An alternate method of classifying allergic bronchopulmonary aspergillosis based on high-attenuation mucus

Background and Aim

Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically based on the findings of central bronchiectasis (CB) and other radiologic features (ORF). However, the long-term clinical significance of these classifications remains unknown. We hypothesized that the immunological activity and outcomes of ABPA could be predicted on HRCT chest finding of high-attenuation mucus (HAM), a marker of inflammatory activity. In this study, we evaluate the severity and clinical outcomes of ABPA with different radiological classifications.

Methods

Patients were classified based on CT chest findings as: (a) serologic ABPA (ABPA-S) and ABPA-CB; (b) ABPA-S, ABPA-CB, and ABPA-CB-ORF; and, (c) ABPA-S, ABPA-CB and ABPA-CB-HAM. The clinical, spirometric and serological (total and A fumigatus specific IgE levels, eosinophil count) severity of the disease and clinical outcomes in various classifications were analyzed.

Results

Of the 234 (123 males, 111 females; mean age, 34.1 years) patients, 55 (23.5%) had normal HRCT, 179 (76.5%) had CB, 49 (20.9%) had HAM, and 27 (11.5%) had ORF. All immunological markers were consistently higher in the HAM classification, while in other classifications these findings were inconsistent. On multivariate analysis, the factors predicting frequent relapses were presence of HAM (OR 7.38; 95% CI, 3.21–17.0) and CB (OR 3.93; 95% CI, 1.63–9.48) after adjusting for ORF.

Conclusions

The classification scheme based on HAM most consistently predicts immunological severity in ABPA. Central bronchiectasis and HAM are independent predictors of recurrent relapses in ABPA. Hence, HAM should be employed in the radiological classification of ABPA.     

QSAR study on the antibacterial activity of some sulfa drugs: building blockers of Mannich bases

Sulfa drugs are building blockers of several types of Mannich bases. Consequently, the antibacterial activities of sulfa drugs are reported in this paper, which will help in explaining and understanding antibacterial activities of Mannich bases. Reported QSAR is carried out using distance-based topological indices and discussed critically on the basis of statistical parameters.     

Sequence-specific DNA binding determined by contacts outside the helix-turn-helix motif of the ParB homolog KorB

The KorB protein of the broad-host-range plasmid RP4 acts as a multifunctional regulator of plasmid housekeeping genes, including those responsible for replication, maintenance and conjugation. Additionally, KorB functions as the ParB analog of the plasmid's partitioning system. The protein structure consists of eight helices, two of which belong to a predicted helix-turn-helix motif. Each half-site of the palindromic operator DNA binds one copy of the protein in the major groove. As confirmed by mutagenesis, recognition specificity is based mainly on two side chain interactions outside the helix-turn-helix motif with two bases next to the central base pair of the 13-base pair operator sequence. The surface of the KorB DNA-binding domain mirrors the overall acidity of KorB, whereas DNA binding occurs via a basic interaction surface. We present a model of KorB, including the structure of its dimerization domain, and discuss its interactions with the highly basic ParA homolog IncC.     

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

We investigated the mechanism of activation and functional role of a hitherto uncharacterized signaling molecule, RhoG, in platelets. We demonstrate for the first time the expression and activation of RhoG in platelets. Platelet aggregation, integrin αIIbβ3 activation, and α-granule and dense granule secretion in response to the glycoprotein VI (GPVI) agonists collagen-related peptide (CRP) and convulxin were significantly inhibited in RhoG-deficient platelets. In contrast, 2-MeSADP- and AYPGKF-induced platelet aggregation and secretion were minimally affected in RhoG-deficient platelets, indicating that the function of RhoG in platelets is GPVI-specific. CRP-induced phosphorylation of Syk, Akt, and ERK, but not SFK (Src family kinase), was significantly reduced in RhoG-deficient platelets. CRP-induced RhoG activation was consistently abolished by a pan-SFK inhibitor but not by Syk or PI3K inhibitors. Interestingly, unlike CRP, platelet aggregation and Syk phosphorylation induced by fucoidan, a CLEC-2 agonist, were unaffected in RhoG-deficient platelets. Finally, RhoG^−/− mice had a significant delay in time to thrombotic occlusion in cremaster arterioles compared with wild-type littermates, indicating the important in vivo functional role of RhoG in platelets. Our data demonstrate that RhoG is expressed and activated in platelets, plays an important role in GPVI-Fc receptor γ-chain complex-mediated platelet activation, and is critical for thrombus formation in vivo.     

Chloroplast‐derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery

Cholera and malaria are major diseases causing high mortality. The only licensed cholera vaccine is expensive; immunity is lost in children within 3 years and adults are not fully protected. No vaccine is yet available for malaria. Therefore, in this study, the cholera toxin‐B subunit (CTB) of Vibrio cholerae fused to malarial vaccine antigens apical membrane antigen‐1 (AMA1) and merozoite surface protein‐1 (MSP1) was expressed in lettuce and tobacco chloroplasts. Southern blot analysis confirmed homoplasmy and stable integration of transgenes. CTB‐AMA1 and CTB‐MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce, respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves. Significant levels of antigen‐specific antibody titres of immunized mice completely inhibited proliferation of the malarial parasite and cross‐reacted with the native parasite proteins in immunoblots and immunofluorescence studies. Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice correlated with CTB‐specific titres of intestinal, serum IgA and IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of interleukin‐10⁺ T cell but not Foxp3⁺ regulatory T cells, suppression of interferon‐γ and absence of interleukin‐17 were observed in protected mice, suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual immunity against two major infectious diseases provided by chloroplast‐derived vaccine antigens for long‐term (>300 days, 50% of mouse life span) offers a realistic platform for low cost vaccines and insight into mucosal and systemic immunity.