Right-eye transient blindness.
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Angiography↗
Biomedical subjects
D Collins
Publications and source records attributed to D Collins.
HIV testing of great value to the ESRD patient.
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AIDS Serodiagnosis↗
The effect of in vitro aging on human lung fibroblast beta-adrenergic receptor density, coupling and response.
Age-related changes in regulation of receptor response have been observed in several tissues and include regulation of beta-adrenergic receptor (beta-receptor) responses. The role of cellular aging in age-related changes in receptor response is not clear. We have examined the effect of aging in vitro on human fibroblast beta-receptor function. MRC-5 (embryonic lung) fibroblasts were aged by replication to produce cells of early, middle and late stages corresponding to the following cumulative population doublings: 15-20, 35-45 and greater than 50, respectively. Fibroblast membrane beta-receptor responses to isoproterenol (ISO, 0.1 mM) did not differ between the three stages. Adenylate cyclase responses to prostaglandin E1 (PGE1, 1 microM), guanosine triphosphate (GTP, 0.1 mM) and 5'-guanylimidodiphosphate (Gpp(NH)p, 0.1 mM) were also similar between the stages. Beta-receptor density (Bmax) was unaffected by in vitro aging. Beta-receptor agonist affinity, an indication of the capacity for beta-receptor coupling to the nucleotide binding protein (NS), was also unaffected by cell aging. These findings suggest that cellular aging in fibroblasts alone is not accompanied by changes in beta-receptor function.
Adenylyl Cyclases↗
Processing of liposome-encapsulated antigens targeted to specific subcellular compartments.
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Animals↗
Edge displacement and deformation of glenoid components in response to eccentric loading. The effect of preparation of the glenoid bone.
The effect of different methods of preparation of glenoid bone on displacement and deformation of a glenoid component under eccentric loading was investigated in a series of scapulae of cadavera. Handburring of the osseous surface was associated with less displacement and deformation than simple removal of cartilage with a curet. Reaming resulted in the least displacement and deformation. Substantial posterior deficiency of the bone of the reamed glenoid was not associated with significant increases of displacement and deformation.
Biomechanical Phenomena↗
An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis.
Sixteen autopsies were performed on patients aged 56 +/- 15 (SD) years who were on continuous ambulatory peritoneal dialysis (CAPD) for 834 +/- 766 (SD) days. Lactate-buffered dialysate and povidone-iodine antiseptic were used in all cases. Multiple peritoneal sections were taken to evaluate peritoneal membrane thickening, inflammation, neovascularization, fibrosis, and adhesions. Peritoneal thickening, inflammation, or adhesions were not related to sex, race, or etiology of renal failure. Time on dialysis was also not a direct determinant of peritoneal adhesions or neovascularization. Peritonitis episodes correlated with chronic peritoneal serosal changes. This study supports the hypothesis that peritoneal alterations in patients on CAPD are related to episodes of peritonitis.
Adult↗
Cerebral activity prior to motion task performance: an electroencephalographic study.
Cerebral activity, as reflected by power in the alpha waveband (8-13 Hz), was examined prior to the performance of three tasks with different effort and accuracy requirements. The study aimed to further investigate changes in activity observed in an earlier study in which expert karate performers exhibited significant increases in alpha band power during preparation for a training task. In contrast to the earlier research, the high effort task produced a significant decrease in 'alpha' power prior to performance. 'Alpha' power prior to the high accuracy task showed significant differences mediated by the outcome. Successful performance was preceded by higher levels of 'alpha' power than unsuccessful attempts. The reported use of a cognitive strategy on the first task produced a significant difference in activity, lower alpha power being associated with the use of such a technique.
Attention↗
Effects of a school-based alcohol education program with a media prevention component.
The effects of an alcohol education presentation with a media component of public service announcements were evaluated. The presentation was conducted over three (consecutive) days with 10th and 11th grade students in a rural area of South Carolina. The professionally produced announcements focused on drinking and driving. 52 subjects were assigned by classroom to either of two treatment groups or a control condition. Both treatment groups received the educational presentation but differed in that Group 2 was also exposed to the videotaped announcements. Effects of exposure were evaluated in separate measures of knowledge, attitudes, and alcohol involvement, using a pre-posttest design, with a 1-mo. follow-up. Analysis showed an effect of over-all program on knowledge at follow-up, but none on attitudes or alcohol involvement. These findings and their implications are discussed in the context of previous evaluations of alcohol education programs and media efforts.
Accidents, Traffic↗
Electronic billing: a cost-reduction opportunity.
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Accounts Payable and Receivable↗
Structural and functional comparisons of pH-sensitive liposomes composed of phosphatidylethanolamine and three different diacylsuccinylglycerols.
The titratable, double-chain amphiphiles 1,2-dipalmitoyl-sn-3-succinylglycerol (1,2-DPSG), 1,2-dioleoyl-sn-3-succinylglycerol (1,2-DOSG) and 1,3-dipalmitoylsuccinylglycerol (1,3-DPSG) have been used in combination with phosphatidylethanolamine (PE) to form pH-sensitive liposomes. The effect of the compounds on dielaidoyl PE bilayer stabilization was examined by differential scanning calorimetry. Only 1,2-DPSG showed bilayer stabilization activity; whereas the other two are destabilizers at pH 7.4. All three amphiphiles became strong destabilizers at pH 5.0. The ability of the amphiphiles to stabilize DOPE liposomes was examined by light scattering and calcein entrapment. In general, 1,2-DPSG is the most potent stabilizer of PE bilayers while 1,3-DPSG is the weakest liposome stabilizer. All three compounds can be combined with DOPE to generate liposomes which are stable at neutral and basic pH. At weakly acidic pH, the liposomes are leaky and exhibit extensive lipid mixing, with protons and calcium showing synergistic effects on lipid mixing. DOPE/1,2-DPSG liposomes are stable in human plasma and remain acid-sensitive even after prolonged plasma incubation. Immunoliposomes prepared from either DOPE/1,2-DPSG or DOPE/1,2-DOSG can deliver diphtheria toxin A fragment to the cytoplasm of cultured cells in a process which involves endocytosis of the liposomes. Immunoliposomes prepared with 1,2-DPSG are more effective drug carriers than those prepared with 1,2-DOSG. These results indicate that the bilayer- and, hence the liposome-stabilization activity of the diacylsuccinylglycerol depends on the structure of the compounds. The potential drug delivery activity of the pH-sensitive liposomes composed of these lipids is discussed.
Animals↗
Evolution of the mitochondrial genetic code. III. Reassignment of CUN codons from leucine to threonine during evolution of yeast mitochondria.
Yeast mitochondria use UUR as the sole leucine codons. CUN, universal leucine codons, are read as threonine by aberrant threonine tRNA with anticodon sequence (UAG). The reassignment of CUN codons to threonine during yeast mitochondrial evolution could have proceeded by the disappearance of CUN codons from the reading frames of messenger RNA, through mutation mainly to UUR leucine codons as a result of AT pressure. We suggest that this was accompanied by a loss of leucine-accepting ability of tRNA Leu(UAG). This tRNA could have then acquired threonine-accepting activity through the appearance of an additional threonyl-tRNA synthetase. CUN codons that subsequently appeared from mutations of various other codons would have been translated as threonine. This change in the yeast mitochondrial genetic code is likely to have evolved through a series of nondisruptive nucleotide substitutions that produced no widespread replacement of leucine by threonine in proteins as a consequence.
Adenine↗
Proton and divalent cations induce synergistic but mechanistically different destabilizations of pH-sensitive liposomes composed of dioleoyl phosphatidylethanolamine and oleic acid.
Protons and divalent cations show synergistic effects on the destabilization of liposomes composed of unsaturated phosphatidylethanolamine and oleic acid (Düzgünes et al., Biochemistry (1985) 24, 3091). We have extended these observations and investigated the effects of Ca2+ and Mg2+ on the proton-induced destabilization of dioleoyl phosphatidylethanolamine/oleic acid (DOPE/OA) (4:1 molar ratio) liposomes. Temperature-induced aggregation was measured by 90 degrees light scattering. Lipid mixing was used to monitor vesicle destabilization and freeze-fracture electron microscopy was used to examine the structures formed from DOPE/OA vesicles in the presence of Ca2+ and/or protons. Both Mg2+ and Ca2+ shift the pH required for 50% lipid mixing to higher values. Temperature-induced vesicle aggregation occurs at lower temperatures in the presence of divalent cations and/or protons, indicating that intervesicular repulsions are decreased. Freeze-fracture electron micrographs show that the structures formed from DOPE/OA in the presence of Ca2+ differ significantly from those found in the presence of protons. In general, protons induce the formation of hexagonal phase, while the presence of Ca2+ leads to the formation of extensive regions of lamellar sheets with numerous lipidic particles. The synergistic effect of divalent cations and proton may be important for the maximal biological activity of DOPE/OA liposomes.
Calcium↗
Thromboxane receptor blockade improves cyclosporine nephrotoxicity in rats.
Cyclosporine A (CyA) nephrotoxicity is associated with impaired renal hemodynamic function and increased production of the vasoconstrictor eicosanoid thromboxane A2 (TxA2). In CyA toxic rats, renal dysfunction can be partially reversed by inhibitors of thromboxane synthase. However, interpretation of these results is complicated since inhibition of thromboxane synthase may cause accumulation of prostaglandin endoperoxides that can act as partial agonists at the TxA2 receptor and may blunt the efficacy of treatment. Furthermore, these endoperoxides may be used as substrate for production of vasodilator prostaglandins causing beneficial effects on hemodynamics which are independent of thromboxane inhibition. To more specifically examine the role of TxA2 in CyA toxicity, we investigated the effects of the thromboxane receptor antagonist GR32191 on renal hemodynamics in a rat model of CyA nephrotoxicity. In this model, administration of CyA resulted in a significant decrease in glomerular filtration rate (GFR) (2.85 +/- 0.26 [CyA] vs 6.82 +/- 0.96 ml/min/kg [vehicle]; p less than 0.0005) and renal blood flow (RBF) (21.65 +/- 2.31 [CyA] vs 31.87 +/- 3.60 ml/min/kg [vehicle]; p less than 0.025). Renal vascular resistance (RVR) was significantly higher in rats given CyA compared to animals treated with CyA vehicle (5.32 +/- 0.55 [CyA] vs. 3.54 +/- 0.24 mm Hg/min/ml/kg [vehicle]; p less than 0.05). These renal hemodynamic alterations were associated with a significant increase in urinary excretion of unmetabolized, "native" thromboxane B2 (TxB2) (103 +/- 18 [CyA] vs 60 +/- 16 pg/hour [vehicle]; p less than 0.05). Only minimal histomorphologic changes were apparent by light microscopic examination of kidneys from both CyA and vehicle treated animals. However, with immunoperoxidase staining, a significantly greater number of cells expressing the rat common leukocyte antigen was found in the renal interstitium of rats given CyA. There was no detectable increase in monocytes/macrophages in the kidneys of CyA toxic animals. In rats treated with CyA, intraarterial infusion of GR32191 at maximally tolerated doses significantly increased GFR and RBF, and decreased RVR. Although both RBF and RVR were restored to levels not different from controls, GFR remained significantly reduced following administration of GR32191. These data suggest that the potent vasoconstrictor TxA2 plays an important role in mediating renal dysfunction in CyA nephrotoxicity. However, other factors may be important in producing nephrotoxicity associated with CyA.
Animals↗
Comparison of 5-fluorouracil pharmacokinetics following intraperitoneal and intravenous administration using in vivo 19F magnetic resonance spectroscopy.
Intrahepatic pharmacokinetic studies of 5-Fluorouracil (5 FU) metabolism following intravenous and intraperitoneal administration have been undertaken in four patients using in vivo 19F nuclear magnetic resonance spectroscopy. Following intravenous administration, 5 FU decayed with "half times" ranging from 5 to 17 min. There was considerable variation of 5 FU pharmacokinetics between patients following intraperitoneal administration. Peritoneal contamination by infused 5 FU was considered to be a significant problem in one patient. A technique for providing superficial signal suppression was therefore investigated and its efficacy for excluding signal from the peritoneal space has been demonstrated. Owing to the potential for contamination from peritoneal 5 FU, the accumulation of fluoro-beta-alanine (FBAL) is a more reliable indicator of drug catabolism than the measurement of unlocalized "hepatic" 5 FU. Rapid intrahepatic catabolism of 5 FU to FBAL was demonstrated in all patients. However, there was greater pharmacokinetic variation following intraperitoneal administration than following intravenous administration. Therapeutic implications of intravenous compared with intraperitoneal administration of 5 FU are discussed.
Fluorouracil↗
Maintaining quality patient care while increasing staff safety: AIDS update.
As nurses, our belief is that not enough is known regarding AIDS or the HIV virus that causes it and because of this, concern among health care workers is justified. Prompted by this concern, we developed a protocol that we think will help improve staff safety while maintaining quality patient care. We are sharing our ideas as this concern affects all nephrology personnel. The intention of this article is to enable others in this field to establish a protocol based on their own individual situations and needs.
Acquired Immunodeficiency Syndrome↗
Immunoliposomes with different acid sensitivities as probes for the cellular endocytic pathway.
By combining dioleoylphosphatidylethanolamine (DOPE) with oleic acid (OA), palmitoylhomocysteine (PHC) or dipalmitoylsuccinylglycerol (DPSG) we have prepared pH-sensitive liposomes with different acid sensitivities. DOPE/OA liposomes are the most acid sensitive, while DOPE/DPSG liposomes are the least acid sensitive. Incubation of DOPE/OA liposomes with mouse L929 cells reduces the pH-sensitivity of these liposomes by altering the lipid composition. Using diphtheria toxin fragment A as a marker for cytoplasmic delivery, we find that the delivery kinetics of pH-sensitive immunoliposomes closely correlates with the modified acid sensitivities of the liposomes. Immunoliposomes encounter pH 6-6.2 with a t1/2 of 5-15 min after internalization. By contrast, acidification of the endosomes to pH 5.0 takes longer (t1/2 approximately 25 min). We also used a whole cell null point technique (Yamishiro and Maxfield (1987) J. Cell Biol. 105, 2713-2721) to directly determine the average pH encountered by the endocytosed immunoliposomes. We find that acidification determined by the null point method proceeds less rapidly than that estimated from DTA delivery data. This is likely due to the fact that the measured DTA delivery is done by those liposomes which first arrive at the endosomes with sufficient acidity. Our data suggests that DOPE/PHC immunoliposomes deliver at the early endosome while DOPE/DPSG immunoliposomes deliver at the late endosomes. The DOPE/OA immunoliposomes, with the altered composition and acid sensitivity, deliver with a kinetics intermediate between the other two immunoliposomes. Thus, pH-sensitive liposomes represent useful probes for studying the kinetics of endosome acidification.
Animals↗
Concentration and turnover of estradiol in the rat uterus in vivo.
The concentrations and turnover of estradiol isolated from cytosolic and nuclear fractions of uteri from ovariectomized rats given estradiol, either in single injections or in continuous infusion, were analyzed by gas chromatography-mass spectrometry. The analytical method was validated for different organs and lower limits of analysis were established. After infusion of 20 ng x h-1 for 18-22 h, mean estradiol levels were 2.0-2.4 fmol x mg-1 uterine wet weight in the nuclear fraction, and 1.2-1.5 fmol x mg-1 in the cytosolic fraction. The concentrations were about five times higher after a single injection of one microgram estradiol but the distribution between nuclear and cytosolic fractions was almost the same. The concentrations of estradiol in nuclei from liver and spleen were 50-200 times lower than those in uterus. Taken together with previous knowledge, the results indicate that the distributions of estradiol and its receptor are not the same and that hormone response cannot be predicted from the concentration of receptors alone. The exchange of estradiol molecules in the uterus was followed after a change of the infusion from unlabelled to [11,12,12-2H3]-labelled estradiol, or vice versa. The uterine uptake of estradiol was calculated to be about 0.7 fmol x h-1 x mg-1 uterine wet weight. The half-life time was calculated to be at least 4 h for estradiol molecules isolated from the nuclear fraction and 3 h (significantly shorter) for those isolated from the cytosolic fraction. The results indicate an uptake of 40-90% of all estradiol passing through the uterus in proestrus with only about 10% of available receptors becoming occupied. When the infusion was changed from estradiol to ethynylestradiol, estradiol disappeared from the uterus at the same rate as in the experiments above. Ethynylestradiol was taken up at a rate of about 0.3-0.4 fmol x h-1 x mg-1 tissue. The percentage of total steroid found in the nuclear fraction was higher for ethynylestradiol, about 70%, than for estradiol, about 60%, indicative of a more stable association of receptor to nuclear binding sites when ethynylestradiol is the ligand.
Animals↗
Pancytopenia, rash and fever caused by diethylstilbestrol used for prostate cancer.
Pancytopenia, rash, and fever developed in a 66-year-old man being treated for metastatic prostate cancer with diethylstilbestrol (DES). Only the withdrawal of DES resulted in the prompt resolution of symptoms, signs, and laboratory manifestations. Both immunologic and endocrinologic mechanisms are implicated and must be considered by physicians using DES for the palliative management of prostate cancer.
Adenocarcinoma↗