Inhibition of leukotriene formation and IL-8 release by the PAF-receptor antagonist SM-12502

We analyzed the effect of the PAF receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) on the release of leukotriene B₄ and IL-8 from human leukocytes. Peripheral blood from healthy donors was separated in two different fractions: polymorphonuclear leukocytes (PMN) and a lymphocyte, monocyte and basophil granulocyte cell fraction (LMB). After incubation of the cell population with different concentrations of SM-12502 the cells were subsequently stimulated with either the Ca ionophore A23187, the bacterial derived peptide fMLP, or with an activator of heterotrimetric G-proteins, the sodium fluoride (NaF, in the presence of Al³⁺). The PAF receptor antagonist led to a concentration and time dependent inhibition of LTB₄ formation and IL-8 release from PMN and LMB. Our data clearly indicate an inhibitory effect of the PAF receptor antagonist SM-12502 on the formation of mediators of the lipoxygenase pathway and on the release of IL-8.     

Lymphocytic Hypophysitis Presenting as a Pituitary Tumor in a 63-Year-Old Man

This report describes a case of lymphocytic hypophysitis in a 63-year-old man who presented with symptoms of a pituitary mass lesion associated with hypothyroidism and hypogonadism. Postoperative endocrinological testing demonstrated gonadotropic, thyrotropic, and corticotropic hypopituitarism, and the patient was commenced on replacement therapy with hydrocortisone and levothyroxine. Histological examination of the pituitary tissue obtained by transsphenoidal surgery revealed lymphocytic hypophysitis without evidence of a pituitary adenoma. The vast majority of patients with lymphocytic hypophysitis are women particularly during pregnancy and the puerperium. Until recently only four men were reported in the literature. The pathogenesis of lymphocytic hypophysitis is uncertain but autoimmune mechanisms are possibly involved.     

Ultrastructural analysis of the male genital system ofCephalobaena tetrapoda Heymons, 1922 (Pentastomida)

The male genital system ofCephalobaena tetrapoda comprises the unpaired testis and seminal vesicle and the paired connecting tubes, ejaculatory bulbs, vasa deferentia, and dilators. These lead into the genital atrium, which can be everted to form the copulatory organ. An ultrastructural analysis of each of these compounds is presented, including spermiogenesis, which was traced in some important stages. The diverging nomenclature of the complicated male genital system was unified and partly changed: where the vas deferens and dilator merge, the former loses its epithelial lining; the cuticular tube is called the cirrus. Anteriorly, the dilator also gives rise to a cuticular, semilunar tube. The cirrus and semilunar tube run parallel and reach the genital atrium, which can be evaginated to form the copulatory organ. Apparently, the male genital system represents an original type from which the complicated porocephalic systems may be derived.     

Temperature experiments on nerve and muscle membranes of frogs

The influence of temperature changes in the range of 25°C to –6°C on the time constants of Na activation (m) and inactivation (h) was studied in twitch muscle fibers and the node of Ranvier under voltage-clamp conditions. Arrhenius plots of m and h exhibit a change in activation enthalpy at temperatures below 10°C. Cooling and subsequent heating induce a hystersis in the temperature dependence of m and h Ni²⁺ and UO ₂ ²⁺ increase the hysteresis width. With fast temperature changes the gating kinetics relax to their new values more slowly than the temperature change. Hence, temperature must be changed more slowly than 5°C/min if an additional apparent hysteresis due simply to this relaxation is to be avoided. The data are explained by the hypothesis of a phase transition in the membrane lipids. This conception is favoured over a temperature-induced change in protein conformation, since the neutral local anaesthetic benzocaine shows use-dependent block as if low temperature restricted the access of the drug through the lipid phase to its receptor.Supported by grant NS 08174 from the U.S. Public Health Service and SFB 38 from Deutsche Forschungsgemeinschaft     

Chain mobility in solid polyelectrolyte complexes

²H NMR is used to study the mobility of the alkylene chain in solid poly[(dimethyliminio)-alkylene]s (α,ω-ionenes) complexed with poly(styrenesulfonate). In 10, 10-ionene the alkylene chain motion was probed on samples selectively deuterated at the 1-, 2-, and 4-position as well as in the methyl part of the quaternary ammonium groups. ²H NMR spectra show that all positions in the polymethylene chains are involved in conformational jumps between trans and gauche states. The mobility of the methylene units adjacent to charged centres was found to be significantly reduced compared with that of units in the inner part of the chain. The charged quaternary ammonium groups themselves, however, do not take part in trans-gauche isomerization. An increase in mobility resulting from increasing the length of the alkylene chains between the charge centres was observed in 3,3-, 6,6- and 10,10-ionene complexes labelled in the 2-position. The differences in chain dynamics were also detected via EPR line shapes of small spin probe molecules incorporated into the complexes.     

Hematopoietic progenitor cells and cellular microenvironment: behavioral and molecular changes upon interaction

Cell-cell contact between stem cells and cellular determinants of the microenvironment plays an essential role in controlling cell division. Using human hematopoietic progenitor cells (CD34+/CD38-) and a stroma cell line (AFT024) as a model, we have studied the initial behavioral and molecular sequel of this interaction. Time-lapse microscopy showed that CD34+/CD38- cells actively migrated toward and sought contact with stroma cells and 30% of them adhered firmly to AFT024 stroma through the uropod. CD44 and CD34 are colocalized at the site of contact. Gene expression profiles of CD34+/CD38- cells upon cultivation with or without stroma for 16, 20, 48, or 72 hours were analyzed using our human genome cDNA microarray. Chk1, egr1, and cxcl2 were among the first genes upregulated within 16 hours. Genes with the highest upregulation throughout the time course included tubulin genes, ezrin, c1qr1, fos, pcna, mcm6, ung, and dnmt1, genes that play an essential role in reorganization of the cytoskeleton system, stabilization of DNA, and methylation patterns. Our results demonstrate directed migration of CD34+/CD38- cells toward AFT024 and adhesion through the uropod and that upon interaction with supportive stroma, reorganization of the cytoskeleton system, regulation of cell division, and maintenance of genetic stability represent the most essential steps.     

Zur Bestimmung des Kaliumspiegels im Blutplasma

Zusammenfassung Die Kaliumkonzentration im Blutserum nach der Gerinnung ist höher als im Blutplasma, dessen Gerinnung durch Heparin, Äthylendiamintetraessigsäure (EDTA) oder Citrat verhindert wurde. Die Differenz beträgt beim Hund 15–20%, beim Menschen 12–16% und beim Rind 8–10%.Der Unterschied wird durch den bei der Gerinnung des Blutes auftretenden Zerfall der Thrombocyten hervorgerufen, deren Kaliumgehalt überraschend hoch ist (mindestens das 10–20fache der Konzentration im Plasma).Aus diesem Grund geben Kaliumbestimmungen im Serum, bei denen das Blut während der Präparation der Proben gerinnt, zu hohe Werte gegenüber der tatsächlich in vivo herrschenden Konzentration im Plasma. Messungen der Kaliumkonzentration sollten immer im Plasma erfolgen, wobei als gerinnungshemmende Substanzen Heparin oder EDTA geeignet sind.