Dilated cardiomyopathy: a new insight into the rare but common cause of heart failure

Heart Failure Reviews - Heart failure is a global health burden responsible for high morbidity and mortality with a prevalence of greater than 60 million individuals worldwide. One of the major...     

Effects of interferon-α on cytokine profile,T cell receptor repertoire and peptide reactivity of human allergen-specific T cells

A large panel of T cell clones (TCC) specific for the recombinant form of Poa pratensis allergen (rKBG7.2 or Poa p9) were established from the peripheral blood of a grass pollen-sensitive donor in the absence or presence of recombinant interferon-α (IFN-α) in bulk culture and their pattern of cytokine secretion, peptide reactivity and TCR Vβ repertoire was examined. The majority of allergen-specific TCC derived in absence of IFN-α produced high amounts of interleukin-4 (IL-4) and IL-5 but not IFN-γ (Th2 cells), while most of TCC derived in presence of IFN-α produced IFN-γ but not, or limited amounts of, IL-4 and IL-5 (Th1 or Th0 cells). Of 24 TCC established in the presence of IFN-α, 22 were able to recognize a single allergen peptide, p26, while none of the clones established in the absence of IFN-α showed a similar specificity. The majority of both clones expressed the Vβ2 element regardless of whether they were established in the presence of IFN-α, but the presence of IFN-α favored the expansion of Vβ2⁺, Vβ17⁺ and Vβ22⁺ Poa p9-specific T cells, whereas in the absence of IFN-α, other TCR Vβ-bearing T cells (Vβ5, Vβ6.7 and Vβ14) were expanded in addition to Vβ2⁺ T cells. None of Vβ2⁺ clones established in the absence of IFN-α reacted with p26, whereas all the Vβ2⁺ clones established in its presence responded to this peptide. IFN-α also shifted the TCR Vβ repertoire of both Poa p9- and Lolium perenne group 1 (Lol p1)-specific T cell lines generated from the same patient and from a different grass-sensitive individual. These data demonstrate that IFN-α modulates the development of allergen-specific T cells in vitro, and suggest that IFN-α may represent an useful tool for novel immunotherapeutic approaches in allergic disorders.     

Multiple B- and T-cell epitopes on a major allergen of Kentucky Bluegrass pollen.

The B- and T-cell epitopes of a recombinant grass allergen, rKBG60, were delineated using a set of overlapping synthetic peptides. Direct binding by enzyme-linked immunosorbent assay (ELISA) utilizing serum pools led to the identification of 13 murine immunoglobulin-, and nine to 13 human IgG- and five to seven human IgE-reactive overlapping peptides. Of the peptides which bound to human IgE antibodies, all but three peptides bound to human and/or murine IgG antibodies. Furthermore, eight out of 12 synthetic peptides induced antigen-specific antibodies in mice, suggesting that these peptides contained epitopes that recognized and/or induced T cells. These results, in conjunction with cross-recognition of different peptides at the C-terminus of rKBG60 by antibodies to neighbouring or non-overlapping peptides suggest that the C-terminus of this antigen represents a dominant antigenic and allergenic site. Peripheral blood mononuclear cell (PBMC) proliferation studies using these synthetic peptides for 13 grass allergic individuals indicated that seven potential human T-cell epitopes exist on this allergen. Taken together, the results demonstrate that multiple B- and T-cell epitopes exist on this major group of grass allergens, the majority of which are localized at the C-terminus of this antigen.     

Prevalence of methicillin resistant Staphylococcus aureus in a tertiary referral hospital in eastern Uttar Pradesh

We report the prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections and their antibiotic susceptibility pattern in our hospital located in eastern Uttar Pradesh. Out of total 549 strains of Staphylococcus aureus isolated from different clinical specimens 301 (54.85%) were found to be methicillin resistant. More than 80% of MRSA were found to be resistant to penicillin, cotrimoxazole, ciprofloxacin, gentamicin, erythromycin, tetracycline, 60.5% to amikacin and 47.5% to netilmicin. However, no strains were resistant to vancomycin. Many MRSA strains (32.0%) were multi-drug resistant. To reduce the prevalence of MRSA, the regular surveillance of hospital associated infection, monitoring of antibiotic sensitivity pattern and formulation of definite antibiotic policy may be helpful.     

A case of severe osteomalacia secondary to phosphate diabetes in a renal transplant recipient

Transient hypophosphatemia is frequently observed during the first months after renal transplantation and is usually asymptomatic. Phosphate diabetes is defined as inadequate tubular phosphorus reabsorption leading to persistent renal phosphorus wasting, which is an important but overlooked cause of osteodystrophy in the post-renal transplantation population. We report the case of a 58-year-old male who presented with severe multiple osteoarticular pains within 3 months after successful first kidney transplantation. Bone disease was attributed initially to mild hyperparathyroidism secondary to vitamin D deficiency. Despite the correction of the hyperparathyroidism, the withdrawal of corticosteroids, and the reduction of immunosuppressive treatment to tacrolimus-based monotherapy, the osteoarticular pains persisted. Skeletal investigations at month 9 post-transplantation demonstrated a significant bone mineral density loss associated with osteomalacia and osteoporosis on the bone biopsy. Laboratory data showed persistent hypophosphatemia, and phosphate diabetes was then diagnosed explaining the post-transplant bone disease. A tacrolimus-induced renal tubular disorder was suspected to contribute to the excessive renal phosphorus wasting. The replacement of tacrolimus by sirolimus, in addition to oral phosphorus and vitamin D supplementations, led to the disappearance of pains, the normalization of urinary and plasma phosphate level, and a significant improvement of bone mineralization.     

Comparative analysis of the large fragment of the 5′ untranslated region (LF-5′ UTR) of serotype A foot-and-mouth disease virus field isolates from India

India is endemic for foot-and-mouth disease (FMD) and in recent years a unique group within serotype A, carrying a codon deletion at an antigenically critical site in capsid protein VP3 has emerged (VP3⁵⁹-deletion group). This tempted us to analyze the noncoding region, which is an under represented area, though critically associated with virus biology and pathogenesis. Analysis of the large fragment of 5′ untranslated region (LF-5′ UTR) of type A FMD virus revealed discrepancy in the overall tree topology between LF-5′ UTR and 1D region possibly due to independent evolution of coding and noncoding regions. The VP3⁵⁹-deletion group maintained its phylogenetic distinctness even at the LF-5′ UTR. Eighteen lineage specific signatures detected here support independent evolutionary paths for the lineages. Extensive deletions of 45 and 89 nucleotides corresponding to the pseudoknot region were noticed. Conservation pattern in the ‘A₂₅₃AACA’ motif in the cre/bus stem-loop indicates the importance of first three ‘A’ residues in VPg uridylylation. Of the three polypyrimidine tract binding protein (PTB) binding sites mapped on the internal ribosome entry site (IRES), the pyrimidine tract (Py tract) in the loop of domain 2 was found to be maximally conserved and it might be the major PTB binding site. Strikingly, a deletion group lineage specific transversion was noticed in the Py tract at the 3′ end of IRES without significantly affecting its in vitro infectious titer. Hence, we presume that for efficient cap-independent viral translation, either a minimum number of pyrimidine residues rather than a complete Py tract or a Py tract tolerating transversions only at specific locations and a core motif ‘CUUU’ within the Py tract is essential.     

Determination of relationships among non-toxigenic Vibrio cholerae O1 biotype El Tor strains from housekeeping gene sequences and ribotype patterns

Sequencing of three housekeeping genes, mdh, dnaE and recA, and ribotyping for seven non-toxigenic Vibrio cholerae O1 strains isolated from different geographic sources indicate a phylogenetic relationship among the strains. Results of MLST and ribotyping indicate a clear difference between three toxigenic strains (N16961, O395, and 569B) and three non-toxigenic strains from India (GS1, GS2, and GW87) and one Guam strain (X392), the latter of which were similar in both MLST and ribotyping, while two other non-toxigenic strains from the USA and India (2740-80 and OR69) appeared to be more closely related to toxigenic strains than to non-toxigenic strains, although this was not supported by ribotyping. These results provide clues to the emergence of toxigenic strains from a non-toxigenic progenitor by acquisition of virulence gene clusters. Results of split decomposition analysis suggest that widespread recombination occurs among the three housekeeping genes and that recombination plays an important role in the emergence of toxigenic strains of V. cholerae O1.