Cluster C personality disorder impedes alleviation of symptoms in major depression

BACKGROUND: We investigated whether cluster C personality disorder (CPD) is associated with recovery from depression. METHODS: The study design was observational. Diagnoses of major depression (MD) and CPD were confirmed by means of the Structured Clinical Interview for DSM-III-R (SCID-I, -II). Changes in symptom scales in 52 patients with MD and CPD were compared with changes in 65 patients with MD alone over a 6-month follow-up period. RESULTS: On the Hamilton Depression Rating Scale and Beck Depression Inventory (BDI) scales, recovery of patients with MD and comorbid CPD was inferior to recovery of patients with MD alone. Findings were similar in relation to several other symptom scales. Of those with MD alone 54% had recovered from their depression, but only 16% of those with CPD and MD (BDI score <10 on follow-up). Logistic regression analysis revealed an independent association between lack of recovery and presence of CPD (OR 7.5, 95% CI 2.6-22.2). LIMITATIONS: Study design was observational. CONCLUSION: The presence of CPD hinders alleviation of depressive symptoms in major depression.     

Deletion analysis of protein kinase c inactivation by calphostin C

Protein kinase C (PKC) undergoes specific inactivation by nanomolar concentrations of calphostin C. Both PKC-α (a Ca²⁺-dependent conventional isoform) and PKC-α (a Ca²⁺-independent novel isoform) are similarly inactivated by calphostin C (75–100 nM produced 50% inhibition), suggesting that inactivation requires a site common to both classes of PKC. We therefore performed studies to identify a critical region in the regulatory domain of PKC-α required for inactivation by calphostin C. A series of N-terminal–truncation mutants of bovine PKC-α expressed in Saccharomyces cerevisiae was tested with 500 nM calphostin C, a concentration sufficient to inactivate wild-type PKC-α by 80–90%. This concentration was as effective with mutant proteins containing deletions of up to 91 amino acid (aa) residues from the amino terminus (ND91), whereas a mutant protein truncated by 140 aa (ND 140) was inactivated by only 20%. These findings imply that the aa sequence 92–140 is a structural determinant of PKC-α inactivation by calphostin C. This sequence contains one of the phorbol ester-binding sites (aa 102–144), which is highly conserved among most PKC isoforms including PKC-α. In addition to aa 92–140, PKC-stimulating cofactors (phosphatidylserine, phorbol ester, and Ca²⁺) are required for inactivation by calphostin C even in the case of PKC mutants that do not require these cofactors for enzymatic activity. These results suggest that cofactors provide a template that is required for productive interaction of PKC and the inhibitor. The significance of the proposed proximity effect of calphostin C action is discussed. © 1995 Wiley-Liss Inc.     

Relationships among alexithymia, adverse childhood experiences, sociodemographic variables, and actual mood disorder: a 2-year clinical follow-up study of patients with major depressive disorder

This 2-year follow-up study examined relationships among alexithymia, adverse childhood experiences, sociodemographic variables, and actual mood disorder among patients with major depressive disorder (N=106). Alexithymia was assessed with the Toronto Alexithymia Scale (TAS-20), depression with the Beck Depression Inventory, and actual mood disorder with the Structured Clinical Interview for DSM-III-R. A questionnaire that assessed sociodemographic characteristics and adverse childhood experiences was also used. Long-lasting alexithymic features were associated with blue-collar work, harsh discipline, unhappiness of the childhood home, depression at 12 months, and major depressive disorder diagnosis at 24 months. Furthermore, the results showed that alexithymic features could also be situational reactions to depression.     

Identification of Pru du 6 as a potential marker allergen for almond allergy

Background

Oral food challenges have demonstrated that diagnosis of almond allergy based on extract-sIgE tests displays low specificity. Molecular allergy diagnosis is expected to improve accuracy, but its value in diagnosing almond allergy remains unknown. The aim of this study was to identify relevant almond allergens and examine their ability to improve almond allergy diagnosis.

Methods

IgE-reactive proteins were purified from almond kernels. IgE binding to almond extract and the allergens was analyzed by quantitative ELISA using sera from 18 subjects with a proven almond allergy. The control group consisted of sera from 18 subjects allergic to peanut and/or tree nuts but tolerant to almond.

Results

Three IgE-binding proteins were identified: legumin (Pru du 6), alpha-hairpinin (Pru du 8), and mandelonitrile lyase (Pru du 10). Positive IgE (≥0.35 kU/L) to almond extract showed 94% sensitivity but only 33% specificity. IgE to Pru du 6 maintained high sensitivity (83%) and provided superior specificity (78%). Sera from almond-allergic subjects had significantly higher IgE levels to almond extract (P < .0001) and Pru du 6 (P < .0001) than sera from tolerant donors. Sensitization to Pru du 6 was highly specific for almond allergy, while frequencies of sensitization to legumins from peanut, walnut, hazelnut, and cashew were similar in both groups. IgE to Pru du 8 and Pru du 10 was less sensitive (41% and 67%), but showed specificities of 100% and 61%.

Conclusion

The use of almond allergens markedly increases the diagnostic specificity compared to the extract. Pru du 6 is a potential new molecular marker for almond allergy.

     

A physiological role for pressure-dependent renin release in long-term blood pressure control

The relationship between pressure-dependent renin release and long-term blood pressure was studied in 14 conscious dogs on a normal salt diet. Stimulus-response curves were obtained by a controlled reduction of renal artery pressure in 5 or 10 mm Hg steps down to 70 mm Hg. Pressure-dependent renin release was characterized by a threshold pressure, a plateau above threshold pressure, and a steep slope below the threshold pressure. In each dog long-term blood pressure was higher than threshold pressure. Threshold pressure and slope were found to describe more than 90% of long-term blood pressure variability between conscious dogs. The following findings suggest that an on-off switch of pressure-dependent renin release stabilizes long-term blood pressure above the threshold pressure: (1) The intermittent activation of pressure-dependent renin release due to physiological variations in arterial blood pressure induced changes in plasma renin activity by as much as 300%. (2) The individual difference between threshold pressure and long-term blood pressure was highly dependent on the slope. (3) A systemic blockade of the reninangiotensin system by converting-enzyme inhibition resulted in a slope-dependent fall of long-term blood pressure. (4) A spontaneous shift of threshold pressure was accompanied by equivalent changes in arterial blood pressure. Taken together, our results provide evidence for a major role of pressure-dependent renin release in the long-term control of blood pressure in conscious dogs. A chronic resetting of threshold pressure may be an important mechanism in the pathogenesis of hypertension.This study was supported by the German Research Foundation within the SFB 320, Heidelberg     

How accurate and safe is the diagnosis of hazelnut allergy by means of commercial skin prick test reagents?

BACKGROUND: Allergy to tree nuts, like hazelnuts, ranks among the most frequently observed food allergies. These allergies can start at early childhood and are, in contrast to other food allergies, not always outgrown by the patient. Tree nut allergy is frequently associated with severe reactions. Diagnosis partially relies on in vivo testing by means of a skin prick test (SPT) using commercially available SPT reagents. METHODS: Protein and allergen composition of nine commercial SPT solutions was evaluated using standard protein detection methods and specific immunoassays for measurement of five individual allergens. Diagnostic performance was assessed by SPT in 30 hazelnut-allergic subjects, of which 15 were provocation proven. RESULTS: Protein concentrations ranged from 0.2-14 mg/ml. SDS-PAGE/silver staining revealed clear differences in protein composition. The major allergen Cor a 1 was present in all extracts but concentrations differed up to a factor 50. An allergen associated with severe symptoms, Cor a 8 (lipid transfer protein), was not detected on immunoblot in three products, and concentrations varied by more than a factor 100 as was shown by RAST inhibition. Similar observations were made for profilin, thaumatin-like protein and a not fully characterized 38-kD allergen. Ratios of individual allergens were variable among the nine extracts. SPT showed significant difference, and 6/30 patients displayed false-negative results using 3/9 products. CONCLUSION: Variability in the composition of products for the diagnosis of hazelnut allergy is extreme. Sometimes, allergens implicated in severe anaphylaxis are not detected by immunoblotting. These shortcomings in standardisation and quality control can potentially cause a false-negative diagnosis in subjects at risk of severe reactions to hazelnuts.     

Hostility as a risk factor for mortality and ischemic heart disease in men

We report the association between hostility and the incidence of ischemic heart disease (IHD) in 3,750 Finnish men aged 40-59. Hostility was assessed from self-ratings on irritability, ease of anger-arousal, and argumentativeness, and four groups were formed from the summed hostility ratings. At baseline, the age-adjusted relative risk (RR) of the prevalence of angina pectoris between the highest and lowest hostility groups was 2.88 (95% confidence limits (CL), range 1.71-4.77). A three-year follow-up yielded 65 deaths and 109 IHD-incident cases. Hostility did not predict IHD among healthy men, but among men with previous IHD and hypertension (N = 104), the age-adjusted RR of IHD between the highest and lowest hostility groups was 12.9 (95% CL, 3.92-42.6). After standardization for smoking, obesity, heavy alcohol use, and snoring, the RR was 14.6 (95% CL, 1.94-110). When the degree of dyspnea at baseline was also standardized, the RR was 21.1 (95% CL, 1.59-282). Our data suggest that extreme hostility is not a consequence of symptom severity; rather, hostility is a strong determinant of coronary attack among hypertensive men with IHD.     

Allergy multivaccines created by DNA shuffling of tree pollen allergens

BACKGROUND: The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment. OBJECTIVE: We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens. METHODS: Fourteen genes of the Bet v 1 family were randomly recombined in vitro by means of DNA shuffling. This library of chimeric proteins was screened for molecules displaying low capacity to induce release of inflammatory mediators but with T-cell immunogenicity higher than that of the parental allergens. RESULTS: Two chimeric proteins were selected from the library of shuffled clones displaying low allergenicity and high immunogenicity, as determined in in vitro assays using human and animal cells and antibodies, as well as in vivo in animal models of allergy. CONCLUSION: Our results show that it is possible to randomly recombine in vitro T- and B-cell epitopes of a family of related allergens and to select chimeric proteins that perfectly match the criteria presently thought to be relevant for improving allergen-specific immunotherapy. CLINICAL IMPLICATIONS: The hypoallergenic chimeras described here recombine epitopes of the major Fagales pollen allergens and thus can efficiently substitute a mixture of extracts used for treating patients with tree pollen-induced spring pollinosis worldwide.