Dermoid cyst in the lumbosacral region: radiographic findings.
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Dermoid Cyst↗
Biomedical subjects
S Hunter
Publications and source records attributed to S Hunter.
Baculovirus-directed expression and secretion of a truncated version of Toxoplasma SAG1.
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Animals↗
Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding site for phosphatidylinositol 3-kinase.
We have investigated the interaction between Cbl and the Src-related tyrosine kinase Fyn. Fyn was observed to be constitutively associated with Cbl in lysates of several different cell types including the interleukin-3-dependent murine myeloid cell line 32Dcl3, and the prolactin-dependent rat thymoma cell line Nb2. Binding studies indicated that Cbl could bind to glutathione S-transferase (GST) fusion proteins encoding the unique, Src homology domain 3 (SH3), and SH2 domains of Fyn, Hck, or Lyn. Fusion proteins encoding either the SH3 or SH2 domains of Fyn bound to Cbl as effectively as the fusion protein encoding the unique, SH3, and SH2 domains of Fyn. The Fyn SH2 domain bound to both tyrosine-phosphorylated and nonphosphorylated Cbl, implying that this interaction might be phosphotyrosine-independent. Binding of the Fyn SH2 domain to Cbl was not disrupted by the addition of phosphotyrosine, phosphoserine, or phosphothreonine. A GST fusion protein encoding the proline-rich region of Cbl bound to Fyn present in a total cell lysate. Far Western blot analysis also indicated that the SH3 domain of Fyn bound preferentially to the proline-rich region of Cbl. The addition of [gamma-32P]ATP to either anti-Cbl immunoprecipitates or anti-Fyn immunoprecipitates resulted in the phosphorylation of both Cbl and Fyn as demonstrated by immunoprecipitation of the phosphorylated proteins with specific antisera. Fyn directly phosphorylated a GST fusion protein containing the C-terminal region of Cbl (GST-CBL-LZIP). In contrast, immunoprecipitated JAK2 was not able to phosphorylate this same region of Cbl. The GST-CBL-LZIP fusion protein contains a binding site for the SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase, which mapped to Tyr731, which is present in the sequence YEAM. Mutation of Tyr731 in GST-CBL-LZIP eliminated binding of the p85 subunit of phosphatidylinositol 3-kinase and substantially reduced the phosphorylation of this fusion protein by Fyn, despite the presence of four other tyrosine residues in this fusion protein. These data are consistent with the hypothesis that Cbl represents a substrate for Src-like kinases that are activated in response to the engagement of cell surface receptors, and that Src-like kinases are responsible for the phosphorylation of a tyrosine residue in Cbl that may regulate activation of phosphatidylinositol 3-kinase.
Animals↗
Structural requirements of Syk kinase for Fcgamma receptor-mediated phagocytosis.
The tyrosine kinase Syk plays a critical role in the phagocytic pathway mediated by Fcgamma receptors (FcgammaR). In transfected COS1 cells co-expression of Syk enhances FcgammaR mediated phagocytosis. The other member of the Syk kinase family, the highly homologous tyrosine kinase Zap70, also plays a role in signaling by immunoglobulin gene family receptors, but does not increase the phagocytic efficiency of FcgammaRs. The homologous tandem SH2 and kinase domains of Syk and Zap70 are separated by a nonhomologous region referred to as the unique domain. Zap70's inability to enhance phagocytosis was not due to unique domain tyrosine 292, previously implicated in negative regulation of Zap70 function. We determined the regions of Syk important for its interaction with the phagocytic pathway. An intact kinase domain was required for Syk's effect on phagocytosis. Furthermore, the Syk variant SykB, lacking 23 amino acids in the unique region, signaled for phagocytosis as efficiently as did Syk. We then constructed exchange chimeras between Syk and Zap70 and determined the contributions of the SH2, unique and kinase domains to phagocytic signaling. Our data suggest that the Syk kinase domain, which has high intrinsic kinase activity, is important for facilitating phagocytic signaling by FcgammaRI and FcgammaRIIIA.
Animals↗
Etoposide-induced activation of c-jun N-terminal kinase (JNK) correlates with drug-induced apoptosis in salivary gland acinar cells.
We have examined the ability of etoposide to induce apoptosis in two recently established rat salivary acinar cell lines. Etoposide induced apoptosis in the parotid C5 cell line as evidenced by the appearance of cytoplasmic blebbing and nuclear condensation, DNA fragmentation and cleavage of PARP. Etoposide also induced activation of c-jun N-terminal kinase (JNK) in parotid C5 cells by 4 h after treatment, with maximal activation at 8 - 10 h. Coincident with activation of JNK, the amount of activated ERK1 and ERK2 decreased in etoposide-treated parotid C5 cells. In contrast to the parotid C5 cells, the vast majority of submandibular C6 cells appeared to be resistant to etoposide-induced apoptosis. Likewise, activation of JNKs was not observed in etoposide-treated submandibular C6 cells, and the amount of activated ERK1 and ERK2 decreased only slightly. Etoposide treatment of either cell line had no effect upon the activation of p38. Treatment of the parotid C5 cells with Z-VAD-FMK, a caspase inhibitor, inhibited etoposide-induced activation of JNK and DNA fragmentation. These data suggest that etoposide may induce apoptosis in parotid C5 cells by activating JNKs and suppressing the activation of ERKs, thus creating an imbalance in these two signaling pathways.
Amino Acid Chloromethyl Ketones↗
Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores.
Patients with chronic viral hepatitis and cirrhosis often have elevated serum alpha-fetoprotein (AFP) values, the causes of which are unclear. We studied 81 patients with chronic hepatitis C and the relationships of serum AFP and alanine aminotransferase (ALT) values, hepatic histologic features, and hepatocyte proliferation activity scores. Twenty-two patients had nil to mild fibrosis, 34 had moderate fibrosis, and 25 had marked fibrosis-cirrhosis. The mean serum AFP value was significantly greater in patients with more fibrosis. Serum ALT values were slightly greater in the marked fibrosis-cirrhosis patient group. The differences in the HAI and in hepatocyte MIB-1 scores were not significant. Among all patients, increasing serum AFP values significantly correlated with increasing ALT values. However, there were no significant correlations with serum ALT or HAI and serum AFP values. There was no association between serum AFP values and immunohistochemical staining for AFP within hepatocytes. These results suggest that elevated serum AFP values are the result of altered hepatocyte-hepatocyte interaction and loss of normal architectural arrangements. The presence of marked fibrosis or cirrhosis, a state of significant altered hepatocyte architecture, may be the underlying cause of increased serum AFP, rather than necrosis or active regeneration.
Alanine Transaminase↗
Motivating the obese child to move: the role of structured exercise in pediatric weight management.
BACKGROUND: The prevalence of childhood obesity is rapidly increasing. Successful prevention and treatment of childhood obesity depends on increasing the physical activity patterns of obese youth. However, motivating the obese child to participate in physical activity is difficult. METHODS: We designed a four-phase physical activity intervention, consisting of a structured progressive exercise program of moderate intensity, along with motivational methods to increase physical activity and improve body movement awareness. RESULTS: Seventy-three overweight children participated in the weight management program. They had a significant weight loss and reduction in body fat, which was maintained at 1-year follow-up. Subjects also maintained lean body mass and showed improved physical activity patterns. CONCLUSIONS: Progressive exercise, used in conjunction with nutrition and behavior modification, provides successful motivational strategies. These strategies encourage increased physical activity patterns, the adoption of regular structured exercise training, and the loss of excess body fat.
Adolescent↗
The natural history of ventricular septal defects.
AIMS: To correlate the size and position of isolated ventricular septal defects with closure rate in a cohort of children with mean follow up of more than six years. DESIGN: A birth cohort was identified using the northern region cardiac database. The following were noted from case notes: defect size, position, means of closure, and age at closure. RESULTS: 68 children were identified. 49 defects were small, 14 were moderate, and 5 were large. 13 cases required surgical closure, including 12 perimembranous defects. 35 defects closed spontaneously. Nine of the small muscular defects remained open and five of the small perimembranous defects remained open. The spontaneous closure rate for muscular defects was significantly greater than for perimembranous defects. Mean age of follow up for patients who still have defects is 76 months. CONCLUSIONS: The position of a ventricular septal defect is extremely relevant to its natural history. Perimembranous defects accounted for most of the moderate and large defects that required surgical intervention. After more than six years almost a third of all perimembranous and just over two thirds of all muscular defects closed spontaneously.
Child, Preschool↗
Haemodynamic effects of altering arterial oxygen saturation in preterm infants with respiratory failure.
AIMS: To examine the haemodynamic effects of brief alteration in arterial oxygenation in preterm infants with respiratory failure. METHODS: Eighteen preterm infants with respiratory failure, aged 9-76 hours, underwent detailed Doppler echocardiographic assessment at 86%, 96%, and 100% SaO2, achieved by altering the FIO2. Sixteen were receiving intermittent positive pressure ventilation, median FIO2 0.45 (0.20-0.65), median mean airway pressure 12 cm H2O (0-20). SaO2 was stable for 15 minutes at each stage. Four parameters of pulmonary arterial pressure were measured: peak velocity of tricuspid regurgitation and peak velocity of left to right ductal flow, TPV:RVET ratio and PEP:RVET ratio, measured at the pulmonary valve, along with flow velocity integrals at the aortic and pulmonary valves, and systemic arterial pressure. Ductal size was graded into closed, small, moderate, large with imaging, pulsed and continuous wave Doppler. RESULTS: Between 86% and 96% SaO2, there were no consistent changes, but in three of the 12 with a patent ductus arteriosus (PDA) there was ductal constriction, with complete closure in one. Between 96% and 100% SaO2, peak ductal flow velocity rose significantly in four of eight with a PDA. Ductal constriction occurred in four infants; in three this was associated with a significant fall in aortic flow integral and a rise in aortic pressure (4-6 mm Hg). Overall, 11 infants went from 86% to 100% SaO2 and pulmonary arterial pressure fell significantly in seven. CONCLUSION: A brief rise in SaO2 within the range maintained by most neonatal units can cause significant ductal constriction. The fall in pulmonary arterial pressure with 100% SaO2 seen in most infants was associated with a fall in pulmonary blood flow (or no change), rather than a rise, indicating that the dominant haemodynamic effect was ductal constriction rather than pulmonary vasodilation.
Confidence Intervals↗
An SCL 3' enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors.
The SCL gene encodes a basic helix-loop-helix transcription factor which is expressed in early haematopoietic progenitors throughout ontogeny and is essential for the normal development of blood and blood vessels. Transgenic studies have characterised spatially distinct 5' enhancers which direct lacZ expression to subdomains of the normal SCL expression pattern, but the same elements failed to produce appropriate haematopoietic expression. We now describe an SCL 3' enhancer with unique properties. It directed lacZ expression in transgenic mice to extra-embryonic mesoderm and subsequently to both endothelial cells and to a subset of blood cells at multiple sites of embryonic haematopoiesis including the yolk sac, para-aortic splanchnopleura and AGM region. The 3' enhancer also targeted expression to haematopoietic progenitors in both foetal liver and adult bone marrow. Purified lacZ(+ )cells were highly enriched for clonogenic myeloid and erythroid progenitors as well as day-12 spleen colony forming units (CFU-S). Within the total gated population from bone marrow, 95% of the myeloid and 90% of the erythroid colony-forming cells were contained in the lacZ(+) fraction, as were 98% of the CFU-S. Activation of the enhancer did not require SCL protein. On the contrary, transgene expression in yolk sacs was markedly increased in an SCL-/- background, suggesting that SCL is subject to negative autoregulation. Alternatively the SCL-/- environment may alter differentiation of extra-embryonic mesoderm and result in an increased number of cells capable of expressing high levels of the transgene. Our data represents the first description of an enhancer that integrates information necessary for expression in developing endothelium and early haematopoietic progenitors at distinct times and sites throughout ontogeny. This enhancer provides a potent tool for the manipulation of haematopoiesis and vasculogenesis in vivo.
Animals↗
Error estimates in novice and expert raters for the KT-1000 arthrometer.
STUDY DESIGN: Single group repeated measures with multiple raters. OBJECTIVES: To determine the inter-rater reliability of KT-1000 measurements of novice and experienced raters and to provide error estimates for these raters. BACKGROUND: The KT-1000 arthrometer is often used clinically to quantify anterior tibial displacement. Few data have been documented, however, about the relative reliability of KT-1000 measurements obtained by novice compared with experienced users. METHODS AND MEASURES: Two novice and two experienced KT-1000 users performed measurements on 29 knees of 25 patients after anterior cruciate ligament (ACL) reconstruction or with a diagnosis of ACL deficiency. Measurements were performed at 131 N. Interrater and intertrial reliability coefficients (interclass correlation coefficient; ICC) and the standard error of measurement were calculated for expert and novice raters. RESULTS: The interrater ICC for novices was 0.65 and the interrate error was +/- 3.52 mm (90% confidence interval [CI]). The interrater ICC for experts was 0.79 and the interrater error was +/- 2.94 mm (90% CI). CONCLUSIONS: These results suggest that experience in using the KT-1000 is related to the interrater error of measurements and that training is an important consideration when using the KT-1000 arthrometer.
Adolescent↗
Confocal laser scanning microscopy of apoptosis in organogenesis-stage mouse embryos.
Confocal laser scanning microscopy combined with a vital stain has been used to study apoptosis in organogenesis-stage mouse embryos. In order to achieve optical sectioning through embryos, it was necessary to use low power objectives and to prepare the sample appropriately. Mouse embryos were harvested on gestation day 8 or 9 and stained with the vital lysosomal dye, LysoTracker Red. Following incubation in the stain, embryos were fixed in 2% paraformaldehyde overnight, dehydrated in a graded methanol series, and cleared in benzyl alcohol/benzyl benzoate. The resulting embryo is almost transparent and retains specific LysoTracker Red staining. The entire embryo can be optically sectioned and reconstructed in three dimensions to reveal areas of dye staining. To test this approach, the chemotherapeutic drug hydroxyurea was added to day 8 embryos in vitro to induce apoptosis. Our results demonstrated specific regions undergoing programmed cell death in normal development and increased apoptosis in embryos exposed to hydroxyurea. The observed patterns of LysoTracker Red staining correlate well with previous studies of cell death using other lysosomotropic dyes such as Nile blue sulfate, acridine orange, or neutral red. LysoTracker Red has the advantages of being aldehyde-fixable and highly fluorescent (bleaching was not observed even after multiple scans). This procedure allows for the optical imaging of whole day 9 (approximately 22 somites) embryos that were greater than 500 microns thick in the Z-axis.
Animals↗
Effect of immunosuppression after cardiac transplantation in early childhood on antibody response to polysaccharide antigen.
BACKGROUND: Three children who had cardiac transplantation before age 4 years later presented with recurrent sinopulmonary infection caused by organisms including Streptococcus pneumoniae, in which capsular polysaccharide plays an important part, one developed bronchiectasis. We therefore studied responses to polysaccharide antigen after immunosuppression started in early childhood. METHODS: Antibodies against pneumococcal and haemophilus polysaccharides, and total IgG, IgG1, IgG2, and IgA concentrations were measured in 33 cardiac-transplant recipients transplanted before the age 4 years (group 1) and after that age (group 2). Patients with low pneumococcal and haemophilus antibody concentrations were immunised with 23 polyvalent pneumococcal and tetanus-haemophilus conjugate vaccines and antibody responses were measured. FINDINGS: Five patients from group 1 and seven from group 2 were transplanted for congenital heart disease and ten patients in each group had heart transplants because of cardiomyopathy; none were asplenic. Group 1 (16 patients) were aged 2-10 years when investigated, group 2 (17 patients), were 6-16 years. Four of 16 patients in group 1 responded to pneumococcal polysaccharide vaccine compared with 14 of 17 in group 2 (p=0.0016). This difference remained when those in group 1, aged less than 4 years at investigation, were excluded (p=0.0060). Response to haemophilus-conjugate vaccine was similar in both groups (14 of 16 vs 14 of 17, p=1.0). Significantly more patients who failed to respond to pneumococcal vaccine had low IgG2 concentrations (p=0.0269). INTERPRETATION: Children who had a transplantation and immunosuppression in early childhood before they had developed antibody responses to pneumococcal polysaccharide, still failed to show a response when older-ie, when such responses are the norm. Ongoing immunosuppression prevents the maturation of antipolysaccharide responses leaving children susceptible to severe and recurrent damaging infection.
Aging↗
Working in management. Doctors do better financially than managers do.
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Humans↗
IT update/patient information. Fountain of knowledge.
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Computer Communication Networks↗
Inhibition of Fcgamma receptor-mediated phagocytosis by a nonphagocytic Fcgamma receptor.
There are three major classes of human Fcgamma receptors (FcgammaRI, FcgammaRII, and FcgammaRIII) and various isoforms of each class are capable of mediating phagocytosis. FcgammaRIIA is an unusual Fcgamma receptor in that it transmits a phagocytic signal in the absence of an additional receptor subunit. The cytoplasmic domain of FcgammaRIIA contains a conserved motif containing two copies of the sequence YXXL. The tyrosines (Y) within the motif are phosphorylated after receptor crosslinking and the integrity of these conserved sequences is required for efficient phagocytosis. The FcgammaRIIB receptors, FcgammaRIIB1 and FcgammaRIIB2, contain one copy of the cytoplasmic YXXL sequence and do not transmit a phagocytic signal. In B cells, FcgammaRIIB negatively regulates B-cell activation by the B-cell antigen receptor. Human macrophages express both FcgammaRIIA and FcgammaRIIB and while FcgammaRIIA mediates phagocytosis, the function of FcgammaRIIB in these cells is unknown. Using the epithelial/fibroblast-like cell line COS-1 as a model to examine the molecular events that regulate the phagocytosis of IgG-coated cells (EA), we investigated the effect of FcgammaRIIB on FcgammaRIIA signaling. FcgammaRIIB inhibited phagocytosis mediated both by FcgammaRIIA and by a chimeric FcgammaRIIA receptor containing the extracellular domain of FcgammaRI and the transmembrane and cytoplasmic domains of FcgammaRIIA. This inhibition occurred at an early signaling stage because tyrosine phosphorylation of the FcgammaRIIA cytoplasmic domain was inhibited after concurrent stimulation of these receptors with EA. FcgammaRIIB mutations showed the importance of the FcgammaRIIB YXXL for inhibition of FcgammaRIIA-mediated phagocytosis. Deletion of the FcgammaRIIB YXXL or conservative replacement of the YXXL tyrosine substantially reduced the inhibitory signal. FcgammaRIIB had a lesser inhibitory effect on phagocytosis by the Fcgamma receptor FcgammaRIIIA, which requires a gamma subunit to mediate a phagocytic signal. These results show that FcgammaRIIB negatively regulates phagocytic signaling by FcgammaRIIA and suggests that FcgammaRIIB plays a role in modulating FcgammaRIIA function in vivo.
Amino Acid Sequence↗
Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis.
The genus Scedosporium contains two medically significant species of emerging mycotic agents, S. apiospermum and S. prolificans, which have received scant attention. Scedosporium apiospermum is the anamorph, or asexual state, of the cosmopolitan fungus Pseudallescheria boydii, with both sharing the same risk factors for infection, clinical spectrum, and histopathologic features. Scedosporium prolificans is a recently recognized agent of bone, soft tissue, and joint infections that occurs with highest frequency in children and young adults. S. prolificans may also cause potentially fatal disseminated infections in immunocompromised persons. The drug sensitivities of both Scedosporium species are significantly different from those of most other fungi, and thus identification of these organisms is important. Unfortunately, the pathological features of Scedosporium infections may be easily confused with other mycotic agents, resulting in delayed or inappropriate medical therapy. Because many pathologists and clinicians are unfamiliar with the significance of Scedosporium spp. infection, this communication describes three persons with differing clinical and pathological presentations of S. apiospermum infection. In one patient with sickle cell disease and chronic mycotic sinusitis, fungal colonies of S. apiospermum removed from the sinuses showed a pattern of alternating zones of mycelial hypercellularity and hypocellularity associated with conidiation, similar to a previous report of P. boydii infection. The clinicopathologic features of an immunocompetent person with S. apiospermum osteomyelitis, and a patient with S. apiospermum infection of the brain after bone marrow transplantation, are also described.
Adult↗