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Biomedical subjects

T Marshall

Publications and source records attributed to T Marshall.

At least 109 records · Page 6Linked to original sources
PubMed1997

Validation of the heat treatment step used in the production of diaspirin crosslinked hemoglobin (DCLHb) for viral inactivation--effect of crosslinking.

Two experiments were performed to assess viral inactivation during the crosslinking and heat treatment steps of the DCLHb manufacturing process. Stroma free hemoglobin (SFHb) collected from a large scale manufacturing lot was tested in a 1:680 scaled down system in which the key parameters used in the manufacturing process were replicated. In the first study Porcine Parvovirus (PPV), a non-enveloped virus, was used to assess inactivation, while in the second study Bovine Viral Diarrhea Virus (BVDV), an enveloped virus, was utilized. In both experiments, the SFHb solution was deoxygenated and an aliquot of virus suspension was added. To initiate the crosslinking reaction, a solution of bis (3,5-dibromosalicyl) fumarate (DBBF) in HEPES buffer was added to the test solution. In both experiments the reaction times and the degree of crosslinking were normal. After crosslinking, the reaction mixtures were heated to 74 +/- 1 degrees C over 30 minutes, held at 74 +/- 1 degrees C for 90 minutes, and cooled to less than 10 degrees C over 30 minutes. In each experiment the degree of crosslinking of final product was 100% and yield of hemoglobin recovery was normal. Samples were removed prior to crosslinking, after crosslinking and before, during and after heat treatment for determination of virus titer and evaluation of key process parameters. The results from these experiments were consistent with those obtained from the full scale manufacturing process for the deoxygenation, crosslinking and the heat treatment step during the production of DCLHb. The results of virus assays showed that crosslinking has no effect on viruses and their subsequent inactivation by heat treatment.

Animals↗
PubMed1997

Contraceptive choice and reproductive morbidity in Istanbul.

A cross-sectional survey was conducted in Istanbul to investigate the relationship between contraceptive choice and reproductive morbidity. Altogether, 918 women who had ever used any means of avoiding pregnancy were interviewed at home, and, among these, 694 parous nonpregnant women were examined by three female physicians. The women were aware of bearing a considerable burden of ill health, with 81 percent reporting at least one episode of illness in the three months prior to the interview. Current users of the intrauterine device were significantly more likely than users of other methods to report menstrual disorders, but pelvic relaxation and reproductive and urinary tract infections, whether perceived or diagnosed, were not significantly related to any of the contraceptive methods. The relatively small amount of switching between methods suggests that most users tended to stay with the same method once chosen and that health concerns played an important part only in the initial choice of the method.

Adolescent↗
PubMed1996

Translocation of cytosolic phospholipase A2 to the nuclear envelope elicits topographically localized phospholipid hydrolysis.

Cytosolic phospholipase A2 (cPLA2) is a good candidate for mediating the agonist-stimulated release of arachidonic acid (AA) from membrane phospholipids. This enzyme undergoes a Ca(2+)-dependent translocation from the cytosol to a membrane site in a variety of cell types, and this site has recently been identified as the nuclear envelope in leucocytes. The functional correlate of this finding has not yet been established. The present study was therefore undertaken to determine whether translocation of cPLA2 to the nuclear envelope was associated with localized phospholipid hydrolysis at this site. Rat alveolar epithelial cells, previously shown to contain cPLA2, were prelabelled with [3H]AA and stimulated with the model agonist, ionophore A23187. Ionophore-induced AA release exhibited characteristics typical of a cPLA2-mediated response, in that it was Ca(2+)-dependent, sn-2 AA-selective, and inhibited by arachidonyl trifluoromethyl ketone. As determined by indirect immunofluorescence microscopic analysis as well as subcellular fractionation with immunoblotting, ionophore treatment resulted in a translocation of cPLA2 protein from the cytoplasm to the nuclear envelope. To determine whether the nuclear membrane was indeed the source of released AA, prelabelled cells were incubated in the presence or absence of A23187, after which the phospholipid radioactivity was quantified in nuclear and non-nuclear membrane fractions. [3H]AA was distributed in both nuclear and non-nuclear membrane phospholipids. Following A23187 stimulation, the loss of [3H]AA from nuclear membrane phospholipids accounted for 88.1 +/- 5.8% of the total loss from phospholipids and for 92.9 +/- 2.3% of the total [3H]AA released into the medium. These results demonstrate for the first time that agonist-stimulated translocation of cPLA2 to the nuclear envelope is associated with phospholipid hydrolysis which is preferentially localized to that site.

Animals↗
PubMed1996

Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass.

OBJECTIVE: To examine the relationship between gastric intramucosal pH, intestinal permeability, endotoxemia, and oxygen delivery in patients undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Tertiary care center. PATIENTS: Fifty patients undergoing elective cardiac surgery and 10 patients awaiting elective cardiac surgery. INTERVENTIONS: Patients received chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) as a marker of intestinal permeability; insertion of a nasogastric tonometer to measure intramucosal pH (pHi); insertion of a pulmonary artery catheter to measure systemic oxygen delivery and consumption variables; arterial blood sampling for plasma endotoxin by the Limulus amebocyte lysate assay; and blood and urine sampling for measurement of 51Cr-EDTA. MAIN OUTCOME MEASURES: Systemic oxygen delivery, duration of gastric mucosal acidosis, absorption of 51Cr-EDTA, appearance of systemic endotoxemia, renal dysfunction, and duration of hospital stay. RESULTS: Median (range) 24-hour urinary recovery of 51Cr-EDTA in patients was 10.6% (2.1% to 40.2%) while that in controls was 1.2% (0.7% to 2.0%, P<.001). Intestinal permeability increased during CPB. The median (range) for the lowest pHi after bypass was 6.98 (6.74 to 7.17). The pHi did not decline until CPB was discontinued and the heart took over the load of the circulation. Endotoxin was detectable (>0.2 endotoxin unit per milliliter) in the plasma of 21 patients (42%) during the study, most of whom were endotoxemic by the end of CPB. There was no evident relationship between the degree of gut permeability, endotoxemia, gut ischemia, or systemic oxygen dynamics. CONCLUSIONS: Cardiopulmonary bypass is associated with increases in gut permeability, which precede gut mucosal ischemia. In cardiac surgical patients, a low pHi is not necessarily indicative of an adverse clinical outcome. Endotoxemia as measured by the Limulus amebocyte lysate assay is common. The increased intestinal absorption of 51Cr-EDTA and gastric mucosal acidosis occur as independent phenomena and are not related in severity or time of onset.

Acidosis↗
PubMed1996

Two-dimensional electrophoresis of human urinary proteins following concentration by dye precipitation.

The use of dye precipitation for concentration of proteins prior to 2-DE has been demonstrated by application to human urine. The precipitation methods (T. Marshall and K. M. Williams, Clin. Chem. 1993, 39, 2314-2318; T. Marshall et al., Electrophoresis 1995, 16, 28-31) have been adapted for two-dimensional electrophoresis (2-DE) by modifying the reagent composition and adding sodium dodecyl sulphate (SDS) to the assay mixture. These modifications extend the precipitation range of the methods and overcome the problem of soluble glycoprotein-dye complexes. The protein-dye complex is recovered by centrifugation and dissolved in a small volume of sample denaturing buffer. The dye separates from the protein on 2-DE (forming a sharp band at the anodal end of the isoelectric focusing gel) so that the positional coordinates of the polypeptides are unaffected by the treatment. Dye precipitation provides a simple, rapid and highly economic method for concentrating urines of low to intermediate protein content (0.02-0.50 g/L) prior to 2-DE analysis.

Animals↗
PubMed1996

Electrophoretic analysis of rat parotid salivary protein composition: investigation of the parasympathetic atropine-resistant secretion.

Rats pretreated with atropine and adrenoceptor antagonists show secretion of saliva upon electrical stimulation of the parasympathetic nerve of the parotid gland. The protein composition of this secretion has been analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and compared with the protein profiles obtained with secretions evoked by parasympathetic stimulation (in the absence of atropine) or infusion of bethanechol with or without vasoactive intestinal peptide (VIP, a probable transmitter conveying parasympathetic secretory impulses). The SDS-PAGE patterns were highly reproducible for an individual rat although minor differences were detected between different rats. The method requires only microlitre volumes of unconcentrated rat saliva and thus is ideal for monitoring sequential aliquots collected from the same rat. The SDS-PAGE patterns indicated (i) little change in the protein profile during prolonged stimulation, (ii) a similar profile with parasympathetic stimulation or infusion of bethanechol, and (iii) a quantitative, rather than qualitative, response to administration of atropine (during parasympathetic stimulation) or VIP (during bethanechol infusion). Thus, the salivary protein composition associated with non-adrenergic, non-cholinergic (NANC) secretion appears similar to that evoked in response to parasympathetic nerve stimulation in the absence of muscarinic receptor blockade.

Animals↗
PubMed1996

Assessing fluoride concentrations of juices and juice-flavored drinks.

Few studies have investigated fluoride exposures from juices and juice-flavored drinks manufactured with water. In this study, the authors analyzed 532 juices and juice drinks for fluoride. Fluoride ion concentrations ranged from 0.02 to 2.80 parts per million, in part because of variations in fluoride concentrations of water used in production. Children's ingestion of fluoride from juices and juice-flavored drinks can be substantial and a factor in the development of fluorosis.

Beverages↗
PubMed1995

Protein concentration by precipitation with pyrogallol red prior to electrophoresis.

The pyrogallol red protein assay (Clinical Chemistry 1986, 32, 1551-1554) is based upon formation of a blue protein-dye complex in the presence of molybdate under acidic conditions. However, centrifugation of the assay mixture results in loss of color yield and precipitation of the protein-dye complex which can be recovered and resolubilized to achieve protein concentration prior to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The method has been evaluated relative to trichloroacetic acid (TCA) precipitation for recovery and electrophoresis of commercial protein and peptide molecular weight markers. Precipitation with pyrogallol red-molybdate (PRM) gives better and more uniform recovery of both proteins and peptides as compared to TCA. The lower limit of PRM precipitation is similar to TCA and corresponds to 1 microgram protein per mL assay mixture. This is equivalent to 100 microL of 10 micrograms/mL protein using the standard protein assay or 1 microgram/mL protein using a modified assay incorporating a fivefold concentrate of the dye reagent. Application of the method is demonstrated by concentration of urinary proteins. The method is simple and economic and useful for conserving trace amounts of precious sample as it allows recovery of protein for electrophoresis following protein assay.

Chemical Precipitation↗
PubMed1995

Determinants of nutritional status in south-west Uganda.

In a cross-sectional survey carried out of 4320 children 0-59 months old in South-west Uganda various socio-economic and environmental factors were related to poor nutritional status. Diarrhoea was strongly associated with all the anthropometric parameters examined, suggesting a bidirectional influence of diarrhoea on malnutrition and of malnutrition on diarrhoea. The other most important variables independently associated with one or more anthropometric parameters were: distance from a health unit, living in a household not able to hire labour, and whose members worked on other people's land, religion, parental education, crowding conditions, sanitation, acreage, ownership of cow, father's occupation, birth order, ethnicity, and prolonged breastfeeding. This data indicates that a range of specific interventions are likely to be necessary for the improvement of nutrition in this community.

Anthropometry↗
PubMed1995

Is an intercalated BSc degree associated with higher marks in examinations during the clinical years?

Do medical students taking an intercalated BSc degree obtain higher marks during their subsequent clinical examination? Fourteen students who did a BSc during the academic year 1988-89 were matched, by sex and preclinical grades, with students in the year they left, and with students in the year they subsequently joined. Marks or grades in 10 subsequent examinations were compared. Seven of 10 comparisons with the year the BSc students left were to the advantage of the intercalated students, and two comparisons were statistically significant. Seven of 10 comparisons with the year the BSc students subsequently joined were to the advantage of the non-intercalating students, though none reached statistical significance. No consistent short-term academic advantages arising from having done a BSc could be found. We suggest the study be replicated in other medical schools with different course examination structures.

Adult↗
PubMed1995

The annual reports of Local Research Ethics Committees.

Each Local Research Ethics Committee (LREC) is expected to produce an annual report for its establishing authority. Reports from 145 LRECs were examined with regard to (a) whether the committees were working within the terms of the most recent guidelines from the Department of Health and (b) observations on the role of LRECs with particular reference to accountability. Most LRECs had produced a report, although their length varied greatly. Most reports showed how seriously the committee took its task. Most committees met many of the guidelines; for example, almost all had two or more lay-members. The guideline most frequently not met was that committees should have no more than 12 members. Many committees review very large numbers of projects (maximum 351). Approximately two-thirds provide details in the annual report of individual project titles, their author and the committee decision; all reports should contain this information. Although it may in fact happen more generally, only 23 per cent of the reports referred to any form of monitoring of the eventual outcome of the research. A significant issue to arise from the reports is the extent to which the framework for the operation of LRECs has been confused by the development of the purchaser-provider split. The paper concludes with suggestions for remedying the situation.

Annual Reports as Topic↗