Glioblastoma multiforme presenting as bilateral internal auditory canal tumors.
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Biomedical subjects
Publications and source records attributed to B Price.
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The production of the enzyme glucose oxidase by Aspergillus niger is well documented. However, its distribution within the fungal culture is less well defined. Since the enzyme location impacts significantly on enzyme recovery, this study quantifies the enzyme distribution between the extracellular fluid, cell wall, cytoplasm and slime mucilage fractions in an A. niger NRRL-3. The culture was separated into the individual fractions and the glucose oxidase activity was determined in each. The extracellular fluid contained 38% of the total activity. The remaining 62% was associated with the mycelia and was distributed between the cell wall, cytoplasm and slime mucilage in the proportions of 34, 12 and 16%, respectively. Intracellular cytoplasmic and cell wall sites were confirmed using immunocytochemical labelling of the mycelia. In the non-viable cell, the mycelial-associated enzyme was distributed between these sites, whereas in the viable cell, it was predominantly associated with the cell wall. The distribution of the enzyme activity indicates that recovery from the solids would result in a 38% loss, whereas recovery from the extracellular fluid would result in a 62% loss. The results also suggest, however, that this 62% loss could be reduced to around 34% by disintegrating the solids prior to separation due to the contribution of the enzyme in the cytoplasm and slime mucilage. This was confirmed by independently establishing the percentage activity in the liquid and solid portions of a disintegrated culture as 62 and 38%, respectively.
AIM: To explore the relationship between central and peripheral temperature in normal infants after being put down to sleep. METHODS: Overnight shin and rectal temperatures of 21 normal infants were continuously recorded at home for three nights at 2 wk, 6 wk, 3 mo and 5 mo of age. Parents documented the start and end of feed/nappy changes during the night. RESULTS: An initial fall in rectal temperature was recorded on 149 out of 161 nights. This was linearly correlated with a rise in shin temperature for 106/149 (71%) nights (median R2 = 0.95, lower quartile 0.92, upper quartile 0.97). It was not possible to rule out a change in thermal insulation over the shins as a confounding variable in this strong association. However, a similar inverse relationship was seen between shin and rectal temperature during 111 of 121 (92%) feed/nappy changes. CONCLUSION: The fall in rectal temperature after being put down to sleep may be due to redistribution of heat rather than decreased production or heat loss. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work is required to distinguish peripheral temperature changes on falling asleep from those associated with changes in thermal insulation.
The purpose was to explore the relationship between the fall in rectal temperature seen in normal infants after being put down to sleep and the concomitant rise in peripheral shin temperature. In this observational study 21 normal infants had continuous overnight peripheral shin and central rectal temperature recorded, for three nights at 2 weeks, 6 weeks, 3 months and 5 months of age. Parents documented the start and end of feed/nappy changing episodes during the night. All recordings were made in the infants' own home. A strong inverse linear correlation (median r2 = 0.95, lower quartile 0.92, upper quartile 0.97) was seen between rectal temperature and shin temperature on falling to sleep when put down on 106 (65%) of 161 nights. On many other nights a significant nonlinear association was present. It was not possible to exclude the process of being put down to sleep as a confounding variable in this strong association. However, a similar inverse relationship between shin and rectal temperature was seen overnight during 111 of 121 (92%) feed/nappy changing episodes. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work including video recording is required to separate the peripheral and central temperature changes that take place on falling to sleep from those associated with removal of clothing during a nappy change.
Previous research has suggested that serotonin 5-HT(2A) receptors modulate the functioning of the mesocortical dopamine (DA) pathway. However, the specific role of 5-HT(2A) receptors localized within the medial prefrontal cortex (mPFC) is not known. The present study employed in vivo microdialysis to examine the role of this receptor in the modulation of basal and K(+)-stimulated (Ca(2+)-dependent) DA release. The selective 5-HT(2A) antagonist M100,907 was infused directly into the mPFC of conscious rats. This resulted in a concentration-dependent blockade of K(+)-stimulated DA release. Intracortical application of M100,907 also blocked increases in DA release produced by the systemic administration of the 5-HT(2A/2C) agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). These findings demonstrate that local 5-HT(2A) antagonism has an inhibitory effect on stimulated, Ca(2+)-dependent DA release. They suggest that cortical 5-HT(2A) receptors potentiate the phasic release of mesocortical DA.
OBJECTIVE: Partial liquid ventilation with the perfluorochemical, perflubron, has been shown to improve lung mechanics and enhance gas exchange in the treatment of severe acute lung injury. However, the most effective strategy to provide optimal intrapulmonary distribution of perflubron has not been fully accessed. The objective of this study was to examine the effect of body position (supine vs. rotational) and mode of ventilation (conventional mechanical ventilation [CMV] vs. high-frequency oscillatory ventilation [HFOV]) on perflubron distribution and oxygenation improvement. DESIGN: Prospective, randomized, animal trial. SETTING: Research laboratory at a university medical center. SUBJECTS: Twenty healthy piglets (4.5-6.6 kg). INTERVENTIONS: Subjects underwent repetitive saline lavage to achieve a uniform degree of lung injury and then were randomized to either CMV or were converted to HFOV. Within each ventilator group, animals were randomized to supine positioning (S) or rotational positioning with alternation between supine and prone position (R) during incremental dosing of three 5-mL/kg doses of perflubron. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas tensions, hemodynamic variables, and the oxygenation index were recorded after each dose of 5 mL/kg. Lateral cinefluoroscopic images after each dose were digitized for computer analysis of density. A density index was calculated for a 2-cm2 window in three dorsal and three ventral lung regions. Uniformity of distribution was calculated by comparing the mean density among the six regions. Oxygenation improvements were compared between groups. There were no significant differences in hemodynamic variables or gas exchange after lung injury in the four groups. Rotational positioning produced significantly more uniform perflubron distribution during both CMV and HFOV. This effect was independent of the mode of ventilation. The mean ventral density index was affected by rotating position and HFOV mode of ventilation after 10 mL/kg of perflubron, and rotating position was affected only after 15 mL/kg of perflubron. There was a significant reduction in the oxygenation index from baseline to end lavage in both CMV groups, as well as all of the animals that were rotated. CONCLUSION: Perflubron is more uniformly dispersed when dosed in a rotational fashion with alternation between supine and prone position during incremental dosing. This effect is independent of mode of ventilation. There was no relationship between oxygenation improvements and nondependent perflubron distribution. CMV and rotating dosing both led to a significant decrease in the oxygenation index after a 15 mL/kg dose of perflubron. This information has important impact on the future development of dosing strategies and clinical trial design.
OBJECTIVE: To examine dose-response relationships regarding the efficiency of gas exchange and hemodynamic function during high-frequency oscillation and partial liquid ventilation (HFO-PLV) of the perfluorocarbon (PFC)-treated lung in a model of acute lung injury. SETTING: An animal research laboratory in a university medical center. DESIGN: A prospective, randomized study comparing animals receiving varying doses (0, 5, 15, and 20 mL/kg) of perflubron during high-frequency oscillatory ventilation (HFOV) with mean airway pressure (Paw) optimized to achieve a minimal percutaneous oxygen saturation (Spo2). SUBJECTS: Nineteen healthy swine (mean weight 28.9 kg) with saline lavage-induced acute lung injury. METHODS: Animals were treated with repetitive saline lavage to achieve a uniform degree of acute lung injury (Spo2 < or =90% on an Fio2 of 1.0). After lung injury, subjects were converted to HFOV, and lung volume was optimized. HFO-PLV was initiated by instillation of perflubron at a rate of 0.5 mL.kg-1.min-1 to achieve total doses of 5, 15, and 20 mL/kg. After PFC dosing, the only experimental manipulation consisted of adjustment of Paw to achieve an Spo2 of 90% +/- 2% with Fio2 of 0.6. Gas exchange, hemodynamic variables, and pulmonary mechanics data were collected over a 1-hr period. Five control animals were not dosed with perflubron and remained on HFOV for the 1-hr period of data collection. MEASUREMENTS AND MAIN RESULTS: After lung volume recruitment with HFOV, the initiation of HFO-PLV was best tolerated with the two lower doses in our protocol. There were essentially no changes in Paco2 or pH between groups over the dosing interval. After dosing, analysis of variance demonstrated a PFC dose-dependent effect for oxygenation index (p =.01) only; the lowest oxygenation index was found in the 15 mL/kg group (p =.01). In the 15 mL/kg group, the Paw decreased steadily from 20.6 +/- 3.4 cm H2O at the end of dosing to 18.0 +/- 4.9 cm H2O at 60 mins. The Pao2 increased from 113 +/- 51 torr (15.06 +/- 6.79 kPa) to 134 +/- 49 torr (17.86 +/- 6.53 kPa) during this period and was associated with a decreasing oxygenation index (from 11.4 +/- 2.0 to 9.3 +/- 1.5). The cardiac index and pulmonary vascular resistance did not change significantly during the dosing period and were relatively stable after the completion of dosing. CONCLUSIONS: The combination of HFOV and perflubron administration was well tolerated hemodynamically and was not associated with deterioration of gas exchange during dosing. Our data suggest that the optimal dose of perflubron to achieve the lowest oxygenation index during HFO-PLV is between 5 and 15 mL/kg. The combination of HFOV and perflubron administration is a novel strategy in the treatment of acute lung injury that shows some promise and merits additional investigation. We hope in future studies to address the histopathologic effects of varying perflubron doses during HFOV in a long-term study of the lung-protective effects of HFO-PLV.
Pelvic inflammatory disease (PID) is a spectrum of inflammatory disorders of the female genital tract involving at least the endrometrium and may include the fallopian tubes, ovaries, and pelvic cavity. Over 1 million women each year are treated for PID in the United States, and it is one of the most serious infections diagnosed in women due to its sequelae. Women with PID acutely experience pain and are at risk for sepsis; however, the significant increases in ectopic pregnancy and infertility are the most disturbing long-term complications. It most often is initiated with an infection by a sexually transmitted disease, but can also involve a variety of pathogenic aerobes and anaerobes secondarily.
The human neutrophil granule location of precursors of matrix metalloproteinases (MMPs), MMP-8 and -9, has been established, but that of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) has not. In this study, labeling for TIMP-1, pro-MMP-8, pro-MMP-9, and established granule marker proteins reveals that TIMP-1 is mainly located in distinct oval, electron translucent organelles, a little larger than azurophil granules. A lack of labeling for the fluid phase endocytic marker, bovine serum albumin-gold, the lysosome-associated membrane protein markers, and for glycosylphosphatidylinositol-linked proteins, which are enriched in secretory vesicles, indicates the non-endosomal, non-lysosomal, and non-secretory nature of this organelle. Density gradient cofractionation with the least dense, secretory population and some pleomorphism of the organelle suggest it is a "vesicle" rather than a "granule" population. Colocalization with pro-MMP-9 or pro-MMP-8, in minor subpopulations, suggests that TIMP-1 vesicle biogenesis occurs between metamyelocytic and terminal differentiation and before secretory vesicle synthesis. Pulse-chased IgG-coated latex beads and immunolabeling show that specific and azurophil granules fuse with the phagosome whereas TIMP-1 and pro-MMP-9-containing organelles do not. This suggests that these play no role in phagosomal destruction of IgG-opsonized bacteria. Separate localization and colocalization of these proteins may, however, facilitate fine regulation of extracellular proteolysis.
Since problem-based learning is classically associated with campus based, small group learning conducted over protracted periods of time, it should not, in theory, be well suited to the distance learning mode of study. Just how do you write distance learning materials which adequately accommodate the problem-based learning process, and which acknowledge the variety of problems that could be identified for study? This paper critically examines one distance learning initiative designed to test whether problem-based learning may be delivered to student benefit at post-registration, undergraduate nurse programme level.
For terminally ill people who are still active within the community, altered body image can pose significant problems. Patients may have an obvious change in appearance or function, but be unsure how to present a positive image to others. Moreover, lay supporters are often equally unsure how to react to the changed appearance of the dying person. Changes in physical appearance and function associated with disease processes (and sometimes treatment) need to be integrated into the interaction that occurs between patients and lay carers. This is likely to be a difficult matter to facilitate, taxing the ingenuity of the palliative care nurse who hopes to assist the patient in this regard. This article uses a case study from the community-based palliative care setting to introduce steps that nurses and patients might consider as the patient sets out to manage such social encounters.
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A highly sensitive method to detect traces of aldehyde-containing apurinic/apyrimidinic (AP) sites in nucleic acids has been developed. Based on this method, a novel approach to detect DNA base mismatches recognized by the mismatch repair glycosylase MutY is demonstrated. Open chain aldehydes generated in nucleic acids due to spontaneous depurination, DNA damage or base excision of mismatched adenine by MutY are covalently trapped by a new linker molecule [fluorescent aldehyde-reactive probe (FARP), a fluorescein-conjugated hydroxylamine derivative]. DNA containing AP sites is FARP-trapped, biotinylated and immobilized onto neutravidin-coated microplates. The number of FARP-trapped aldehydes is then determined via chemiluminescence using a cooled ICCD camera. AP sites induced in plasmid or genomic calf thymus DNA via mild depurination or by simple incubation at physiological conditions (pH 7, 37 degreesC) presented a linear increase in chemiluminescence signal with time. The procedure developed, from a starting DNA material of approximately 100 ng, allows detection of attomole level (10(-18) mol) AP sites, or 1 AP site/2 x 10(7) bases, and extends by 1-2 orders of magnitude the current limit in AP site detection. In order to detect MutY-recognized mismatches, nucleic acids are first treated with 5 mM hydroxylamine to remove traces of spontaneous aldehydes. Following MutY treatment and FARP-labeling, oligonucleotides engineered to have a centrally located A/G mismatch demonstrate a strong chemiluminescence signal. Similarly, single-stranded M13 DNA that forms mismatches via self-complementation (average of 3 mismatches over 7429 bases) and treated with MutY yields a signal approximately 100-fold above background. No signal was detected when DNA without mismatches was used. The current development allows sensitive, non-isotopic, high throughput screening of diverse nucleic acids for AP sites and mismatches in a microplate-based format.
Streptomyces coelicolor produces four genetically and structurally distinct antibiotics in a growth-phase-dependent manner. S. coelicolor mutants globally deficient in antibiotic production (Abs(-) phenotype) have previously been isolated, and some of these were found to define the absB locus. In this study, we isolated absB-complementing DNA and show that it encodes the S. coelicolor homolog of RNase III (rnc). Several lines of evidence indicate that the absB mutant global defect in antibiotic synthesis is due to a deficiency in RNase III. In marker exchange experiments, the S. coelicolor rnc gene rescued absB mutants, restoring antibiotic production. Sequencing the DNA of absB mutants confirmed that the absB mutations lay in the rnc open reading frame. Constructed disruptions of rnc in both S. coelicolor 1501 and Streptomyces lividans 1326 caused an Abs(-) phenotype. An absB mutation caused accumulation of 30S rRNA precursors, as had previously been reported for E. coli rnc mutants. The absB gene is widely conserved in streptomycetes. We speculate on why an RNase III deficiency could globally affect the synthesis of antibiotics.
The endoderm forms the gut and associated organs, and develops from a layer of cells which emerges during gastrula stages in the vertebrate embryo. In comparison to mesoderm and ectoderm, little is known about the signals which induce the endoderm. The origin of the endoderm is intimately linked with that of mesoderm, both by their position in the embryo, and by the molecules that can induce them. We characterised a gene, zebrafish gata5, which is expressed in the endoderm from blastula stages and show that its transcription is induced by signals originating from the yolk cell. These signals also induce the mesoderm-expressed transcription factor no tail (ntl), whose initial expression coincides with gata5 in the cells closest to the blastoderm margin, then spreads to encompass the germ ring. We have characterised the induction of these genes and show that ectopic expression of activin induces gata5 and ntl in a pattern which mimics the endogenous expression, while expression of a dominant negative activin receptor abolishes ntl and gata5 expression. Injection of RNA encoding a constitutively active activin receptor leads to ectopic expression of gata5 and ntl. gata5 is activated cell-autonomously, whereas ntl is induced in cells distant from those which have received the RNA, showing that although expression of both genes is induced by a TGF-beta signal, expression of ntl then spreads by a relay mechanism. Expression of a fibroblast growth factor (eFGF) or a dominant negatively acting FGF receptor shows that ntl but not gata5 is regulated by FGF signalling, implying that this may be the relay signal leading to the spread of ntl expression. In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5.
Practitioners in mental health care have long utilized the work of Hildegard Peplau, both for nursing discourse and for practice. At a time when the role of theory in practice is once more being debated, and when theories are being applied in new contexts, this paper examines the contribution that Peplau's work may have to offer altered body image nursing care. A case study is used to highlight concepts in practice, the paper examining the ways in which Peplau's Theory of Interpersonal Relations complement the other elements of practice knowledge that the nurse uses to assist patients and lay carers alike.
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Mutations in Ras family members that confer oncogenic potential are frequently observed in specific human cancers. We report that human non-small cell lung cancer (NSCLC) lines that harbor oncogenic mutations in Ki-Ras (H460, A549, H2122) synthesized high levels of prostaglandin E2 (PGE2) compared with NSCLC lacking Ras mutations or non-transformed lung epithelial cells (BEAS-2B). This increased PGE2 production was mediated by constitutively high expression of 85-kDa cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2). The increased expression of cPLA2 protein was mediated through elevated mRNA levels and activation of the cPLA2 promoter. Induction of cPLA2 promoter activity was blocked by expression of dominant-negative forms of Ras. Inhibition of Ras by the farnesyltransferase inhibitor BZA-5B inhibited prostaglandin synthesis in H2122 cells by decreasing expression of both cPLA2 and COX-2. Finally, inhibitors of eicosanoid synthesis blocked anchorage-independent growth of NSCLC lines exhibiting Ki-Ras mutations. These results identify cPLA2 as a novel Ras-inducible regulator of eicosanoid synthesis that participates in cellular transformation.