Showing papers by "Free University of Berlin published in 1993"

Inhaled Nitric Oxide for the Adult Respiratory Distress Syndrome

Abstract: Background The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange. Methods Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days. Results Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (±SE) pulmonary-artery pressure from 37 ±3 mm Hg to 30 ±2...

Physical Exertion as a Trigger of Acute Myocardial Infarction

Abstract: Background It is controversial whether the onset of myocardial infarction occurs randomly or is precipitated by identifiable stimuli. Previous studies have suggested a higher risk of cardiac events in association with exertion. Methods Consecutive patients with acute myocardial infarction were identified by recording all admissions to our hospital in Berlin and by monitoring a general population of 330,000 residents in Augsburg, Germany. Information on the circumstances of each infarction was obtained by means of standardized interviews. The data analysis included a comparison of patients with matched controls and a case-crossover comparison (one in which each patient serves as his or her own control) of the patient's usual frequency of exertion with the last episode of exertion before the onset of myocardial infarction. Results From January 1989 through December 1991, 1194 patients (74 percent of whom were men; mean age [±SD], 61 ±9 years) completed the interview 13 ±6 days after infarction. We found tha...

An identified neuron mediates the unconditioned stimulus in associative olfactory learning in honeybees

Abstract: DURING classical conditioning, animals learn to associate a neutral stimulus with a meaningful, or unconditioned, stimulus. The unconditioned stimulus is essential for forming associations, and modifications in the processing of the unconditioned stimulus are thought to underlie more complex learning forms1–4. Information on the neuronal representation of the unconditioned stimulus is therefore required for understanding both basic and higher-order features of conditioning. In honeybees, conditioning of the proboscis extension reflex occurs after a single pairing of an odour (conditioned stimulus) with food (unconditioned stimulus)5,6 and shows several higher-order features of conditioning6–8. I report here the identification of an interneuron that mediates the unconditioned stimulus in this associative learning. Its physiology is also compatible with a function in complex forms of associative learning. This neuron provides the first direct access to the cellular mechanisms underlying the reinforcing properties of the unconditioned stimulus pathway.

IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor.

Abstract: Normal melanocytes require a number of exogenous growth factors in contrast to most metastatic malignant melanomas. This investigation demonstrates that endogenously produced human IL-8 can act as an important growth factor for human melanoma cells. In the present study, six out of eight human melanoma cell lines tested secrete IL-8 protein into the culture supernatant. In two of these IL-8-secreting melanoma cell lines, SK-MEL 13 and SK-MEL 23, we have determined the IL-8 requirement for their proliferative capacity. These melanoma cell lines produced significant amounts of bioactive IL-8 as measured by the ELISA technique. Secretion of human IL-8 was inducible by IL-1 and by PMA. Human IL-8-specific mRNA was already detected in unstimulated melanoma cells. In addition, human IL-8-R mRNA could be detected for the first time in human melanoma cells. Exposure of the two melanoma cell lines in vitro to antisense oligonucleotides targeted against two different sites of human IL-8 mRNA-inhibited cell proliferation, colony formation in soft agar, and secretion of IL-8 protein into culture supernatant in a dose dependent fashion. Effects were reversible either by removal of the oligomers or by addition of exogenous IL-8 protein. In contrast, exposure to IL-8 sense probes or oligonucleotides in sense or antisense orientation specific for IL-7, TGF-alpha, TGF-beta, and MGSA had no such effect. A monospecific immune serum and two IL-8-specific mAb were also capable of inhibiting melanoma cell proliferation in the same manner. These results provide strong evidence for an autocrine IL-8 synthesis and for an IL-8-dependent proliferation in a subgroup of human melanomas. Furthermore, they suggest that IL-8 may play a role not only in immunomodulation but also in melanoma progression and metastatic spread.

Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins

Abstract: Various heterotrimeric guanine nucleotide-binding proteins have been identified on the basis of the individual subtypes of their alpha subunits. The beta gamma complexes, composed of beta and gamma subunits, remain tightly associated under physiological conditions and have been assumed to constitute a common pool shared among various guanosine triphosphate (GTP)-binding (G) protein heterotrimers. Particular alpha and beta subunit subtypes participate in the signal transduction processes between somatostatin or muscarinic receptors and the voltage-sensitive L-type calcium channel in rat pituitary GH3 cells. Among gamma subunits the gamma 3 subtype was found to be required for coupling of the somatostatin receptor to voltage-sensitive calcium channels, whereas the gamma 4 subtype was found to be required for coupling of the muscarinic receptor to those channels.

Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome

Abstract: Inhalation of nitric oxide (NO), an endogenous vasodilator, was recently described to reduce pulmonary vascular resistance, and to improve arterial oxygenation by selective vasodilation of ventilated areas in patients with adult respiratory distress syndrome (ARDS). We describe the time-course and dose-response of initial short-term NO inhalation in 12 patients with ARDS. Enhanced oxygenation was achieved within 1-2 min after starting NO inhalation; after inhalation, baseline conditions were re-achieved within 5-8 min. Effective doses for improvement of oxygenation [baseline: PaO2 = 10.2 +/- 2.5 KPa (76.4 +/- 18.7 mmHg)] were low: ED50 was about 100 ppb--a concentration similar to the atmosphere. NO doses of more than 10 ppm [10 ppm NO: PaO2 = 17.3 +/- 3.3 KPa (129.4 +/- 25.1 mmHg)] re-worsen the arterial oxygenation. The ED50 for reduction of mean pulmonary artery pressure was 2-3 ppm. This indicates that inhalation of NO for improvement of oxygenation in severe ARDS should be performed using lower doses, with lower risk of toxic side effects.

Percutaneous endoscopic discectomy: surgical technique and preliminary results compared to microsurgical discectomy

Abstract: ✓ Percutaneous endoscopic discectomy is a new technique for removing “contained” lumbar disc herniations (those in which the outer border of the anulus fibrosus is intact) and small “noncontained” lumbar disc herniations (those at the level of the disc space and occupying less than one-third of the sagittal diameter of the spinal canal) through a posterolateral approach with the aid of specially developed instruments. The technique combines rigid straight, angled, and flexible forceps with automated high-power suction shaver and cutter systems. Access can thus be gained to the dorsal parts of the intervertebral space where the disc herniation is located. Percutaneous endoscopic discectomy is monitored using an endoscope angled to 70° coupled with a television and video unit and is performed with the patient under local anesthesia and an anesthesiologist available if needed. Its indication is restricted to discogenic root compression with a minor neurological deficit. Two groups of patients with contained ...

Modern cryptic microbialite/metazoan facies from Lizard Island (Great Barrier Reef, Australia) formation and concepts

Abstract: From shallow water caves of fringing reefs related to continental islands of the Lizard Island Section thrombolitic micritic microbialites were observed. The microbialites exhibit always a light decreasing facies succession. The succession starts with a coralgal community and ends with light independent microbial biofilms and benthos (coralline sponges). The sessile mineralized benthos community is constructed of crustose foraminifera, serpulids, thecidean brachiopods, bryozoans, and coralline sponges. The observed benthic community is very similar to those one observed in cryptic habitates of Aptian and Albian reefs of northern Spain. For longtime studies of the microbialite formation and growth rates of coralline sponges the specimens were stained in vivo, within their natural habitat with histochemical fluorochromes and nonfluorescent agents. Main results are a very slow growth of the microbialite and associated sponges (50–100 μm/y). Only few calcifying microbes are participators during microbialite formation. Calcifying acidic organic macromolecules are mainly responsible for microbialite formation by cementing detritical material. Fe/Mn-bacterial biofilms are responsible for strong corrosion of the microbialite. Beside the corrosive activity of the Fe/Mn-bacterial biofilms boring sponges (Aka, Cliona) are the main destructors. Geochemically the observed microbialites are composed of mainly high-Mg calcites and exhibit high positive δ13C (+3 to +4) values.

Three-dimensional structure of system I of photosynthesis at 6 Å resolution

Abstract: X-ray structure analysis shows that the monomer of trimeric photosystem I (PS I) of Synechococcus sp. consists of a catalytic domain and a smaller domain that connects the monomers. The 4Fe–4S clusters FX,FA and FB, 28 α-helices and 45 chlorophyll a molecules were located. The two large subunits of PS I are represented by nine a-helices each; they are related by a local 2-fold rotation axis passing through Fx. Electron densities close to this axis are interpreted as carriers of the electron transfer chain.

Universal nucleic acid-binding domain revealed by crystal structure of the B. subtilis major cold-shock protein.

Abstract: The cold-shock response in both Escherichia coli and Bacillus subtilis is induced by an abrupt downshift in growth temperature. It leads to the increased production of the major cold-shock proteins, CS7.4 and CspB, respectively. CS7.4 is a transcriptional activator of two genes. CS7.4 and CspB share 43 per cent sequence identity with the nucleic acid-binding domain of the eukaryotic gene-regulatory Y-box factors. This cold-shock domain is conserved from bacteria to man and contains the RNA-binding RNP1 sequence motif. As a prototype of the cold-shock domain, the structure of CspB has been determined here from two crystal forms. In both, CspB is present as an antiparallel five-stranded beta-barrel. Three consecutive beta-strands, the central one containing the RNP1 motif, create a surface rich in aromatic and basic residues that are presumably involved in nucleic acid binding. Preferential binding of CspB to single-stranded DNA is observed in gel retardation experiments.

Dynamics of strong and fragile glass formers: Differences and correlation with low-temperature properties.

Abstract: Low-frequency Raman spectra of strong and fragile glass forming liquids were measured in a wide temperature range. From an analysis of the spectra and literature data it is found that the main difference in the dynamic structure factor is the ratio of vibrational to relaxational contributions: The stronger the glass former the higher this ratio. It is shown that this difference survives even at very low temperatures and determines the low-temperature anomalies of glasses. A possible way how the observed difference influences the fragility of a liquid is discussed.

PG-M1: A new monoclonal antibody directed against a fixative-resistant epitope on the macrophage-restricted form of the CD68 molecule

Abstract: A new anti-macrophage monoclonal antibody (PG-M1) was produced by immunizing BALB/c mice with fresh spleen cells from a patient with Gaucher's disease. PG-M1 reacts strongly with a fixative-resistant epitope of an intracytoplasmic molecule, selectively expressed by virtually all macrophages of the human body. Although attempts to immunoprecipitate the molecule recognized by PG-M1 have failed so far, the reactivity of the antibody with COS-1 and WOP cells transfected with a human complementary DNA clone encoding for the CD68 antigen suggests that PG-M1 is a new member of the CD68 cluster. However, unlike other CD68 antibodies (KP1, EBM11, etc.), which react with both macrophages and myeloid cells, PG-M1 detects a fixative-resistant epitope on the macrophage-restricted form of the CD68 antigen. In 957 routinely fixed, paraffin-embedded samples, PG-M1 showed a more restricted reactivity with elements of the monocyte/macrophage lineage than the previously described monoclonal antibodies MAC-387 (anti-calgranulins), KP1 (CD68) and Ki-M1P. Among hematological malignancies, PG-M1 only labels acute leukemias of M4 and M5 type and rare examples of malignant histiocytosis/true histiocytic sarcoma. In contrast, acute leukemias of the M1, M2, M3, M6, M7, and L1-L3 types, non-Hodgkin's lymphomas, and Hodgkin and Reed-Sternberg cells of Hodgkin's disease are consistently PG-M1-negative. In the daily diagnostic practice, PG-M1 seems to be particularly valuable for the diagnosis of myelomonocytic or monocytic leukemia and neoplasms of true histiocytic origin in routine paraffin sections.

Toxicology of the synthetic antioxidants BHA and BHT in comparison with the natural antioxidant vitamin E

Abstract: The toxicology of the food preservatives butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT) as well as the naturally occurring vitamin E (alpha-tocopherol) is described. In high dosages all three compounds induce in animals impairment of blood clotting, which can be explained by an antagonism with vitamin K. Specific toxic effects to the lung have only been observed with BHT. The other described toxic effects of BHA and BHT are less characteristic and often occur only after high dosage and long-term treatment. However, BHA induces in animals tumours of the forestomach, which are dose dependent, whereas BHT induces liver tumours in long-term experiments. Because there is no indication of genotoxicity of BHA and BHT, all published findings agree with the fact that BHA and BHT are tumour promoters. In contrast to BHA and BHT, vitamin E is not carcinogenic. On the other hand, all three antioxidants have also anticarcinogenic properties. The intake of the necessary high doses as for these effects are, however, contraindicated with BHA and BHT because of their carcinogenic effects. The present overview concludes that the concentrations of BHA and BHT nowadays used in food, drugs and cosmetics are probably harmless. In addition, vitamin E can also be used in higher doses without the occurrence of adverse effects.

Human mast cells produce IL-8.

Abstract: Recruitment of neutrophils is a common feature in diseases that are associated with mast cell activation. The mechanisms that mediate neutrophil activation are not well understood. IL-8 is a recently described potent chemotactic factor that might be pathogenetically involved in this process. We therefore studied the human mast cell line HMCI and human skin mast cells for their ability to produce IL-8 using various stimuli. IL-8-mRNA was expressed in a stimulus- and time-dependent fashion as detected by Northern blot analysis with an IL-8-specific cDNA probe. The molecular mass of HMCI-derived IL-8 was determined to be about 8 kDa by immunoblot analysis. Immunoreactive and biologically active IL-8 protein was measured in the cell culture supernatants of HMCI cells by an ELISA and a chemotaxis assay, respectively. On immunoelectron microscopy of stimulated skin mast cells, IL-8 was found along cytoplasmatic membranes and in intracellular granules. Our data indicate that mast cells may contribute to neutrophil recruitment by secretion of IL-8.

Optical detection of magnetic resonance in a single molecule

Abstract: MAGNETIC resonance spectroscopy1 is a powerful tool for molecular characterization and structure determination. The sensitivity of conventional approaches is limited to about 1010 electron spins or 1016 nuclear spins; this sensitivity can be improved to about 105 spins by polarizing the spins via optical pumping and detecting optical rather than microwave photons2. Recently, fluorescence from single molecules was detected by tuning a single-frequency laser in the inhomogeneously broadened fluorescence excitation band of a dilute dispersion of pentacene in a host crystal of p-terphenyl3,4. Here we report that, by combining single-molecule fluorescence spectroscopy with optically detected magnetic resonance for the pentacene-doped p-terphenyl system, we can detect magnetic resonance in a single pentacene molecule. We observe two of the three possible transitions between sublevels of the metastable triplet state. The spectral lineshapes indicate that the proton nuclear spin states change during the measurement, leading to spectral diffusion within the magnetic resonance line.

Anatomy of the mushroom bodies in the honey bee brain: The neuronal connections of the alpha-lobe

Abstract: Neural connections between the mushroom body (MB) and other protocerebral areas of the honeybee's brain were studied with the help of cobalt chloride and Golgi staining methods. Focal injections of cobalt ions into the α-lobe neuropil of the MB reveal seven clusters of somata located in the protocerebrum and deutocerebrum of each brain hemisphere. These neurons connect the mushroom body neuropil with protocerebral areas and number approximately 400. They contact the layered organization of the α-lobe at different locations. Some project not only into the α-lobe, but also into the β-lobe and pedunculus neuropils. Fifteen cell types which form intraprotocerebral circuits are morphologically described. They can be divided into three categories: (1) unilateral neurons, with projection fields restricted to the ipsilateral protocerebrum; these neurons connect the α-lobe with areas in the protocerebral lobe and ramify with densely layered arborisations arranged perpendicularly to the longitudinal axis of the α-lobe; (2) recurrent neurons, which interconnect subcompartments of the MB, forming loops at different leveles of the neuropil; their arborisations are mainly restricted to the α-lobe, β-lobe, pedunculus, and calyces of the ipsilateral MB; they also ramify sparsely around the neuropil of the α-lobe; and (3) bilateral neurons, which either interconnect both α-lobes or connect the ipsilateral α-lobe and protocerebral lobe with the dorsolateral protocerebral lobe of the conntralateral hemisphere. The connections of different compartments of the MB with other parts of the protocerebrum as revealed in this study are discussed in the context of hypotheses about the functional role of MBs in the honeybee brain. © 1993 Wiley-Liss, Inc.

Sudden cardiac death. Support for a role of triggering in causation.

Abstract: Epidemiological studies have identified associations between time of day and risk of sudden cardiac death. The marked peak in the occurrence of sudden cardiac death after awakening suggests that the disease is triggered by changes that occur during this time period. Increased sympathetic stimulation is a likely cause of such triggering. In the light of the circadian variation of sudden cardiac death and the evidence linking physical activity or mental stress (both associated with activation of the sympathetic nervous system) to the disease, the role of potential triggering events should be investigated. Controlled studies are needed to determine the relative risk of activities that may trigger sudden cardiac death. Since such studies must rely on witnesses (or resuscitated patients), data quality must be closely scrutinized, and studies using case-control and case-crossover designs are needed. The epidemiological and pathophysiological data reviewed in the present article suggest a number of pathways through which activities may trigger sudden cardiac death. Different extrinsic stimuli may cause similar physiological changes that subsequently lead to acute pathological events, a decrease in the ventricular fibrillation threshold through a direct myocardial effect, or a harmful effect on the conduction system. Myocardial ischemia induced by plaque rupture and thrombosis may lead directly to myocardial electric instability. The presence of chronic structural abnormalities of the myocardial tissue or the conduction system may further lower the threshold for electric instability and ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface‐modified latex particles evaluated by two‐dimensional polyacrylamide gel electrophoresis

Abstract: Targeting to specific sites of the body via colloidal carriers is sought in order to reduce drug side effects. The adsorption of plasma proteins on intravenously injected particles is regarded as the key factor in explaining their organ distribution: total bound protein, or, more likely, the presence of specific proteins and their conformation, are expected to influence macrophage uptake. Polystyrene beads, 60 nm in diameter, were used as model carriers; their surface was differentially modified by adsorption of increasingly hydrophilic block copolymers, poloxamers 184, 188 and 407. After incubation in plasma, the patterns of protein adsorption onto coated beads were analyzed by high-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The behavior of some representative proteins was monitored, including albumin, fibrinogen, IgG, factor B and the apolipoproteins, A-I, A-IV, C-III, E and J. The more hydrophobic the particles, the larger the total amount of bound protein. However, this correlation was not valid for all of the analyzed protein species, which proves that it is insufficient to look only at physicochemical data to predict organ distribution. On the contrary, it is essential to use 2-D PAGE to establish the correlation between adsorbed proteins and carrier behavior in vivo.

Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon gamma

Abstract: Interleukin (IL)-2, IL-4, IL-7, tumor necrosis factor (TNF), or interferon-gamma (IFN-gamma) has been shown to be able to induce tumor rejection if produced locally by the tumor cells after gene transfer. To analyze whether the cellular rejection mechanisms are different or redundant we have expressed the cytokines in the same tumor cell line (J558L). Cell depletion experiments revealed that all cytokines required CD8+ T cells for complete long-term tumor eradication, although effective but transient host-dependent tumor suppression was also observed in the complete absence of CD8+ T cells. The transient tumor suppression induced by IL-2, IL-4, TNF, or IFN-gamma was also operative in nude and severe combined immunodeficient mice, whereas only tumor suppression induced by IL-7 was dependent on the presence of CD4+ T cells and was not evident in nude mice. The T-cell-independent effector arm of IL-2 and IFN-gamma but not IL-4 and TNF was mediated in part by natural killer cells. The transience of tumor suppression in the absence of T cells reflected loss of cytokine production in the case of TNF, IL-2, and IL-4 but not IFN-gamma. Immunohistologic analysis revealed all cytokine-producing tumors to be heavily infiltrated by macrophages. IL-4 and IL-7 tumors additionally contained eosinophils. The infiltration by T cells did not necessarily reflect their contribution to tumor rejection. Thus, the different cytokines activate heterogeneous transient tumor-suppressive mechanisms but always require CD8+ T cells for complete tumor rejection.

Molecular biology of hydrogen utilization in aerobic chemolithotrophs.

Abstract: The aerobic bacteria capable of obtaining energy from the oxidation of H2 form a heterogenous group that includes both facultative and obligate chemolithotrophs and representatives of both gram-negative and gram-positive genera. H2-oxidizing aerobes inhabit such diverse biotypes as soil, oceans, and hot springs. The oxidation of H2 in these bacteria is catalyzed by [NiFe] metalloenzymes called hydrogenases. The hydrogenases studied so far belong to two families: dimeric, membrane-bound enzymes (MBH) coupled to electron transport chains and tetrameric, cytoplasmic NAD-reducing enzymes (SH). Ni2+ is an essential component of the active site contained in the large subunit of the MBH enzymes. The genes for the MBH enzymes are located in conserved clusters of accessory genes, some of which encode maturation functions and hydrogenase-related redox proteins. Maturation of both types of hydrogenase is apparently complex, involving specific nickel incorporation and proteolytic processing steps. In Alcaligenes eutrophus and Rhodobacter capsulatus, hydrogenase expression is regulated by transcriptional activators belonging to the response-regulator family.

Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain

Abstract: 1. Sensitization and classical odor conditioning of the proboscis extension reflex were functionally analyzed by repeated intracellular recordings from a single identified neuron (PE1-neuron) in th...

Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome

Abstract: Objective To evaluate the lowest dose of inhaled nitric oxide (NO) in patients with adult respiratory distress syndrome (ARDS), which is able to improve arterial oxygenation more than 30% compared to baseline data.

Information science: the study of postmodern knowledge usage

Abstract: There is a lot of discussion about paradigms. Most of the approaches seem to have the same basic structure: Assuming a fixed problem and stating solutions. The alternative view would be to look at the deeper structural problem which could be illustrated by comparison with actors dealing with knowledge under conditions of a change in the role of knowledge. This is observed in four dimensions related to the development of sets of technologies: depersonalization and communication technologies, believability and observation technologies, fragmentation and presentation technologies, and rationalization and information technologies. This change is furthermore supported by the phenomenon of “informatization.” If information science considers itself to be that science, it has to learn that such a science would be established (together with some others like ecology) as a prototype of a new or postmodern science. Postmodern science is not like classical science, driven by the search for complete understanding of how the world works, but by the need to develop strategies to solve in particular those problems which have been caused by classical sciences and technologies. Such a science has to face a new theoretical situation for which three approaches are envisaged: (a) development of basic models by redefinition of broad scientific concepts (e.g., “system,” leading to the concept of actor, “communication,” leading to the concept of complexity reduction); (b) scientific reformulation of inter-concepts, that is, concepts that are that familiar and common in that they are not yet scientifically worked out as such (e.g., “knowledge”, “image”); and (c) interweaving of models and inter-concepts.