Showing papers by "University of Mainz published in 1993"

Cooperative Formation of Inorganic-Organic Interfaces in the Synthesis of Silicate Mesostructures

Abstract: A model is presented to explain the formation and morphologies of surfactant-silicate mesostructures. Three processes are identified: multidentate binding of silicate oligomers to the cationic surfactant, preferential silicate polymerization in the interface region, and charge density matching between the surfactant and the silicate. The model explains present experimental data, including the transformation between lamellar and hexagonal mesophases, and provides a guide for predicting conditions that favor the formation of lamellar, hexagonal, or cubic mesostructures. Model Q(230) proposed by Mariani and his co-workers satisfactorily fits the x-ray data collected on the cubic mesostructure material. This model suggests that the silicate polymer forms a unique infinite silicate sheet sitting on the gyroid minimal surface and separating the surfactant molecules into two disconnected volumes.

Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas.

Abstract: The epithelial-specific cell-cell adhesion molecule E-cadherin was analyzed immunohistochemically on tissue sections of 89 human primary infiltrating breast carcinomas, using monoclonal antibodies 6F9 (for cryostat sections) and 5H9 (for cryostat and paraffin sections). The tumors included 41 well and moderately differentiated infiltrating ductal carcinomas (IDCs) most of which (78%) showed strong linear staining at the cell borders at a level, as high as luminal cells of normal mammary glands. The 26 poorly differentiated, more highly malignant IDCs examined also were all positive for E-cadherin, although a higher proportion of them (54%) showed reduced staining, which was heterogeneous and dotted over the cell borders. In contrast, 19 of 22 infiltrating lobular carcinomas (ILCs), which were either of the dispersed (classical), solid, or the mixed type, did not express E-cadherin, whereas three cases showed weak staining. In situ lesions of ILCs and pure lobular carcinoma in situ (four cases) were all E-cadherin negative, whereas intraductal carcinomas (11 cases) exhibited mostly strong staining. The results were confirmed by Western blotting. The data indicate that loss of E-cadherin expression is an early event in the formation of the lobular type of breast carcinomas. The absence of E-cadherin signifies a partial loss of epithelial differentiation and may account for the extended spread of lobular carcinoma in situ and the peculiar diffuse invasion mode of ILC. The generation of dedifferentiated IDCs can only in part be correlated with reduced expression of the intercellular adhesion molecule E-cadherin. Other factors are obviously also involved during invasion of this carcinoma type.

Transient photoconductivity in a discotic liquid crystal.

Abstract: Using a time-of-flight technique, different transport mechanisms, deep trapping, multiple shallow trapping, and ideal itrinsic transport, can be observed in the different temperature and phase regions of the liquid-crystalline photoconductor hexapentyloxytriphenylene. The temperature and field dependences of carrier mobilities up to 1\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}3}$ ${\mathrm{cm}}^{2}$/V s have been determined; this value exceeds considerably the mobilities of the most commonly used organic photoconductors. The experiments reflect a variety of transport phenomena which are novel in the field of liquid-crystalline systems.

Continuity and Discontinuity of Affective Disorders and Schizophrenia: Results of a Controlled Family Study

Abstract: Background: It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping. Methods: Index probands met Research Diagnostic Criteria for SCZ (n=146), schizoaffective (SA [n=115]), bipolar (BP [n=80]), or unipolar major depressive (UP [n=184])disorder. Comparison probands met Research Diagnostic Criteria for alcoholism (n=64) or were sampled from the general population (n=109). A total of 2845 first-degree relatives were blindly diagnosed from interview, informant, and/or record data, with direct interviews completed in 2070 (82% of living first-degree relatives). Results: By Cox's proportional hazards analysis, SCZ, SA, BP, and UP disorders were familial, in that each group of relatives had an increased lifetime morbid risk (vs those with alcoholism and those from the general population) for the proband's diagnosis. The SCZ and BP disorders were transmitted independently: only probands with manic disorders (BP or SA-BP subtype) showed increased familial risks of BP disorder, and only probands with prominent SCZ features (SCZ or SA) showed increased familial risks of SCZ disorder. However, SCZ probands had an increased familial risk for UP disorder (as did SA, BP, and UP probands) and for the SA-UP subtype. Aggregation of depression in families of SCZ probands could not be explained by the subtype of depression, broad or narrow definition of SCZ disorder, presence or absence of history of depression in SCZ probands, whether onset of depression in a relative occurred before or after onset of a proband's SCZ disorder, or assortative mating. Conclusions: These data suggest that there could be a familial relationship between the predispositions to schizophrenia and to major depression. We discuss a number of alternative hypotheses about the nature of this possible relationship.

Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues

Abstract: The human Wilms' tumor gene WT1 encodes a putative transcription factor implicated in tumorigenesis and in specifying normal urogenital development. We have studied the distribution of WT1 protein and mRNA using immunohistochemistry and in situ hybridization. Monoclonal antibodies were raised against a peptide specific to the first alternative splice site of WT1. Two antibodies specifically reacted on Western blot to this WT1 isoform. Immunofluorescence localized WT1 protein to podocytes during mesonephric and metanephric development. In situ hybridization revealed a similar pattern of expression except that WT1 mRNA was also present in metanephric blastema and renal vesicles. Messenger RNA expression was most pronounced in the kidneys during early fetal development and declined thereafter. In contrast, WT1 protein was readily detectable in glomerular podocytes throughout adulthood. WT1 protein in Wilms' tumor was present in blastema and glomeruloid structures. Expression in the female gonad was linked to the different stages of granulosa cell development. In the male gonad, expression was restricted to Sertoli cells and their precursors, the embryonic tunica albuginea and the rete testis. The intracellular distribution of the WT1 protein was investigated by confocal laser microscopy and was demonstrated to be exclusively nuclear. The nuclear distribution and the selective pattern of expression support the proposed role of WT1 as a transcription factor active during urogenital development. The persistence of WT1 expression in the adult kidney suggests a role in homeostasis of the podocyte.

Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer: Computer-assisted image analysis (QIC score) vs. subjective grading (IRS)

Abstract: Immunohistochemistry of Estrogen Receptor (ER) and Progesterone Receptor (PR) has been performed in 687 cases of human breast cancer. The staining results have been compared by (1) computer-assisted image analysis (QIC Score) and (2) subjective grading of the cryostat sections ("German" IRS). Tumors without or with only weak ER or PR content may be distinguished by both methods from tumors with a high receptor content. The QIC Score values belonging to the intermediate IRS grades are distributed over a wide range, but no negative cases were found in these categories. It is concluded from our results that subjective grading of the slides is a simple, rapid and useful method for the determination of the tissue receptor content and must not be replaced by the expensive and time-consuming computer-assisted image analysis in daily practice.

In vivo ANALYSIS OF SLOW CHLOROPHYLL FLUORESCENCE INDUCTION KINETICS IN ALGAE: PROGRESS, PROBLEMS AND PERSPECTIVES

Abstract: Kautsky and Hirsch’ were the first who observed that intact plants emit small amounts of red light of variable intensity when transferred from dark to light. At the very beginning of the fluorescence analysis it became clear by the work of Kautsky and his coworkers that the fluorescence signal during a dark-light transition reflects complex photosynthetic events in the primary light reactions as well as in the enzymatic a p p a r a t ~ s . ~ , ~ In the following, many scientists have invested a lot of work to understand the complexity of the kinetics and t o set up improved devices to measure fluorescence signals in vivo. Intensive fluorescence research has been motivated by the apparent advantages ofthe technique for fluorescent measurement: It is a noninvasive method that yields reproducible results in short time, and it can be applied to all photosynthetic organisms, even if only very small amounts of material ( ie . few p g chlorophyll [Chl]?) are available. These characteristics and the technical progress in light sources and electronics lead to very sophisticated instruments that are now widely commercially distributed and used in photosynthesis research as well as in ecophysiology of land plants and algae. In particular, in hydrobiology the measurement of in vivo Chl a fluorescence is routinely applied to estimate the algal biomass or to monitor chemicals that impair algal photosyn thesis. Although fluorescence measurements are routinely done, a theory explaining the Kautsky kinetics is still under dis-

A guide to the use of pore-forming toxins for controlled permeabilization of cell membranes

Abstract: Depending on the size of the pores one wishes to produce in plasma membranes, the choice will probably fall on one of the three toxins discussed above. S. aureus alpha-toxin should be tried first when pores of 1-1.5 nm diameter are required. This is generally the case when Ca2+ and nucleotide dependence of a given process is being studied. If alpha-toxin does not work, this is probably due to the fact that the toxin either does not produce pores, or that the pores are too small. In this case, high concentrations of alpha-toxin should be tried. If this still does not work, we recommend the use of HlyA. When very large pores are to be created, e.g. for introduction of antibodies into the cells, SLO or another member of this toxin family are the agents of choice. SLO preparations need to be checked for presence of protease contaminants. Tetanolysin currently offers advantages since it is protease-free, and the size of the pores can probably be controlled by varying the toxin dose. Methods for assessing the size of pores created by such agents have been published in the recent literature, and the appropriate papers can be consulted whenever the need arises.

Heat shock protein vaccines against cancer

Abstract: Vaccination of mice with heat shock proteins (HSPs) derived from a tumor makes the mice resistant to the tumor from which the HSP was obtained. This phenomenon has been demonstrated with three HSPs--gp96, hsp90, and hsp70. Vaccination with HSPs also elicits antigen-specific cytotoxic T lymphocytes (CTLs). The specific immunogenicity of HSPs derives apparently, not from the HSPs per se, but from the peptides bound to them. These observations provide the basis for a new generation of vaccines against cancer. The HSP-based cancer vaccines circumvent two of the most intractable hurdles to cancer immunotherapy. One of them is the possibility that human cancers, like cancers of experimental animals, are antigenically distinct. The prospect of identification of immunogenic antigens of individual cancers from patients is daunting to the extent of being impractical. The observation that HSPs chaperone antigenic peptides of the cells from which they are derived circumvents this extraordinary hurdle. Second, most current approaches to cancer immunotherapy focus on determining the CTL-recognized epitopes of cancer cell lines. This approach requires the availability of cell lines and CTLs against cancers. These reagents are unavailable for an overwhelming proportion of human cancers. In contrast, the HSP-based vaccines do not depend on the availability of cell lines or CTLs nor do they require definition of the antigenic epitopes of cancer cells. These advantages, among others, make HSPs attractive and novel immunogens against cancer.

Subjective objectivity. How journalists in four countries define a key term of their profession

Abstract: 'Objectivity' is one of the core professional values of journalism. However, there are many different definitions and interpretations of the term in the profession. These notions have changed over time in one country, and they differ between journalists in different cultural and political settings. In this paper we present comparative results of how journalists in different countries look at the term objectivity. The data are gathered from an international study of news journalists in democracies. In this survey, representative samples of reporters and editors who are involved in daily news decisions were interviewed with the same questionnaire. We show how journalists differ in their notion of objectivity and in the subjective importance which the professional value of objectivity has for them. Besides showing country-to-country differences, we try to assess what factors contribute to different professional attitudes towards objectivity within a single country. In a final part, the paper discusses the co...

Domain structures in langmuir-blodgett films investigated by atomic force microscopy.

Abstract: Investigations of phase-separated Langmuir-Blodgett films by atomic force microscopy reveal that on a scale of 30 to 200 micrometers, these images resemble those observed by fluorescence microscopy. Fine structures (less than 1 micrometer) within the stearic acid domains were observed, which cannot be seen by conventional optical microscopic techniques. By applying the force modulation technique, it was found that the elastic properties of the domains in the liquid condensed phase and grains observed within the liquid expanded phase were comparable. Small soft residues in the domains could also be detected. The influence of trace amounts of a fluorescence dye on the micromorphology of monolayers could be detected on transferred films.

Pathogenesis and clinical relevance of bone marrow embolism in medullary nailing — demonstrated by intraoperative echocardiography

Abstract: For the clarification of pulmonary impairment after medullary nailing of femoral fractures, the intramedullary pressure in the femoral cavity during the operative procedure was investigated In addition, an intraoperative transoesophageal echocardiography was performed which revealed two phenomena occurring once the intramedullary pressure had increased: snow-flurry and configured emboli An experimental study in sheep was performed in order to define the substrata of the sonographic echoes The level of intrafemoral pressure which would result in bone marrow intravasation and the substrata of the echocardiographic echoes were studied in sheep by applying pressure to the femoral cavity Sonography of the distal vena cava by laparotomy and macroscopic and histological investigation of the venous blood received throughout a proximal subdiaphragmal venotomy were undertaken The intrafemoral pressure peaks correlated with the appearance of sonographic echoes in both patients and sheep Snow-flurry is an indication of small amounts of bone marrow and already appears at an intramedullary pressure of 50 mmHg, which can easily occur during movement of non-stabilised fractures (values up to 90 mmHg were observed) — configured emboli consist of a core of bone marrow surrounded by thrombotic aggregate and only appeared at pressure increases of over 200 mmHg in the animal experiments During medullary nailing in patients the intrafemoral pressure increases up to 200–600 mmHg in all reaming procedures Configured emboli were seen in 8 of 20 patients being treated with reamed nailing In five nailing procedures performed using the unreamed technique, no pressure increases greater than 70 mmHg and no configured emboli were observed Iv injected bone marrow results in pulmonary impairment In non-stabilised fractures intramedullary pressure peaks constantly press small amounts of bone marrow into the circulation This process helps to explain the benefit of early operations in multiply injured patients During reaming large amounts of bone marrow pass into the circulation and may contribute to pulmonary damage and ARDS (adult respiratory distress syndrome) if cofactors are present (volume deficit, shock, thoracic trauma and preexisting restrictive lung disease) In patients with these conditions, nailing should be performed without reaming In the case of a narrow medullary cavity in which nailing without reaming is impossible other forms of stabilisation (plate or external fixator and later nailing) should be applied

S-type lectins occur also in invertebrates: High conservation of the carbohydrate recognition domain in the lectin genes from the marine sponge Geodia cydonium

Abstract: The marine sponge Geodia cydonium contains several lectins. The main component, called lectin-1, is composed of three to four identical subunits. The subunits of the lectins were cloned from a cDNA library; two clones were obtained. From the deduced aa sequence of one clone, LECT-1, a mol. wt of 15,313 Da is calculated; this value is in good agreement with mass spectrometric analysis of 15,453 +/- 25 Da. The sequence of another clone, LECT-2, was analysed and the aa sequence was deduced (15,433 Da). The two subunits have a framework sequence of 38 conserved aa which are characteristic for the carbohydrate-binding site of vertebrate S-type lectins. Clustering of lectin sequences of various species following their pairwise comparison establishes a dendrogram, which reveals that the sponge lectin could be considered as the ancestor for vertebrate S-type lectins.

Thirty years of synaptosome research.

Abstract: Detached synapses (synaptosomes), first isolated by the author in 1958 and identified as such in 1960, are sealed presynaptic nerve terminals often with a portion of the target cell — sometimes amounting to a complete dendritic spine — adhering to their external surface. They can be prepared in high yield from brain tissue and also in decreasing yield from spinal cord, retina, sympathetic ganglia, myenteric plexus and electric organs. They are sealed structures which, under metabolizing conditions, respire, take up oxygen and glucose, extrude Na+, accumulate K+, maintain a normal membrane potential and, on depolarization, release transmitter in a Ca2+-dependent manner. They thus provide an excellent preparation with which to investigate synaptic function without the complications encountered with synapsesin situ. They also serve as the parent fraction for preparations of synaptic vesicles and other synaptic components.

Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1‐ but not type 2‐associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats

Abstract: The phosphodiesterase inhibitor pentoxifylline (POX), which is known to have pharmacological effects in animal models of multiorgan failure and endotoxin-mediated shock, was tested for its immunosuppressive potential on T lymphocyte activation in vitro and in vivo. POX was found to have a profound inhibitory effect on both mitogen- and antigen-induced proliferation of CD4+ T cells in vitro. This inhibitory activity of the drug could be reproduced by treating T lymphocytes with cAMP analogues during stimulation. Responses of repeatedly in vitro stimulated cells were much more strongly inhibited by the drug and by cAMP analogues than responses of fresh resting lymphocytes. Furthermore, POX could drastically down-regulate tumor necrosis factor regulate production and to a lesser extent interleukin (IL)-2 secretion in activated T cells, but an excess of exogenous IL-2 did not override the antiproliferative effect of the drug. In contrast, the same doses of POX had no inhibitory effect on spontaneous or induced IL-4 and IL-6 production by short-term cultured T lymphocytes, indicating a selective sparing of T helper type 2 (Th2)-associated lymphokine functions by the drug. To test a potential use of POX as an antiinflammatory agent in T cell-mediated autoimmune disease, the influence of POX on myelin basic protein (MBP)-induced experimental autoimmune encephalomyelitis (EAE) was assessed. The onset of EAE in Lewis rats could almost completely be abrogated by oral administration of POX during the induction phase of disease. Lack of clinical symptoms in POX-treated animals coincided with a marked suppression of MBP-specific T cell reactivity in vitro, without any evidence for a generalized impairment of T cell activity. Collectively, our data suggest the potential use of xanthine derivatives of the POX type as a supporting antiinflammatory therapeutic agent in Th1 CD4+ T cell-mediated autoimmune diseases in animal models and possibly in man.

Antimutagenic effects of flavoniods, chalcones and structurally related compounds on the activity of 2-amino-3-methylinidazo[4,5-ƒ]quinoline (IQ) and other heterocyclic amine mutagens from cooked food

Abstract: Sixty-four flavonoids were tested for their antimutagenic potencies with respect to IQ in Salmonella typhimurium TA98 and in part also towards MeIQ, MeIQx, Trp-P-2, and Glu-P-1 and in S. typhimurium TA100. Antimutagenic potencies were quantified by the inhibitory dose for 50% reduction of mutagenic activity (ID 50 ). A carbonyl function at C-4 of the flavane nucleus seems to be essential for antimutagenicity: two flavanols and four anthocyanidines were inactive. Again, five isoflavons, except biochanin A, were inactive. Within the other groups of 21 flavones, 16 flavonols and 16 flavanones the parent compounds flavone, flavonol, and flavonone possessed the highest antimutagenic potencies (ID 50 : 4.1, 2.5, 5.5 nmoles). Increasing polarity by introduction of hydroxyl functions reduced antimutagenic potency. Reducing polarity of hydroxy flavonoids by methyl etherification, however, increased antimugenic potency again. 6-Hydroxy- and 2′-hydroxy substituted flavonoids were considerably less potent antimutagens. Of 11 flavonoid glycosides tested all compounds except apigenin- and luteolin-7-glucoside (ID 50 :74, 115 nmoles) were inactvie or only weakly antimutagenic. Rings C and A of the nucleus were not essential for antimutagenicity: chalcone and three derivatives were nearly as active as comparable flavones while antimutagenicity of benzylidenacetone was considerably redcued (ID 50 : 95 nmoles). Cinnamylaldehyde and cinnamoates, however, were inactive. A planar structure in the vacinity of the carbonyl group may also be important for antimutagenicity. Flavanones were less potent antimutagens than the corresponding flavones, but dihydrochalcones and 14 structurally related saturated aromatic carbonyl compounds were inactive. Fisetin and 6-hydroxyflavone were competitive inhibitors, but luteolin was a mixed type inhibitor. The inhibition mechanisms of flavone, kaempferol, morin, flavanone, and 2′-hydroxyflavanone were concentration dependent, being competitive at low concentrations and mixed or non-competitive (2′-hydroxyflavanone) at concentrations about the ID 50 value. No fundamental differences between the two tester strains and no clear influence of mutagen structure on antimutagenic potency could be detected.

Staphylococcal alpha-toxin kills human keratinocytes by permeabilizing the plasma membrane for monovalent ions.

Abstract: Incubation of human keratinocytes with nanomolar concentrations of Staphylococcus aureus alpha-toxin leads to irreversible depletion of cellular ATP. The toxin forms hexamers in the target cell membranes, and rapid transmembrane flux of K+, Na+, and 86Rb+ is observed. Unexpectedly, pores formed in keratinocytes through application of low but lethal doses of alpha-toxin appeared to be considerably smaller than those formed in erythrocyte membranes. They permitted neither rapid influx of Ca2+ or propidium iodide, nor efflux of carboxyfluorescein. Larger pores allowing flux of all three markers did form when the toxin was applied at high concentrations. Flux of monovalent ions and reduction in cellular ATP levels evoked by low toxin doses correlated temporally with a fall in oxygen consumption, which was interpreted to reflect breakdown of mitochondrial respiration. The lethal event could not be thwarted by manipulating the extracellular K+ or Ca2+ concentrations. Realization that alpha-toxin may form very small pores in nucleated cells is important for future research on cellular toxin effects and membrane repair processes.