Buchbesprechungen

Ohne Zusammenfassung     

Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain.

The 2-deoxy-D-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n. basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticulata. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.     

The human leucocyte P30 antigen: properties and assessment of value as a clonal marker

FMC3 and FMC29 are monoclonal antibodies which react with a 30,000 Dalton molecule expressed on the lymphocyte surface membrane. The molecule is a protein which does not appear to be N-glycosylated. The antigen, which is also expressed intracellularly, does not appear to be a marker of differentiation or maturation. Polyclonal cell populations, such as peripheral blood lymphocytes, show a bimodal distribution of surface antigen density, whilst monoclonal cell populations analysed quantitatively showed unimodal antigen density distributions. This suggests the antigen may be a clonal marker.     

The use of computer-assisted video image analysis in the enumeration of immuno-stained cells in tissue sections.

A novel method of computer-assisted video image analysis (VIA) was used to determine the number of immunostained cells in tissue sections. This method permitted an accurate and objective quantification of cells of a particular phenotype. This enumeration was achieved by measuring the area stained by a test monoclonal antibody (such as the T cell marker, CD3) and comparing it with the area stained by a leukocyte common (LCA) monoclonal antibody (CD45). The proportion of T cells within the total leukocyte population in a particular tissue was then calculated. The differentiation of positive (stained) and negative (unstained) cells was uniformly maintained by setting the computer to detect a threshold for staining intensity. This enabled consistency to be maintained within a tissue section as well as between sections stained with the same antibody. In the present study, we determined the phenotype of leukocytes in colonic carcinomas by VIA and compared this with results obtained by normal visual analysis. The VIA method showed distinct advantages over normal visual analysis especially in sections which contained moderate numbers of stained cells.     

Suppression of noxious stimulus-evoked expression of Fos protein-like immunoreactivity in rat spinal cord by a selective cannabinoid agonist

In rats, cannabinoids inhibit behavioral responses to noxious stimulation with a potency and efficacy similar to that of morphine. However, because cannabinoids depress motor function, it has not been possible to state beyond any doubt that these effects were related to a dampening of noxious sensory input. Therefore, c-fos immunocytochemistry was used to explore the possibility that cannabinoids reduce behavioral responses to noxious stimuli by decreasing spinal processing of nociceptive inputs. Rats received systemic injections of the potent and selective cannabinoid agonist WIN 55,212-2, the receptor-inactive enantiomer WIN 55,212-3 or vehicle prior to observations in a model of tonic pain, the formalin test. As demonstrated previously, plantar injections of formalin led to lifting and licking of the injected paw, with two peaks of activity occurring at 5 and 30 min after injection. The cannabinoid agonist suppressed these pain responses and produced a reduction in mobility. Immunocytochemical processing of sections with an antibody to the Fos protein revealed that the cannabinoid markedly suppressed pain-evoked c-fos expression in the superficial and neck regions of the spinal dorsal horn, but not in the nucleus proprius. Decreased expression of c-fos also occurred in the ventral horn. The specificity of this effect and its probable mediation by cannabinoid receptors are suggested by three findings: (i) the suppression by the drug of both behavioral and immunocytochemical responses to pain was dose-dependent; (ii) neither the behavioral nor the immunocytochemical response to the noxious stimulus was significantly affected by the receptor-inactive enantiomer of the agonist; (iii) animals rendered tolerant to cannabinoids by repeated injections of the agonist showed reduced responses to the drug. These findings suggest that cannabinoids inhibit the spinal processing of nociceptive stimuli and support the notion that endogenous cannabinoids may act naturally to modify pain trnasmission within the central nervous system.     

Pilot study of phoP/phoQ-deleted Salmonella enterica serovar typhimurium expressing Helicobacter pylori urease in adult volunteers

Attenuated Salmonella enterica serovar Typhi has been studied as an oral vaccine vector. Despite success with attenuated S. enterica serovar Typhimurium vectors in animals, early clinical trials of S. enterica serovar Typhi expressing heterologous antigens have shown that few subjects have detectable immune responses to vectored antigens. A previous clinical study of phoP/phoQ-deleted S. enterica serovar Typhi expressing Helicobacter pylori urease from a multicopy plasmid showed that none of eight subjects had detectable immune responses to the vectored antigen. In an attempt to further define the variables important for engendering immune responses to vectored antigens in humans, six volunteers were inoculated with 5 x 10(7) to 8 x 10(7) CFU of phoP/phoQ-deleted S. enterica serovar Typhimurium expressing the same antigen. Two of the six volunteers had fever; none had diarrhea, bacteremia, or other serious side effects. The volunteers were more durably colonized than in previous studies of phoP/phoQ-deleted S. enterica serovar Typhi. Five of the six volunteers seroconverted to S. enterica serovar Typhimurium antigens and had strong evidence of anti-Salmonella mucosal immune responses by enzyme-linked immunospot studies. Three of six (three of five who seroconverted to Salmonella) had immune responses in the most sensitive assay of urease-specific immunoglobulin production by blood mononuclear cells in vitro. One of these had a fourfold or greater increase in end-point immunoglobulin titer in serum versus urease. Attenuated S. enterica serovar Typhimurium appears to be more effective than S. enterica serovar Typhi for engendering immune responses to urease. Data suggest that this may be related to a greater stability of antigen-expressing plasmid in S. enterica serovar Typhimurium and/or prolonged intestinal colonization. Specific factors unique to nontyphoidal salmonellae may also be important for stimulation of the gastrointestinal immune system.