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Biomedical subjects

P K Dash

Publications and source records attributed to P K Dash.

At least 37 records · Page 2Linked to original sources
PubMed2001

Transseptal catheterization without needle puncture.

OBJECTIVE: The aim was to see if probing the fossa ovalis for transseptal puncture during balloon mitral valvuloplasty will reduce time consumed for the procedure. DESIGN: Twenty-five patients had probing of fossa ovalis for left atrial entry (group I). In 30 patients (group II), standard needle puncture was done for left atrial entry. Puncture time and fluoroscopy time were noted and oxymetry was done. Later, a further 60 patients underwent probing of fossa ovalis for validation of the technique. RESULTS: Puncture times in groups I and II were 84.7 +/- 27.5 and 116.1 +/- 37.9 s, respectively (p < 0.02). Fluoroscopy time was 51.2 +/- 19.6 and 73.6 +/- 22.3 s in groups I and II, respectively (p < 0.03). During validation of the technique, 54 of 60 patients (90%) had successful left atrial entry through probing. Atrial level shunt was not seen. CONCLUSION: Probing the fossa achieves left atrial entry in 90% of patients. It avoids needle puncture and reduces puncture time as well as fluoroscopy time. It is a safe technique.

Adolescent↗
PubMed2001

Atrial fibrillation in patients with pure isolated severe rheumatic mitral regurgitation.

OBJECTIVE: This study examines the significance of the parameters that identify patients with mitral regurgitation (MR) and atrial fibrillation (AF) and discusses the indications for surgery in such patients. METHODS: Patients with MR and chronic AF (group I, n=64) and those without AF (group II, n=138) were studied by clinical and echocardiographic methods. Stepwise regression analysis identified factors associated with the presence of atrial fibrillation. RESULTS: Group I patients were older and more symptomatic. They had larger left ventricular (LV) end systolic dimension (4.6+/-1.1 cm vs 3.8+/-0.8 cm, p=0.03), left atrial (LA) dimension (5.4+/-2.0 cm vs 4.1+/-1.3 cm, p=0.02), LA area (55.9+/-27.1 cm2 vs 35.9+/-17.5 cm, p=0.003) and lower LV ejection fraction (58.8+/-8.0% vs 72.4+/-7.4%, p=0.0003). Right ventricular systolic pressure was higher (57.6+/-18.1 mm Hg vs 33.6+/-12.1 mm Hg, p=0.02). By stepwise regression analysis, factors that predicted the presence of AF were age (p < 0.03) and LA dimension (p < 0.01). A higher LV end systolic dimension and lower LV ejection fraction than the recommended value for good operative outcome were present in them. Emerging indications for surgery and predictors of poor outcome were seen. CONCLUSIONS: Atrial fibrillation in MR indicates a more chronic and severe disease process with worsening of left as well as right sided haemodynamics in spite of digoxin. Drifting towards decompensation, these patients are likely candidates for early surgery.

Adult↗
PubMed2001

Teratoma masquerading as catamenial pleural effusion.

Pleural effusion is a common clinical entity in medical practice. We report a case wherein extensive investigations failed to yield a diagnosis and medical management including repeated thoracocentesis left the effusion refractory. The patient, a 26 years lady, gave a definite history of catamenial dry cough and wheeze. The mystery was unraveled following exploratory thoracotomy when a giant mediastinal teratomatous cyst with luteinized ovarian tissue was discovered and removed, leading to eventual cure for the patient.

Adult↗
PubMed2001

Evaluation of a dipstick ELISA and a rapid immunochromatographic test for diagnosis of Dengue virus infection.

Here we report standardization of a dipstick enzyme-linked immunosorbent assay (ELISA, Dipstick ELISA) and its comparative evaluation with a commercial Rapid PanBio Immunochromatographic test (IC test) for detection of Dengue (DEN) virus-specific IgM and IgG antibodies in patient sera. Among crude and purified viral antigens prepared from mouse brains or cell cultures, a DEN virus type 2 antigen purified from cell cultures by sucrose density gradient centrifugation was found superior in terms of the signal/ noise (S/N) ratio in the assay system. The sensitivity of detection of the virus by specific IgM antibody was improved by removal of IgG from patient sera prior to testing. The evaluation of the Dipstick ELISA by use of 156 serum samples revealed an overall accordance of 96% and 93% with the IC test in detection of IgM antibodies to DEN viruses (IgM antibodies) and IgG antibodies to DEN viruses (IgG antibodies), respectively. The sensitivity of the Dipstick ELISA and the IC test with reference to the mu-capture ELISA was 83% and 87%, respectively, with a specificity of 98% in both cases. The sensitivity of the Dipstick ELISA with reference to the IC test in detecting IgM and IgG antibodies was 84% and 94%, respectively, and the specificity of the Dipstick ELISA was 98% and 92%, respectively.

Animals↗
PubMed2000

Caspase activity plays an essential role in long-term memory.

Activation of intracellular second messenger cascades has been linked to learning and memory in various organisms. Identification of down-stream targets of these second messengers that play a role in learning and memory is an active area of research. Recently, it has been reported that increases in intracellular calcium can activate a cysteine-dependent aspartate-directed protease (caspase) cascade in mice. Using an antibody that selectively recognizes activated caspase-3, we detected the presence of this enzyme in hippocampal neurons. Inhibition of caspase activity in the hippocampus blocked long-term, but not short-term, spatial memory. These results suggest that a caspase-mediated cellular event(s) in hippocampal neurons is critical for long-term spatial memory storage.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2000

Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury.

Prostaglandins, potent mediators of inflammation, are generated from arachidonic acid (AA) via the action of cyclooxygenase-1 and -2 (COX-1 and COX-2). In this study, we report that lateral cortical impact injury in rats significantly increases COX-2 protein levels both in the cortex surrounding the injury site and the ipsilateral hippocampus. COX-2 protein level was elevated as early as 3 h postinjury and persisted for up to 3 days. Increases in immunoreactivity were detected not only in the adjacent cortex and hippocampus, but were also observed in the contralateral cortex and hippocampus, the ipsilateral piriform cortex and the ipsilateral amygdaloid complex. COX-2 immunoreactive cells appear morphologically normal and do not present any of the characteristic features of apoptosis. Double immunostaining experiments using either a neuron-specific or an astroglial-specific marker show that the expression of COX-2 is localized almost exclusively in neuronal cells. Administration of the COX-2 inhibitor 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona mide (celecoxib, marketed as Celebrex) worsens motor, but not cognitive, performance, suggesting that COX-2 induction following traumatic brain injury may play a protective role.

Amygdala↗
PubMed1999

A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory.

Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training in a spatial memory task, the Morris water maze. The activation was expressed as enhanced phosphorylation of MAPK in the pyramidal neurons of the CA1/CA2 subfield. In contrast, no increase in the percentage of phospho-MAPK-positive cells was detected in either the CA3 subfield or the dentate gyrus. The enhanced phosphorylation was observed only after multiple training trials but not after a single trial or after multiple trials in which the location of the target platform was randomly changed between each trial. Inhibition of the MAPK/ERK cascade in dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK), did not interfere with memory storage. These results demonstrate a MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal hippocampus that is critical for long-term spatial memory.

Amino Acid Sequence↗
PubMed1999

Sphingosine-1-phosphate induces apoptosis of cultured hippocampal neurons that requires protein phosphatases and activator protein-1 complexes.

In this study, we report that mobilization of internal Ca2+ by sphingosine-1-phosphate, a metabolite of ceramide, induces apoptosis in cultured hippocampal neurons. This sphingosine-1-phosphate-induced apoptosis is dependent upon the activation of protein phosphatases, possibly calcineurin and phosphatase 2A (or a related phosphatase). In addition, pretreatment of neurons with double-stranded oligonucleotides containing the metallothionein phorbol-12-myristate-13-acetate response element sequence as transcription factor decoys suppressed apoptosis. In contrast, double-stranded oligonucleotides containing either the c-jun or SV40 phorbol-12-myristate-13-acetate response element sequences were ineffective. Electrophoretic mobility shift assays and supershift assays revealed that c-Fos-containing activator protein- complexes preferentially bound the metallothionein phorbol-12-myristate-13-acetate response element sequence-containing oligonucleotides. Furthermore, antisense oligonucleotides to c-fos and c-jun were also protective. The apoptotic death of hippocampal neurons has been hypothesized to contribute to the cognitive impairments observed following insults to the brain. While increases in intracellular calcium are thought to be key mediators of neuronal apoptosis, the biochemical cascade(s) activated as a result of increased Ca2+ which mediates apoptosis of hippocampal neurons is (are) not well understood. The findings presented in this study suggest that mobilization of internal calcium via prolonged exposure of sphingosine-1-phosphate induces apoptosis of hippocampal neurons in culture. Sustained increases in intracellular calcium activate a phosphatase cascade that includes calcineurin and a phosphatase 2A-like phosphatase, and leads to the expression of genes containing metallothionein phorbol-12-myristate-13-acetate response element (TGAGTCA)-type enhancer sequences. The expression of genes containing TGAGTCA-type enhancer sequences appears to be essential for sphingosine-1-phosphate-induced apoptosis of hippocampal neurons.

Animals↗
PubMed1998

Sequestration of cAMP response element-binding proteins by transcription factor decoys causes collateral elaboration of regenerating Aplysia motor neuron axons.

Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce gene expression, which is thought to be a key event for regeneration. Increases in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a family of transcription factors that bind to and modulate the expression of CRE (Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia motor neurons to examine the role of CRE-binding proteins in axonal regeneration after injury. We report that axonal injury increases the binding of proteins to a CRE sequence-containing probe. In addition, Western blot analysis revealed that the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result of axonal injury. The sequestration of CRE-binding proteins by microinjection of CRE sequence-containing plasmids enhanced axon collateral formation (both number and length) as compared with control plasmid injections. These findings show that Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors participates in the regeneration of motor neuron axons.

Animals↗
PubMed1997

Long-term enhancement but not short-term in Hermissenda is dependent upon mRNA synthesis.

The reversible transcription inhibitor 5,6-dichloro-1-beta-D-ribobenzimidazole (DRB) was used to examine the contribution of mRNA synthesis to long-term enhancement (LTE) following one-trial conditioning of Hermissenda. Inhibition of mRNA synthesis by DRB or inhibition of protein synthesis by anisomycin did not significantly affect the induction and maintenance of short-term enhancement (STE) examined 1 h after one-trial conditioning. In contrast to the absence of an effect of the inhibitors on STE, LTE was blocked by DRB or anisomycin applied shortly before and during the presentation of the conditioning trial. Consistent with previous reports, animals that received an unpaired CS and US did not exhibit LTE. In addition, a control group that received a concentration of DRB (10(-7) M) that does not significantly affect mRNA synthesis exhibited typical LTE when tested 24 h postconditioning. These results demonstrate that the induction of LTE produced by one-trial conditioning is dependent upon transcription and the regulation of gene expression.

Animals↗
PubMed1997

Inhibition of PDGF-mediated proliferation of vascular smooth muscle cells by calcium antagonists.

BACKGROUND AND PURPOSE: The mechanism by which calcium antagonists (CAs) inhibit proliferation in vascular smooth muscle cells (VSMCs) is not yet fully understood. We investigated the effects of four CAs (clentiazem, verapamil, diltiazem, and nifedipine) on signal transduction pathways activated by platelet-derived growth factor (PDGF). To determine these effects, the levels of inositol phosphates (IPs), protein kinase C (PKC), and the induction of the transcription factor activator protein-1 (AP-1) were measured. METHODS: The mitogenic effect of PDGF on VSMCs was measured by [3H]thymidine incorporated into DNA. IP production was monitored by [3H]myo-inositol incorporation. PKC activation was determined by measurement of myristoylated, alanine-rich C kinase substrate (MARCKS) phosphorylation in digitonin-permeabilized VSMCs. The induction of AP-1 complex was detected by electrophoretic mobility shift assays. RESULTS: Each CA significantly inhibited the [3H]thymidine incorporation into DNA in unstimulated cells. Similar significant decreases in [3H]thymidine incorporation by CAs were observed when cells were stimulated by rPDGF-BB. The phosphorylation of MARCKS mediated by rPDGF-BB was significantly reduced by each CA. Clentiazem and verapamil significantly reduced the expression of AP-I induced by rPDGF-BB (P < .01, P < .05). Clentiazem also significantly reduced the expression of AP-1 induced by rPDGF-AB (P < .05). CONCLUSIONS: PDGF-mediated proliferation of VSMCs correlates with activation of PKC but not with induction of the AP-1 complexes. In addition, our results suggest that CAs block proliferation of VSMCs by inhibiting DNA synthesis, possibly via PKC.

Animals↗
PubMed1996

Extracellular ATP induces formation of AP-1 complexes in astrocytes via P2 purinoceptors.

The transcription activator protein-1 (AP-1) complex is a heterodimer consisting of Fos and Jun family members. We found that extracellular ATP stimulated AP-1 DNA binding activity in cerebral cortical astrocyte cultures. This activity was maximal at 1 h and persisted for at least 3 h post-treatment. Shift-Western blotting indicated the presence of c-Fos in the AP-1 complexes. Stimulation of AP-1 binding by ATP was due to activation of P2 rather than P1 purinoceptors. The protein kinase C (PKC) inhibitor Ro 31-8220 markedly reduced P2 purinoceptor-mediated AP-1 induction. The induction of AP-1 complexes by ATP may contribute to changes in gene expression which underlie the trophic effects of extracellular ATP on astrocytes.

Adenosine Triphosphate↗
PubMed1996

Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits.

Clinical and experimental studies show that loss of neurons in the hippocampus and/or the entorhinal cortex can impede formation and storage of spatial memory. Using a controlled cortical impact model of traumatic brain injury (TBI) in rats, we have examined the temporal and spatial pattern of neuronal death using silver impregnation and cresyl violet staining. Dystrophic neurons can be detected in the dentate gyrus, and the CA1 and CA3 subfields of the hippocampus for up to 2 weeks following injury. These dystrophic cells appeared shrunken and possessed features of apoptosis. Areas containing the dystrophic cells suffer substantial cell loss as demonstrated by thinning of the neuronal layers. Dystrophic cells are also found in the amygdala, entorhinal and piriform cortices, thalamic and hypothalamic regions, and surrounding the contusion site. The loss of these cells may contribute to the memory deficits observed following TBI.

Animals↗
PubMed1996

Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits.

Loss of hippocampal neurons as a result of traumatic brain injury (TBI) is thought to contribute to the observed spatial memory deficits. Using a rodent model of experimental brain injury, we have examined the nature of hippocampal cell death following TBI. Light microscope examination of stained sections showed the presence of a large number of hyperchromatic and dystrophic neurons in the dentate gyrus of the hippocampus. These cells appeared to be undergoing nuclear condensation. Electron microscope examination demonstrated the presence of cell shrinkage, condensed chromatin, nuclear segmentation, and cytoplasmic vacuolization. Detection of a DNA ladder and in situ labeling (TUNEL) were also consistent with the process of apoptosis. However, in some dystrophic neurons these morphologies were also accompanied by the presence of swollen mitochondria and a lack of distinctive rough endoplasmic reticulum which are typically associated with necrosis. These findings show that cortical impact injury produces cell death in the hippocampus which has both apoptotic and necrotic features.

Animals↗
PubMed1996

Neuronal activity increases the phosphorylation of the transcription factor cAMP response element-binding protein (CREB) in rat hippocampus and cortex.

Activity-mediated gene expression is thought to play an important role in many forms of neuronal plasticities. We have used pentylenetetrazol-induced seizure that produces synchronous and sustained neuronal activity as a model to examine the mechanism(s) of gene activation. The transcription factor CREB (Ca2+/cAMP response element-binding protein) is thought to be necessary for long-term memory formation both in invertebrates and vertebrates. When phosphorylated on Ser133 either by cAMP-dependent protein kinase and/or Ca2+/calmodulin-dependent protein kinases, CREB increases transcription of genes containing the CRE (cAMP response element) sequence. Using an antibody that detects Ser133-phosphorylated CREB protein, we show that CREB phosphorylation is maximal between 3 and 8 min after the onset of seizure activity and declines slowly both in the hippocampus and the cortex. The total amount of CREB protein did not change at the time points examined. The increased phosphorylation of CREB protein is preceded by an increase in the amount of cAMP, suggestive of cAMP-dependent protein kinase activation, in the hippocampus and activation of Ca2+/calmodulin-dependent protein kinases in the cortex. Subsequent to CREB phosphorylation, the expression of the CRE-containing gene, c-fos, and the AP-1 complexes (heterodimers of Fos and Jun family members) is increased. These findings support the role of CREB-mediated gene expression in activity-dependent neuronal plasticities.

Animals↗