Locking the Luer lock.
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Aged, 80 and over↗
Biomedical subjects
P Pandey
Publications and source records attributed to P Pandey.
Foot drop after spinal anesthesia in a patient with a low-lying cord.
Damage to the spinal cord/conus medullaris due to incorrect identification of the lumbar space is a known complication of lumbar puncture. However, damage to a low-lying cord using an appropriate interspace is extremely rare. We describe a 26-year-old woman who underwent emergency caesarean section under spinal anesthesia. She developed right foot drop immediately after surgery, which gradually recovered over the next 10 months. Magnetic resonance imaging revealed a low lying cord with a fatty filum terminale and intramedullary T2 hyperintensity, suggestive of needle damage.
Adult↗
Pediatric pituitary adenoma: a series of 42 patients.
Pituitary adenomas are uncommon in childhood. This report describes the presentation, endocrinological profile, management and outcome of 42 children with pituitary adenomas. The majority of the tumors were functioning adenomas (40/42, 95.2%). Only two patients (4.8%) had non-functioning tumors. Amongst the functioning tumors, there were 20 patients (47.6%) with prolactinomas, 11 patients (26.2%) with Cushing's disease and nine patients (21.4%) with growth hormone (GH)-secreting adenomas. The most common presenting features were endocrinopathy and visual disturbances. The majority of tumors were macroadenomas, with only eight patients (all with Cushing's disease) having a microadenoma. Transsphenoidal tumor decompression was performed in most cases (71.4%). Complications following transcranial surgery were more frequent when compared to transsphenoidal surgery. There was one death following surgery. Response to radiotherapy was satisfactory. Overall, 67.6% of patients achieved endocrinological remission. Of these, 89% of the children with GH-secreting tumors and 100% of the children with Cushing's disease achieved remission. We conclude that the transsphenoidal approach is effective and safe in surgery for pituitary adenomas in children and is the procedure of choice if there is no contraindication. The combination of surgery and radiotherapy, as well as medical therapy with bromocriptine, achieves good results in the management of these uncommon tumors.
Adenoma↗
Brain abscess--an unusual complication of ventriculo-peritoneal shunt.
The authors report a case of a 10-year-old boy, who was operated for a craniopharyngioma with hydrocephalus. He succumbed to delayed development of brain abscess and its consequence, secondary to incompletely treated shunt tract infection. This unfortunate complication developed, despite the fact that conventional steps (removal of VP shunt and intravenous antibiotics) recommended for the treatment of VP shunt infection were adopted. The pathogenesis, management and review of literature of this extremely rare clinical entity is presented.
Brain Abscess↗
Rhizobia as a biological control agent against soil borne plant pathogenic fungi.
Rhizobia promote the growth of plants either directly through N2 fixation, supply of nutrients, synthesis of phytohormones and solubilization of minerals, or indirectly as a biocontrol agent by inhibiting the growth of pathogens. The biocontrol effect of rhizobia is due to the secretion of secondary metabolites such as antibiotics and HCN. Siderophore production in iron stress conditions provides rhizobia an added advantage, resulting in exclusion of pathogens due to iron starvation.
Fungi↗
Subarachnoid hemorrhage and intracereebral hematoma following lumboperitoneal shunt for pseudotumor cerebri: a rare complication.
Placement of lumboperitoneal (LP) shunt as a surgical treatment for benign intracranial hypertension (BIH) is generally a safe procedure, with complications like mechanical failure, overdrainage and infections. Subarachnoid hemorrhage and intracerebral hematoma were seen after lumboperitoneal shunt in a patient having BIH. These complications were the cause of the patient's deterioration. After removal of the hematoma and performing a decompressive procedure, patient's neurological condition improved. The clinical features, investigations and clinical course are described and the literature reviewed.
Adult↗
Interaction of hematopoietic progenitor kinase 1 and c-Abl tyrosine kinase in response to genotoxic stress.
The c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents and regulates induction of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The hematopoietic progenitor kinase 1 (HPK1) has also been shown to act upstream to the SAPK/JNK signaling pathway. We report here that exposure of hematopoietic Jurkat T cells to genotoxic agents is associated with activation of HPK1. The results demonstrate that exposure of Jurkat cells to DNA-damaging agents is associated with translocation of active c-Abl from nuclei to cytoplasm and binding of c-Abl to HPK1. Our findings also demonstrate that c-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. The functional significance of the c-Abl-HPK1 interaction is supported by the demonstration that this complex regulates SAPK/JNK activation. Overexpression of c-Abl(K-R) inhibits HPK1-induced activation of SAPK/JNK. Conversely, the dominant negative mutant of HPK1 blocks c-Abl-mediated induction of SAPK/JNK. These findings indicate that activation of HPK1 and formation of HPK1/c-Abl complexes are functionally important in the stress response of hematopoietic cells to genotoxic agents.
Enzyme Activation↗
Immunohistochemical and ultrastructural evidence that dendritic cells infiltrate stenotic aortocoronary saphenous vein bypass grafts.
We earlier speculated that antigen-presenting dendritic cells may be involved in the immune reactions leading to saphenous vein bypass graft failure. The purpose of this study was to confirm whether dendritic cells are present in stenotic human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts were explanted from 14 patients at re-do bypass operation and ten normal saphenous veins were harvested during femoro-popliteal grafting. Sections of specimens were analysed using cell type specific antibodies to identify dendritic cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal immunofluorescent laser scanning microscopy and electron microscopy were used. Stenotic grafts showed structural alterations of intimal hyperplasia and varying degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were observed in the intima and media of normal saphenous veins. Cells expressing these antigens were present around areas of medial neovascularization and within intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron microscopy demonstrated the presence of cells containing a well-developed tubulovesicular system which is unique to cells from the dendritic cell family. Double immunohistochemistry and confocal immunofluorescent microscopy revealed the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are present in stenotic saphenous vein bypass grafts. Dendritic cells may be responsible for antigen presentation and modulation of immune reactions in accelerated graft atherosclerosis through their interaction with T-lymphocytes.
Adult↗
The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism.
The oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a multifunctional molecule that induces monocytic differentiation of human myeloid leukemia cells and inhibits proliferation of diverse human tumor cell lines. The present studies on human osteosarcoma cells demonstrate that CDDO induces mitochondrial cytochrome c release, caspase-3 activation, and internucleosomal DNA fragmentation. Overexpression of the caspase-8 inhibitor CrmA blocked CDDO-induced cytochrome c release and apoptosis. By contrast, overexpression of the antiapoptotic Bcl-x(L) protein blocked CDDO-induced cytochrome c release, but only partly inhibited caspase-3 activation and apoptosis. In concert with these findings, we demonstrate that CDDO: 1) activates caspase-8 and thereby caspase-3 by a cytochrome c-independent mechanism and 2) induces cytochrome c release by caspase-8-dependent cleavage of Bid. The results also demonstrate that treatment of osteosarcoma cells with CDDO induces differentiation, as assessed by alkaline phosphatase activity and osteocalcin production, and that this response is abrogated in cells that overexpress CrmA. These findings demonstrate that CDDO induces both osteoblastic differentiation and apoptosis by caspase-8-dependent mechanisms.
Apoptosis↗
Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis.
The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in the ER was confirmed by immunoelectron microscopy. Subcellular fractionation studies further indicate that over 20% of cellular c-Abl is detectable in the ER. The results also demonstrate that induction of ER stress with calcium ionophore A23187, brefeldin A, or tunicamycin is associated with translocation of ER-associated c-Abl to mitochondria. In concert with targeting of c-Abl to mitochondria, cytochrome c is released in the response to ER stress by a c-Abl-dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl-deficient cells. These findings indicate that c-Abl is involved in signaling from the ER to mitochondria and thereby the apoptotic response to ER stress.
Animals↗
Spontaneous decompression of a posterior fossa arachnoid cyst: a case report.
The authors present a case of spontaneous regression of a posterior fossa, supracerebellar arachnoid cyst causing hydrocephalus in a 7-month-old male child. The patient presented with macrocrania, bulging fontanelle and upgaze paresis of the eyes. There was complete improvement of these symptoms on the morning of the day of surgery without any obvious precipitating factors, including trauma. CT scan showed complete resolution of the cyst and hydrocephalus. The child was doing well at 1 year of follow-up. To the best of our knowledge, this is the first case report of spontaneous resolution of a posterior fossa arachnoid cyst.
Arachnoid Cysts↗
Phorbol ester-induced generation of reactive oxygen species is protein kinase cbeta -dependent and required for SAPK activation.
Treatment of human U-937 myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with protein kinase C (PKC) betaII-mediated activation of the stress-activated protein kinase (SAPK) pathway. The present studies demonstrate that the TPA response of U-937 cells includes the generation of reactive oxygen species (ROS). By contrast, the TPA-resistant U-937 cell variant (TUR), which is deficient in PKCbetaII expression, failed to respond to TPA with the induction of ROS. Moreover, we show that TPA-induced ROS production is restored in TUR cells stably transfected to express PKCbetaII. The results also demonstrate that TPA-induced ROS production is required for activation of the MEK kinase-1 (MEKK-1)--> SAPK pathway. In concert with this observation, treatment of U-937 with H(2)O(2) as a source of ROS is associated with activation of the MEKK-1-->SAPK cascade. These findings indicate that PKCbetaII is required for TPA-induced ROS production and that the MEKK-1-->SAPK pathway is activated by a ROS-mediated mechanism.
Enzyme Activation↗
SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells.
Our previous studies have shown that activation of a related adhesion focal tyrosine kinase (RAFTK) (also known as Pyk2) is required for dexamethasone (Dex)-induced apoptosis in multiple myeloma (MM) cells and that human interleukin-6 (IL-6), a known growth and survival factor for MM cells, blocks both RAFTK activation and apoptosis induced by Dex. However, the mechanism whereby IL-6 inhibits Dex-induced apoptosis is undefined. In this study, we demonstrate that protein-tyrosine phosphatase SHP2 mediates this protective effect. We show that IL-6 triggers selective activation of SHP2 and its association with RAFTK in Dex-treated MM cells. SHP2 interacts with RAFTK through a region other than its Src homology 2 domains. We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM.
Apoptosis↗
Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and activation of procaspase-9 by heat shock protein 90.
The release of cytochrome c from mitochondria results in the formation of an Apaf-1-caspase-9 apoptosome and induces the apoptotic protease cascade by activation of procaspase-3. The present studies demonstrate that heat shock protein 90 (Hsp90) forms a cytosolic complex with Apaf-1 and thereby inhibits the formation of the active complex. Immunodepletion of Hsp90 depletes Apaf-1 and thereby inhibits cytochrome c-mediated activation of caspase-9. Addition of purified Apaf-1 to Hsp90-depleted cytosolic extracts restores cytochrome c-mediated activation of procaspase-9. We also show that Hsp90 inhibits cytochrome c-mediated oligomerization of Apaf-1 and thereby activation of procaspase-9. Furthermore, treatment of cells with diverse DNA-damaging agents dissociates the Hsp90-Apaf-1 complex and relieves the inhibition of procaspase-9 activation. These findings provide the first evidence for a negative cytosolic regulator of cytochrome c-dependent apoptosis and for involvement of a chaperone in the caspase cascade.
Amino Acid Sequence↗
Requirement for caspase activation in monocytic differentiation of myeloid leukemia cells.
Human myeloid leukemia cells respond to 12-tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PKC) with the induction of terminal monocytic differentiation. The present studies demonstrate that TPA treatment of U-937 leukemia cells is associated with release of mitochondrial cytochrome c, activation of caspase-3 and induction of internucleosomal DNA fragmentation. By contrast, the TUR cell variant, which is deficient in PKCbeta, failed to respond to TPA with release of cytochrome c and induction of the caspase-3 cascade. Moreover, stable overexpression of PKCbeta in TUR cells reconstituted sensitivity to TPA-induced cytochrome c release and activation of caspase-3. The results also demonstrate that treatment of cells with the caspase inhibitor Z-VAD-fmk blocks both TPA-induced apoptosis and monocytic differentiation. Similar results were obtained in U-937 cells stably expressing the CrmA caspase inhibitor. These findings demonstrate that TPA induces cytochrome c release by a PKCbeta-dependent mechanism and that activation of caspase-mediated signaling is required for induction of the differentiated monocytic phenotype.
Amino Acid Chloromethyl Ketones↗
Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome c release and apoptosis.
Apoptosis is induced by the release of cytochrome c from mitochondria to the cytoplasm. The present studies demonstrate that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces translocation of protein kinase C (PKC) delta from the cytoplasm to mitochondria. The results also show that translocation of PKCdelta results in release of cytochrome c. The functional significance of this event is further supported by the demonstration that PKCdelta translocation is required for TPA-induced apoptosis. These findings demonstrate that translocation of PKCdelta to mitochondria is responsible, at least in part, for inducing cytochrome c release and apoptosis.
Apoptosis↗
Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase.
BACKGROUND: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. RESULTS: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl show telomere lengthening. CONCLUSIONS: The ubiquitously expressed c-Abl tyrosine kinase is activated by DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function.
Catalytic Domain↗
Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase.
The c-Abl protein-tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. The rapamycin and FKBP-target 1 (RAFT1), also known as FKBP12-rapamycin-associated protein (FRAP, mTOR), regulates the p70S6 kinase (p70(S6k)) and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). The present results demonstrate that c-Abl binds directly to RAFT1 and phosphorylates RAFT1 in vitro and in vivo. c-Abl inhibits autophosphorylation of RAFT1 and RAFT1-mediated phosphorylation p70(S6k). The functional significance of the c-Abl-RAFT1 interaction is further supported by the finding that eIF4E-dependent translation in mouse embryo fibroblasts from Abl(-/-) mice is significantly higher than that compared in wild-type cells. The results also demonstrate that exposure of cells to ionizing radiation is associated with c-Abl-mediated binding of 4E-BP1 to eIF4E and inhibition of translation. These findings with the c-Abl tyrosine kinase represent the first demonstration of a negative physiologic regulator of RAFT1-mediated 5' cap-dependent translation.
Animals↗