Intravenous immunoglobulin ameliorates ITP via activating Fc gamma receptors on dendritic cells

Despite a more than 20-year experience of therapeutic benefit, the relevant molecular and cellular targets of intravenous immunoglobulin (IVIg) in autoimmune disease remain unclear. Contrary to the prevailing theories of IVIg action in autoimmunity, we show that IVIg drives signaling through activating Fc gamma receptors (Fc gammaR) in the amelioration of mouse immune thrombocytopenic purpura (ITP). The actual administration of IVIg was unnecessary because as few as 10(5) IVIg-treated cells could, upon adoptive transfer, ameliorate ITP. IVIg did not interact with the inhibitory Fc gammaRIIB on the initiator cell, although Fc gammaRIIB does have a role in the late phase of IVIg action. Notably, only IVIg-treated CD11c+ dendritic cells could mediate these effects. We hypothesize that IVIg forms soluble immune complexes in vivo that prime dendritic-cell regulatory activity. In conclusion, the clinical effects of IVIg in ameliorating ITP seem to involve the acute interaction of IVIg with activating Fc gammaR on dendritic cells.     

The application of psychoanalytic principles to the study of "magic"

In this paper Freud's work on animism and magic is elaborated. Those two subjects are presented mainly in his work "Totem and Taboo" (1913). The true motives, which lead primitive man to practice magic are, according to Freud, human whishes and his immense belief in their power. Importance attached to wishes and to the will has been extended from them to all those psychical acts, which are subjected to will. A general overvaluation has thus come about of all mental processes. Things become less important than ideas of things. Relations, which hold between the ideas of things, are equally hold between the things. The principle of governing magic or the technique of animistic way of thinking is one of the 'omnipotence of thoughts'. The overvaluation of psychic acts could be brought into relation with narcissism and megalomania, a belief in the thaumaturgic force of words and a technique for dealing with the external world--'magic'--which appears to be a logical application of these grandiose premises. Recent psychoanalytic authors dealing with the problem of magic emphasize that magic survived culturally to the present days and even in adults who are otherwise intellectually and scientifically 'modern'. Their explanations for that derive from Ferenczi's and especially Róheim's work that pointed out that magic facilitates adaptive and realistically effective endeavors. Balter pointed out that magic employs ego functioning, and conversely ego functioning includes magic.     

Microzooplankton in the open waters of the northern Adriatic Sea from 1990 to 1993: the importance of copepod nauplii densities

Zooplankton was sampled during 39 cruises, from 1990 to 1993, at four fixed stations in the open northern Adriatic. Hydrographic factors were important in determining the abundance of the smallest and largest components of the northern Adriatic food chain during this period. Nauplii—especially those of the smallest size fractions—were the major mediators of material transfer between primary producers and higher trophic levels. There was a significant difference in the vertical distribution of nauplii size fractions between the eastern and western parts of the northern Adriatic, but not in their population density. According to multiple correlation analyses, the abundance of naupliar size fractions in the western area correlated strongly with temperature and with certain biological factors. This study confirms the important influence of the Po River and of mid-Adriatic waters on the planktonic ecosystem of the northern Adriatic. Electronic Publication     

Conformational preference functions for predicting helices in membrane proteins

A suite of FORTRAN programs, PREF, is described for calculating preference functions from the data base of known protein structures and for comparing smoothed profiles of sequence-dependent preferences in proteins of unknown structure. Amino acid preferences for a secondary structure are considered as functions of a sequence environment. Sequence environment of amino acid residue in a protein is defined as an average over some physical, chemical, or statistical property of its primary structure neighbors. The frequency distribution of sequence environments in the data base of soluble protein structures is approximately normal for each amino acid type of known secondary conformation. An analytical expression for the dependence of preferences on sequence environment is obtained after each frequency distribution is replaced by corresponding Gaussian function. The preference for the α-helical conformation increases for each amino acid type with the increase of sequence environment of buried solvent-accessible surface areas. We show that a set of preference functions based on buried surface area is useful for predicting folding motifs in α-class proteins and in integral membrane proteins. The prediction accuracy for helical residues is 79% for 5 integral membrane proteins and 74% for 11 α-class soluble proteins. Most residues found in transmembrane segments of membrane proteins with known α-helical structure are predicted to be indeed in the helical conformation because of very high middle helix preferences. Both extramembrane and transmembrane helices in the photosynthetic reaction center M and L subunits are correctly predicted. We point out in the discussion that our method of conformational preference functions can identify what physical properties of the amino acids are important in the formation of particular secondary structure elements. © 1993 John Wiley & Sons, Inc.     

Lecithin Requirement for the Sporulation Process in Neurospora crassa

Reversible inhibition of conidiogenesis occurred when lecithin was depleted from Neurospora membranes by choline starvation.     

Lacustrine basin to delta evolution in the Zagorje Basin,a Pannonian sub-basin (Late Miocene: Pontian,NW Croatia)

Pontian deposits of the Zagorje Basin constitute a coarsening-upward succession, which reflects the infilling style of this Pannonian sub-basin, i.e. the progradation of clastic systems into the brackish lake. Six facies differentiated correspond to lake floor, channelled slope, distal and proximal pro-delta, distal and proximal mouth bars, and lagoon/bay to swamp and alluvial environments. The deposition in the mouth-bar area was dominated by frictional forces. The upper-stage plane-bed sands are the main mouth-bar facies, which is uncommon in the geological record. The main factors for the origin of such bars include an abundant sand supply by the high-energy fluvial system(s), low-energy of the receiving basin and shallow depositional depth. Prolonged, catastrophic floods generated sustained hyperpycnal flows, which bypassed the mouth-bar area and fed the slope/pro-delta. The high ratio between sediment supply and subsidence rate resulted in a fast moving progradational wave, which involved the entire SW Pannonian Basin, including the Zagorje Basin.     

Croatian experience with sibutramine in the treatment of obesity--multicenter prospective study

Obesity is a chronic disease with a marked impact on health and the prevalence of obesity in Croatia is rapidly rising. Since obesity plays a significant role in the etiology of cardiovascular diseases, diabetes mellitus type 2 and of some cancers, it is an obvious target of public health activities. Weight-reducing drugs, like sibutramine, in combination with diet, exercise and behavioral changes have a role in the management of obesity. Sibutramine acts centrally as a serotonergic and noradrenergic reuptake inhibitor. It reduces body weight by enhancing satiety and stimulating thermogenesis. The aim of this multicenter prospective study was to evaluate the efficacy, tolerability and safety profile of sibutramine in the treatment of overweight patients in Croatia. Patients received 10 mg of sibutramine daily for 12 weeks. The main outcome measures were changes in body weight, BMI, waist and hip circumferences, laboratory assessments (serum triglicerida, cholesterol, glucose, HbA1c), blood pressure and heart rate profile. Of 461 patients included (mean BMI = 35.81+/-6.48 kg/m2, mean age = 43.65+/-10.90 years), 392 completed the study. Three months of sibutramine treatment lead to a significant reduction in body weight, BMI, waist and hip circumferences and improvement in metabolic parameters. Loss of over 5% of their initial body weight was found in 359 patients (91.58%), while 179 patients (45.66%) achieved weight loss over 10%. A decrease of both systolic (-3.39%) and diastolic (-3.75%) blood pressure was noted, while the pulse rate rose slightly (+0.13%). Adverse events were reported by 124 (26.90%) patients, but they precipitated only 17 (3.69%) withdrawals. Results of our study confirmed that sibutramine is an effective and safe weight-reducing drug.     

Diels–Alder reactivity of benzannulated isobenzofurans as assessed by density functional theory

Density functional theory (DFT) calculations at the B3LYP/6-31G* level for isobenzofuran 1 and eleven benzannulated derivatives of types 2 and 3 have been performed in order to compare their relative reactivities as dienes in Diels–Alder reactions. The transition state (TS) energies for their reactions with ethylene have been determined and shown to form a linear correlation between activation energies and structure count (SC) ratios. TS energies as a method for comparison of diene reactivities can be applied to IBFs bearing substituents on the ring as well as those containing heteroatoms, for which the SC ratio method failed. Different measures of aromaticity of benzannulated IBFs indicated a decrease in aromaticity going from 4 to 14, which is also reflected in their reactivity as a dienes in Diels–Alder reaction. Figure Isobenzofuran 1 and benzannulated isobenzofurans 2 and 3