Cellular immune response to Mycobacterium tuberculosis-specific antigen culture filtrate protein-10 in south India

The Mycobacterium tuberculosis (M. tuberculosis)-specific culture filtrate protein-10 (CFP-10) is highly recognized by M. tuberculosis infected subjects. In the present study, the proliferative response and IFN-γ secretion was found for C-terminal peptides of the protein (Cfp6_51–70, Cfp7_61–80, Cfp8_71–90, and Cfp9_81–100). The alleles HLA DRB1 *04 and HLA DRB1 *10 recognized the C-terminal peptides Cfp7, Cfp8, and Cfp9 in HHC. Cfp6 was predominantly recognized by the alleles HLA DRB1 *03 and HLA DRB1 *15 by PTB. The minimal nonameric epitopes from the C-terminal region were CFP-10_56–64 and CFP-10_76–84. These two peptides deserve attention for inclusion in a vaccine against tuberculosis in this region.     

Escitalopram (Lexapro) for depression

Escitalopram (Lexapro) is the active s-enantiomer of the selective serotonin reuptake inhibitor (SSRI), citalopram (Celexa). It is labeled for the treatment of major depressive disorder.     

fQRS as a marker of granulomatous disease in patients presenting with ventricular tachycardia and normal left ventricular ejection fraction

Background

Granulomatous myocarditis may present with sustained monomorphic ventricular tachycardia (SMVT) in the presence of normal left ventricular ejection fraction (LVEF), and could be mistaken for idiopathic ventricular tachycardia (IVT). The use of cardiac imaging for diagnosis can be limited by availability and high cost. ECG is readily available and inexpensive. Fragmented QRS (fQRS) on ECG has been found to be associated with myocardial scar. We hypothesized that fQRS could be useful in the diagnosis of granulomatous VT (GVT).

Methods

We compared the 12-lead ECG of 16 patients with GVT and 42 patients with IVT who presented with SMVT.

Results

The presence of fQRS was significantly higher in the GVT group compared to the IVT group (75% versus 19.1%, p < 0.001). The location of fQRS correlated with delayed enhancement cardiac magnetic resonance imaging (DE-CMR) in the same segment in 4/16 patients in the GVT group. It correlated with an affected segment on either DE-CMR or 18FDG positron emission computed tomography in 4/11 patients in the GVT group who had both imaging modality. Whenever fQRS was present in contiguous leads other than the inferior leads, it always corresponded to an affected segment on imaging.

Conclusions

In patients presenting with SMVT and no structural heart disease, the presence of fQRS is strongly associated with granulomatous myocarditis. fQRS on the surface ECG is a helpful tool the presence of which should prompt a CMR for a definitive diagnosis.     

Endosomal trafficking of the ligated FcvarepsilonRI receptor

In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcvarepsilonRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcvarepsilonRI. Here we demonstrate that in RBL-2H3 cells, aggregated FcvarepsilonRI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15min after ligation. Minimal co-localization of FcvarepsilonRI with Rab5 was observed by 30min, followed by its appearance in the Rab7(+) late endosomes and lysosomes at later time points. During endosomal sorting, FcvarepsilonRIalpha and gamma subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated FcvarepsilonRI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of FcvarepsilonRI in endosomes.     

Comparative proteomic analysis between normal skin and keloid scar

Background Keloids are pathological scars and, despite numerous available treatment modalities, continue to plague physicians and patients. Objectives Identification of molecular mediators that contribute to this fibrotic phenotype. Methods Two‐dimensional gel electrophoresis, MALDI‐TOF, Mascot online database searching algorithm and Melanie 5 gel analysis software were employed for comparative proteomic analysis between normal skin (NS) and keloid scar (KS) tissue extracts. Results Seventy‐nine protein spots corresponding to 23 and 32 differentially expressed proteins were identified in NS and KS, respectively. Isoforms of heat shock proteins, gelsolin, carbonic anhydrase and notably keratin 10 were strongly expressed in NS along with manganese superoxide dismutase, immune components, antitrypsin, prostatic binding protein and crystalline. Various classes of proteins were found either to be present or to be upregulated in keloid tissue: (i) inflammatory/differentiated keratinocyte markers: S100 proteins, peroxiredoxin I; (ii) wound healing proteins: gelsolin‐like capping protein; (iii) fibrogenetic proteins: mast cell β‐tryptase, macrophage migration inhibitory factor (MIF); (iv) antifibrotic proteins: asporin; (v) tumour suppressor proteins: stratifin, galectin‐1, maspin; and (vi) antiangiogenic proteins: pigment epithelium‐derived factor. Significant increases in expression of asporin, stratifin, galectin‐1 and MIF were observed by Western blot analysis in KS. Conclusions This work has identified differentially expressed proteins specific to KS tissue extracts which can potentially be used as specific targets for therapeutic intervention.     

Diagnosis of liver cancer and cirrhosis by the fluorescence spectra of blood and urine

Liver cancer or hepato cellular carcinoma (HCC) is a serious malady with only 10% survival rate and is fatal next only to pancreatic cancer. This disease is conventionally detected and diagnosed by ultra sound, CT or MRI scans which are quite expensive. Also the discrimination between cirrhosis and HCC, by these imaging techniques, is poor. The conventional tissue biopsy is quite invasive and painful. In the new diagnostic procedure presented in this paper we have obtained fluorescence emission spectra with excitation at 400?nm and the synchronous emission spectra (Delta lambda = 10 nm) for a set of blood and urine samples (Normal control N =?25, Liver Malfunction N =?58). Based on the ratio fluorometric parameters, all the three liver maladies (minor inflammation like Hepatitis C, serious diseases like Cirrhosis and hepatoma) could be detected and discriminated with an accuracy of about 80%. Hence this inexpensive, non invasive, optical technique may have significant impact in screening, diagnosis and also prognosis of HCC in large segment of people in the populous Asian countries.     

Cancer detection by native fluorescence of urine

Because cancer is a dreaded disease, a number of techniques such as biomarker evaluation, mammograms, colposcopy, and computed tomography scan are currently employed for early diagnosis. Many of these are specific to a particular site, invasive, and often expensive. Hence, there is a definite need for a simple, generic, noninvasive protocol for cancer detection, comparable to blood and urine tests for diabetes. Our objective is to show the results of a novel study in the diagnosis of several cancer types from the native or intrinsic fluorescence of urine. We use fluorescence emission spectra (FES) and stokes shift spectra (SSS) to analyze the native fluorescence of the first voided urine samples of healthy controls (N=100) and those of cancer patients (N=50) of different etiology. We show that flavoproteins and porphyrins released into urine can act as generic biomarkers of cancer with a specificity of 92%, a sensitivity of 76%, and an overall accuracy of 86.7%. We employ FES and SSS for rapid and cost-effective quantification of certain intrinsic biomarkers in urine for screening and diagnosis of most common cancer types with an overall accuracy of 86.7%.