity of human and chimpanzee TNF alpha. This antibody was further used during in vivo studies to neutralize human TNF alpha in a murine animal model. The mAb 114 is a weakly neutralizing antibody that binds to a different epitope of TNF alpha than mAb 195. mAb 114 shows a wide range of cross-reactivity with TNF alpha of the following species: dog, pig, cynomolgus, rhesus, baboon and chimpanzee. The mAb 199 binds to human TNF alpha, but does not neutralize the cytotoxic activity. The epitope recognized by this mAb is in close proximity to mAb 114. A reproducible, sensitive immunoassay for human TNF7 alpha has been developed using the antibodies mAb 199 and mAb 195. The test is performed within 6 hr and detects TNF7 alpha in serum samples, with a limit of detection of 5 to 10 pg/mL.
Animals↗
Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression.
Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC.
Biological Factors↗
Immunomodulating cytokines in atopic dermatitis and psoriasis: production of tumour necrosis factor and lymphotoxin by mononuclear cells in vitro.
The immunomodulating cytokines, tumour necrosis factor/cachectin (TNF) and lymphotoxin (LT) are thought to play an essential role as mediators of inflammatory reactions. To evaluate the role of TNF and LT in atopic dermatitis (AD) and psoriasis, we investigated their production by mononuclear cells (MNC) in vitro. The 24-h supernatants of lipopolysaccharide (LPS)- and phytohaemagglutinin (PHA)-stimulated and unstimulated MNC from 26 patients with AD and 20 with psoriasis and from 17 non-atopic healthy controls were tested for the concentrations of TNF and LT using an ELISA technique. In patients with AD, TNF levels were significantly decreased in the supernatant of PHA-stimulated (P less than or equal to 0.005) and LPS-stimulated (P less than or equal to 0.02) MNC in comparison to controls. There was no significant difference in TNF production between psoriatic patients and the control group. Release of LT in the supernatant of PHA-stimulated MNC by patients and controls did not differ significantly. There was no significant spontaneous production of TNF and LT by MNC of patients and controls. These studies indicate that different immunomodulating mechanisms are responsible for triggering the inflammatory response in AD and psoriasis.
Adolescent↗
Differential effect of diacylglycerols and phorbol ester on arachidonic acid metabolism in bone marrow-derived macrophages.
Murine bone marrow-derived macrophages were induced to prostaglandin synthesis by activators of protein kinase C, the phorbolester TPA and the diacylglycerols dioctanoylglycerol (diC8) and diolein (diC18:1). As short term stimulation of prostaglandin synthesis is mainly dependent on the availability of free arachidonic acid, the modulation of arachidonic acid liberation and reacylation was investigated. DiC8 inhibited the reacylating enzyme lysophosphatide acyltransferase in the in vitro assay, but there was no evidence for an inhibitory effect of TPA or diacylglycerols on the activity of the lysophosphatide acyltransferase in whole cells. The release of arachidonic acid from prelabelled cells was stimulated by TPA and the diacylglycerols even in the presence of an inhibitor of reacylation, indicating an activation of phospholipase A2. An activation of phospholipase A2 was measured in membranes derived from TPA-stimulated macrophages. These data indicate that the enhanced pool of free arachidonic acid, which drives prostaglandin synthesis, is primarily due to a stimulation of the liberation of arachidonic acid from membrane phospholipids.
Animals↗
[Alpha tumor necrosis factor in the serum of patients with sarcoidosis, tuberculosis or bronchial cancer].
Tumor-necrosis-factor-alpha (TNF-alpha), which is secreted by cells of the macrophage/phagocytic system, interact in a variety of different ways with other cytokines and immunologically active substances. To investigate a possible role of TNF-alpha in granulomatous lung diseases and to determine whether sarcoidosis can be differentiated from tuberculosis on the basis of serum TNF-alpha levels, we studied sera from patients with sarcoidosis and active tuberculosis. Ninety-one percent of the patients with sarcoidosis and 83% of the patients with tuberculosis exhibited significantly elevated TNF-alpha levels as compered with controls. Since these levels remained elevated irrespective of clinical stage and even under therapy, it is believed that patients with sarcoidosis and tuberculosis experience continuous activation of TNF-2-alpha-producing cells of the myelomonocytic system. In addition, determination of serum TNF-alpha levels does not permit differentiation between sarcoidosis, tuberculosis or malignant disease.
Adult↗
[Infertility is not only a medical phenomenon but a life crisis].
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Female↗
Aberrant eating behavior in elderly parkinsonian patients with and without dementia: analysis of video-recorded meals.
Aberrant eating behavior among 14 elderly, non-demented and 10 demented patients with Parkinson's disease was studied by means of video-recordings. The findings revealed problems in handling food on the plate, transporting food into the mouth, manipulating food in the mouth, and swallowing. Interpretations were performed based on impairments of autonomic processes, perception, cognition, emotion, and motor performance that occur in the disease.
Aged↗
Creatine transport in cultured cells of rat and mouse brain.
Astroglia-rich cultures derived from brains of newborn rats or mice use a transport system for the uptake of creatine. The uptake system is saturable, Na+-dependent, and highly specific for creatine and Na+. Kinetic studies on rat cells revealed a Km value for creatine of 45 microM, a Vmax of 17 nmol x h-1 x (mg of protein)-1, and a Km value of 55 mM for Na+. The carrier is competitively inhibited by guanidinopropionate (Ki = 15 microM). No such transport system was found in neuron-rich primary cultures from embryonic rat brain. It is hypothesized that creatine transport is an astroglial rather than a neuronal function.
Animals↗
[Incidence and pathogenesis of ocular symptoms in HIV infection].
202 patients with HIV infections of different stages [1 (n = 59): symptomless HIV seropositivity, 2 (n = 64): pre-AIDS (LAS = Lymphadenopathy syndrome, ARC = AIDS related complex), 3 (n = 79): AIDS] were prospectively examined. The findings of the first examination were analyzed statistically in a cross-section-study. In 15 AIDS autopsy cases the eyes were examined histopathologically and with immunohistochemical techniques. Patients with stage 1 had only some Sicca syndromes (3%) and neuroophthalmological signs (dyscoria with neurosyphilis) (2%). 14% of the patients with stage 2 had a microvascular retinal syndrome, 11% a Sicca syndrome and 2% neuroophthalmological signs. Among the AIDS patients (stage 3), however, 61% had a microvascular syndrome of the retina, 24% a retinitis resp. choroiditis as an opportunistic infection (in 15% Cytomegalovirus was the causative organism), 16% had neuroophthalmological symptoms, 14% a Sicca syndrome and 5% Kaposi's sarcoma of the eyelids or conjunctiva. The microvascular retinal syndrome was found to be the most sensitive ocular indicator for an advanced stage of HIV infection. Further changes of the anterior eye segments (especially conjunctival vessel abnormalities and precipitates of the corneal endothelium in Cytomegalovirus retinitis) are demonstrated.
Adult↗