Ophthaproblem. Corneal abrasion.
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Adult↗
Biomedical subjects
S Sharma
Publications and source records attributed to S Sharma.
Myospherulosis of maxillary sinus--a case report with review of literature.
Myospherulosis is a rare condition. The authors report a unique case of this entity arising in paranasal sinus. The review of literature with emphasis on pathogenesis is also discussed.
Adult↗
Ophthaproblem. Valsalva retinopathy.
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Adult↗
Iris neovascularization following branch retinal artery occlusion.
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Aged↗
The N-methyl-D-aspartate (NMDA) receptor is postsynaptic to substance P-containing axon terminals in the rat superficial dorsal horn.
The N-methyl-D-aspartate (NMDA) receptor is thought to mediate the postsynaptic effects of excitatory amino acids released from primary afferent terminals in the superficial layers of the dorsal horn of the spinal cord where synergistic associations with substance P (SP) have been implicated in the production of hyperalgesia. We examined the electron microscopic dual immunocytochemical localization of SP and the R1 subunit of the NMDA receptor (NMDAR1) in this region to determine the cellular basis for interactions between SP and NMDA receptor ligands. Of 971 profiles immunolabeled for NMDAR1, 40% were dendrites and the remainder were primarily unmyelinated axons and astrocytic processes. In dendrites, NMDAR1-like immunoreactivity (NMDAR1-LI) was associated with synaptic and non-synaptic portions of the plasma membrane, as well as intracellular membranes including smooth endoplasmic reticulum. These NMDAR1-labeled dendrites received synaptic input from unlabeled terminals and from terminals containing SP and/or NMDAR1-LI and they occasionally (25/389) also contained SP. In contrast, of 540 SP-immunoreactive profiles, 60% were axon terminals and the majority (252/324) of these SP-labeled terminals were presynaptic to NMDAR1-containing dendrites. These results provide anatomical evidence that the synergistic nociceptive effects of SP and NMDA ligands are attributed mainly to dual modulation of the activity of single dendritic targets in the dorsal horn of the spinal cord. They also suggest that activation of NMDA receptors may also play a role in the modulation of SP neurons, presynaptic release of SP or other neurotransmitters, and in glial function in the dorsal horn.
Animals↗
Cocaine inhibits human endothelial cell IL-8 production: the role of transforming growth factor-beta.
Cocaine use is associated with modulation of a broad range of biological functions including the capacity to influence cytokine production in murine and human immunoeffector cells. Little is known, however, regarding the effects of cocaine on endothelial cell cytokine production. Because the vascular endothelium actively participates in acute and chronic inflammatory responses and interleukin-8 (IL-8) is one of the key cytokines involved in the inflammatory process, modification of the production of IL-8 by vascular endothelial cells may interfere with the host response to infection or tissue injury. We investigated the effect of cocaine on endothelial cell IL-8 production. Conditioned supernatant from EA.hy 926 cells were evaluated by ELISA following in vitro cocaine exposure. Cocaine decreased IL-8 production in a dose-responsive manner, and this reduction correlated with down-regulation of IL-8 mRNA expression. Cocaine also increased the production of TGF-beta by EA.hy 926 cells and anti-TGF-beta abrogated the cocaine-mediated decrement of IL-8 production, indicating that cocaine down-regulates endothelial IL-8 production by increasing TGF-beta. Our findings suggest that the immunomodulatory effects of cocaine may be mediated, in part, by modification of endothelial-derived cytokine production.
Cell Line↗
The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila.
Swiss cheese (sws) mutant flies develop normally during larval life but show age-dependent neurodegeneration in the pupa and adult and have reduced life span. In late pupae, glial processes form abnormal, multilayered wrappings around neurons and axons. Degeneration first becomes evident in young flies as apoptosis in single scattered cells in the CNS, but later it becomes severe and widespread. In the adult, the number of glial wrappings increases with age. The sws gene is expressed in neurons in the brain cortex. The conceptual 1425 amino acid protein shows two domains with homology to the regulatory subunits of protein kinase A and to conceptual proteins of yet unknown function in yeast, worm, and human. Sequencing of two sws alleles shows amino acid substitutions in these two conserved domains. It is suggested that the novel SWS protein plays a role in a signaling mechanism between neurons and glia that regulates glial wrapping during development of the adult brain.
Amino Acid Sequence↗
Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents.
Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 10(5) colony-forming units per ml.
Cell Line↗
Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.
Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.
Adrenocorticotropic Hormone↗
Expression of individual members of a tRNA(Gly)1 multigene family in vivo follows the same pattern as in vitro.
Individual members of a tRNA(Gly)1 multigene family from Bombyx mori are transcribed to different levels in vitro in homologous nuclear extracts but their transcription status in vivo is not known. Two sets of tRNA(Gly)1 belonging to the extreme groups of highly transcribed and barely transcribed copies have been examined for their expression patterns in vivo in B. mori-derived cell lines following transfection. We have developed a sensitive and reliable method for directly quantifying the transcription levels of transfecting tRNA genes without relying on the biological activity of the transcript. The strategy involved the insertion of synthetic oligodeoxyribonucleotide sequences into the coding region of the transfecting gene and monitoring the transcripts in an RNase protection assay using an antisense probe that clearly distinguished them from the endogenous tRNAs. The oligonucleotide insertion did not significantly affect the transcriptional status of the genes, even though the distance between the A and B boxes was enhanced by 10-15 nt. In vivo also the transcription of tRNA(Gly)1 reached very high levels, whereas the transcripts arising from tRNA(Gly)1-6:7 accounted for only 2-5% of the former, closely resembling the transcription patterns in vitro. These individual gene copies having identical coding sequences and consequently the same internal conserved regions, differed only in their flanking sequences which modulate their transcription levels.
Animals↗
Altered immune responses in interleukin 10 transgenic mice.
Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigen-specific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.
Animals↗
Transballoon intravascular ultrasound imaging during balloon angioplasty in animal models with coarctation and branch pulmonary stenosis.
BACKGROUND: Intravascular ultrasound (IVUS) studies performed after balloon dilation provide a method for evaluating the adequacy of angioplasty and the nature of associated changes in vessel walls. Previously, IVUS studies required the use of separate scanning catheters inserted independently before and after balloon angioplasty. We tested a 0.035-in, 30-MHz IVUS transducer wire that images from within commercially available 5F balloon dilation catheters. METHODS AND RESULTS: Seven stenoses were created in the left pulmonary artery (n = 3) and in the aortic isthmus (n = 4) in six lambs (weight, 3.4 to 12.5 kg). The balloon catheter selected was advanced across the stenotic area and the IVUS wire advanced in the guide lumen to the center of the balloon. Continuous IVUS images were obtained through balloons before, during, and after dilation. Transballoon imaging confirmed balloon location within the stenotic segment. Luminal diameters of stenotic and adjacent vessel segments before and after angioplasty by IVUS showed good correlation with angiographic measurements (r = .93, P < or = .001). After successful dilation, imaging during deflation allowed the assessment of vascular elastic recoil, mural dissection, and luminal size without requiring changes in balloon position. Repeat dilation could be undertaken and the inflation pressure and technique modified on the basis of the observed results. CONCLUSIONS: This transballoon IVUS system provides important on-line information about lumen diameter and wall structure for evaluation of angioplasty without the need for catheter changes, providing a method to possibly reduce the likelihood of excessive wall damage and to potentially reduce the number of angiograms required to accomplish and confirm results.
Angiography↗
Characterization of P0, a ribosomal phosphoprotein of Plasmodium falciparum. Antibody against amino-terminal domain inhibits parasite growth.
A cDNA expression clone of the human malarial parasite Plasmodium falciparum, lambdaPf4, which was reactive only to the immune sera and not to the patient sera, has recently been found to be the P. falciparum homologue of the P0 ribosomal phosphoprotein gene. A Northern analysis of the P0 gene revealed the presence of two transcripts, both present in all the different intraerythrocytic stages of the parasite life cycle. A 138-base pair amino-terminal domain of this gene was expressed as a fusion protein with glutathione S-transferase in Escherichia coli. Polyclonal antibodies raised against this domain immunoprecipitated the expected 38-kDa P0 protein from the 35S-labeled as well as 32P-labeled P. falciparum cultures. Monospecific human immune sera affinity-purified using the expression clone lambdaPf4 also immunoprecipitated the same size protein from [35S]methionine-labeled P. falciparum protein extract. Purified IgG from polyclonal antibodies raised against the amino-terminal domain of P0 protein completely inhibited the growth of P. falciparum in vitro. This inhibition appears to be mainly at the step of erythrocyte invasion by the parasites.
Animals↗
Fatal falciparum malaria in Canadian travellers.
The authors report 2 cases of severe falciparum malaria in Canadians that had fatal outcomes. In the first case a man presented to a local hospital shortly after returning from Africa, but a diagnosis of malaria was not considered. He was transferred to a secondary and then to a tertiary care facility, where he subsequently died. Intravenous quinidine therapy, the treatment of choice, was unavailable at all 3 hospitals. In the second case, a woman taking chloroquine prophylaxis while visiting Nigeria developed cerebral malaria and died. These cases illustrate critical management issues: appropriate advice on malaria prevention before departure; consideration of malaria in all febrile people returning from an endemic area; ready access to parenteral therapy for severe malaria in Canadian hospitals; and an increase in awareness of travel medicine among family physicians.
Africa↗
Surgical training: an objective assessment of recent changes for a single health board.
The reduction in doctors' hours and the introduction of specialist training have reduced general surgical training by 60%. This study assessed the implications for a single health board. A questionnaire listing 13 representative operations was sent to 44 trainees and 52 trainers to determine the number of operations a trainee should perform. The total number of operations required for training was compared against the total actually performed across the health board. Operating times for five representative operations were audited prospectively. Trainers and trainees recommended a similar and conservative number of operations. The total number of operations available for training (4913) was 38% less than the number recommended (7946). Trainees required 50-75% more operating time than consultants. To increase the proportion of operations undertaken by trainees from the current 30% to 70% would require an extra 270 theatre days (of pounds 1.3m) yearly. The minimum number of operations required for training must be defined and the proportion of supervised operations undertaken by trainees substantially increased. Service and financial implications will have to be addressed. Action is needed urgently, as the first trainees will become consultants in less than five years.
Consultants↗
alpha-MSH modulates local and circulating tumor necrosis factor-alpha in experimental brain inflammation.
Tumor necrosis factor (TNF-alpha) underlies pathological processes and functional disturbances in acute and chronic neurological disease and injury. The neuroimmunomodulatory peptide alpha-MSH modulates actions and production of proinflammatory cytokines including TNF-alpha, but there is no prior evidence that it alters TNF-alpha induced within the brain. To test for this potential influence of the peptide, TNF-alpha was induced centrally by local injection of bacterial lipopolysaccharide (LPS). alpha-MSH given once i.c.v. with LPS challenge, twice daily intraperitoneally (i.p.) for 5 d between central LPS injections, or both i.p. and centrally, inhibited production of TNF-alpha within brain tissue. Inhibition of TNF-alpha protein formation by alpha-MSH was confirmed by inhibition of TNF-alpha mRNA. Plasma TNF-alpha concentration was elevated markedly after central LPS, indicative of an augmented peripheral host response induced by the CNS signal. The increase was inhibited by alpha-MSH treatments, in relation to inhibition of central TNF-alpha. Presence within normal mouse brain of mRNA for the alpha-MSH receptor MC-1 suggests that the inhibitory effects of alpha-MSH on brain and plasma TNF-alpha might be mediated by this receptor subtype. The inhibitory effect of alpha-MSH on brain TNF-alpha did not depend on circulating factors because the effect also occurred in brain tissue in vitro. This indicates that alpha-MSH can act directly on brain cells to inhibit their production of TNF-alpha. If central TNF-alpha contributes to pathology in CNS disease and injury, and promotes inflammation in the periphery, agents that act on brain alpha-MSH receptors should decrease the pathological TNF-alpha reaction and promote tissue survival.
Animals↗
Proteasome- and p53-dependent masking of signal transducer and activator of transcription (STAT) factors.
Hepatoma Hep3B cell lines stably expressing a temperature-sensitive p53 species (p53-Val-135) displayed a reduced response to interleukin-6 (IL-6) when cultured at the wild-type (wt) p53 temperature (Wang, L., Rayanade, R., Garcia, D., Patel, K., Pan, H., and Sehgal, P. B. (1995) J. Biol. Chem. 270, 23159-23165). We now report that in such cultures IL-6 caused a rapid (20-30 min) and marked loss of cellular immunostaining for STAT3 and STAT5, but not for STAT1. The loss of STAT3 and STAT5 immunostaining was transient (lasted 120 min) and tyrosine kinase-dependent, and even though the loss was blocked by the proteasome inhibitors MG132 and lactacystin it was not accompanied by changes in cellular levels of STAT3 and STAT5 proteins suggesting that IL-6 triggered a rapid masking but not degradation of these transcription factors. STAT3 and STAT5 masking was accompanied by a reduction in IL-6-induced nuclear DNA-binding activity. The data suggest that p53 may influence Jak-STAT signaling through a novel indirect mechanism involving a wt p53-dependent gene product which upon cytokine addition is activated into a "STAT-masking factor" in a proteasome-dependent step.
Carcinoma, Hepatocellular↗
Absent pericardium during coronary bypass.
The importance of recognizing congenitally absent left pericardium in the setting of acquired cardiovascular disease was recently appreciated during a case of coronary artery bypass grafting. An associated defect in the left hemidiaphragm and an abnormal location of the left phrenic nerve were found. Careful dissection of the phrenic nerve from the surface of the heart and closure of the diaphragmatic defect were necessary to avoid injury to the former and prevent hernia through the latter structure. Absent left pericardium discovered during cardiac surgery requires attention to the location of the left phrenic nerve and recognition of associated defects in the diaphragm.
Abnormalities, Multiple↗