Physical studies of phospholipids. IV. High resolution nuclear magnetic resonance spectra of phospholipids and related substances.
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Biomedical subjects
Publications and source records attributed to D Chapman.
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On heating pure, fully saturated 2,3-diacyl-DL-phosphatidyl-ethanolamines and 2,3-diacylphosphatidyl-cholines (lecithins) in water to the transition temperature at which large endothermic heat changes occur, they are observed, by light microscopy, to form myelin figures. This result is discussed in terms of the large difference in the transition temperature for "melting" of the hydrocarbon chains of unsaturated and saturated phospholipids and is illustrated by means of differential thermal analysis (D.T.A.) curves. These structures have been examined by electron microscopy after negative staining and after reaction with osmium tetroxide. Typical phospholipid lamella structures are seen in the phosphatidylcholines after negative staining, and in the phosphatidyl-ethanolamines after both negative staining and osmium fixation. The distances across these lamellae have been measured. Some preliminary investigations of the nature of the osmium tetroxide reaction with the phosphatidyl-ethanolamines have been made.
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Lumbar punctures were performed in 40 Gambian children with acute cerebral malaria aged between 18 months and 10 years. The mean opening pressure was elevated in 32 (80%) of the children, but was not significantly different in the 14 fatal cases compared with survivors: 110 (standard deviation 71) versus 131 (58) mm of cerebrospinal fluid respectively. Cerebral perfusion pressures were also similar in the 2 groups: 64 (20) mm Hg versus 64 (11) mm Hg respectively. There was no clear clinical evidence of raised intracranial pressure, and no evidence of deterioration immediately following lumbar puncture. Nevertheless brain swelling, and consequent brain-stem compression, may contribute to a fatal outcome in cerebral malaria--particularly in those children who die from sudden respiratory arrest. A prospective evaluation of osmotic agents in childhood cerebral malaria seems to be justified.
The sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs may cause large discrepancies between the peripheral blood parasite count and the total body parasite burden in falciparum malaria. Despite this, parasitaemia is widely used as an indicator of prognosis and response to treatment. A simple mathematical model describing the changes in circulating and sequestered parasite numbers during acute falciparum malaria is presented. The model uses two parameters only; the standard deviation (SD) of parasite age since merogony (schizogony) as as a measure of synchronicity, and a multiplication factor each 48 h asexual life cycle. The model predicts that during the rising phase of the infection the ratio of circulating to sequestered parasites is dependent largely on the synchronicity of infection rather than multiplication rate, and that in synchronous infections parasitaemias will show considerable fluctuation when the mean stage of parasite development is in the second half of the asexual life cycle. The model fitted well to serial parasite counts from 4 patients with acute uncomplicated falciparum malaria whose infections failed to respond to ciprofloxacin. All four infections were synchronous (SD < or = 4 h), and showed large fluctuations in parasitaemia over short periods related to synchronous sequestration and subsequent reinvasion following merogony. The parasite multiplication rate was determined mainly by the efficiency of merogony or merozoite invasion rather than clearance of circulating parasitized erythrocytes. This suggests that the spleen is relatively inactive during the rising phase of the infection. Quinine treatment did not prevent sequestration but did stop subsequent multiplication.(ABSTRACT TRUNCATED AT 250 WORDS)
Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5-12 years old) with severe malaria. Fifty-three children (46%) had cerebral malaria (coma score < or = 2) and 21 (18%) died. Admission geometric mean venous blood lactate concentrations were almost twice as high in fatal cases as in survivors (7.1 mmol/L vs. 3.6 mmol/L; P < 0.001) and were correlated with levels of tumour necrosis factor (r = 0.42, n = 79; P < 0.0001) and interleukin 1-alpha (r = 0.6, n = 34; P < 0.0001). Admission blood venous glucose concentrations were lower in fatal cases than survivors (3.2 mmol/L, vs. 5.8 mmol/L; P < 0.0001). Treatment with quinine was associated with significantly more episodes of post-admission hypoglycaemia when compared with artemether or chloroquine. After treatment, lactate concentrations fell rapidly in survivors but fell only slightly, or rose, in fatal cases. Plasma cytokine levels fluctuated widely after admission. Sustained hyperlactataemia (raised lactate concentrations, 4 h after admission) proved to be the best overall prognostic indicator of outcome in this series. Lactic acidosis is an important cause of death in severe malaria.
A water-soluble homogeneous catalyst has been applied to the hydrogenation of the double bonds within phospholipid liposomes in water. When the catalyst is added to an aqueous system, containing liposomes of unsaturated phospholipids, it partitions between the water and the liposomes. The structure of the liposomes as indicated by electron microscopy is not affected at low concentrations of the catalyst. The permeability properties of the liposomes are also unaffected. In the presence of hydrogen gas the unsaturated bonds of the lipids are readily hydrogenated. Potential applications of water-soluble homogeneous catalysts using liposome systems are described.
Strategies for the expression of precursors of eukaryotic secreted proteins as part of fused proteins in Escherichia coli have been explored. A fusion protein with beta-galactosidase at the N-terminal end and honeybee prepromelittin at the C-terminal end (beta-gal-pM) was expressed in low amounts as a cleaved polypeptide, from which the promelittin portion had been removed. Inclusion in the induction culture of 10 mM MgCl2 or 8.3% (v/v) ethanol, inhibitors of signal peptidase, gave rise to the full-length beta-gal-pM fusion protein. The results suggest that a soluble recombinant fusion protein with a signal peptide in an internal location 660 residues from the N-terminus is recognized by the E. coli translocation apparatus in the inner membrane and by leader peptidase. High-level production (about 45% of total cellular proteins) of prepromelittin was achieved when it was part of a fusion protein at the C-terminus of a truncated insoluble polypeptide from bacteriophage gene 10. This fusion protein separated into inclusion bodies in an aggregated form. In contrast, attempts to express prepromelittin by itself or at the N-terminal end of a fusion with mouse dihydrofolate reductase (pM-DHFR) proved unsuccessful.
A study designed to examine factors that contribute to effective team functioning in inpatient psychiatric facilities showed that most respondents, who were all members of such teams, agreed that teamwork helped to improve treatment plans for individual clients. Using data from the study, roles that social workers take as team members are examined and important issues about team functioning are raised.
Post-myocardial infarction (MI) remodeling of cardiac myocytes and the myocardial interstitium results in alteration of gross ventricular geometry and ventricular dysfunction. To investigate the mechanisms of the remodeling process of the heart after large MI, the expression of various genes in viable left ventricle and infarct scar tissue were examined at 16 weeks post-MI. Steady-state expression of Na(+)-K+ ATPase alpha-1 and -2, phospholamban (PLB), alpha-myosin heavy chain (alpha-MHC), ryanodine receptor (Rya) and Ca2+ ATPase (Serca2) mRNAs were decreased in the infarct scar vs noninfarcted sham-operated controls (P < 0.05). On the other hand, Gialpha2 and beta-MHC mRNAs were upregulated (P < 0.05, respectively) in the infarct scar whereas Na(+)-K+ ATPase-beta, Na(+)-Ca2+ exchanger and Gs mRNAs were not altered vs control values. In viable left ventricle, the alpha-1 subunit of Na(+)-K+ ATPase, alpha-3, beta-isoforms, Rya, beta-MHC, Gialpha2, Gs and Na(+)-Ca2+ exchanger were significantly elevated while expression of the alpha-2 subunit of Na(+)-K+ ATPase, PLB and Serca2 were significantly decreased compared to controls. Expression of CK2alpha mRNA was elevated in noninfarcted heart (145 +/- 15%) and diminished in the infarct scar (66 +/- 13%) vs controls. Expression of beta-MHC mRNA was elevated in both viable and infarct scar tissues of experimental hearts (140 +/- 31% and 183 +/- 30% vs. controls, respectively). These results suggest that cardiac genes in the infarcted tissue and viable left ventricle following MI are differentially regulated.
The aim of this study was to evaluate a policy of early discharge at 48 hours with suction drains in situ in a cohort of patients undergoing surgery for breast cancer and to compare this with a similar cohort of patients discharged 5 days postoperatively. This was an integrated qualitative/quantitative study using a questionnaire given to both groups providing comparable results by using averages and percentages to describe and synthesize the data. A questionnaire of open and closed questions was given to 19 patients who chose to be discharged at 48 hours with drains in situ, and 16 patients who opted to be discharged at 5 days after drain removal. The study demonstrated that patients regarded early discharge as being safe and were satisfied with their care when they were given a high level of support from hospital and community staff. The results also identified that it was important for patients to make their own decision about either early discharge or standard discharge in order to be satisfied with the outcome of their care.
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A human serum based tumor marker control containing 13 antigen associated with tumors or cancer cell proliferation has been developed for use in quality control of various cancer diagnostic test methodologies. The menu is comprehensive including several new antigens: the Carbohydrate Antigens 125 and 19-9, Tissue Polypeptide Antigen (TPA), Beta-2-microglobulin, as well as some traditional markers; CEA, AFP and PAP. The control is bilevel; Level I representing low values and Level II showing elevated or clinically significant values, designed to control the linear range of the assays. Stability of reconstituted material is 14 days at 2-8 degrees C and 30 days at -20 degrees C. Accelerated stress testing shows that the lyophilized material is stable for 3 years when stored at 2-8 degrees C. Testing was completed using commercially available RIA and IRMA assays. The product contains no azide or other preservatives that may interfere in these immunoassays. This product is designed for use in cancer antigen testing as part of a quality assurance program. This control will effectively assist in evaluating the accuracy and precision of immunoassay methods used in cancer evaluation.
Within 48 hours of variceal hemorrhage, 82 patients were randomly assigned to conventional treatment including balloon tamponade or to conventional treatment supplemented by sclerotherapy. The prerandomization general clinical characteristics of the two groups were similar. Seventy-nine percent of patients were alcoholic and 57% were in Child's class C. In the sclerotherapy group of 44 patients, sclerotherapy was performed twice in 28 patients and thrice in 13 patients over the two weeks of follow-up. The number of patients who rebled was significantly lower in the sclerotherapy group than in the group treated conventionally (23% vs 53%). The number of bleeding episodes also was significantly lower in the sclerotherapy group (15 vs 32). Moreover, blood transfusion requirements were significantly decreased in the sclerotherapy group. This was true even for patients who were bleeding at the time of randomization or who were in Child's class C, but this primarily was because fewer patients who underwent sclerotherapy (10 of 24 vs 18 of 23) required transfusions. Although there was no difference in survival between the two groups, we conclude that sclerotherapy is better than conventional treatment in the acute management of variceal bleeding.