Hypercalcemia due to Nasopharyngeal Carcinoma.

Hypercalcemia is a rare metabolic disorder associated with hyperparathyroidism, malignancy and various other causes. Although common in adult malignancies, hypercalcemia is rare in pediatrics and purports poor prognosis. Nasopharyngeal carcinoma is rare with no reported hypercalcemic presentation. We present here a case of hypercalcemia in a child of nasopharyngeal carcinoma. A 10 year girl presented with backache for 1 month, epistaxis, cough, chest-pain for 1 week alongwith anorexia and weight loss. Investigations revealed anemia and hypercalcemia (23mg/dl; normal range 9-11 mg/dl) with hyperphosphatemia, normal parathyroid levels. Hypercalcemic crisis was managed with saline, furosemide and bisphosphonate. Computed Tomography of paranasal sinuses revealed mass in right nasal cavity. Endoscopic biopsy disclosed undifferentiated nasopharyngeal carcinoma. The child expired despite supportive measures. Thus, hypercalcemia, though rare, may complicate advanced tumors. NPC, being rare in children, requires high index of suspicion with careful clinicoradiological examination and timely management for better chances of survival.

Low dose UV-B induced modification of chromophore conformation and it's interaction with microenvironment in cyanobacterial phycobilisomes.

Phycobilisomes (Pbsomes) are the supra macromolecular pigment protein complexes of cyanobacteria. Synechococcus Pbsomes are comprised of phycocyanins (PC) and allophycocyanins (APC). Pbsomes are major light harvesting antennae and also absorb ultraviolet-B (UV-B) radiation (280-320 nm). Synechococcus Pbsomes, upon exposure to low dose of UV-B (0.28 mW cm-2) for different time intervals showed profound alteration in their steady state absorption, fluorescence excitation and emission characteristics (Sah et. al. Biochem. Mol. Biol.Int., Vol. 44, No. 2, 245-247). In the present study, we investigated the effect of low dose of UV-B on isolated Pbsome of Synechococcus. Our results demonstrate the following alterations. Absorbance at 623 nm initially showed a sharp decrease with increasing exposure time to UV-B radiation. The changes in the visible to near ultraviolet absorption and excitation ratio indicated a change in chromophore conformation, upon prolonged exposure of Pbsomes to UV-B radiation. This modification of chromophore conformation appeared to be associated with the loss of energy transfer from PC to APC. Circular dichroism spectra in the amide region showed a significant loss of the alpha helical content of Pbsomes when exposed for longer duration to UV-B. CD spectra in the visible region revealed a marked decrease in the rotational strength at 620 nm. Close monitoring of CD signals emanating in the 500 to 700 nm range further revealed that the decrease in the rotational strength was closely associated with an initial red shift in the positive CD band of Pbsomes when exposed to UV-B for short duration. However, the peak became constant over prolonged exposure to UV-B radiation and accompanied a prominent blue shoulder in the positive CD band which suggests the modification and uncoupling of the various phycocyanobilin (PCB) chromophores of the Synechococcus Pbsomes.

Effects of ultraviolet-B radiation on phycobilisomes of Synechococcus PCC 7942: alterations in conformation and energy transfer characteristics.

Phycobilisomes (PBS), the major light harvesting antenna of the cyanobacterium Synechococcus contain phycocyanin (PC) and allophycocyanin (APC) as major pigment-protein complexes. PBS also absorb ultraviolet-B (280-320 nm) radiation. Exposure of Synechococcus PBS to low dose of UV-B (approximately 0.28 mw.cm-2) for 90 min induced change in absorption, emission and excitation characteristics of PBS and these changes got enhanced after 3 h of exposure. Room temperature excitation and emission spectra clearly indicated uncoupling of energy transfer from PC to APC on exposure to UV-B. Also, the 77K emission spectra suggested that F682 emission originating from APC decreased by 42% after 3 h of exposure. Circular dichroism (CD) spectra of UV-B exposed PBS indicated changes (14% decrease) in the alpha-helical content after 90 min treatment. SDS-PAGE analysis indicated degradation of a 75 kDa polypeptide (which appear to be a linker polypeptide) on UV-B treatment. The degradation of this polypeptide seems to induce changes in pigment-protein interaction and decoupling of energy transfer within the PBS. Our results for the first time clearly indicate that the PBS of Synechococcus are targets for UV-B damage.

Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes.

The primary determinant for telomere replication is the enzyme telomerase, responsible for elongating the G-rich strand of the telomere. The only component of this enzyme that has been identified in Saccharomyces cerevisiae is the TLC1 gene, encoding the telomerase RNA subunit. However, a yeast strain defective for the EST1 gene exhibits the same phenotypes (progressively shorter telomeres and a senescence phenotype) as a strain deleted for TLC1, suggesting that EST1 encodes either a component of telomerase or some other factor essential for telomerase function. We designed a multitiered screen that led to the isolation of 22 mutants that display the same phenotypes as est1 and tlc1 mutant strains. These mutations mapped to four complementation groups: the previously identified EST1 gene and three additional genes, called EST2, EST3 and EST4. Cloning of the EST2 gene demonstrated that it encodes a large, extremely basic novel protein with no motifs that provide clues as to function. Epistasis analysis indicated that the four EST genes function in the same pathway for telomere replication as defined by the TLC1 gene, suggesting that the EST genes encode either components of telomerase or factors that positively regulate telomerase activity.

Studies on electron donation to photosystem I sites by exogenous donors in Spirulina thylakoids.

The kinetic parameters of different sites of electron donation to photosystem I (PS I) were evaluated in Spirulina platensis thylakoids. Reduced 2,6-dichlorophenolindophenol (DCIPH2) exhibited two sites of electron donation, with apparent K(m) values of 8 and 40 microM each. The corresponding value for reduced N-tetramethyl-p-phenylenediamine (TMPDH2) and diaminodurene (DADH2) which donate electrons at a single site to PS I were 103 and 48 microM, respectively. The electron donation by these three exogenous donors were differentially inhibited by KCN (70 mM) affecting the apparent K(m) and Rmax values to varying extent. This cyanide inhibition of PS I catalyzed electron transport suggests the presence of plastocyanin in the photosynthetic electron transport chain of Spirulina platensis.

Purification and characterization of an ATPase inhibitor protein from buffalo mitochondria.

A heat stable, 12kDa protein was purified to homogeneity from buffalo heart mitochondria. It suppressed hydrolytic activity of membrane bound mitochondrial ATPase and its functional activity was Mg++ and ATP dependent. Maximal inhibition was achieved at slightly acidic pH. Its ability to inhibit ATP hydrolysis was significantly diminished at alkaline pH and high ionic strength and the purified protein had a tendency to aggregate under such conditions. Circular dichroism (CD) studies revealed that the protein undergoes reversible changes in secondary structure from a predominantly alpha-helical form at alkaline pH to a beta-sheet structure at slightly acidic pH. These distinctly different conformations could be correlated with functionally 'inactive' and 'active' forms.

pH dependent conformational changes modulate functional activity of the mitochondrial ATPase inhibitor protein.

A 12kDa, heat stable protein (IF1) inhibiting hydrolytic activity of submitochondrial particles was purified to electrophoretic homogeneity from buffalo heart mitochondria. Specific activity of the purified fraction was > 5000 units/mg. Maximal inhibition was observed at pH 6.0 and was Mg++ and ATP dependent. Circular dichroism studies showed that the inhibitor peptide undergoes a dramatic, reversible conformational change in response to pH which correlates well with its ability to inhibit ATP hydrolysis catalyzed by inhibitor depleted submitochondrial particles. It is shown for the first time that IF1 with a predominantly beta-sheet component is more efficient at suppressing ATPase activity.