Simultaneous measurement of opiate-induced histamine release in the periaqueductal gray and opiate antinociception: an in vivo microdialysis study

Histamine release and the subsequent activation of H2 receptors in the periaqueductal gray (PAG) are thought to be important components of morphine antinociception. In vivo microdialysis and antinociceptive testing were simultaneously applied in rats to characterize the effects of morphine on PAG histamine release and determine the relationship between histamine release and antinociception. In the absence of nociceptive (tail pinch) testing, morphine (12.8 mg/kg) induced a delayed, long-lasting release of histamine in the PAG. This effect of morphine was abolished by the opiate antagonist naltrexone (1 mg/kg) but was not mimicked by the mu-preferring agonist fentanyl (0.3 mg/kg), suggesting that activation of an opiate receptor other than, or in addition to, the mu receptor is necessary. In contrast to the findings with fentanyl in untested animals, fentanyl combined with nociceptive testing increased histamine release, even though testing alone had no such effect. Unexpectedly, tail pinch testing inhibited morphine-induced histamine release. These results show that the test procedure alters the action of opiates on histamine release, an effect likely to be the result of the stress of repeated tail pinch testing. Therefore, although histamine release may not be obligatory for all types of opiate antinociception, histamine in the PAG may function as a mediator of stress-induced potentiation of opiate antinociception. Even though the microdialysis technique has been acclaimed for its ability to assess neurochemical and behavioral characteristics simultaneously, the introduction of nociceptive testing clearly can alter the neurochemical systems under study.     

Myeloma stem cells in autografting in multiple myeloma

Autologous transplantation has been used increasingly over the last 10 years for the treatment of multiple myeloma. As is the case in other cancers treated by high-dose therapy and stem cell rescue, the contribution of occult tumor cells in the graft to relapse posttransplant remains to be resolved. In this report, we review the biology and differentiation of plasma cells in the context of their significance as an origin of relapse in multiple myeloma.     

Zehn weitere Briefe zwischen K.E. v. Baer und L.F. und R. Froriep aus den Jahren 1825–1851

Following the publication of 7 letters from Baer to the Frorieps by H.E. Müller-Dietz inNTM N.S. 1 (1993), 2 further letters from Baer and 8 from the Frorieps are published. A curious technical problem in the presentation of the journalNotizen published by Froriep in his Landes-industriecomptoir in Weimar is discussed at length. Froriep recommends his son Robert, to whom Baer sends several enquiries and commissions, which Robert deals with carefully (1831 in Jena, 1849 in Paris). Robert explains in great detail his intention to leave Jena for Berlin in 1831. After his father's death in 1847 he returns to take charge of the Landesindustriecomptoir and begins to cooperate with the newly founded Russian Geographic Society as publisher on behalf of the Society. But about 1850 the cooperation is discontinued by the Russians, and Froriep, who is in economic difficulties, asks Baer (who lives and works in St. Petersburg) urgently (but in vain) to help him with the Society.     

Possible involvement of phosphatidylinositol 3-kinase in regulated exocytosis: studies in chromaffin cells with inhibitor LY294002

Several lines of evidence suggest that phosphorylated products of phosphatidylinositol play critical functions in the regulation of membrane trafficking along the secretory pathway. To probe the possible involvement of phosphatidylinositol 3-kinase (PI 3-kinase) in regulated exocytosis, we have examined its subcellular distribution in cultured chromaffin cells by immunoreplica analysis and confocal immunofluorescence. We found that the PI 3-kinase heterodimer consisting of the regulatory and catalytic subunits was associated essentially with the subplasmalemmal cytoskeleton in both resting and nicotine-stimulated chromaffin cells. Attempts to immunoprecipitate PI 3-kinase with anti-phosphotyrosine antibodies failed, suggesting that the activity of PI 3-kinase was not modulated by tyrosine phosphorylation and/or physical interaction with SH2-containing proteins in stimulated chromaffin cells. LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent inhibitor of PI 3-kinase, produced a dose-dependent inhibition of catecholamine secretion evoked by various secretagogues. Furthermore, cytochemical experiments with rhodamine-labeled phalloidin revealed that LY294002 blocked the disassembly of cortical actin in chromaffin cells stimulated by a depolarizing concentration of potassium. Our results suggest that PI 3-kinase may be one of the important regulatory exocytotic components involved in the signaling cascade controlling actin rearrangements required for catecholamine secretion.     

Study of lithium intercalation into tungsten oxide films prepared by different methods

The interaction of lithium atoms into amorphous tungsten oxide films deposited by thermal evaporation, sputtering and sol-gel synthesis is studied spectroscopically. The mechanism of insertion of lithium into the film depends on the amount and the bonding state of water to the tungsten oxide network. Thermally evaporated tungsten oxide film contains water bonded chemically in the form of a hydrogen tungsten bronze which facilitates the accommodation of a high number of lithium atoms. In the sputtered film, water is physisorbed and the lithiation is incomplete. Tungsten oxide films prepared by sol-gel synthesis have structural water molecules directly involved in the lithiation process. The formation of lithium tungstate independent of the preparation method is demonstrated.     

Ornithine-delta-aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes: toward metabolic sink therapy for gyrate atrophy

There is now strong evidence that the chorioretinal degeneration associated with ornithine-delta-aminotransferase (OAT) deficiency is a consequence of hyperornithinemia. Therefore development of a metabolic system for clearing ornithine from the circulation is being pursued as a potential treatment. The skin is considered an attractive location for such a metabolic system because autologous cells can be safely and easily utilized. This study was undertaken to determine the ornithine metabolizing capacity of epidermal keratinocytes expressing normal and superphysiologic amounts of OAT. The data show that overexpression of OAT in keratinocytes cultured from a gyrate atrophy patient restores ornithine metabolism and results in a rate of ornithine disappearance from the medium that is significantly higher than the rate of disappearance from the medium bathing normal keratinocytes. In addition, OAT activity determined in soluble protein prepared from sonicates suggests that the capacity to maintain plasma ornithine within the normal range is contained within an accomplishable graft of keratinocytes overexpressing OAT. However, the actual rate of ornithine disappearance from the media was significantly less than predicted from enzyme activity assays. Following ornithine metabolite production by intact cells suggests that ornithine metabolism is limited primarily by clearance of downstream metabolites, as opposed to substrate delivery.     

Immunocytochemical localization of chymase to cytoplasmic vesicles after rat peritoneal mast cell stimulation by compound 48/80

The subcellular events responsible for release of mediators by mast cells may help to clarify roles for mast cells in health and disease. In this study we show that the granule-associated protease chymase is also within cytoplasmic vesicles in appropriately stimulated rat peritoneal mast cells. Rat peritoneal mast cells were recovered before or 1-10 sec after exposure to the secretogogue compound 48/80 (10 micrograms/ml) and then were examined by radioimmunoassay to quantify histamine release or were processed, using routine methods for postembedding immunoelectron microscopy, to identify the subcellular localization of chymase. In comparison to unstimulated cells, compound 48/80 stimulated cells in two independent experiments showed an increase (15%, 28%) in the surface area of the cell and a decrease (12%, 6%) in the surface area of the total granule compartment before degranulation channel formation. These global cellular changes occurred in a background of transient but significant (p < 0.01) increases in the area and number of chymase-immunoreactive vesicles per microns2 cytoplasm. These changes were detectable at 5 or 7 sec after stimulation with compound 48/80 but returned to near prestimulation levels by 9 or 10 sec after addition of compound 48/80 (total cumulative histamine release was 28% by 8 sec and 47% by 14 sec). These observations suggest that vesicles participate in the early stages of regulated secretion of chymase from rat peritoneal mast cells.     

Bovine IgG2a antibodies to Haemophilus somnus and allotype expression

AIMS/BACKGROUND: To characterise clinically a large kindred segregating retinitis pigmentosa and sensorineural hearing impairment in an autosomal dominant pattern and perform genetic linkage studies in this family. Extensive linkage analysis in this family had previously excluded the majority of loci shown to be involved in the aetiologies of RP, some other forms of inherited retinal degeneration, and inherited deafness. METHODS: Members of the family were subjected to detailed ophthalmic and audiological assessment. In addition, some family members underwent skeletal muscle biopsy, electromyography, and electrocardiography. Linkage analysis using anonymous microsatellite markers was performed on DNA samples from all living members of the pedigree. RESULTS: Patients in this kindred have a retinopathy typical of retinitis pigmentosa in addition to a hearing impairment. Those members of the pedigree examined demonstrated a subclinical myopathy, as evidence by abnormal skeletal muscle histology, electromyography, and electrocardiography. LOD scores of Zmax = 3.75 (theta = 0.10), Zmax = 3.41 (theta = 0.10), and Zmax = 3.25 (theta = 0.15) respectively were obtained with the markers D9S118, D9S121, and ASS, located on chromosome 9q34-qter, suggesting that the causative gene in this family may lie on the long arm (q) of chromosome 9. CONCLUSIONS: These data indicate that the gene responsible for the phenotype in this kindred is located on chromosome 9 q. These data, together with evidence that a murine deafness gene is located in a syntenic area of the mouse genome, should direct the research community to consider this area as a candidate region for retinopathy and/or deafness genes.     

The scaphoid shift test

The scaphoid test described by Watson has generally been accepted as the definitive test for scaphoid instability and uses pressure against the scaphoid tubercle as the wrist moves from ulnar to radial deviation for the evaluation. This article describes a stress test done with the wrist in neutral position, which actively provokes scaphoid instability. Variations in stability can be used to grade scaphoid laxity.     

Characterization of resol resins modified by the addition of PVC plastisols

Plastisols, which are a blend of poly(vinyl chloride) resin and a plasticizer (DEHP), were used as a toughening agent of a resol resin in order to improve the mechanical properties. It was not possible to formulate resol blends by adding more than 10 % of plastisol owing to a lack of apparent homogeneity in the systems, which also showed many air bubbles. The relationship between dynamic mechanical, mechanical and thermal properties and the amount of plastisol added was studied. It was determined from the infrared spectroscopy and dynamic mechanical results that the resol–plastisol blends seem to be formed by a reaction between the phenol and PVC giving a higher crosslinked structure. An improvement in the thermal resistance of the blends at lower temperatures was observed with an increase in the percentage of plastisol. Flexural analysis showed the elastic behaviour of the systems. However, it was not possible to observe the effect of the plasticizer (DEHP) owing to the low quantity of plastisol that was added to the resol. Copyright © 2004 Society of Chemical Industry