Biomarkers in congenital adrenal hyperplasia.

Monitoring of hormone replacement therapy represents a major challenge in the management of congenital adrenal hyperplasia (CAH). In the absence of clear guidance and standardised monitoring strategies, there is no consensus among clinicians regarding the relevance of various biochemical markers used in practice, leading to wide variability in their application and interpretation. In this review, we summarise the published evidence on biochemical monitoring of CAH.

A vaccine targeting resistant tumours by dual T cell plus NK cell attack.

Most cancer vaccines target peptide antigens, necessitating personalization owing to the vast inter-individual diversity in major histocompatibility complex (MHC) molecules that present peptides to T cells. Furthermore, tumours frequently escape T cell-mediated immunity through mechanisms that interfere with peptide presentation. Here we report a cancer vaccine that induces a coordinated attack by diverse T cell and natural killer (NK) cell populations.

Immunosuppressive Myeloid Cells Induce Nitric Oxide-Dependent DNA Damage and p53 Pathway Activation in CD8 T Cells.

Tumor-infiltrating myeloid-derived suppressor cells (MDSC) are associated with poor survival outcomes in many human cancers. MDSCs inhibit T cell-mediated tumor immunity in part because they strongly inhibit T-cell function. However, whether MDSCs inhibit early or later steps of T-cell activation is not well established.

Case report on two diabetic donor eyes with no retinopathy: Clinicopathological and molecular studies.

We were intrigued to analyze donor eyes of two individuals without retinopathy even after 40 years of type 2 diabetes mellitus. Targeted molecular factors associated with angiogenesis and the key antioxidant enzymes in retinal tissue were analyzed. Accordingly PEDF, Adiponectin and Paraoxonase 2 showed augmented mRNA expression in both the retina with no significant change in VEGF expression.

Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity.

MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells.

A facile approach to enhance antigen response for personalized cancer vaccination.

Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR-PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations.

A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A(*)24 Allotypes.

While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A(*)24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A(*)24:06(156Trp) and HLA-A(*)24:13(156Leu) showed high levels of cell surface expression while HLA-A(*)24:02(156Gln) was expressed at low levels in tapasin deficient cells.

A study of impact of cost-effective nutritional supplement in patients on maintenance hemodialysis.

Nutritional status in patients on hemodialysis is always of concern as malnutrition predisposes to excess morbidity and mortality. Most of the nutritional supplements available in the market are expensive. We explored the possibility of improving nutrition of the patients on maintenance hemodialysis by supplementation of calories and proteins that can be given in the form of a palatable and economical gruel in this prospectively designed, open labeled study.

Are smartphones comparable to laptops for image diagnosis in teleophthalmology?

Objective: To assess the reliability and accuracy of smartphones in diagnosing transmitted fundus images in comparison with a laptop.

Materials And Methods: Fundus images captured with a Topcon NW 200 camera were transferred onto a conventional laptop and a smartphone and given to ophthalmologists for diagnosis. The smartphone and the laptop diagnosis were compared with the actual face to face diagnosis statistically to assess their diagnostic accuracy.

Ophthalmic contributions of Raja Serfoji II (1798-1832).

Purpose: To investigate and describe the ophthalmic contribution of Raja Serfoji II (1798-1832).

Materials And Method: A team of 2 ophthalmologists, director of laboratory services, one archeologist and a photographer visited Sarasvathi Mahal Library, March 2004. Photographs of ophthalmic records were taken and analysed.

Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB.

Mucopolysaccharide diseases (MPS) are caused by deficiency of glycosaminoglycan (GAG) degrading enzymes, leading to GAG accumulation. Neurodegenerative MPS diseases exhibit cognitive decline, behavioural problems and shortened lifespan. We have characterised neuropathological changes in mouse models of MPSI, IIIA and IIIB to provide a better understanding of these events.

Position 45 influences the peptide binding motif of HLA-B*44:08.

Position 45 represents a highly polymorphic residue within HLA class I alleles, which contacts the p2 position of bound peptides in 85% of the peptide-HLA structures analyzed, while the neighboring residues 41 and 46 are not involved in peptide binding. To investigate the influence of residue 45 at the functional level, we sequenced peptides eluted from recombinant HLA-B*44:08(41Ala/45Met/46Ala) molecules and compared their features with known peptides from B*44:02(41Thr/45Lys/46Glu). While HLA-B*44:02 has an anchor motif of E at the p2 anchor position, HLA-B*44:08 exhibits Q and L as anchor motif.

Non-expression of HLA-C*07:55N is caused by a premature stop codon in exon 3.

Sequencing of HLA-C*07:55N assessed the presence of a premature TAG stop codon at residue 113.

Position 156 influences the peptide repertoire and tapasin dependency of human leukocyte antigen B*44 allotypes.

Background: Polymorphic differences between donor and recipient human leukocyte antigen class I molecules can result in graft-versus-host disease due to distinct peptide presentation. As part of the peptide-loading complex, tapasin plays an important role in selecting peptides from the pool of potential ligands. Class I polymorphisms can significantly alter the tapasin-mediated interaction with the peptide-loading complex and although most class I allotypes are highly dependent upon tapasin, some are able to load peptides independently of tapasin.

Mismatches outside exons 2 and 3 do not alter the peptide motif of the allele group B*44:02P.

Sequence variations outside exons 2 and 3 do not appear to affect the function of human leukocyte antigen (HLA) class I alleles. HLA-B*44:02:01:01 and -B*44:27 are considered functionally identical because they differ by a single amino acid substitution of Val > Ala at position 199, which is located in the α3 domain. To validate that HLA-B*44:02:01:01 and -B*44:27 represent functionally identical alleles that might reflect a permissive mismatch in hematopoetic stem cell transplantation (HSCT), we determined their peptide-binding features.

A hospital-based study of splenomegaly with special reference to the group of indeterminate origin.

In any study there remains a proportion of cases, about 25-40%, where cause of splenomegaly is not identified on usual evaluation, that is labelled as indeterminate group. The aim of this study was to evaluate various causes of splenomegaly. Thereafter the patients with splenomegaly of indeterminate origin were to be re-evaluated with detailed investigations (for the cause of splenomegaly).

Anti - H. pylori IgG seroprevalence rates in asymptomatic children and adults from South India.

This study was undertaken to determine the seroprevalence of H.pylori in asymptomatic children and compare it with that seen in the asymptomatic adult population from south India. One hundred and five children and one hundred adults admitted to the wards for conditions other than gastrointestinal disorders were included for this study.

Pneumolysin in urine: a rapid antigen detection method to diagnose pneumococcal pneumonia in children.

Purpose: Etiological diagnosis of pneumococcal pneumonia is difficult in small children in whom blood culture cannot be done or who have already been started on antibiotics. A simple technique which can be applied at the bedside or in the outpatient department may help in obviating this problem. Detection of pneumolysin, a product of invasive pneumococci is being exploited as a diagnostic tool.

Seroprevalence of Hepatitis C virus in a hospital based general population in south India.

Seroprevalence of Hepatitis C virus (HCV) among hospital based general population was determined using a third generation ELISA. The study population comprised of 661 individuals (including 36 health care workers) attending a tertiary care hospital in Pondicherry, south India. The overall seroprevalence was found to be 4.

Learning from an outbreak: ESBL- the essential points.

Extended spectrum beta-lactamase (ESBL) producing strains of Klebsiella pneumoniae have emerged as important nosocomial pathogens. The present report describes an outbreak of ESBL positive K. pneumoniae in a neonatal intensive care unit of a tertiary care center in southern India.

In vitro susceptibility pattern of Acinetobacter species to commonly used cephalosporins, quinolones, and aminoglycosides.

Purpose: Acinetobacter spp. is an emerging important nosocomial pathogen. Clinical isolates of this genus are often resistant to many antibiotics.