Modulation of acetylcholine release in the ventral striatum by histamine receptors

Inflammation Research -     

Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology

Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.     

Pro-megakaryoblasts in bone marrow tissue from patients with primary (idiopathic) osteo-myelofibrosis (agnogenic myeloid metaplasia). An immunomorphometric study on trephine biopsies

An immunomorphometric study was performed on bone marrow biopsies from 40 patients with primary osteomyelofibrosis--OMF, (agnogenic myeloid metaplasia) by employment of a monoclonal antibody against glycoprotein IIIa (Y2/51) to determine the number of pro-megakaryoblasts. Specimens from 15 individuals without any hematological disorder served as controls. With reference to the pertinent literature on megakaryocyte precursors and following a pilot study on corresponding smears, in tissue sections pro-megakaryoblasts were characterized by a size of 42.1 +/- 2.6 microns 2 (diameter 7.5 +/- 0.3 microns). In comparison with controls, in OMF no relevant increase in the number of pro-megakaryoblasts per square and cubic millimeter bone marrow was evaluable. The relative frequency of these precursors was significantly reduced due to an increase in the total amount of conspicuously large and abnormal megakaryocytes. Statistical analysis failed to reveal any correlations between counts for pro-megakaryoblasts or the total number of Y2/51--positive megakaryocytic elements with the density of argyrophilic fibers (determined by morphometry) or the platelet values. Our findings imply that in OMF the marked increase in circulating progenitor cells of the megakaryocyte lineage may be generated by extramedullary, probably splenic hematopoiesis. Moreover, the evolution of medullary fibrosis is thought to be associated with the striking predominance of large atypical, possibly overaged and hyperpolyploid megakaryocytes and not with an increase in precursor cells.     

Specific Pseudomonas Immunoglobulin E Antibodies in Sera of Patients with Cystic Fibrosis

Immunoglobulin E antibodies to Psuedomonas aeruginosa were demonstrated in patients with cystic fibrosis colonized with the bacterium.     

Expression of putative virulence factors by clinical isolates of Klebsiella planticola

A total of 92 clinical isolates of Klebsiella planticola from man was examined with respect to the production of haemagglutinins and siderophores, serum resistance and distribution of capsular types. For comparison, a group of 207 clinical isolates of K. pneumoniae was also studied. The percentages of K. planticola strains able to express mannose-sensitive haemagglutination, indicating type 1 fimbriae (83%) and mannose-resistant and Klebsiella-like agglutination, indicating type 3 fimbriae (69%), as well as to produce the siderophores enterobactin (100%) and aerobactin (2.2%) were almost identical to those of the K. pneumoniae strains. Similarly, the proportion of serum-resistant strains (30%) was comparable to that of K. pneumoniae (25%). The capsule types most often detected in K. planticola were K14 (13%), K2 (9%) and K70 (9%). The incidence of K2, which is the predominant capsular type in K. pneumoniae, was similar in both species. These findings show that K. planticola, which is being detected with increasing frequency in clinical specimens from man, has the ability to express similar putative virulence factors to K. pneumoniae, suggesting that they may have similar pathogenicity.     

Megakaryocytes and sinus walls in primary osteomyelofibrosis: transendothelial migration as revealed by three-dimensional reconstruction of serial sections following sequential double-immunostaining

Using sequential double-immunostaining and a newly-developed three-dimensional (3D-) reconstruction technique on serially cut sections from bone marrow trephines, we studied the transmural passage of megakaryocytes through the sinus wall. Biopsies derived from patients with primary (idiopathic) osteomyelofibrosis were exposed to monoclonal antibody against type IV collagen to delineate the sinus walls and also the frequently thickened basement membrane. Staining with the primary antibody was followed by Y2/51 (CD61) to identify all elements of megakaryopoiesis. In most instances serial sectioning and 3D-reconstruction revealed an amoeboid shape of megakaryocytes and a tandem-like arrangement in close spatial contact with the abluminal surface of the sinus wall. Preceded by formation of cytoplasmic processes, straight penetration of entire megakaryocytes through gaps in the sinus walls into the lumen was seen. Where collagen deposits apparently presented a barrier, a mole-like tunnelling through the basement membrane material (type IV collagen) was recognizable. Our findings are in keeping with the assumption that megakaryocyte locomotion is an essential requirement for normal thrombocytogenesis.     

Effect of age on the accumulation of lung protein following unilateral pneumonectomy in rats

The effects of unilateral pneumonectomy (PNX) on the net synthesis of right lung protein were investigated in vivo using three groups of rats with body weights (BW) ranging from 85 to 330 g. These data were compared to those from sham-operated and normal growing control animals. After PNX, both the 2-day lag prior to the compensatory increase in right lung mass (LW) and the subsequent rate of increase in LW and LW/BW ratio were independent of two-fold differences in the basal rate of lung growth. In all PNX groups, both right LW and LW/BW reached control values for both lungs, but in the older rats the time required for complete compensation was extended from 5 days to 12 days. The rate of net accumulation of right lung protein increased two-fold in the youngest PNX rats and 6 to 8-fold in the older animals, but when these changes were normalized to the protein content of the remaining tissue, the older rats appeared to respond to PNX less efficiently. Increased tissue levels of RNA and the resulting increased capacity of the lungs for protein synthesis could account for the accelerated rate of gain in right lung protein following PNX in both adult and young animals.     

Systematic investigations on the reactivity of oxazolinium salts

The termination reaction of the cationic polymerization of 2-phenyl- and 2-nonyl-2-oxazolines was examined by reacting the corresponding model oxazolinium salts having tosylate and trifluoromethansulfonate counterions with various nucleophiles. The reaction was monitored by ¹H NMR spectroscopy. Piperidine and KOH react with the oxazolinium salts very fast and quantitatively. In the case of piperidine, the use of a double molar amount of piperidine is necessary to achieve complete conversion. The addition of piperidine, pyridine, 4-dimethylaminopyridine and morpholine takes place in position 5 of the oxazolinium ring, whereas water and KOH add in position 2. The rate of the termination reaction depends on the electron density of the nucleophile which can be correlated with the pK_a value. With CF₃SO as counterion the addition of nucleophiles in position 5 is distinctly faster, whereas the addition of water in position 2 is much slower than with TsO^? as counterion. The ring-opening of the nonyl oxazolinium ion is slower than that of the phenyl oxazolinium ion.     

SV40-related T-antigen expression in human meningiomas with normal and G-22-monosomic karyotype.

Six of 16 meningiomas tested in early subcultures by indirect immunofluorescence showed SV40 T-antigen. Two different antisera specific for T-antigen were used. One serum gave a positive reaction with six tumours and the other with only two. In one T-antigen positive meningioma, the typical nuclear fluorescence changed, beginning with the second subculture, into an unusual brilliant granular pattern irregularly distributed over the nuclei. In six meningiomas, a specific chromosome aberration (monosomy G 22) was established. However, up to now, no clear correlation between karyotype and T-antigen expression could be found: cells from three meningiomas with positive reactions had normal karyotypes, whereas those from three tumours with typical chromosome loss showed no T-antigen.