Search PubMed⌕ Search

Biomedical subjects

M Parsons

Publications and source records attributed to M Parsons.

At least 55 records · Page 3Linked to original sources
PubMed1999

Raspberry leaf and its effect on labour: safety and efficacy.

The purpose of this study was to examine the safety and efficacy of raspberry leaf products consumed by a group of mothers during their pregnancy, by comparison with a group of mothers who did not. A retrospective observational design was used. Subjects were women who birth their babies at Westmead Hospital between January 1998-July 1998. The sample consisted of 108 mothers; 57 (52.8%) consumed raspberry leaf products while 51 (47.2%) were in the control group. The findings suggest that the raspberry leaf herb can be consumed by women during their pregnancy for the purpose for which it is taken, that is, to shorten labour with no identified side effects for the women or their babies. The findings also suggest ingestion of the drug might decrease the likelihood of pre and post-term gestation. An unexpected finding in this study seems to indicate that women who ingest raspberry leaf might be less likely to receive an artificial rupture of their membranes, or require a caesarean section, forceps or vacuum birth than the women in the control group.

Adolescent↗
PubMed1999

Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI.

BACKGROUND AND PURPOSE: Combined echoplanar MRI diffusion-weighted imaging (DWI), perfusion imaging (PI), and magnetic resonance angiography (MRA) can be used to visualize acute brain ischemia and predict lesion evolution and functional outcome. The appearance of a larger lesion by PI than by DWI quantitatively defines a mismatch of potential clinical importance. Qualitative lesion variations exist in the topographic concordance of this mismatch. We examined both the topographic heterogeneity and relative frequency of mismatched patterns in acute stroke using these MRI techniques. METHODS: Acute DWI, PI, and MRA studies of 34 prospectively recruited patients with supratentorial ischemic lesions scanned within 24 hours of stroke onset (range 2.5 to 23.3 hours, 12 patients <6 hours) were analyzed. RESULTS: Ischemic lesions were predominantly in the middle cerebral artery (MCA) territory (94%), with DWI lesions most commonly affecting the insular region. Mismatched patterns with PI lesion larger than DWI lesion occurred in 21 patients (62% overall), in all 4 patients imaged within 3 hours, and in 44% of patients imaged after 18 hours. A patient with a large PI but no DWI lesion and severe clinical deficit at 2.5 hours after stroke onset recovered completely. Regional variations in DWI and PI lesion loci were found, inferring site of proximal MCA occlusion, embolic pathogenesis, and regional arterial reperfusion. CONCLUSIONS: Analysis of the topographic concordance of PI and DWI lesions in acute stroke reveals regional PI lesions without concomitant DWI lesions, which do not necessarily progress to infarction but may suggest stroke pathogenesis and site of current arterial occlusion. Location of DWI lesions may suggest an earlier site of arterial occlusion and regions of maximal perfusion deficit.

Aged↗
PubMed1999

The logic of play in psychoanalysis.

The paper puts forward the idea that play is at work all the time in psychoanalysis. The play element functions continuously to sustain a paradoxical reality where things may be real and not real at the same time. This paradox is what allows the work of psychoanalysis to take place. The concept of play covers different activities with complex interrelations, and general definitions may be misleading. The essential element is the framework that makes the paradoxical reality possible. The logical structure of the play framework is investigated, and the paper clarifies the relations between the play frame, transference and enactment. Play and humour are compared. Spontaneity is the essence of both, and the criterion for analytic validity in both cases is whether they deepen the analytic process. The tragic and ironic aspects of psychoanalysis are related to the intrinsic connection between play and loss. The relation between play and games is discussed. The rule-bound quality of games can block more exploratory kinds of play, but it may be necessary to accept this, in order for analysis to feel safe enough. Clinical material illustrates the importance of the play framework, both in a case marked by prolonged hostile and negative states of mind, and in others where more straightforward playfulness was possible.

Hostility↗
PubMed1999

Performance of a reagent strip device for quantitation of the urine albumin: creatinine ratio in a point of care setting.

AIM: We have evaluated the performance of a reagent strip (Clinitek, Bayer plc, Newbury) incorporating a novel dip and read device for the quantitation of the albumin: creatinine ratio together with their individual concentrations in urine. METHODS: The performance was compared with that of a lateral flow device for the semi-quantitation of albumin (Micral II, Roche Diagnostics, Lewes) and also a laboratory based procedure. The device employs novel methods for both analytes, using a sulphonephthalein dye binding at pH 1.5 for albumin and the peroxidase-like activity of copper creatinine complexes. The color yields of the separate reaction pads are monitored with the Clinitek 50TM bench top urine chemistry analyzer and compared to a pre-programmed calibration algorithm. RESULTS: The imprecision of the device was assessed by observing the discrepancy between duplicates in a total of 144 urine samples collected from patients with diabetes and/or renal disease; there were 10 discrepancies in the case of the albumin estimation (6.9%), 12 in the case of the creatinine estimation (12.5%) and 23 in the case of the albumin: creatinine ratio (16.0%). In the case of the Micral II, where 96 of the urines were analyzed there were 12 discrepancies (12.5%). When considered as a two-class test for albumin with a cut off of 20 mg/L the Clinitek gave a sensitivity of 95.4% with specificity of 78.9% and a positive predictive value of 87.4%. When analyzing four urines (two controls, two patient pools) with replicate analysis on the Clinitek system we found 100% agreement for the albumin estimation, 95% for creatinine and 96.7% for the albumin: creatinine for 60 analysis within a day and 100, 95 and 97.5% on single analyses each day for 20 days for the two urine controls. The discrepant results were always within one color block. When considering the albumin: creatinine ratio with a cut off of < 30 mg/g the Clinitek gave a sensitivity of 76.3% with a specificity of 89.1% and a positive predictive value of 89.7%. CONCLUSION: The Clinitek system provides a reliable means to screen for microalbuminuria with the opportunity of a semi-quantitative assessment when microalbuminuria is found.

Albuminuria↗
PubMed1999

Role clarity, organizational commitment, and job satisfaction during hospital reengineering.

This study investigated the relationships among role conflict, role ambiguity, organizational commitment, and job satisfaction experienced by clinical team members in a hospital undergoing reengineering. The sample consisted of 409 registered nurses (RNs) and 278 non-RNs. Participants who experienced much role conflict and ambiguity exhibited less organizational commitment and job satisfaction. RNs had more role conflict and ambiguity than non-RNs. No significant differences in role conflict and role ambiguity, organizational commitment, and job satisfaction were observed between RNs working on medical-surgical units and those on specialty units. Strategies that reduce role conflict and role ambiguity to increase organizational commitment and job satisfaction are discussed.

Adult↗
PubMed1998

Changes in polysome profiles accompany trypanosome development.

Development of the protozoan pathogen Trypanosoma brucei involves regulated changes in parasite structure, biochemistry, and the cell cycle. The transition of slender blood forms into stumpy bloodforms includes cell cycle arrest and a decrease in protein synthesis. The next stage in the development cycle, the procyclic form, shows increased protein synthesis and proliferates. To address the mechanism of the cyclical changes in protein synthesis, we examined two parameters: polyadenylation of mRNA and ribosome loading. We developed a method for analytical polyribosome analysis in T. brucei which provided excellent results with regard to reproducibility, yield of mRNA densely loaded with ribosomes, and separation of mRNA associated with different numbers of polyribosomes. Use of this technique allowed us to determine that the polysome profiles of the different developmental stages are distinctly different, with higher ribosome loading in the proliferating stages. The lengths of the poly(A) tails on the total population of RNA from the different developmental stages showed no significant variation. These data indicate that changes in polysome loading of mRNAs accompany development, and that they do not reflect bulk changes in polyadenylation. We speculate that developmental changes in translation reflect reduced translational initiation.

Animals↗
PubMed1998

Trypanosoma brucei: molecular cloning and stage-regulated expression of a malate dehydrogenase localized to the mitochondrion.

African trypanosomes exhibit dramatic developmental changes in carbohydrate and energy metabolism, with cytochrome-mediated respiration playing an important role only in the insect stages. The parasites possess three isozymes of malate dehydrogenase, each of which has a different subcellular localization and, likely, a distinct metabolic role. We have cloned and characterized a cDNA encoding one of these malate dehydrogenases. Epitope tagging and transfection experiments demonstrate that the corresponding protein is localized to the mitochondrion and that an intact amino terminus is required for proper compartmentalization. The abundance of transcript is developmentally regulated, with higher levels in procyclic stage parasites.

Amino Acid Sequence↗
PubMed1998

Effect of pregnancy on the metabolic clearance rate and the volume of distribution of oxytocin in the baboon.

Pharmacokinetic parameters of oxytocin (OT) metabolism were determined during the last third of pregnancy and again 4-8 wk after delivery in the baboon. Animals were placed on a tether system with venous and arterial access and a continuous monitoring of uterine contractions during gestation. Two methods of determining OT pharmacokinetics were utilized (bolus injection vs. continuous infusion). The metabolic clearance rate of OT as determined during the bolus trials (n = 7) was 22.2 +/- 1.5 ml.min-1.kg-1 in pregnancy and 16.3 +/- 1.4 ml.min-1.kg-1 postpartum (P < 0.05), respectively, and 23.7 +/- 2.8 vs. 16.9 +/- 3.7 ml.min-1.kg-1 (P < 0.05), respectively, as determined during the 1-h infusion trials (n = 4). The initial dilution volume and the volume of distribution at steady state of OT after administration did not differ between pregnant and postpartum animals (P > 0.05). The mean residence time (MRT) of OT was shorter during pregnancy, 7.7 +/- 0.8 vs. 10.8 +/- 1.2 min postpartum (P < 0.05). In summary, OT metabolism during pregnancy in the baboon is characterized by 1) increased clearance rate (1.4-fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered distribution.

Animals↗
PubMed1998

Immune cells in a mouse airway model of obliterative bronchiolitis.

Obliterative bronchiolitis (OB), a form of chronic lung rejection, affects 50% of all lung-transplant recipients and is a major cause of morbidity and mortality. We used the mouse tracheal allograft model of OB to quantitate inflammatory cells during disease progression to evaluate the pathogenesis of this disorder. Tracheas of BALB/c mice were implanted into C57BL/6, severe combined immunodeficiency (SCID), and BALB/c mice. Cyclosporin was administered at 25 mg/kg/d. Grafts were harvested at 2, 6, 10, and 15 wk, and analyzed immunohistochemically. Tracheal allografts developed epithelial injury and cellular infiltrates at 2 wk, epithelial denudation and complete luminal obliteration at 6 wk, and dense collagenous scarring by 15 wk. SCID allografts and isografts demonstrated intact epithelium throughout, although a mononuclear infiltrate was initially present at 2 wk in the SCID allografts. Immunohistochemical staining, using antibodies to mouse CD4(+) (T-helper lymphocyte), CD8(+) (T-cytotoxic/suppressor lymphocyte), and B lymphocytes, macrophages, and myofibroblasts, revealed large numbers of macrophages and CD4(+) and CD8(+) lymphocytes in allografts at 2 wk, compared with isografts. The allograft CD4(+)/CD8(+) ratio was 0.75 at 2 wk. Allografts demonstrated macrophage, myofibroblast, and CD4(+) predominance at 6 and 10 wk (CD4(+)/CD8(+) = 2/1), but by 15 wk had minimal cellularity and were densely scarred. SCID allografts demonstrated a macrophage-predominant infiltrate at 2 wk, with minimal cellularity at later time points. These results indicate that: (1) OB is predominantly an immunologic airway injury; and (2) CD4(+) and CD8(+) lymphocytes and macrophages play an important role in the evolution of airway inflammation and fibrosis. Additionally, this model suggests that chronic airway fibrosis follows a period of intense airway-directed, cell-mediated rejection.

Animals↗
PubMed1998

Distinct domains of a nucleolar protein mediate protein kinase binding, interaction with nucleic acids and nucleolar localization.

Nopp44/46 is a phosphoprotein of the protozoan parasite Trypanosoma brucei that is localized to the nucleolus. Based on the primary sequence, Nopp44/46 appears to be a protein composed of distinct domains. This communication describes the relationship of these domains to the known functional interactions of the molecule and suggests that the amino-terminal region defines a novel homology region that functions in nucleolar targeting. We have previously shown that Nopp44/46 is capable of interacting with nucleic acids and associating with a protein kinase. Using in vitro transcription and translation, we now demonstrate that the nucleic acid binding function maps to the carboxy-terminal domain of the molecule, a region rich in arginine-glycine-glycine motifs. Our experiments reveal that a central region containing a high proportion of acidic residues is required for association with the protein kinase. Analysis of transfectants expressing epitope-tagged Nopp44/46 deletion constructs showed that the amino-terminal 96 amino acids allowed nuclear and nucleolar accumulation of the protein. This region of the molecule shows homology to several recently described nucleolar proteins. Deletion of a 27-amino-acid region within this domain abrogated nucleolar, but not nuclear, localization. These studies show that Nopp44/46 is composed of distinct modules, each of which plays a different role in molecular interactions. We suggest that this protein could facilitate interactions between sets of nucleolar molecules.

Amino Acid Sequence↗
PubMed1997

TCR engagement of CD4+CD8+ thymocytes in vitro induces early aspects of positive selection, but not apoptosis.

Immature CD4/CD8 double-positive (DP) thymocytes expressing self MHC-restricted TCR are positively selected in response to TCR signals to survive and differentiate into functionally competent CD4 or CD8 single positive (SP) T cells. In contrast, DP precursors expressing autoreactive TCR are clonally deleted in response to TCR signals. We show here that in vitro TCR engagement of TCR(low) DP thymocytes rapidly triggers a variety of events considered to be hallmarks of positive selection in vivo. These include increased expression of CD5 and Bcl-2, termination of RAG-1 and pre-T(alpha) gene expression, and a switch in lck promoter usage. We also demonstrate that CD4- or CD28-mediated signals synergize with TCR signals to induce these outcomes. Finally, we show that the response of DP thymocytes to TCR engagement is selective in that clonal deletion, CD4/CD8 lineage commitment, and other events associated with maturation, such as changes in expression of Thy-1, HSA, MHC class I, and CD45-RB, were not induced. Thus, only subsets of maturational processes associated with positive selection in vivo were shown to be directly coupled to TCR signaling pathways at the DP stage. These observations support conclusions from in vivo systems suggesting that multiple, temporally separated TCR engagements are required to effect the entire spectrum of developmental changes associated with positive selection, and provide a conceptual and experimental framework for unraveling the complexity of positive selection.

Animals↗
PubMed1997

Trypanosoma brucei: identification of an internal region of phosphoglycerate kinase required for targeting to glycosomal microbodies.

Among the microbodies found in eukaryotes are the glycosomes of Trypanosoma brucei, thought to be closely related to peroxisomes. Two types of targeting signals for glycosomes have been identified thus far: type 1 at the C-terminus and type 2 at the N-terminus. In this report, we use an epitope-tagging system to characterize the targeting signal found on the minor glycosomal isozyme of phosphoglycerate kinase, 56PGK. No type 1 or 2 signal was found; rather, the topogenic information was found to be internal. Chimeric molecules formed with the cytoplasmic phosphoglycerate kinase isozyme indicate that a region between amino acids 24 and 91 of 56PGK is essential for glycosomal targeting. No homology was found between this region and peroxisomal proteins containing internal targeting signals.

Amino Acid Sequence↗
PubMed1997

Daily changes in plasma and amniotic fluid prolactin during the last third of pregnancy in the baboon.

Alterations in plasma and amniotic fluid prolactin (PRL) levels have not been previously described in the pregnant baboon. In addition, PRL increases dramatically in response to estrogens and thus might be a good marker for expression of estrogen's biologic action. Therefore, the purpose of this study was to characterize the changes in plasma and amniotic fluid PRL with advancing gestational age and assess whether there was a correlation between plasma estradiol and PRL levels. A tethered pregnant baboon model was utilized for these studies. Blood was collected from five animals every day at 0900-1000 h (AM value) and 1800 h (PM value) from 125 to 135 days of pregnancy until delivery. Amniotic fluid was collected every day in the morning. Samples were analyzed by RIA for PRL, estradiol, and progesterone. PRL did not change with advancing gestational age. However, PRL showed a significant diurnal variation, with the PM values significantly higher (p < 0.05) than the AM values. In contrast to findings for PRL, AM values for estradiol and progesterone were on average higher that PM values (p < 0.05). A significant correlation was observed between the log10 estradiol (AM+PM) and log10 PRL (AM) from the following day (r = 0.52; p < 0.05). Finally, amniotic fluid PRL was present in high concentrations (200-400 ng/ml) but did not vary with gestational age. In conclusion, PRL, estradiol, and progesterone show distinct diurnal variations during the last one-third of pregnancy in the baboon. In addition, plasma PRL is positively correlated with estradiol.

Amniotic Fluid↗
PubMed1997

Functional identification of a Leishmania gene related to the peroxin 2 gene reveals common ancestry of glycosomes and peroxisomes.

Glycosomes are membrane-bounded microbody organelles that compartmentalize glycolysis as well as other important metabolic processes in trypanosomatids. The compartmentalization of these enzymatic reactions is hypothesized to play a crucial role in parasite physiology. Although the metabolic role of glycosomes differs substantially from that of the peroxisomes that are found in other eukaryotes, similarities in signals targeting proteins to these organelles suggest that glycosomes and peroxisomes may have evolved from a common ancestor. To examine this hypothesis, as well as gain insights into the function of the glycosome, we used a positive genetic selection procedure to isolate the first Leishmania mutant (gim1-1 [glycosome import] mutant) with a defect in the import of glycosomal proteins. The mutant retains glycosomes but mislocalizes a subset glycosomal proteins to the cytoplasm. Unexpectedly, the gim1-1 mutant lacks lipid bodies, suggesting a heretofore unknown role of the glycosome. We used genetic approaches to identify a gene, GIM1, that is able to restore import and lipid bodies. A nonsense mutation was found in one allele of this gene in the mutant line. The predicted Gim1 protein is related the peroxin 2 family of integral membrane proteins, which are required for peroxisome biogenesis. The similarities in sequence and function provide strong support for the common origin model of glycosomes and peroxisomes. The novel phenotype of gim1-1 and distinctive role of Leishmania glycosomes suggest that future studies of this system will provide a new perspective on microbody biogenesis and function.

Amino Acid Sequence↗
PubMed1996

Mammalian mitogen-activated protein kinase pathways are regulated through formation of specific kinase-activator complexes.

Mammalian cells contain at least three signaling systems which are structurally related to the mitogen-activated protein kinase (MAPK) pathway. Growth factors acting through Ras primarily stimulate the Raf/MEK/MAPK cascade of protein kinases. In contrast, many stress-related signals such as heat shock, inflammatory cytokines, and hyperosmolarity induce the MEKK/SEK(MKK4)/SAPK(JNK) and/or the MKK3 or MKK6/p38(hog) pathways. Physiological agonists of these pathway types are either qualitatively or quantitatively distinct, suggesting few common proximal signaling elements, although past studies performed in vitro, or in cells using transient over-expression, reveal interaction between the components of all three pathways. These studies suggest a high degree of cross-talk apparently not seen in vivo. We have examined the possible molecular basis of the differing agonist profiles of these three MAPK pathways. We report preferential association between MAP kinases and their activators in eukaryotic cells. Furthermore, using the yeast 2-hybrid system, we show that association between these components can occur independent of additional eukaryotic proteins. We show that SAPK(JNK) or p38(hog) activation is specifically impaired by co-expression of cognate dominant negative MAP kinase kinase mutants, demonstrating functional specificity at this level. Further divergence and insulation of the stress pathways occurs proximal to the MAPK kinases since activation of the MAPK kinase kinase MEKK results in SAPK(JNK) activation but does not cause p38(hog) phosphorylation. Therefore, in intact cells, the three MAPK pathways may be independently regulated and their components show specificity in their interaction with cognate cascade members. The degree of intermolecular specificity suggests that mammalian MAPK signaling pathways may remain distinct without the need for specific scaffolding proteins to sequester components of individual pathways.

Animals↗
PubMed1996

A major tyrosine-phosphorylated protein of Trypanosoma brucei is a nucleolar RNA-binding protein.

We have previously identified a set of tyrosine-phosphorylated proteins with apparent molecular masses of 44-46 kDa as some of the major tyrosine phosphorylated species in the protozoan parasite Trypanosoma brucei. We now show that these molecules, herein named Nopp44/46, are localized in the nucleolus. Using monoclonal antibodies, we have isolated Nopp44/46 cDNA clones from expression libraries. Sequence analysis reveals that the predicted amino acid sequence of the molecule is composed of an N-terminal unique region, an internal acidic region, and C-terminal repeat region. Analysis of the cDNA clones and genomic Southern analysis indicated that Nopp44/46 belongs to a multigene family in which different gene copies are very similar but vary in the number of repeats. Interestingly, the repetitive amino acid sequence motif contains multiple RGG (Arg-Gly-Gly) boxes characteristic of RNA-binding proteins. In vitro binding experiments demonstrated that Nopp44/46 is indeed capable of binding nucleic acids. Competition experiments with different RNA homopolymers demonstrated that Nopp44/46 preferentially binds to poly(U). These studies suggest that Nopp44/46 may play a role in RNA metabolism in trypanosomes and raise the possibility that tyrosine phosphorylation may regulate the process.

Amino Acid Sequence↗