Antibodies against 9-O-acetylated sialoglycans: a potent marker to monitor clinical status in childhood acute lymphoblastic leukemia

Background: Although childhood acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, reliable techniques are needed to determine treatment outcome and predict impending relapse. In ALL, the cell surface over expression of 9-O-acetylated sialoglycans (9-OAcSGs) on lymphoblasts and concomitant high antibody titers in patients' sera was reported. Objectives: The present study was aimed to evaluate whether anti-9-OAcSG titers can be harnessed to monitor the clinical outcome of ALL. Design and methods: Anti-9-OAcSGs were analyzed by ELISA in children receiving either UK ALL X (n = 69, Group I) in India or UK ALL 97 (n = 47, Group II) in UK along with age-matched normal healthy controls at different time points over a period of > 2 years. An attempt was also made to investigate subclass distribution of disease-specific IgG. Moreover, 17 patients having a higher sample size were longitudinally monitored. Results: Antibody levels were raised at disease presentation, decreased with remission induction, and importantly, reappeared with clinical relapse. Sera from patients with other hematological disorders and normal controls showed negligible levels of circulating anti-9-OAcSGs. In patients of both Groups I and II, the assay showed high sensitivity (98.92% and 96.77%) and specificity (92.1% and 95.91%), respectively. IgG subclass analyses during different phases of treatment revealed that 9-OAcSG-specific IgG1 could serve as a better prognostic marker in ALL. Conclusions: This study demonstrated the potential of this disease-specific antibody as an alternate marker in diagnosis and long-term assessment of ALL patients, suggesting its application in detection and prediction of impending relapse. Therefore, the expression of anti-9-OAcSGs, irrespective of their treatment protocol, may serve as an economical yet effective index for monitoring of childhood ALL

Faktor snage nanostrukturiranog bizmut telurida određen oblicima

Bismuth telluride is a thermoelectric material with high figure of merit, used for cooling applications at room temperature. To investigate the effect of morphology and grain size on transport parameters, nanostructured bismuth telluride has been synthesized under different reaction conditions and characterized by X-ray diffraction, transmission electron microscopy and scanning electron microscopy. From the measurement of electrical conductivity and thermoelectric power, power factor for different samples has been obtained. The results show that the transport parameters are critically influenced by the morphology and dimension of the samples that in turn depend on the condition of synthesis. The experimentally observed variation of electrical conductivity with the change of dimensionality of the samples from 2D to 0D, which is in line with the theoretical prediction made by other workers, is discussed. There is a variation of the power factor of the samples prepared under different conditions of synthesis.Bizmut telurid je termoelektrična tvar s visokom učinkovitošću koja se rabi za hlađenje na sobnim temperaturama. Radi istraživanja učinka oblika i veličine zrna na transportne parametre, sintetizirali smo nanostrukturirani bizmut telurid u različitim uvjetima i ispitivali rentgenskom difrakcijom, te propusnom i pretražnom elektronskom mikroskopijom. Mjerenjem električne vodljivosti i termoelektrične snage niza uzoraka odredili smo faktore snage. Ishodi analize pokazuju da transportni parametri jako ovise o obliku i veličini uzoraka, koji pak ovise o uvjetima njihove sinteze. Raspravljamo o opaženim promjenama električne vodljivosti ovisnim o dimenzionalnosti uzoraka od 2D do 0D i nalazimo sklad s teorijskim predviđanjima drugih autora. Nalazimo promjene faktora snage uzoraka pripremljenih uz različite uvjete sinteze

Glycosylation of Erythrocyte Spectrin and Its Modification in Visceral Leishmaniasis

Using a lectin, Achatinin-H, having preferential specificity for glycoproteins with terminal 9-O-acetyl sialic acid derivatives linked in α2-6 linkages to subterminal N-acetylgalactosamine, eight distinct disease-associated 9-O-acetylated sialoglycoproteins was purified from erythrocytes of visceral leishmaniaisis (VL) patients (RBCVL). Analyses of tryptic fragments by mass spectrometry led to the identification of two high-molecular weight 9-O-acetylated sialoglycoproteins as human erythrocytic α- and β-spectrin. Total spectrin purified from erythrocytes of VL patients (spectrinVL) was reactive with Achatinin-H. Interestingly, along with two high molecular weight bands corresponding to α- and β-spectrin another low molecular weight 60 kDa band was observed. Total spectrin was also purified from normal human erythrocytes (spectrinN) and insignificant binding with Achatinin-H was demonstrated. Additionally, this 60 kDa fragment was totally absent in spectrinN. Although the presence of both N- and O-glycosylations was found both in spectrinN and spectrinVL, enhanced sialylation was predominantly induced in spectrinVL. Sialic acids accounted for approximately 1.25 kDa mass of the 60 kDa polypeptide. The demonstration of a few identified sialylated tryptic fragments of α- and β-spectrinVL confirmed the presence of terminal sialic acids. Molecular modelling studies of spectrin suggest that a sugar moiety can fit into the potential glycosylation sites. Interestingly, highly sialylated spectrinVL showed decreased binding with spectrin-depleted inside-out membrane vesicles of normal erythrocytes compared to spectrinN suggesting functional abnormality. Taken together this is the first report of glycosylated eythrocytic spectrin in normal erythrocytes and its enhanced sialylation in RBCVL. The enhanced sialylation of this cytoskeleton protein is possibly related to the fragmentation of spectrinVL as evidenced by the presence of an additional 60 kDa fragment, absent in spectrinN which possibly affects the biology of RBCVL linked to both severe distortion of erythrocyte development and impairment of erythrocyte membrane integrity and may provide an explanation for their sensitivity to hemolysis and anemia in VL patients

A comparative study of the management decisions by IMNCI algorithm and by pediatricians of a teaching hospital for the children between 2 months to 5 years

Background: Integrated management of neonatal and childhood illness (IMNCI) is already operational in many states of India, but there are very few studies in Indian scenario comparing its validity and reliability with the pediatricians′ decisions. Objectives: 1) To compare the IMNCI decision with the decision of pediatricians; 2) to assess the significance of multiple presenting symptoms in the IMNCI algorithm. Materials and Methods : The study was conducted among the sick children between 2 months to 5 years presented in pediatric department from January to March 2009. The IMNCI decision was compared with pediatrician′s decisions by percent agreement, Kappa and weighted Kappa with the aids of SPSS version 10. Results: The overall diagnostic agreement between IMNCI algorithm and pediatrician′s decisions was 36.64%, (Kappa 0.16 and weighted Kappa 0.29) with 51.15% over diagnosis and 12.21% under diagnosis. The importance given by IMNCI algorithm in cases of multiple presenting symptoms was also reflected as it was evident that 37.50% children presented with three symptoms were categorized as red, whereas it was 28.57% and 11.67% for those presented with two and one symptom, respectively, (P < 0.0001). Pediatricians also gave importance for presence of multiple symptoms by considering 50% as admissible in the group presented with three symptoms, 30.16% in the group presented with two symptoms, and 16.67% in the group presented with only one symptom. The association was also statistically significant (P = 0.018). Conclusion: Diagnostic discordance is seen mainly due to over diagnosis of all fever cases as malaria. Importance of presence of comorbidities was also reflected

Investigation of 9-o-acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia

Modern treatment protocols of childhood acute lymphoblastic leukaemia (ALL) utilize the biological and clinical features of the disease to tailor the intensity of therapy to the risk of relapse by evaluation of minimal residual disease (MRD) using several molecular techniques. To minimize the likelihood of false negative results, tandem application of at least two methods for detection of MRD is currently recommended. To address this question, the present review deals with the recently evolved information reported by our group regarding the presence of O-acetylated sialoglycoconjugates (O-AcSGs) in childhood ALL and their potential as novel biomarkers for monitoring the disease

Assessment of validity and reliability of IMNCI algorithm in comparison to provisional diagnosis of senior pediatricians in a tertiary hospital of Kolkata

Background: Integrated management of childhood illness (IMNCI) is already operational in many states of India, but there are only limited studies in Indian scenario comparing its validity and reliability with the decisions of pediatricians. Aims and Objectives: To assess the validity and reliability of the IMNCI algorithm with provisional diagnosis of senior pediatricians for each IMNCI classifications. Materials and Methods: The present study is done with all the young infants between 0-2 months presented during the study period with a fresh episode of illness to test the validity and reliability of the algorithm in comparison to provisional diagnoses of senior pediatricians. The study was done in a tertiary care hospital. Validity characteristics such as sensitivity, specificity, positive predictive value, negative predictive value, and reliability characteristics such as percent agreement and Kappa were assessed for individual IMNCI classifications. Results: The sensitivity of possible serious bacterial infection, local bacterial infection, jaundice, no dehydration and possible serious bacterial infection, not able to feed were 88.89, 14.29, 66.67, 25 and 44.44% respectively. The specificities for the same conditions were 71.72, 99.09, 99.07, 94.50 and 86.87%. Percent agreements for similar conditions were 74, 94, 97, 90 and 80% respectively and the Kappa ratios were 0.38, 0.20, 0.73, 0.19 and 0.29 respectively. Conclusion: It could be concluded that IMNCI is quite a sensitive strategy and could identify severe illnesses of young infants requiring referral to higher facility. Further studies, particularly in primary health care setting, are required

Codon and Amino Acid Usage in Two Major Human Pathogens of Genus Bartonella — Optimization Between Replicational- Transcriptional Selection, Translational Control and Cost Minimization

Intra-genomic variation in synonymous codon and amino acid usage in two human pathogens Bartonella henselae and B. quintana has been carried out through multivariate analysis. Asymmetric mutational bias, coupled with replicational-transcriptional selection, has been identified as the prime selection force behind synonymous codon selection — a characteristic of the genus Bartonella, not exhibited by any other alphaproteobacterial genome. Distinct codon usage patterns and low synonymous divergence values between orthologous sequences of highly expressed genes from the two Bartonella species indicate that there exists a residual intra-strand synonymous codon bias in the highly expressed genes, possibly operating at the level of translation. In the case of amino acid usage, the mean hydropathy level and aromaticity are the major sources of variation, both having nearly equal impact, while strand-specific mutational pressure and gene expressivity strongly influence the inter-strand variations. In both species under study, the highly expressed gene products tend not to contain heavy and/or aromatic residues, following the costminimization hypothesis in spite of their intracellular lifestyle. The codon and amino acid usage in these two human pathogens are, therefore, consequences of a complex balance between replicational-transcriptional selection, translational control, protein hydropathy and cost minimization