Circling behavior in honey bees

Unilateral microinjections of gamma-aminobutyric acid (GABA), acetylcholine (ACh) and related substances into central parts of the brain of the honey bee elicit a quantifiable circling behavior. GABA (40 nl, 10(-2) M, muscimol (40 nl, 10(-4) M) and flaxedil (10(-3) M, 40 nl) induce contralateral circling whilst ACh (40 nl, 10(-2) M), nicotine (40 nl, 10(-4) M) and picrotoxin (40 nl, 10(-3) M) induce ipsilateral circling if injected in the proximity of the alpha-lobe (50-100 microns) of the of the mushroom body. Mechanical lesions of the pedunculus induce ipsilateral circling. This can be reversed by ipsilateral injections of GABA and flaxedil. Intracellular recordings demonstrate a hyperpolarizing effect of GABA and a depolarising effect of ACh on individual neurons in this region. These results suggest that circling behavior in the bee is controlled by the balance of GABA in the alpha-lobes and mediated by acetylcholinergic neurons.     

Revision surgery for failed back surgery syndrome.

Results of surgical treatment in 50 failed back surgery patients were retrospectively reviewed to determine what factors influenced surgical outcome. Before surgery, all patients had disabling pain and limited function. Overall significant improvement in pain and function was obtained in 66% of the patients. Thirteen of 16 patients (81%) who had successful fusion of pseudarthrosis had a satisfactory outcome, whereas only 3 of 13 patients (23%) who had failed pseudarthrosis repair had a satisfactory outcome. Successful pseudarthrosis repair is the key to a high clinical success rate in revision surgery for failed back surgery syndrome. Pseudarthrosis repair by conventional posterolateral fusion with postoperative lumbosacral corset immobilization showed a high failure rate. The success rate of reoperation on failed back surgery syndrome patients is low.     

Influence of zinc on Pseudomonas aeruginosa susceptibilities to imipenem.

Serial dilution susceptibility testing of imipenem against 59 clinical isolates of Pseudomonas aeruginosa, conducted simultaneously on single lots of Difco and BBL Mueller-Hinton agar (MHA), resulted in MICs for 90% of strains tested of 8 and 16 micrograms/ml, respectively. MICs for Escherichia coli, Klebsiella pneumoniae, and Pseudomonas spp. were also higher on BBL MHA. Quantification of the cation content of the two MHAs by atomic absorption spectroscopy demonstrated that the zinc concentration in BBL MHA was 15 times greater than that measured in Difco MHA (2.61 and 0.17 micrograms/ml, respectively). Concentrations of calcium, magnesium, iron, manganese, and copper in the two agars were similar. Addition of zinc to Difco MHA resulted in increases in MICs of imipenem for P. aeruginosa but not in the MICs of ceftazidime or cefpirome for P. aeruginosa (P < 0.01). A lesser zinc effect was seen on the activity of imipenem against E. coli, K. pneumoniae, and Pseudomonas spp. The activities of ceftazidime and cefpirome were similar on both MHAs when tested against all gram-negative organisms in this study. Thus, the effect of zinc in MHA was clearly demonstrated by a significant increase in the MICs of imipenem for P. aeruginosa, and, to a lesser extent, for other gram-negative bacilli.     

TNF-alpha impairs peripheral tolerance towards beta-cells,and local costimulation by B7.1 enhances the effector function of diabetogenic T cells

Maintenance of peripheral tolerance and inactivation of autoreactive T cells is based on a delicate balance between pro-inflammatory and protective cytokines that is poorly understood. We have here addressed how the local expression of the inflammatory cytokine TNF-alpha can impair peripheral tolerance and lead to autoreactivity. After transplantation of pancreata that are immunogenic due to beta-cell expression of B7.1 and TNF-alpha, into thymectomized and euthymic syngeneic mice, we found that only euthymic mice rejected the grafts. This result suggests that under normal circumstances autoreactive T cells are functionally inactivated, and initiation of an autoreactive response requires de-novo generation of T cells. By contrast, thymectomized mice expressing TNF-alpha on the endogenous islets rejected the grafts, showing that expression of TNF-alpha prevents functional silencing of the autoreactive T cells. Thus, this study provides a mechanism by which TNF-alpha and possibly chronic inflammatory responses may promote autoimmune diseases. Furthermore, we have investigated whether B7.1 can enhance T cell responses of already activated T cells leading to islet rejection. By transplantation of wild-type and B7.1-expressing islets into overtly diabetic mice we found that only the wild-type islets could restore normoglycemia, suggesting that costimulation by B7.1 is required in the expansion or effector phase of the response.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Removal of immunoglobulins by a protein A versus an antihuman immunoglobulin G-based system: evaluation of 602 sessions of extracorporeal immunoadsorption

Elimination of IgG can be achieved by extracorporeal immunoadsorption (IA) based on specific binding to either staphylococcal protein A (Excorim) or sheep polyclonal antibodies directed against human IgG (Therasorb). In 602 analyzed sessions of IA, elimination of IgG was 60% through 80% depending on the treated plasma volume, with no significant difference between the mentioned systems. However, the decrease of IgM and IgA was approximately 50% in the anti-IgG compared to 20-40% in the protein A system. Plasma albumin concentration decreased by 20% in the anti-IgG system compared to 15% in the protein A system, and hemoglobin values increased by 2% in the anti-IgG system and decreased by 6% in the protein A system. In conclusion, a clinical relevance for these findings cannot be ruled out, and the individual choice might depend on the clinical situation and laboratory findings.