Biomedical subjects

S Nigam

Publications and source records attributed to S Nigam.

At least 19 recordsLinked to original sources

PubMed2006

Acetylsalicylic acid as antifungal in Eremothecium and other yeasts.

Interesting distribution patterns of acetylsalicylic acid (ASA, aspirin) sensitive 3-hydroxy (OH) oxylipins were previously reported in some representatives of the yeast genus Eremothecium--an important group of plant pathogens. Using immunofluorescence microscopy and 3-OH oxylipin specific antibodies in this study, we were able to map the presence of these compounds also in other Eremothecium species. In Eremothecium cymbalariae, these oxylipins were found to cover mostly the spiky tips of narrowly triangular ascospores while in Eremothecium gossypii, oxylipins covered the whole spindle-shaped ascospore with terminal appendages. The presence of these oxylipins was confirmed by chemical analysis. When ASA, a 3-OH oxylipin inhibitor, was added to these yeasts in increasing concentrations, the sexual stage was found to be the most sensitive. Our results suggest that 3-OH oxylipins, produced by mitochondria through incomplete beta-oxidation, are associated with the development of the sexual stages in both yeasts. Strikingly, preliminary studies on yeast growth suggest that yeasts, characterized by mainly an aerobic respiration rather than a fermentative pathway, are more sensitive to ASA than yeasts characterized by both pathways. These data further support the role of mitochondria in sexual as well as asexual reproduction of yeasts and its role to serve as a target for ASA antifungal action.

Aspirin↗

PubMed2005

Oxylipin covered ascospores of Eremothecium coryli.

Eremothecium coryli is known to produce intriguing spindle-shaped ascospores with long and thin whip-like appendages. Here, ultra structural studies using scanning electron microscopy, indicate that these appendages serve to coil around themselves and around ascospores causing spore aggregation. Furthermore, using immunofluorescence confocal laser scanning microscopy it was found that hydrophobic 3-hydroxy oxylipins cover the surfaces of these ascospores. Using gas chromatography-mass spectrometry, only the oxylipin 3-hydroxy 9:1 (a monounsaturated fatty acid containing a hydroxyl group on carbon 3) could be identified. Sequential digital imaging suggests that oxylipin-coated spindle-shaped ascospores are released from enclosed asci probably by protruding through an already disintegrating ascus wall.

Fatty Acids↗

PubMed2004

Mapping 3-hydroxy oxylipins on ascospores of Eremothecium sinecaudum.

3-Hydroxy oxylipins were uncovered on ascospores of Eremothecium sinecaudum using immunofluorescence microscopy. This was confirmed by gas chromatography mass spectrometry. These oxylipins were observed only on ascospore parts characterised by nano-scale surface ornamentations simulating a corkscrew as demonstrated by scanning electron microscopy. Conventional ascospore staining further confirms its hydrophobic nature. Using confocal laser scanning microscopy we found that the corkscrew part with spiky tip of needle-shaped ascospores may play a role in rupturing the ascus in order to affect its release. Through oxylipin inhibition studies we hypothesise a possible role for 3-hydroxy oxylipins in facilitating the rupturing process.

Hydroxyeicosatetraenoic Acids↗

PubMed2004

Unilateral gestational macromastia--a rare disorder.

Macromastia is the massive enlargement of the breast, unilateral or bilateral, disproportionate to the growth of the rest of the body. It is called gravid macromastia or gigantomastia of pregnancy when it occurs during pregnancy. It may or may not regress following parturition. Gestational macromastia is exceptionally rare. We report a 28-year-old female with gigantomastia of the left breast. She presented at four months post-partum with painful massive enlargement of the left breast since the third month of pregnancy. The overlying skin was stretched out and showed multiple ulcers with foul smelling discharge. The nipple and areola were unremarkable. Simple mastectomy was done, as fine needle aspiration cytology was suggestive of phylloides tumour. The breast specimen measured 30 x 30 x 9 cm and was replaced totally by grey-white tissue involving all the resection margins. No normal breast tissue or fat was identified. Histopathology showed periductal as well as diffuse fibrosis, adenosis and lactational changes. No features of phylloides tumour or carcinoma were present and it was diagnosed as unilateral gestational macromastia.

Adult↗

PubMed2003

Oxylipins and ascospore morphology in the ascomycetous yeast genus Dipodascus.

Immunofluorescence microscopy was used to assess members of the yeast genus Dipodascus for the presence of 3-hydroxy oxylipins. Fluorescence was associated with the aggregating ascospores in all species tested, thus suggesting the association of 3-hydroxy oxylipins with these cells, especially the surrounding slime sheaths. An ultrastructural study of the ascospores revealed sheaths with indentations, probably caused by the close packing of the ascospores to form clusters. In addition, an increase in the neutral and glycolipid fractions as well as a decrease in the phospholipid fraction during ascosporogenesis in D. ambrosiae was found.

Fatty Acids, Unsaturated↗

PubMed2003

Malignant nasal paraganglioma: a case report and review of the literature.

A rare case of malignant nasal paraganglioma is described. A 30 year old female patient presented with a one year history of bilateralnasal obstruction, nasal deformity and recurrent epistaxis. CT scan demonstrated an enhancing mass occupying both nasal cavities, right maxillary antrum and anterior ethmoid sinus. Histopathologic diagnosis was malignant paraganglioma. A total maxillectomy with excision of growth was performed. Post-operative radiotherapy and chemotherapy was given but patient expired before the completion of therapy. Nose being a rare site for paragangliomas, these lesions present a diagnostic challenge to histopathologists and clinicians alike. A review of the four previously described malignant nasal paragangliomas is also presented.

Adult↗

PubMed2001

Characterization of Aspergillus fumigatus protein disulfide isomerase family gene.

Aspergillus fumigatus is an opportunistic fungus which causes pulmonary complications in humans and animals. The clinical spectrum observed with A. fumigatus is attributed to the multifunctional nature of its antigens. Lack of understanding on the molecular processes and complexity of the fungus have spurred interest in the identification and characterization of its antigens/allergens with biological activities and virulence functions. For identification of some of these antigens/allergens, a cDNA library of A. fumigatus was screened with antibodies of allergic bronchopulmonary aspergillosis (ABPA) patients. One of the reactive clones was sequenced and observed to have an open reading frame of 1095 nucleotides corresponding to a polypeptide of 364 amino acids. The nucleotide and deduced amino acid sequence showed significant homology with the protein disulfide isomerase (PDI) superfamily. The expressed recombinant fusion protein exhibited specific IgG and IgE binding with antibodies present in ABPA patients' sera. The recombinant protein in vitro catalyzed folding of scrambled RNase. The probable epitopic regions of the deduced amino acid sequence were mapped by algorithmic analysis. This is the first report of isolation of a gene encoding a member of the PDI family from A. fumigatus. The PDI superfamily of proteins may play an important role in the protein folding mechanisms of A. fumigatus antigens/allergens for their interaction with the host.

Amino Acid Sequence↗

PubMed2001

Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud.

Endostatin (ES) inhibits endothelial cell migration and has been found to bind to glypicans (Gpcs) on both endothelial cells and renal epithelial cells. We examined the possibility that ES might regulate epithelial cell morphogenesis. The addition of ES to cultured epithelial cells causes an inhibition of both hepatocyte growth factor- and epidermal growth factor-dependent process formation and migration. In contrast, ES does not inhibit epidermal growth factor-dependent morphogenesis in renal epithelial cells derived from Gpc-3 -/mice, whereas expression of Gpc-1 in these cells reconstitutes ES responsiveness. Gpc-3 -/mice have been shown to display enhanced ureteric bud (UB) branching early in development, and cultured UB cells release ES into the media, suggesting that ES binding to Gpcs may regulate UB branching. The addition of ES inhibits branching of the explanted UB, whereas a neutralizing Ab to ES enhances UB outgrowth and branching. Thus, local expression of ES at the tips of the UB may play a role in the regulation of UB arborization.

Animals↗

PubMed2001

Acetylation by histone acetyltransferase CREB-binding protein/p300 of STAT6 is required for transcriptional activation of the 15-lipoxygenase-1 gene.

Interleukin-4 (IL-4) induces expression of reticulocyte-type 15-lipoxygenase-1 (15-LOX-1) in various mammalian cells via the Janus kinase/signal transducer and activator of transcription 6 (STAT6) signaling system. We studied the mechanism of 15-LOX-1 induction in A549 lung epithelial cells and found that genistein, a potent tyrosine kinase inhibitor, prevented phopsphorylation of STAT6, its binding to the 15-LOX-1 promoter, and the expression of catalytically active enzyme. In contrast, cycloheximide did not prevent 15-LOX-1 induction. Surprisingly, we found that IL-4 up-regulated the histone acetyltransferase activity of CREB-binding protein (CBP)/p300, which is responsible for acetylation of nuclear histones and STAT6. The acetylation of both proteins appears to be essential for the IL-4-induced signal transduction cascade, because inhibition of CBP/p300 by the viral wild-type E1A oncoprotein abrogated acetylation of both histones and STAT6 and strongly suppressed transcriptional activation of the 15-LOX-1 gene. Moreover, we found that the inhibition by sodium butyrate of histone deacetylases, which apparently suppress 15-LOX-1 gene transcription, synergistically enhanced the IL-4-stimulated 15-LOX-1 expression. These data suggest that both phosphorylation and acetylation of STAT6 as well as acetylation of nuclear histones are involved in transcriptional activation of the 15-LOX-1 gene, although these reactions follow differential kinetics. STAT6 phosphorylation proceeds within the first hour of IL-4 stimulation. In contrast, CBP/p300-mediated acetylation requires 9-11 h, and similar kinetics were observed for the expression of the active enzyme. Thus, our results suggest that in the absence of IL-4, nuclear histones may be bound to regulatory elements of the 15-LOX-1 gene, preventing its transcription. IL-4 stimulation causes rapid phosphorylation of STAT6, but its binding to the promoter appears to be prevented by nonacetylated histones. After 9-11 h, when histones become acetylated, STAT6 binding sites may be demasked so that the phosphorylated and acetylated transcription factor can bind to activate gene transcription.

Acetylation↗

PubMed2001

Involvement of aspirin-sensitive oxylipins in vulvovaginal candidiasis.

3(R)-Hydroxyoxylipins are produced via an aspirin-sensitive pathway in Candida albicans, an abundant pathogen in vulvovaginal candidiasis. In the present study, we have investigated the effect of aspirin on vaginal isolates of C. albicans from patients with recurrent candidiasis. Aspirin alone and with clotrimazole, a commonly used drug, strongly suppressed growth of C. albicans. 3(R)-Hydroxyoxylipins, which were selectively located in hyphae and other filamentous structures, but not in free blastospores, were almost totally suppressed by aspirin. Moreover, C. albicans stimulated prostaglandin E(2) (PGE(2)) production in HeLa cells. PGE(2) is a stimulus for germ tube formation in C. albicans. We conclude therefore that the administration of aspirin should be beneficial in the treatment of vulvovaginal candidiasis by dual ways: (i) by inhibition of 3(R)-hydroxyoxylipin formation, and (ii) by inhibition of PGE(2) formation in the infected host tissue.

Antifungal Agents↗

PubMed2001

Characterization of the polarity of reversed-phase liquid chromatographic stationary phases in the presence of 1-propanol using solvatochromism and multivariate curve resolution.

This work characterizes solvation effects in reversed-phase liquid chromatography in the presence of 1-propanol. The solvatochromic method combined with a multivariate curve resolution-alternating least-squares analysis method has been used to characterize two modified silica surfaces--phenyl bonded and C18 bonded silica in mobile-phase mixtures of methanol--water and acetonitrile--water in the presence of 1-propanol. The presence of a small amount of 1-propanol has been shown to affect mainly the polarity properties of the stationary phases while the mobile-phase properties are largely unaffected. The chain collapse mechanism for the C18 stationary phase at higher concentrations of water seems to be inhibited in the presence of 1-propanol, and partitioning is the predominant solute retention mechanism. The phenyl-based phase shows considerably different behavior from that of the C18 phase, and propanol appears to disrupt the pi-stacking interactions between the solute and the phenyl rings anchored to the silica support.

Journal Article↗

PubMed2001

Evidence for the presence of phospholipid hydroperoxide glutathione peroxidase in human platelets: implications for its involvement in the regulatory network of the 12-lipoxygenase pathway of arachidonic acid metabolism.

The 12-lipoxygenase pathway of arachidonic acid metabolism in platelets and other cells is bifurcated into a reduction route yielding 12-hydroxyeicosatetraenoic acid (12-HETE) and an isomerization route forming hepoxilins. Here we show for the first time the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPx) protein and its activity in platelets. The ratio of the activity of PHGPx to that of cytosolic glutathione peroxidase (GPx-1) was consistently found to be approx. 1:60 in platelets and UT7 megakaryoblasts. Moreover, short-lived PHGPx mRNA was detected in megakaryocytes but not in platelets. Carboxymethylation of selenium-containing glutathione peroxidases by iodoacetate, which results in the inactivation of PHGPx and GPx-1 without inhibition of 12-lipoxygenase, markedly altered the pattern of arachidonic acid metabolism in human platelets. Whereas the formation of 12-HETE was inhibited by 80%, a concomitant accumulation of 12-hydroperoxyeicosatetraenoic acid (12-HpETE) by two orders of magnitude as well as the formation of hepoxilins A(3) and B(3) were observed. The formation of hepoxilins also occurred when 12-HpETE was added to untreated platelets. In selenium-deficient UT7 cells, which were devoid of GPx-1 but not of PHGPx, the reduction of 12-HPETE was retained, albeit with a lower rate than in control cells containing GPx-1. We therefore believe that both GPx-1 and PHGPx are involved in the regulatory network of the 12-lipoxygenase pathway in platelets and other mammalian cells. Moreover, the diminution of hydroperoxide tone in platelets incubated with arachidonic acid leads primarily to the formation of 12-HETE, whereas the increase in hydroperoxide tone (a situation found under oxidative stress or selenium deficiency or on incubation with 12-HPETE) partly diverts the 12-lipoxygenase pathway from the reduction route to the isomerization route, thus resulting in the formation of hepoxilins.

8,11,14-Eicosatrienoic Acid↗

PubMed2001

Oral cysticercosis--report of six cases.

BACKGROUND: Cysticercosis cellulosae rarely involves the oral region in humans. METHODS: Six cases of oral cysticercosis were diagnosed, three each in lips and buccal mucosa. Diagnosis was made by characteristic gross and histopathologic appearances. RESULTS: Of 146 cases of cysticercosis, 6 (4.1%) were of the oral cavity. All 6 cases were initially seen with painless swellings. Clinical differential diagnosis ranged from retention cyst, lipoma, fibroma, neurofibroma, and angular stomatitis. Histopathologic examination revealed cysticercus larvae. CONCLUSIONS: The oral cavity is a rare site of involvement by cysticercosis, even in an endemic area. Histopathologic findings of the excised cyst are diagnostic of the lesion.

Adolescent↗

PubMed2001

Nongestational pure ovarian choriocarcinoma with contralateral teratoma.

BACKGROUND: Nongestational pure ovarian choriocarcinoma is a rare malignancy with only 29 cases described to date. CASE: We describe a case associated with mature cystic teratoma of the contralateral ovary. Details of all 30 cases including clinical features, associations, surgicopathological findings, operative procedures, postoperative chemotherapy, and outcome are summarized. CONCLUSION: This rare malignancy responds well to surgery and postoperative chemotherapy including the methotrexate-based regimes.

Adolescent↗

PubMed2001

Bioprospecting for novel oxylipins in fungi: the presence of 3-hydroxy oxylipins in Pilobolus.

As previously found in various members of the Mucorales, 3-hydroxy oxylipins in Mucor genevensis are associated with the sporangia, i.e. mainly the columella structure and between aggregating sporangiospores. To determine if this phenomenon is also true in distantly related members, the mucoralean fungus Pilobolus was examined. This fungus is characterized by relatively large sub sporangial-columella structures which actively eject sporangia in a sticky liquid for attachment onto herbage surrounding its growth medium--in this case horse dung. Strikingly, this fungus produced a novel oxylipin i.e. a 3-hydroxy monounsaturated fatty acid, possibly a nonenoic acid, which is mainly associated with the sub sporangial-columella structure and aggregating sporangiospores. The specificity of the antibody against 3-hydroxy oxylipins used in immunofluorescence mapping of the mucoralean fungi, was further confirmed in the yeast, Saccharomycopsis malanga which produces 3-hydroxy palmitate in crystal form. These crystals occur between aggregating yeast cells. On the basis of the available data, we hypothesize that 3-hydroxy oxylipins probably function as adhesives, attaching fungal cells to each other or to other surfaces through entropic based hydrophobic forces and/or hydrogen bonds.

Fatty Acids, Unsaturated↗

PubMed2001

Bioprospecting for novel hydroxyoxylipins in fungi: presence of 3-hydroxy palmitic acid in Saccharomycopsis malanga.

Electron microscopy studies indicated that the major oxylipin 3-hydroxy palmitic acid (16:0) was associated with aggregating vegetative cells and formed a web-like structure around these cells. Cross sections through this structure showed a hydrophilic outer layer and a more hydrophobic inner layer suggesting that the web-like structure is in fact tube-like micelles. This information sheds more light on the role of these hydroxyoxylipins in fungi.

Cell Wall↗

PubMed2001

Clinical, hematological and histomorphological profile of myelodysplastic syndrome.

AIM: The present study was designed to analyse clinical, haematological and histomorphogical features in 37 cases of myelodysplasic syndrome (MDS). MATERIAL AND METHODS: FAB criteria was used to diagnose MDS in 37 patients. Clinical details, peripheral blood findings, bone marrow aspirate and biopsy were reviewed. RESULTS: Of 37 cases, there were 25 females and 12 males in age range of 2 years to 75 years. There were three children. There were nine cases of refractory anaemia (RA), 18 of refractory anaemia with excess blasts (RAEB), nine of refractory anaemia with excess blasts in transformation (RAEB-t) and one of chronic myelomonocytic leukemia (CMML). All were denovo MDS. All patients had pallor. Hepato and/or splenomegaly was seen in 15 cases. Anemia, leukopenia and thrombocytopenia was seen in 37, 6 and 23 cases respectively. Bone marrow aspiration (BMA) was hyper to normo cellular in 35 cases. Dyshemopoiesis was seen in one or more cell lines in all cases. Bone marrow biopsy (BMB) was available in 16 cases. Abnormal localisation of immature precursors (ALIP) was seen in 11/12 biopsies of RAEB and 3/4 of RAEB-t. BMB was helpful in diagnosis of 3 doubtful cases (one RAEB and two RAEB-t), and upgrading of 2 cases of RAEB to RAEB-t. On follow up, 1 case of RA, 3 of RAEB, 1 of RAEB-t developed AML. One case of RAEB developed ALL and 2 progressed to RAEB-t. CONCLUSION: Primary MDS is seen in all age groups. Pallor is commonest presentation. RAEB was commonest subgroup seen. BMB is helpful in diagnosis of doubtful cases. ALIP is a reliable diagnostic feature of MDS. BMB is a diagnostic as well as prognostic tool in MDS cases which should be taken as a mandatory investigation.

Adolescent↗

PubMed2000

Phospholipase A(2)s and lipid peroxidation.

Lipid peroxidation of membrane phospholipids can proceed both enzymatically via the mammalian 15-lipoxygenase-1 or the NADPH-cytochrome P-450 reductase system and non-enzymatically. In some cells, such as reticulocytes, this process is biologically programmed, whereas in the majority of biological systems lipid peroxidation is a deleterious process that has to be repaired via a deacylation-reacylation cycle of phospholipid metabolism. Several reports in the literature pinpoint a stimulation by lipid peroxidation of the activity of secretory phospholipase A(2)s (mainly pancreatic and snake venom enzymes) which was originally interpreted as a repair function. However, recent experiments from our laboratory have demonstrated that in mixtures of lipoxygenated and native phospholipids the former are not preferably cleaved by either secretory or cytosolic phospholipase A(2)s. We propose that the platelet activating factor (PAF) acetylhydrolases of type II, which cleave preferentially peroxidised or lipoxygenated phospholipids, are competent for the phospholipid repair, irrespective of their role in PAF metabolism. A corresponding role of Ca(2+)-independent phospholipase A(2), which has been proposed to be involved in phospholipid remodelling in biomembranes, has not been addressed so far. Direct and indirect 15-lipoxygenation of phospholipids in biomembranes modulates cell signalling by several ways. The stimulation of phospholipase A(2)-mediated arachidonic acid release may constitute an alternative route of the arachidonic acid cascade. Thus, 15-lipoxygenase-mediated oxygenation of membrane phospholipids and its interaction with phospholipase A(2)s may play a crucial role in the pathogenesis of diseases, such as bronchial asthma and atherosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗