Enhancement of Lipopolysaccharide-Induced Neutrophil Oxygen Radical Production by Tumor Necrosis Factor Alpha

Although tissues become exposed to both exogenous and endogenous cell-activating mediators during infection, there is little appreciation of the effects of subjecting cells to multiple mediators. We examined the hypothesis that the response of neutrophils to bacterial lipopolysaccharide (LPS) is significantly altered in the presence of the endogenous mediator tumor necrosis factor alpha (TNF). The data showed that human neutrophils pretreated with TNF for 10 to 30 min, displayed significantly enhanced superoxide production in response to LPS (from either Escherichia coli K-235 or E. coli 0127:B8), measured as lucigenin-dependent chemiluminescence (CL), seen as an increase in the initial peak rate as well as the total CL accumulated over the incubation period. TNF amplified the response to LPS at 1 to 100 U of TNF/10⁶ neutrophils and was able to enhance the response to a wide range of concentrations of LPS (0.01 to 1,000 ng/ml). The TNF-induced increase in the LPS response was paralleled by an increase in LPS binding to the neutrophils, which could be abrogated by an anti-CD14 monoclonal antibody. The results demonstrate that TNF significantly increases the LPS-induced release of oxygen radicals in neutrophils through the upregulation of cell surface CD14.     

Psychiatric rehabilitation in a secure treatment setting

Working with severely mentally ill persons within the locked environment of a secure residential treatment facility presents a provocative challenge in attempting to establish a rehabilitative program. The author describes the mission, goals and methods of one of Oregon's newly organized facilities for "hard to place" former state hospital patients. The value of teaching the residents self-control is emphasized. Clinical vignettes illustrate how the staff involve the residents in real-life tasks, apply natural consequences to problem behaviors, and make attempts at minimizing the potential sources of confrontation.     

Comparison of tissue impedance measurements with nerve fiber architecture in human telencephalon: value in identification of intact subcortical structures

OBJECT: After establishing the general possibility of real-time impedance monitoring during stereotactic procedures in five postmortem human brains, the authors proceeded to analyze the value of impedance measurements in intact cerebral structures. METHODS: The authors performed impedance measurements at 24 selected points in the brain of a human cadaver and labeled the points by using 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). The texture of the nerve fibers was visualized using confocal laser scanning microscopy, which allowed classification of distinct anatomical regions in the white and gray matter according to their fiber structure (density, direction, structure, and diameter). These regions displayed characteristic differences in impedances according to their fiber structure at frequencies between 8000 and 10,000 Hz. Differences in tissue impedance are not removed, although they are shifted to higher values by fixation with formalin. The reference frequency used in clinical environments (50,000 Hz) is not useful for distinct localization purposes. Finally, the orientation of the electrode in relation to the tissue is a crucial factor. CONCLUSIONS: It should be possible to draw conclusions about the correct position of the stereotactic needle on the basis of the proposed location, the texture of the fibers (orientation and density), and the orientation of the electrode.     

Hierarchy of susceptibility of dendritic cell subsets to infection by Leishmania major: inverse relationship to interleukin-12 production

Dendritic cells (DCs) are professional antigen-presenting cells which initiate and regulate T-cell immune responses. Here we show that murine splenic DCs can be ranked on the basis of their ability to phagocytose and harbor the obligately intracellular parasite Leishmania major. CD4(+) CD8(-) DCs are the most permissive host cells for L. major amastigotes, followed by CD4(-) CD8(-) DCs; CD4(-) CD8(+) cells are the least permissive. However, the least susceptible CD4(-) CD8(+) DC subset was the best interleukin-12 producer in response to infection. Infection did not induce in any DC subset production of the proinflammatory cytokine gamma interferon and nitric oxide associated with the induction of Th1 responses. The number of parasites phagocytosed by DCs was low, no more than 3 organisms per cell, compared to more than 10 organisms per macrophage. In infected DCs, the parasites are located in a parasitophorous vacuole containing both major histocompatibility complex (MHC) class II and lysosome-associated membrane protein 1 molecules, similar to their location in the infected macrophage. The parasite-driven redistribution of MHC class II to this compartment indicates that infected DCs should be able to present parasite antigen.     

Classification of prostatic carcinoma with artificial neural networks using comparative genomic hybridization and quantitative stereological data

Staging of prostate cancer is a mainstay of treatment decisions and prognostication. In the present study, 50 pT2N0 and 28 pT3N0 prostatic adenocarcinomas were characterized by Gleason grading, comparative genomic hybridization (CGH), and histological texture analysis based on principles of stereology and stochastic geometry. The cases were classified by learning vector quantization and support vector machines. The quality of classification was tested by cross-validation. Correct prediction of stage from primary tumor data was possible with an accuracy of 74– 80% from different data sets. The accuracy of prediction was similar when the Gleason score was used as input variable, when stereological data were used, or when a combination of CGH data and stereological data was used. The results of classification by learning vector quantization were slightly better than those by support vector machines. A method is briefly sketched by which training of neural networks can be adapted to unequal sample sizes per class. Progression from pT2 to pT3 prostate cancer is correlated with complex changes of the epithelial cells in terms of volume fraction, of surface area, and of second-order stereological properties. Genetically, this progression is accompanied by a significant global increase in losses and gains of DNA, and specifically by increased numerical aberrations on chromosome arms 1q, 7p, and 8p.     

Localization and age-related changes of nitric oxide- and ANP-mediated cyclic-GMP synthesis in rat cervical spinal cord: an immunocytochemical study

An immunocytochemical technique was used to study the localization and developmental aspects of cyclic GMP (cGMP)-synthesizing structures in the cervical spinal cord of 2-week and 3-month-old Lewis rats in response to the nitric oxide (NO) donor sodium nitroprusside (SNP) and/or atrial natriuretic peptide (ANP). By using cell-specific markers, the cell structures involved were investigated. To visualize cGMP, a combined technique of low- and high-power magnification, using a confocal laser scanning microscope was used. NOS-mediated cGMP synthesis was observed in the cervical spinal cord in laminae I, II and III in 14-day-old rats, which activity was mainly absent at the age of 3 months. The involvement of NO in the NMDA-mediated increase in cGMP immunostaining (cGMP-IS) was demonstrated by the absence of cGMP-IS in slices incubated in the presence of NMDA together with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). This NO-mediated effect of NMDA on cGMP-IS was completely absent in the 3-month-old rats. ANP-mediated cGMP synthesis resulted in an increase in cGMP in laminae I and II, which was generally similar at both ages. Astrocytes in both white and gray matter were found to be cGMP-IS in the basal, NO- and ANP-stimulated conditions. Using confocal laser microscopy, NO-mediated cGMP synthesis was observed in large cholinergic terminals nearby motor neurons in the ventral horn. An extensive colocalization between NO-stimulated cGMP synthesis and parvalbumin-positive (GABAergic) neurons and fibers was observed in all laminae. In the ANP-stimulated condition, a colocalization with parvalbumin structures was found in laminae II and III. No NO- or ANP-mediated cGMP synthesis was found in fibers immunopositive for the presynaptic glutamate transporter, serotonin, or tyrosine hydroxylase.     

Coagulation studies on umbilical arterial and venous blood from normal newborn babies

Coagulation studies using conventional methods and chromogenic substrates were performed on umbilical arterial and venous blood from 33 newborns after delivery. In the arterial samples, thrombin time (TT) was significantly prolonged and the activities of factors I, II, V and VII, as well as the inhibitors heparin, antithrombin III and antiplasmin, were significantly decreased. This could probably be explained by a mild form of disseminated intravascular coagulation (DIC) occurring in the baby during delivery.With support of the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen     

Vitamin E concentrations in term and preterm newborns and their clinical course

Vitamin E deficiency in premature infants has been described as being associated with low hemoglobin levels in the 2nd month of life. Recently, low vitamine E concentrations were suspected as being associated with sudden death in infancy. As vitamin E is absorbed incompletely from the premature's intestine, vitamin E levels in the serum were determined in 80 prematures on the 10th day of life. The result was correlated to the clinical course of the infants and to the hemoglobin levels up to the 30th day.Low concentrations of vitamin E and lower hemoglobin levels were found more frequently in newborns, whose clinical course was characterized by additional complications and who received parenteral nutrition. A group of uncomplicated newborns showed no correlation of vitamin E to hemoglobin values. Thus early diagnosis of vitamin E-dependent anemia is not possible and the usefulness of vitamin E should be investigated only in newborns with an uneventful clinical course.Auszugsweise vorgetragen anläßlich der 24. Tagung der Nordwestdeutschen Gesellschaft für Kinderheilkunde, Kiel, 6.-8. 6. 1975.     

Bilateral cavernous degeneration of the optic nerve associated with multiple arteriosclerotic ischemic infarctions

Supported by grants from the Alexander von Humboldt-Foundation (no. 13648, T. Kubota) and the Deutsche Forschungsgemeinschaft (Klinische Forschergruppe Glaukome, DFG Na 55/6-1, G.O.H. Naumann)