Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 2H-NMR spectra of 50 wt.% aqueous multilamellar dispersions of dipalmitoylphosphatidylcholine (DPPC) containing either selectively deuterated 1-decanol (25 mol%) or [2H17]-1-octanol (25 mol%) have been measured as a function of temperature. Both alkanols are potent anesthetics. A detailed carbon-deuterium bond order parameter profile of 1-decanol in liquid crystalline phospholipid dispersions at 50 degrees C was determined from the quadrupolar splittings of 1-decanols deuterated at eight different positions. A maximum order parameter SCD = 0.20 was obtained for [5,5-2H2]-1-decanol, with labels at both ends of the 1-decanol exhibiting reduced order parameters. Explanations for the reduced order towards the hydroxyl group of 1-decanol are discussed in terms of either increased amplitudes of motion or geometric effects due to hydrogen bonding. By comparing the order parameter profile of sn-2 chain deuterated phosphatidylcholine dispersions containing 25 mol% 1-decanol (J.L. Thewalt, S.R. Wassall, H. Gorrissen and R.J. Cushley, Biochim. Biophys. Acta, 817 (1985) 355) with the profile of deuterated 1-decanol in DPPC, we estimate that decanol is approximately parallel to the C-3 to C-13 region of the phosphatidylcholine's sn-2 chain. Variation of the spectral moments M1 with temperature indicates that both 1-decanol and 1-octanol are sensitive to the packing of the lipid in which they are dissolved. Below the phase transition temperature, the 2H-NMR spectra of either 1-decanol (selectively deuterated) or 1-octanol (perdeuterated) are broad powder patterns, characteristic of axially symmetric rotation about the alcohol's long axis. This is in contrast to the 2H-NMR spectra obtained from deuterated phosphatidylcholine under similar conditions, which implies that the phospholipid acyl chain conformations are more restricted than those of the alcohol at these temperatures. From the M1 behavior of the various alkanol chain segments with temperature, the gel to liquid crystalline phase transition is seen to initiate in the middle of the DPPC/1-alkanol bilayer.
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PMID:A deuterium NMR study of labelled n-alkanol anesthetics in a model membrane. 375 4

Deuterium order parameters have been determined for approximately 5 mol% selectively deuterated palmitic acid incorporated into the outer monolayer of high-density lipoproteins (HDL3). The values are SCD = 0.38 for [2,2-2H2]palmitic acid, 0.38 for [4,4-2H2]palmitic acid, 0.37 for [5,5,6,6-2H4]palmitic acid, 0.23 for [11,11,12,12-2H4]palmitic acid, and 0.05 for [16,16,16-2H3]palmitic acid. Comparison of the acyl chain order parameters in HDL3 with acyl chain order parameters determined recently [Parmar, Y.I., Wassall, S.R., & Cushley, R.J. (1984) J. Am. Chem. Soc. 106, 2434-2435] for approximately 5 mol% deuterated palmitic acid in sonicated unilamellar vesicles, composed of the same ratio of phosphatidylcholine/sphingomyelin (85/15 w/w) found in HDL3, shows that acyl chain order in the HDL3 monolayer is approximately 3-5 times higher than in the vesicle bilayer. The acyl chain order in the lipoprotein monolayer is approximately 1.5-2 times higher than in the bilayer of phosphatidylcholine multilamellar dispersions. Deuterium longitudinal relaxation times have been measured for deuterated palmitic acid in HDL3, and the values T1 approximately 16 ms for C2H2 and 170 ms for C2H3 groups are a factor of more than 2 times smaller than found in phospholipid bilayers.
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PMID:Chain dynamics of selectively deuterated fatty acids in high-density lipoproteins studied by deuterium NMR. 399 64

The effects of 25 mol% incorporation of two anesthetics, 1-octanol and 1-decanol, on a deuterated, saturated phospholipid in 50 wt% aqueous multilamellar dispersions have been studied by 2H-NMR spectroscopy and differential scanning calorimetry (DSC). The phospholipid used is sn-2 substituted '[2H31]-palmitoylphosphatidylcholine' (PC-d31). DSC thermograms demonstrate that PC-d31 has phase behavior qualitatively similar to that of dipalmitoylphosphatidylcholine, with a pretransition at 31 degrees C and a main gel to liquid crystalline transition at 40 degrees C. Analysis of the temperature-dependent 2H-NMR spectra in terms of the first moment, which is extremely sensitive to the phospholipid phase, shows that 1-octanol and 1-decanol depress and broaden the main transition. This is confirmed by DSC, which shows that the pretransition is eliminated by the 1-alkanols. The carbon-deuterium bond order of the phospholipid deuterated acyl chains, in the presence and absence of 1-alkanols, was determined from deuterium quadrupolar splittings. Spectra were analyzed using the depaking technique. A 1-alkanol concentration of 25 mol% had no significant effect on the profile of the carbon-deuterium bond order parameter SCD along the phospholipid acyl chain at 50 degrees C. Thus, it appears that the liquid crystalline phase is able to accommodate large amounts of linear anesthetic molecules without substantial effect on molecular ordering within the membrane bilayer. Preliminary results show that the transverse relaxation rates of the acyl chain segments are significantly decreased by the presence of 1-octanol or 1-decanol.
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PMID:Deuterium NMR study of the effect of n-alkanol anesthetics on a model membrane system. 401 11

Intermediates of pheomelanin in tissue cultured B16 melanoma cells were analyzed by high performance liquid chromatography, and reduced glutathione (GSH), L-dopa, 2-[(L)-S-cysteinyl]-L-dopa (2-SCD) and 5-[(L)-S-cysteinyl]-L-dopa (5-SCD) were quantified. The effects of 4-tertiary butylcatechol (TBC), an antioxidant which causes skin depigmentation, on the levels of the intermediate were then examined. A concentration of 10(-4) M TBC increased the intracellular levels of GSH, 2-SCD and 5-SCD, whereas the L-dopa level was unchanged. The time-course of the increased intermediates corresponded to the elevation of glutathione-metabolizing enzyme activities previously reported by Kawashima et al. [J. invest. Derm. 82, 53 (1984)] in the same cell line exposed to 10(-4) M TBC. The findings establish chemical evidence that TBC stimulates pheomelanogenesis in melanocytes.
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PMID:Stimulation of pheomelanogenesis in cultured B16 melanoma cells by 4-tertiary butylcatechol. 405 96

Seminal fluid parameters of ejaculates collected via intercourse with the use of a new Silastic seminal fluid collection device (SCD; HDC Corporation, Mountain View, CA) and via masturbation were compared. Thirty couples participated in this study. All males produced two specimens within 8 days with exactly 4 days of sexual abstinence each time. Thirteen patients were classified as oligospermic and the remaining 17 as normospermic on the basis of sperm numbers per milliliter. Each male patient subjectively rated (scale, 0 to 10) his sexual stimulation elicited during production of specimens with the use of the two methods. Specimens were evaluated and compared. Significant increases (P less than 0.05) were observed in all parameters observed within each group of patients when the SCD and masturbation methods were compared. The improvements in sperm parameters because of the method of collection were greater (P less than 0.05) in the oligospermic group than in the normospermic group of patients. The results point out that the SCD, as applied in this study, can assist in the improvement of the collected specimens and produce a specimen that closely resembles the ejaculate obtained during intercourse. In addition, the SCD, as shown in this study, can be of greater assistance to male infertility patients with oligospermia and other spermatogenic dysfunctions.
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PMID:Seminal parameters of ejaculates collected from oligospermic and normospermic patients via masturbation and at intercourse with the use of a Silastic seminal fluid collection device. 405 24

We now have a wide variety of potentially very effective means to approach the major health problem of SCD, but each carries its own intrinsic risk of worsening the problem. Consequently, it seems prudent to expend much greater effort in obtaining accurate risk assessment. The data from several investigators suggest that this is a real possibility and not something that must await future development. If we can attain accurate risk assessment, we should expect reduction in the study population size, improvement in the therapeutic risk/benefit to the individual patient who enters the study, and dramatic reduction in study costs, and we can also arrive at a quicker answer to the question of the effectiveness of the means of therapy under investigation. It also appears likely that a more rational and cost-effective approach to the problem of the SCD will be by means of an entire treatment strategy or program of management rather than by a single therapy.
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PMID:Ventricular premature beats, ventricular tachycardia, and sudden cardiac death: identification of patients and drug treatment. 608 36

A multiple-pulse nuclear magnetic resonance technique has been used to measure the order parameter, SFF, at 40 MHz for dimyristoylphosphatidylcholine labeled with a difluoromethylene group at the 4-, 8-, or 12-position of the sn-2-acyl chain dispersed in water in the liquid-crystalline phase. The Carr-Purcell-Meiboom-Gill multiple-pulse sequence can resolve the homonuclear dipolar coupling between the two fluorine nuclei, thus making a direct determination of the order parameter, SFF, for the F-F internuclear vector possible. Other interactions, such as the 19F chemical shift anisotropy, heteronuclear dipolar couplings, and field inhomogeneity, which normally obscure the dipolar splitting, are effectively canceled. The order parameters obtained in this work compare well with those obtained by 19F nuclear magnetic resonance line-shape analysis of the 19F-labeled phospholipids reported in the following paper [Dowd, S. R., Simplaceanu, V., & Ho, C. (1984) Biochemistry (following paper in this issue)] as well as comparable SCD order parameters, determined for the deuterium-carbon internuclear vector of deuterium-labeled phospholipids [Oldfield, E., Meadows, M., Rice, D., & Jacobs, R. (1978) Biochemistry 17, 2727-2740]. The present results clearly show the usefulness of using nuclear magnetic resonance spectroscopy to investigate lipid-lipid and protein-lipid interactions, especially for those systems containing a difluoromethylene group in the acyl chain of a phospholipid molecule.
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PMID:Fluorine-19 nuclear magnetic resonance investigation of fluorine-19-labeled phospholipids. 1. A multiple-pulse study. 652 52

Fluorine-19 nuclear magnetic resonance spectra at 282.4 MHz of dimyristoylphosphatidylcholine specifically labeled with a difluoromethylene group at the 4-, 8-, or 12-position of the sn-2-acyl chain and dispersed in excess water show the characteristic powder-pattern line shapes associated with an anisotropic axially symmetric chemical shift tensor, altered by the presence of the homonuclear dipolar interaction of the fluorine nuclei and of heteronuclear dipolar interactions between fluorine and nearby protons. Values for the anisotropy of the fluorine-19 chemical shift and for the fluorine-fluorine internuclear vector order parameter, SFF, as a function of temperature have been determined for the phospholipid dispersions with and without cholesterol. An increased mobility is evidenced in both cases as the temperature is raised. For the phospholipid dispersions in water, the values of SFF parallel quite well the behavior of the carbon-deuterium internuclear vector order parameter, SCD, as determined by deuterium nuclear magnetic resonance spectroscopy for the same labeled position. The effect of adding cholesterol is seen as a restriction of the chain mobility and the eventual disappearance of the phase transition. These new experiments provide a value of 166 ppm for the anisotropy of the axially symmetric chemical shift tensor of a difluoromethylene group in a phospholipid acyl chain. They also demonstrate the feasibility as well as the advantages of using a difluoromethylene group as a probe for molecular motions in the phospholipid bilayers.
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PMID:Fluorine-19 nuclear magnetic resonance investigation of fluorine-19-labeled phospholipids. 2. A line-shape analysis. 652 53

Thirty-seven patients with SCD were studied: 24 were diagnosed as homozygous Hb S on the basis of their haematological findings, and alpha:non-alpha globin chain ratios were found to be balanced in all. Thirteen patients were thought to have alpha or beta thalassaemia interaction with Hb S on the basis of low MCV and MCH, family history and/or presence of Hb A on electrophoresis. Six of them had abnormal alpha:non-alpha ratio (one had a ratio of 0.72 suggestive of alpha thalassaemia, and five had ratios between 1.4 and 1.9, compatible with beta thalassaemia interaction). The remaining seven patients with microcytosis had balanced globin chain synthesis and five were found to be iron deficient. Five additional patients (3 with Hb SS and 2 with Hb S/beta thalassaemia) had lower than normal serum ferritin concentration. The analysis of case histories disclosed that peptic ulceration, recurrent epistaxis and multiple pregnancies could account for iron loss in seven patients. These findings indicate that iron deficiency may be common in SCD and should be excluded as a cause of microcytosis. Microcytosis, in the absence of conclusive family studies and/or presence of Hb A on electrophoresis, is an unreliable indicator of alpha or beta thalassaemia interaction with Hb S.
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PMID:Iron deficiency in sickle cell anaemia. 688 17

The most common cause of SCD is coronary heart disease. Epidemiologic and pathologic studies have demonstrated the presence of chronic myocardial damage and extensive multivessel coronary disease as the substrate for SCD in ASHD. Instantaneous coronary death is an electrical event and not the result of acute coronary thrombosis. Patients resuscitated from out-of-hospital cardiac arrest who do not evolve acute myocardial infarction are at a greater risk of subsequent SCD than are infarctive patients. In studies of the posthospital phase of myocardial infarction, there are no predictive clinical variables that distinguish between sudden and non-sudden cardiac death. Current investigations suggest that activation of the sympathetic nervous system and the neurogenic release of catecholamines are important triggering factors in the genesis of arrhythmic SCD. Reduction in the occurrence of SCD will require community (mobile resuscitation units), public health (control of primary risk factors), and physician-initiated (anti-arrhythmic therapy) measures.
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PMID:Prediction and prevention of sudden cardiac death. 699 99


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