Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms

Two experiments tested the hypothesis that the deficits in conditional discrimination learning produced by ibotenic acid-induced lesions of the ventral pallidum and substantia innominata are produced by loss of the magnocellular cholinergic cells in the nucleus basalis and adjacent regions. Experiment 1 replicated the previously reported deficit in conditional learning produced by ibotenate-induced lesions of the ventral pallidum/substantia innominata, but failed to demonstrate any restoration of learning by a subchronic regimen of the acetylcholinesterase inhibitor physostigmine sufficient to produce significant (30%), but equivalent, degrees of inhibition in the frontal cortex of ventral pallidum/substantia innominata-lesioned or sham-operated rats. Experiment 2 examined the effects of quisqualic acid-induced lesions of the ventral pallidum/substantia innominata. According to most of the measures of learning employed, the quisqualic acid-induced lesion of the ventral pallidum/substantia innominata failed to impair conditional learning, even though the quisqualate-induced lesion produced greater degrees of cholinergic neuron destruction than the ibotenate-induced lesion, as measured in terms of reductions in cortical choline acetyltransferase activity (44% vs 27%). Although consideration of individual data suggested that very high (60%) levels of choline acetyltransferase reduction in Experiment 2 might have detrimental effects of conditional learning, the overall failure of the quisqualate-induced lesions of the ventral pallidum/substantia innominata to impair learning is to be contrasted with the significant behavioural effects of ibotenate-induced lesions. Histological and immunocytochemical analysis showed that the quisqualate-induced lesion, unlike that produced by ibotenate, tended to produce less damage to the overlying dorsal globus pallidus and to parvocellular neurons of the ventral pallidum/substantia innominata, thus implicating these nonspecific effects of ibotenate-induced lesions in their behavioural effects. The present results question previous interpretations of the behavioural effects of ibotenate-induced lesions of the ventral pallidum/substantia innominata in terms of damage inflicted on the cortically-projecting cholinergic cells of the nucleus basalis, and suggest that quisqualic acid, although also nonspecific in its excitotoxic effects, is nevertheless more selective for producing damage to cholinergic neurons in the ventral pallidum/substantia innominata than ibotenic acid.     

Comparison between radioimmunoassay and direct and indirect enzyme-linked immunosorbent assays for determination of antibodies against Haemophilus influenzae type b capsular polysaccharide.

Levels of antibodies against Haemophilus influenzae type b capsular polysaccharide were determined in acute-phase and convalescent-phase serum samples obtained from 21 children with invasive H. influenzae type b infections and from 44 children vaccinated with two H. influenzae type b vaccines. Amounts of immunoglobulin G (IgG), IgM, and IgA antibodies were measured by direct and indirect enzyme-linked immunosorbent assay (ELISA), and the total amount of antibodies was measured by radioimmunoassay (RIA). Results obtained by ELISA were calculated by multiple-point parallel-line comparison and by endpoint analysis. A very good correlation was obtained between direct and indirect ELISA values. In the lower range of antibody concentrations, the correlation between ELISA values obtained by endpoint analysis and those obtained by multiple-point parallel-line comparison was poor, since the latter method of calculation yielded values of up to 1 microgram/ml in sera that were negative according to endpoint analysis. These sera with negative endpoint titers also had undetectable or very low antibody concentrations as measured by RIA. Consistent with this finding, in acute-phase and prevaccination sera with undetectable or low antibody concentrations as measured by RIA, ELISA values calculated by multiple-point parallel-line comparison were much higher. In sera with higher antibody concentrations, however, parallel-line comparisons showed good correlation between RIA and ELISA values. Although no reference method for measuring true antibody concentrations is available, ELISA values as calculated by multiple-point parallel-line comparison appear to overestimate antibody concentrations in sera containing low antibody concentrations, whereas ELISA values obtained by endpoint analysis are less well correlated with RIA values at higher concentrations.     

Strain variation in glycosaminoglycan recognition influences cell-type-specific binding by lyme disease spirochetes

Lyme disease, a chronic multisystemic disorder that can affect the skin, heart, joints, and nervous system is caused by Borrelia burgdorferi sensu lato. Lyme disease spirochetes were previously shown to bind glycosaminoglycans (GAGs). In the current study, the GAG-binding properties of eight Lyme disease strains were determined. Binding by two high-passage HB19 derivatives to Vero cells could not be inhibited by enzymatic removal of GAGs or by the addition of exogenous GAG. The other six strains, which included a different high-passage HB19 derivative (HB19 clone 1), were shown to recognize both heparan sulfate and dermatan sulfate in cell-binding assays, but the relative efficiency of binding to these two GAGs varied among the strains. Strains N40, CA20-2A, and PBi bound predominantly to heparan sulfate, PBo bound both heparan sulfate and dermatan sulfate roughly equally, and VS461 and HB19 clone 1 recognized primarily dermatan sulfate. Cell binding by strain HB19 clone 1 was inhibited better by exogenous dermatan sulfate than by heparin, whereas heparin was the better inhibitor of binding by strain N40. The GAG-binding preference of a Lyme disease strain was reflected in its cell-type-specific binding. Strains that recognized predominantly heparan sulfate bound efficiently to both C6 glioma cells and EA-Hy926 cells, whereas strains that recognized predominantly dermatan sulfate bound well only to the glial cells. The effect of lyase treatment of these cells on bacterial binding was consistent with the model that cell-type-specific binding was a reflection of the GAG-binding preference. We conclude that the GAG-binding preference varies with the strain of Lyme disease spirochete and that this variation influences cell-type-specific binding in vitro.     

Executive function in Tourette's syndrome and obsessive-compulsive disorder

BACKGROUND: Cognitive performance was compared in the genetically and neurobiologically related disorders of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control. METHOD: Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making. RESULTS: Compared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group. CONCLUSIONS: TS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology.     

Inhibition of inducible nitric oxide synthase expression by interleukin-4 and interleukin-13 in human lung epithelial cells.

Oral feeding of proteins causes peripheral T-cell tolerance, as revealed by reduced delayed-type hypersensitivity (DTH) reactivity after immunization. This type of tolerance can be due both to passive T-cell anergy and active immunosuppression. Using ovalbumin-fed mice we studied whether putatively immunostimulatory cytokines could break this state of mucosal tolerance. Cytokines were administered locally at the site of attempted sensitization. It was found that neither interleukin-2 (IL-2), interferon-gamma (IFN-gamma) nor granulocyte-macrophage colony-stimulating factor (GM-CSF) could restore the response to immunization. In contrast, local administration of IL-12 at the site of attempted immunization resulted in full recovery of DTH reactivity. The dichotomy between the two Th1 stimulatory cytokines IFN-gamma and IL-12 was also reflected by different effects on ovalbumin-specific antibody isotypes. Although both IFN-gamma and IL-12 downregulated serum IgG1-levels in tolerant mice, suggesting decreased ovalbumin-specific Th2 function, only local administration of IL-12 led to increased serum IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.     

Synthesis and immunologic properties in mice of vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides conjugated to Pseudomonas aeruginosa exotoxin A.

Epidemiological, serological and in vitro phagocytosis experiments provide evidence that the newly discovered type 5 and type 8 capsular polysaccharides (CPs) are both virulence factors and protective antigens for bacteremia caused by Staphylococcus aureus. Neither type 5 nor type 8 CP elicited serum antibodies when injected into mice. These two CPs were bound to Pseudomonas aeruginosa exotoxin A (ETA) to form conjugates by using the synthetic scheme devised for the CP (Vi) of Salmonella typhi and of pneumococcus type 12F (A. Fattom, W. F. Vann, S. C. Szu, A. Sutton, X. Li, D. Bryla, G. Schiffman, J. B. Robbins, and R. Schneerson, Infect. Immun. 56:2292-2298, 1988; S. C. Szu, A. L. Stone, J. D. Robbins, R. Schneerson, and J. B. Robbins, J. Exp. Med. 166:1510-1524, 1987). Both S. aureus CP-ETA conjugates elicited a rise in CP antibodies. As components of conjugates, both S. aureus CPs acquired T-cell-dependent properties, as shown by their ability to respond to carrier priming and to stimulate booster responses. The conjugate-induced antibodies facilitated type-specific opsonization of S. aureus by human polymorphonuclear leukocytes. The conjugates also induced ETA antibodies which neutralized the native toxin in vitro. Clinical studies of these two conjugates for active or passive immunization of patients at risk for S. aureus bacteremia are planned.     

Polysaccharides of the Genus Bacillus Cross-Reactive with the Capsular Polysaccharides of Diplococcus pneumoniae Type III, Haemophilus influenzae Type b, and Neisseria meningitidis Group A

We studied 174 strains of the genus Bacillus for cross-reacting antigens to the capsular polysaccharides of groups A and C meningococcus, types I and III pneumococcus, and Haemophilus influenzae type b. Cross-reactions were detected by immunodiffusion in agarose gel by using type-specific antisera and confirmed by absorption and inhibition experiments. Of 20 Bacillus pumilis strains, six had an antigen cross-reacting with group A meningococcal polysaccharide. Other cross-reactions included one strain of B. pumilis with H. influenzae type b, one of B. cereus var. mycoides with pneumococcus type III, and one of B. alvei with both type b and SIII polysaccharides. These cross-reacting antigens are polysaccharides of vegetative cells and may be extracellular in location. Because these bacilli have antigens cross-reacting with the virulence factors of pyogenic bacteria, they may, as normal flora, be an antigenic stimulus for "natural" serum anti-capsular antibodies to the type b Haemophilus and group A meningococcus polysaccharides.     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.