Attachment in OCD: A meta-analysis.

INTRODUCTION: It has been proposed to extend the cognitive-behavioural model of obsessive-compulsive disorder (OCD) with attachment theory to shed light on the affective and developmental factors underlying the disease. With a growing number of empirical studies on the subject, this meta-analysis aims to quantify a possible relationship between attachment insecurity and OCD. METHODS: A systematic search was conducted for studies in adult populations of patients with OCD as well as general populations displaying symptoms of OCD. Effect sizes of attachment anxiety and attachment avoidance were calculated separately. Covariates of demographic variables were used in meta-regressions. RESULTS: Sixteen studies were included. Meta-analyses showed an association of medium to large effect size (Hedges' g = 0.69; 95 % CI 0.58 - 0.80; p < 0.001) between OCD and attachment anxiety, and an association of medium effect size (Hedges' g = 0.47; 95 % CI 0.39 - 0.54; p < 0.001) between OCD and attachment avoidance. Effect sizes in OCD population and general population studies did not differ significantly. DISCUSSION: Robust effect sizes of both attachment anxiety and avoidance in relation to OCD symptomatology corroborate an attachment-centred view of OCD. These findings furthermore suggest that integrating cognitive and attachment-based therapeutic approaches to OCD may benefit patients in which developmental or emotional factors hinder successful treatment.

[The subclinical course of a paracetamol intoxication: pitfall for patient and clinician]. / Het subklinische beloop van een paracetamolintoxicatie: valkuil voor patiënt en behandelaar.

A 24-year-old man took 20 grams of paracetamol during a hospital stay in the department of psychiatry. It was not until 60 hours later that therapy with acetylcysteine was initiated. Paracetamol intoxication has a long latency period. If there is no intervention, severe hepatic damage can develop within three days. Even after a few days have passed it is still advisable to start treating the patient with acetylcysteine.

Allergenicity assessment of apple cultivars: hurdles in quantifying labile fruit allergens.

BACKGROUND: Assessment of allergenicity of foods is important for allergic consumers and regulators. Immunoassays to measure major food allergens are widely applied, often giving variable results. Using the major apple allergen Mal d 1 as a model, we aimed to establish at the molecular level why different immunoassays for assessing allergenicity of apple cultivars produce conflicting outcomes. METHODS: Mal d 1 was measured in 53 cultivars from Italy and 35 from The Netherlands, using four different immunoassays. Purified Mal d 1 standards were molecularly characterized by size-exclusion chromatography (SEC) and mass spectrometry (MS). RESULTS: Three immunoassays using an identical standard gave similar results. Minor differences in sample preparation already resulted in significant loss of allergenicity. The fourth assay, using a different Mal d 1 standard, gave 10- to 100-fold lower outcomes. By SEC, this standard was shown to be almost fully aggregated. This aggregation was accompanied by a decrease of the mass of the Mal d 1 molecule by approximately 1 kDa as analyzed by MS. The deviating immunoassay was shown to selectively recognize this aggregated form of Mal d 1, whereas the other three assays, including the one based on IgE antibody recognition, preferentially bound non-aggregated allergen. CONCLUSIONS: Variable and poorly controllable major allergen modification in both extracts and standards hamper accurate allergenicity assessments of fruits.

Combining Hebbian and reinforcement learning in a minibrain model.

A toy model of a neural network in which both Hebbian learning and reinforcement learning occur is studied. The problem of 'path interference', which makes that the neural net quickly forgets previously learned input-output relations is tackled by adding a Hebbian term (proportional to the learning rate nu) to the reinforcement term (proportional to delta) in the learning rule. It is shown that the number of learning steps is reduced considerably if 1/4

Purified natural and recombinant Fel d 1 and cat albumin in in vitro diagnostics for cat allergy.

BACKGROUND: Current diagnostics and therapeutics for cat allergy are based on cat epithelial extracts originating from highly variable source materials. This gives rise to several problems: variability of allergen composition, contamination with house dust mite allergens, and potential transfer of pathogenic agents. OBJECTIVE: The aim of this study was to investigate the feasibility of replacing cat epithelial extracts with purified natural or recombinant allergens. METHODS: Sera (n = 509) were selected on the basis of a positive cat RAST result and tested in a RAST for IgE reactivity to purified Fel d 1, cat albumin (CA), or both. The analysis was performed with both natural and recombinant allergens. In addition, some sera were further analyzed by means of immunoblotting. A serum pool was used for cat RAST inhibition with purified natural and recombinant allergens as inhibitors. RESULTS: Natural and recombinant Fel d 1 caused very similar results: 94.1% and 96.1% positive test results, respectively. In general, the negative sera were low responders to cat extract. The addition of CA (16.7% positive sera) resulted in a decrease in the number of discrepencies between purified allergens and whole extract to 2.8%. Only for 2% of all sera, sensitization to cat was largely explained by IgE reactivity to CA. IgE reactivity to Fel d 1 accounts for 88% of the total IgE response to cat allergens, as was demonstrated by RAST, with Fel d 1 concentrations nearing saturation. Recombinant Fel d 1 performed equally well in the RAST analysis. Recombinant CA was succesfully expressed in the yeast Pichia pastoris, and its immune reactivity closely resembled that of its natural counterpart. CONCLUSION: Natural and recombinant Fel d 1 and CA are good candidates for replacing ill-defined cat dander extracts in diagnostics for cat allergy. Although CA is not essential for the vast majority of cat-sensitized patients, some subjects are selectively sensitized to this serum protein.

How far can we simplify in vitro diagnostics for Fagales tree pollen allergy? A study with three whole pollen extracts and purified natural and recombinant allergens.

BACKGROUND: Current diagnostic tests for Fagales tree pollen allergy are often composed of mixtures of pollen of birch, alder and hazel. Their complex composition hampers accurate standardization. OBJECTIVE: The aim of this study was to investigate whether mixtures of tree pollen extracts can be replaced by a single pollen species, and whether a single pollen species can be replaced by a limited number of purified natural or recombinant major allergens. METHODS: Sera (n = 1725) were selected on ground of a general suspicion for inhalant allergy, and tested in a RAST for birch, alder and hazel pollen. Sera with > 0.5 RU/mL for any of the three species were tested in a RAST for natural Bet v 1 and Bet v 2 as well as for recombinant versions of both allergens. RESULTS: Specific IgE antibodies (> 0.3 RU/mL) against birch, alder and hazel were found in 242, 298 and 292 sera, respectively. All sera with a positive RAST for alder and/or hazel and a negative RAST for birch were low-responder sera on alder and hazel, only five sera having a RAST value > 1.0 (all < 2.0). For all sera with a RAST > 0.5 RU/mL (n = 250), the mean of individual ratio's alder/birch and hazel/birch was 1.02 and 0.54, respectively. Of 223 of these sera, 63.2% had specific IgE against natural Bet v 1 and 63.7% against natural Bet v 2. When responses to both allergens were combined 93.7% were positive. The mean ratios Bet v 1 + 2/extract were 1.00, 1.04 and 2. 11 in case of birch, alder and hazel, respectively. For 211 sera the same analysis was performed with recombinant Bet v 1 and Bet v 2. Only six sera with Bet v 1-specific IgE (all < 0.5 RU/mL) were negative (< 0.3 RU/mL) on recombinant Bet v 1. For Bet v 2, 77/132 sera with specific IgE to the natural allergen did not react to the recombinant version. Twelve false-negatives had RAST values > 1.0 RU/mL. The mean of the individual recombinant/natural ratios was 0. 98 for Bet v 1 and 0.38 for Bet v 2 (P < 0.001). The mean ratio rBet v 1 + 2/birch was 0.75 with 17.5% false-negatives on the combination of recombinant allergens. CONCLUSION: Reliable in vitro diagnosis is possible with a single tree pollen extract (birch or alder). The same is true for purified natural Bet v 1 and Bet v 2. A combination of recombinant molecules is slightly less efficient.

How far can we simplify in vitro diagnostics for grass pollen allergy?: A study with 17 whole pollen extracts and purified natural and recombinant major allergens.

BACKGROUND: Current diagnostics for grass pollen allergy are composed of mixtures of pollen of different grass species. Their complex composition hampers accurate standardization. OBJECTIVE: The aim of the study was to investigate whether mixtures of grass pollen extracts can be replaced by a single pollen species and whether a single pollen species can be replaced by a limited number of purified natural or recombinant major allergens. METHODS: Sera (n = 800) were selected on the basis of a general suspicion for inhalant allergy and tested in a RAST for IgE reactivity with pollen from 17 different grass species. Cross-reactivity of IgE responses was studied by means of RAST inhibition. Sera with positive test results for grass pollen were tested in a RAST for natural Lol p 1 and Lol p 5 and recombinant Phl p 1 and Phl p 5. RESULTS: Specific IgE antibodies against one or more of the 17 pollen species were detected in 209 of 800 sera (26.1%). The highest responses were observed against Poa pratensis followed by Festuca rubra, Phleum pratense, and Dactylis glomerata. IgE responses were clearly lower (approximately by a factor of 5) against only three species (Phragmites communis, Cynodon dactylon, and Zea mays). With the exception of a few low-responder sera, no sera were found to have negative test results to the high responder species and positive results to any of the other species. Sera with positive test results for grass pollen (n = 154) were tested with purified Lol p 1 and Lol p 5. IgE anti-Lol p 1 and Lol p 5 accounted for an average of 81% +/- 7% of total anti-grass pollen IgE. For 14 sera (all with low anti-grass pollen IgE titers), a RAST with purified allergens resulted in a false-negative diagnosis for grass pollen allergy. With recombinant Phl p 1 and Phl p 5, the mean IgE reactivity was 57% +/- 6% of the anti-grass pollen IgE response (n = 141), with 13 false-negative results. CONCLUSION: One grass species is sufficient for in vitro diagnosis of grass pollen allergy. With purified natural Lol p 1 and Lol p 5, greater than 90% of grass-positive sera is detected. Around 80% of the IgE response to grass pollen is directed to these major allergens. Recombinant allergens, produced in Escherichia coli, did not equal the IgE-binding capacity of their natural counterparts.

Coherency and connectivity in oscillating neural networks: linear partialization analysis.

This paper studies the relation between the functional synaptic connections between two artificial neural networks and the correlation of their spiking activities. The model neurons had realistic non-oscillatory dynamic properties and the networks showed oscillatory behavior as a result of their internal synaptic connectivity. We found that both excitation and inhibition cause phase locking of the oscillating activities. When the two networks excite each other the oscillations synchronize with zero phase lag, whereas mutual inhibition between the networks resulted in an anti-phase (half period phase difference) synchronization. Correlations between the activities of the two networks can also be caused by correlated external inputs driving the systems (common input). Our analysis shows that when the networks exhibit oscillatory behavior and the rate of the common input is smaller than a characteristic network oscillator frequency, the cross-correlation functions between the activities of two systems still carry information about the mutual synaptic connectivity. This information can be retrieved with linear partialization, removing the influence of the common input. We further explored the network responses to periodic external input. We found that when the input is of a frequency smaller than a certain threshold, the network responds with bursts at the same frequency as the input. Above the threshold, the network responds with a fraction of the input frequency. This frequency threshold, characterizing the oscillatory properties of the network, is also found to determine the limit to which linear partialization works.

Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy.

BACKGROUND: IgE titres tend to rise early after the start of immunotherapy, followed by a decline to pre-immunotherapy levels or lower. OBJECTIVES: We were interested to know whether the early increase in IgE antibodies includes new specificities of IgE, and whether these responses persist. METHODS: Sera of 64 patients undergoing grass pollen immunotherapy were tested for IgE against four purified grass pollen allergens: Lol p 1, 2, 3, and 5. At least two serum samples were taken, one before the start of therapy and one between 5 and 18 months after the first immunization (mean: 10 months). RESULTS: The mean IgE responses to Lol p 1, 2 and 3 showed a moderate but not significant increase. In contrast, the mean IgE response to Lol p 5 showed a significant decrease of > 30%. IgE against total Lohum perenne pollen extract moderately increased (> 20%), showing that a RAST for total pollen is not always indicative for the development of IgE against its major allergens. For > 40% of the patients it was found that IgE against one or more of the four allergens increased, while IgE against the remaining allergen(s) decreased. For 10 sera the ratio of IgE titres against at least two allergens changed by at least a factor of 5. The changes in specific IgE also included conversions from negative (< 0.1 RU) to positive (0.6 to 5.0 RU) for five patients. For two patients, the induction of these 'new' IgE antibodies against major allergens was shown to result in a response that was persistent over several years. CONCLUSION: Although active induction of new IgE specificities by immunotherapy was not really proven, the observations in this study indicate that monitoring of IgE against purified (major) allergens is necessary to evaluate changes in specific IgE in a reliable way.

Lol p XI, a new major grass pollen allergen, is a member of a family of soybean trypsin inhibitor-related proteins.

BACKGROUND: Monoclonal antibodies were obtained against an unknown allergen from Lolium perenne grass pollen. The allergen had an apparent molecular mass of 18 kd on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Earlier immunoblotting studies had shown that carbohydrate-specific IgG antibodies recognize an antigen of similar size. OBJECTIVE: We sought to characterize the allergen biochemically and immunologically. METHODS: The amino acid sequence of the allergen was determined by automated Edman degradation, and its monosaccharide composition was determined by gas chromatographic analysis. A panel of 270 grass pollen-positive sera was assessed in a RAST with the purified allergen. Protease digestion (proteinase K) and chemical deglycosylation (trifluoromethane sulfonic acid) were used to distinguish between carbohydrate and peptide epitopes for IgE antibodies. RESULTS: The allergen was shown to be a glycoprotein with a molecular mass of 16 kd, of which 8% is carbohydrate. Its amino acid sequence shares 32% homology with soybean trypsin inhibitor (Kunitz) but lacks its active site. No homology was found with known grass pollen allergens, hence it was designated Lol p XI. A high degree of homology (44%) was found with a tree pollen allergen, Ole e I, the major allergen of olive pollen. More than 65% of grass pollen-positive sera had IgE against Lol p XI. IgE reactivity was demonstrated both with the carbohydrate moiety and the peptide backbone. CONCLUSIONS: Lol p XI is a new major grass pollen allergen carrying an IgE-binding carbohydrate determinant. Lol p XI is structurally related to the major allergen from olive pollen.

IgE and IgG cross-reactivity among Lol p I and Lol p II/III. Identification of the C-termini of Lol p I, II, and III as cross-reactive structures.

In this study, the homologous C-termini of Lol p I, Lol p II, and Lol p III were shown to contain cross-reactive B-cell epitopes. This was demonstrated by inhibition studies with purified Lol p I, II, and III and synthetic peptides of their C-termini. It was ruled out that the observed cross-reactivity was caused by cross-contamination of the purified allergens. Both human IgE and IgG bound to the C-terminus of Lol p I. These antibodies were cross-reactive with Lol p II and, more specifically, with its C-terminus. Within a small panel of allergic patients, no cross-reactivity with Lol p III was found. A hyperimmune polyclonal rabbit antiserum against Lol p I also recognized the Lol p I C-terminus. As for human antibodies, cross-reactivity with Lol p II and its C-terminus was demonstrated. Cross-reactivity with Lol p III was demonstrated with C-terminal peptides, but not with native Lol p III. A polyclonal rabbit antiserum against Lol p II bound to the C-terminal peptides of both Lol p II and III. This binding was inhibited with Lol p I, confirming that cross-reactive structures exist not only on the C-termini of Lol p II and Lol p I, but also of Lol p III and Lol p I. The existence of cross-reactivity between Lol p I and Lol p II and III possibly contributes to the frequently observed cosensitization for these allergens in grass-pollen-allergic patients.

Variability of crossreactivity of IgE antibodies to group I and V allergens in eight grass pollen species.

Crossreactivity to Dactylis glomerata, Festuca rubra, Phleum pratense, Anthoxanthum odoratum, Secale cereale, Zea mays, and Phragmites communis of IgE antibodies against Lol p I or Lol p V was investigated by means of RAST-inhibition. Within a group of sera the degree of crossreactivity was demonstrated to be highly variable. Individual sera were not always equally crossreactive to all pollen species. A high degree of crossreactivity for Group I allergens did not necessarily implicate the same for Group V. Group I and Group V representatives were found to be present in all eight species. It was demonstrated that within this group of grass species significant quantitative and qualitative differences exist, with respect to Group I and Group V allergens. Species with a low phylogenetic affinity to Lolium perenne, like Zea mays and Phragmites communis showed a very low degree of reactivity, even when measured with the most crossreactive sera. A higher taxonomic relationship however, did not always implicate a closer antigenic resemblance. Antigenically both allergens from Zea mays are more similar to Lol p I and Lol p V, than the analogues in Secale cereale.

Profilin is a cross-reactive allergen in pollen and vegetable foods.

Sera with IgE antibodies against grass pollen often contain IgE against vegetable foods. We investigated the role of the ubiquitous protein profilin in this cross-reactivity. Profilin was purified from Lolium perenne grass pollen by means of affinity purification with Sepharose-coupled poly(L-proline). This solid phase was also used as capturing agent for profilin from pollen and food extracts for application in a radioallergosorbent test. It was shown that profilin is an allergen in grass pollen and in a wide range of vegetable foods, like potato and celery. Within a grass-pollen-sensitive population, patients with IgE to vegetable foods have a high incidence of antibodies against profilin. IgE antibodies against grass pollen profilin were shown to be cross-reactive with respect to vegetable foods.