Murray Llewellyn Barr, O.C.,20 June 1908-4 May 1995.
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Biomedical subjects
Publications and source records attributed to P Potter.
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Evidence suggests that peptide loading onto MHC class II molecules occurs in a specialized late endocytic compartment (MIIC) where HLA-DM predominantly resides and in which MHC class II transiently accumulates before transport to the cell surface. We examined the targeting signals and compartments involved in the intracellular trafficking of human HLA-DM by expressing hybrid molecules comprising the cytoplasmic domain of DMB and luminal and transmembrane domains of CD8 in HeLa cells. A tyrosine-based tetrapeptide motif present in the cytoplasmic domain of DMB targeted hybrid molecules to intracellular vesicles. Mutation of the tyrosine residue to alanine resulted in redistribution of hybrid molecules to the cell surface. Correct intracellular targeting of HLA-DM was crucial for normal function in B cells. Immunoelectron microscopy on ultrathin cryosections showed that CD8-DMB molecules accumulated in late endocytic compartments sharing characteristics with lysosomes, like MHC class II compartments in APCs. Thus far, the exit of DMB from the Golgi complex has not been elucidated. Interestingly, we found that although the mannose 6-phosphate receptor and CD8-DMB contain similar tyrosine signals, no co-localization was observed in the trans-Golgi network, suggesting that these proteins are differentially sorted at this site. Co-transfection of CD8-DMB, HLA-DR alpha, HLA-DR beta, and an invariant chain revealed that HLA-DR molecules accumulated together with CD8-DMB in these lysosomal compartments. The similarity of these lysosomal-like compartments in wild-type and transfected cells suggests that they are part of the normal endocytic pathway in non-APCs.
OBJECTIVES: Intraoperative autotransfusion of shed blood is widely utilized in surgery. However, several studies have raised concern about the transmission of tumor cells during oncologic procedures. We compared the ability of a leukocyte depletion filter (RC-400; LDF) to a standard red blood cell filter (SBF) to remove tumor cells derived from urologic malignancies. METHODS: Cells were suspended in media and passed through a SBF or a LDF. The filtrate was evaluated for the presence of viable cells utilizing the trypan blue exclusion method as well as cell culture. In a second experiment, cells were suspended in fresh bovine blood and processed through a cell saver apparatus followed by filtration with either a SBF or a LDF. Aliquots were cultured after admixture with blood, after processing, and after filtration. RESULTS: The LDF was able to remove tumor cells completely, as demonstrated by both counting with the trypan blue exclusion test and by cell culture. In contrast, admixture with blood processing through the cell saver apparatus nor a standard red blood cell filter removed these cells. CONCLUSIONS: Tumor cells derived from urologic malignancies are easily removed with a LDF but not with a SBF. Filtration of blood salvaged at the time of uro-oncologic surgery with a LDF but not with a SBF reduces the potential for reinfusion of viable tumor cells.
To identify modifiable risk factors for wheezing illness in childhood, the associations between current asthma or wheezing and factors such as household smoking, damp and dietary salt preference were measured in a questionnaire-based prevalence study of schoolchildren 7 to 9 yr of age in Cape Town. In a random sample of 15 schools, questionnaires were completed by parents of 1,955 children, from which 368 cases and 294 controls were selected on the basis of reported asthma diagnosis or symptoms. Urinary cotinine concentrations were measured, and the parents were interviewed. An exposure-response relationship between the urinary cotinine creatinine ratio and asthma/wheeze was observed. In multivariate analysis, predictors of asthma/wheeze were hay fever (odds ratio [OR] - 5.30; 95% confidence interval [CI] = 3.16 to 8.89), eczema (OR = 2.19; 95% CI = 1.33-3.62), parental asthma (OR = 1.77; 95% CI = 1.11 to 2.84), absence of paternal contribution to income (OR = 1.72; 95% CI = 1.17 to 2.54), maternal smoking in pregnancy (OR = 1.87; 95% CI = 1.25 to 2.81), and each additional household smoker (OR = 1.15; 95% CI = 1.01 to 1.30). Findings were similar, with higher odds ratios for most variables, except number of household smokers, when the group was restricted to children with parent-reported asthma. The findings confirm that household smoking is an important modifiable risk factor in asthma/wheeze among young schoolchildren, and they suggest that maternal smoking in pregnancy and current household exposure are independent contributors to this effect.
BACKGROUND: Maternal antibodies to RhE may cause severe hemolytic disease. Based on recent RhD and RhCE sequence information, we have developed a DNA-based testing methodology to determine the RhEe genotype of fetuses at risk for RhE hemolytic disease from amniotic fluid (AF) or chorionic villus samples. CASE: RhEe testing was undertaken in a fetus at risk for RhE hemolytic disease. Maternal serum anti-E titers had risen between 12-15 weeks' gestation. Optical density (OD450) AF readings also rose slightly between 22-24 weeks' gestation. Both maternal serum titers and AF bilirubin measurements provided early indications that the fetus might have the RhE antigen. Using amniotic cells obtained at the first amniocentesis, DNA was extracted and analyzed for the RhE gene sequence. The use of two primer pairs from distinct sites in the RhCE gene, plus analysis of parental DNA, greatly minimized the possibility of false results. The fetus was determined to be Rhe/Rhe by molecular analysis. The DNA result was confirmed by serologic typing at birth. CONCLUSION: DNA-based RhEe genotyping of at-risk fetuses provides accurate and timely information that is useful in the management of RhE-sensitized pregnancies.
Three of the most important libraries sold during the first 100 years of English book auctions belonged to doctors. By examining the contents of these sales and the prices achieved in them, I hope to be able to throw some light on the extent and expertise of English book collecting by physicians to discover the principles that governed book values through this period, and to illustrate how three prominent medical men's libraries fitted into the century's wider cultural development.
Reflex sympathetic dystrophy (RSD) is a symptom complex characterized by pain, hyperesthesia, and vasomotor instability. RSD has long been considered a manifestation of sympathetic nervous system dysfunction because of characteristic edema and vasomotor instability in addition to frequent alleviation of RSD symptoms by sympathetic blockade. RSD generally only affects one limb although it is recognized that the contralateral limb is also abnormal and at risk of also developing clinical RSD without the advent of a new injury. An unusual case of three-limb RSD is presented where classical RSD was first seen in the right lower extremity followed by involvement of the left upper extremity and finally the left lower extremity. Each limb went on to develop dystrophic changes. This case underscores the importance of the central nervous system in the pathophysiology of RSD and suggests this central influence is not confined to one or adjacent segments of the spinal cord.
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OBJECTIVE: We attempted to determine the impact of "early" (before delivery of the chest) oronasopharyngeal DeLee suctioning at the perineum in the prevention of meconium aspiration syndrome and to confirm that meconium aspiration syndrome is a postnatal event. STUDY DESIGN: We compared infants with meconium-stained fluid who underwent "early" oronasopharyngeal DeLee suctioning with a similar group of infants whose airways were suctioned "late" (after chest delivery). Practicing obstetricians did not know the study was being conducted by the pediatric staff, and an independent observer documented whether obstetricians performed "early" or "late" oronasopharyngeal DeLee suctioning. Immediate postnatal tracheal suctioning was performed in both groups. The study was conducted in a private tertiary care center averaging 5800 deliveries annually. A consecutive sample of 438 infants with meconium-stained fluid was analyzed. Of these infants, 221 received "early" oronasopharyngeal DeLee suctioning, while 217 infants were suctioned "late". RESULTS: Of the 438 infants with meconium-stained fluid, meconium aspiration syndrome developed in 38 (9%). These infants had higher rates of fetal distress (i.e., abnormal fetal heart rates) and lower Apgar scores (< or = 6) than infants without meconium aspiration syndrome (58% vs 17% and 65% vs 13%, respectively; p < 0.001). Forty-five percent of the infants with meconium aspiration syndrome had renal failure during the first 20 hours of life. In spite of "early" oronasopharyngeal DeLee suctioning, 53% of the infants in this group had meconium below the vocal cords and meconium aspiration syndrome developed in 7%. The time of oronasopharyngeal DeLee suctioning did not affect the rate of meconium aspiration syndrome or the presence of meconium below the vocal cords. CONCLUSIONS: We concluded that "early" oronasopharyngeal DeLee suctioning at the perineum does not affect the rate of meconium aspiration syndrome. We speculate that meconium aspiration syndrome is predominantly an intrauterine event associated with fetal distress and that meconium in the airways is merely a "marker" of previous fetal hypoxia.
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Two sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation.
The immersed clo value of a series of 11 marine work suits has been measured using both humans and a thermal manikin. In still water, there is no significant difference in the measurements. Turbulent water significantly reduces the immersed clo value. The manikin errs on the safe side and consistently overestimates this decrement in insulation, and the reasons for this are discussed. Not intended to replace human physiological testing, the manikin is an excellent apparatus for the examination of conditions not easily or ethically possible to represent using humans. A good fitting suit with efficient neck, wrist and ankle closures which reduce flushing of water is essential to make an effective marine work suit.
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Recognizing that collaboration is essential for the continuing development of the nursing profession, nursing leaders in the St. Louis area organized the Nursing Consortium for Research in Practice, uniting four university schools of nursing and four large hospitals. The aim of consortium is to assist nursing faculty and nursing service personnel in the conduct of collaborative clinical research. The consortium also seeks to educate nurses about research as a component of professional nursing practice and to assist them in implementing research findings in clinical practice. The efforts of the consortium during its first four years are discussed.
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Problems in the literature in the appraisal of brain deep white-matter changes are considered. The identification of the changes with Binswanger's disease alone is rejected, and evidence is reviewed that demonstrates that they are associated with cognitive impairment and, to some extent, with vascular disease. Possible causes of white-matter changes and their relationships to Alzheimer's disease are examined, and it is argued that a neutral term, exact enough to define white-matter changes, sufficient as a description or label, and demanding enough to require precise clinical and imaging descriptions is needed. We suggest herein the term "leuko-araiosis" on the basis of Greek etymology and Hippocratic usage.