A thylakoid biogenesis BtpA protein is required for the initial step of tetrapyrrole biosynthesis in cyanobacteria.

Biogenesis of the photosynthetic apparatus requires complicated molecular machinery, individual components of which are either poorly characterized or unknown. The BtpA protein has been described as a factor required for the stability of photosystem I (PSI) in cyanobacteria; however, how the BtpA stabilized PSI remains unexplained. To clarify the role of BtpA, we constructed and characterized the btpA-null mutant (ΔbtpA) in the cyanobacterium Synechocystis sp. PCC 6803. The mutant contained only c. 1% of chlorophyll and nearly no thylakoid membranes. However, this strain, growing only in the presence of glucose, was genetically unstable and readily generated suppressor mutations that restore the photoautotrophy. Two suppressor mutations were mapped into the hemA gene encoding glutamyl-tRNA reductase (GluTR) - the first enzyme of tetrapyrrole biosynthesis. Indeed, the GluTR was not detectable in the ΔbtpA mutant and the suppressor mutations restored biosynthesis of tetrapyrroles and photoautotrophy by increased GluTR expression or by improved GluTR stability/processivity. We further demonstrated that GluTR associates with a large BtpA oligomer and that BtpA is required for the stability of GluTR. Our results show that the BtpA protein is involved in the biogenesis of photosystems at the level of regulation of tetrapyrrole biosynthesis.

Late Onset Pompe's Disease: Clinical, Pathological & Molecular Analysis of Two Adolescent Patients.

INTRODUCTION: The estimated global prevalence of late onset Pompe's disease is 1/57000 live birth(1). We present the case of two patients diagnosed to have Pompe's disease with a rare association of cardiomyopathy. MATERIALS: Two siblings born out of non consanguineous marriage presented with proximal myopathy of 5 years duration. Patient 1 - 19 year female, there was atrophy and weakness of face, neck, girdle and limbs. Her Echocardiogram showed LV dilation with low ejection fraction, ECG showed LV hypertrophy with incomplete LBBB. Her CK-NAC values came to be 918 U/L. Patient 2 - 16 year male; progression, distribution and severity slightly different to his sister but had exertional dyspnea since last one year. His echocardiogram showed LV diastolic dysfunction, ECG showed short PR interval partial LBBB and his CK-NAC came to be 2347 U/L. His skeletal muscle biopsy showed deposition of glycogen. Genetic analysis revealed pathogenic mutation in GAA gene (c.2040G>A) in both patients. RESULT: Late onset Pompe disease is of less severity but progressive. The involvement of heart is less likely compared to infantile onset(2). It is also interesting that the same variant presents differently in both patients. CONCLUSION: Genetic diseases manifest as rare phenotype which in itself is a clinical puzzle. When rare disease present with a rare manifestation of itself, this pose a great diagnostic challenge. Pompe's disease is one of the very few inherited disorder which has definitive treatment- enzyme replacement therapy. Molecular characterization of the variant is absolutely necessary before initiating therapy. References Ausems MG, Verbiest J, Hermans MM, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet 1999;7(6):713-716. Van der Beek NA, Soliman OI, Van Capelle CI, et al. Cardiac evaluation in children and adults with Pompe disease sharing the common c.-32-13T>G genotype rarely reveals abnormalities. J Neurol Sci 2008;275(1-2):46-50.

Primary retroperitoneal fibrosis presenting as a renal mass.

A 67-year-old male was incidentally found to have a large left perinephric mass with a poorly functioning left kidney. A differential diagnosis of renal cell carcinoma, lymphoma, retroperitoneal fibrosis (RPF), and IgG4 renal disease was suggested on imaging studies and biopsy of the mass. A left radical nephrectomy was performed as malignancy could not be ruled out. The final diagnosis was RPF without periaortitis and the patient is doing well at 9 months of follow-up. RPF, although characterized as a manifestation of periaortitis and large vessel vasculitis, might also present as an isolated perinephric mass without aortic involvement. Surgical management is an alternative, especially when malignancy is suspected.

Human telomerase RNA component (hTERC) gene expression and chromosome 7 ploidy correlate positively with histological grade of cervical intraepithelial neoplasia.

OBJECTIVE: Cervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology-histology correlation remains modest. Biomarkers associated with early genetic events in cervical squamous carcinogenesis and detectable in cytology material are likely to be relevant. Human telomerase RNA component (hTERC) gene overexpression and aneuploidy are promising candidates in view of their reported early and consistent association with cervical squamous oncogenesis. METHODS: We analysed hTERC gene expression and chromosome 7 ploidy by fluorescent in-situ hybridisation (FISH) in 50 women with cytological precursor squamous intraepithelial lesions and available histology outcomes. Results were expressed as percentages of cells showing ≥3 signals, mean signals/nucleus, and maximum amplitude across various cytology and histology categories. Proportions of positive cases were calculated from threshold values derived from 6 controls. Distribution of above indices with respect to ≥cervical intraepithelial neoplasia 2 (CIN2) was explored. RESULTS: For both genetic aberrations, there was significant positive correlation (for all indices) between the proportion of positive cases and worsening cytological and histological outcomes (P < .05), with significant intergroup differences (P < .05). High-grade lesions (≥CIN2) had significantly higher results compared to

Analysis of 24 cases of epithelioid glioblastoma: Experience from a tertiary centre of North India.

BACKGROUND: Epithelioid glioblastoma (eGB) is a recently recognized and a rare variant of glioblastoma. This study aimed to describe the clinical, histological and immunohistochemical spectrum and outcome of eGB from a tertiary care hospital in north India. MATERIALS AND METHODS: Twenty four cases of eGB diagnosed over past 10 years were reviewed with detailed morphological and immunohistochemical analysis (GFAP, EMA, Vimentin, Myogenin, INI-1, Cytokeratin, Synaptophysin, CD99, S100, MelanA, IDH1, ATRX, p16, EZH2, Ki-67, and BRAF V600E mutant antibody). RESULT: The mean age was 29.9 years (3-54 years), with equal male and female patients. All had supratentorial tumor. All cases showed epithelioid cells in sheets; however, focal spindling (7 cases, 29.2%), grouping/nesting (6 cases, 25%) and papillary configuration (5 cases, 20.8%) were also noted. All showed microvascular proliferation (MVP) and all except one demonstrated areas of necrosis. INI1 was retained in all cases, while 2 showed patchy loss. EZH2 overexpression (>25%) was observed in 4 cases, while 5 cases showed loss of p16 expression. BRAF V600E mutant protein expression was seen in 12/23 (52.2%) cases. Outcome was available in 8 cases, out of which 6 (75%) experienced recurrence. The median survival was 25.5 months. Cases with tumor infiltrating lymphocytes had a better outcome. CONCLUSION: eGB is a distinct variant of glioblastoma which has predilection towards younger age group. It shows high percentage of BRAF V600E mutation and a subset of it shows longer survival. Cases with presence of tumor infiltrating lymphocytes are associated with better outcome.

Addressing health inequity through strategic planning and management.

Substantial progress has been made to improve health in India in terms of availability, accessibility, cost-effectiveness, and quality. However, there are major health inequalities between and within the states. Strategic planning of health programs is required to address inequities in health. Need of the hour is to address this using a simplified strategic approach; who is left out, why are they left out, what causes are responsible for it and what are the determinants of inequality. The basic steps of strategic management, including strategic assessment, objectives, strategy formulation, and implementation, can be used to address the health equity. This article cites the examples of Serbia immunization programme, Government of India programme on Mission Indradhanush, and Thailand's universal health coverage to get better understanding to use strategic management to address health inequity. This approach is crucial in achieving sustainable development goals.

Progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia: A case report and review of literature.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by polyoma virus (JC virus) infection. PML usually occurs in a setting of severe immunosuppression and is most commonly associated with human immunodeficiency virus (HIV) infection. Idiopathic CD4+ lymphocytopenia is a very rare cause of PML and only a few cases have been reported in the literature. We present a case of a 45-year-old man who presented with behavioral alteration followed by progressive weakness of right side of the body. Contrast-enhanced magnetic resonance imaging of the brain revealed confluent irregular areas of T2-weighted/fluid-attenuated inversion recovery hyperintensities in left frontoparietal and right temporoparietal regions. His hematological work up showed a decreased absolute CD4+ count of 217 per microliter, but was negative for HIV serology. Keeping a differential diagnoses of central nervous system lymphoma, brain biopsy was performed. Histopathology revealed demyelination with presence of intranuclear inclusions in the oligodendrocytes, which were positive for SV40 immunostain. Adjacent areas showed reactive gliosis with hypertrophic astrocytes, hence a diagnosis of PML was made. The patient died due to aspiration pneumonia. PML can occur very rarely in association with idiopathic CD4+ lymphocytopenia in the absence of other immunosuppressive illnesses. This report highlights the importance of high index of clinical suspicion and need for a careful histological examination for diagnosis of PML to facilitate adequate patient management.