A case of refractory idiopathic pure red cell aplasia responsive to fludarabine treatment.
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Female↗
Biomedical subjects
K Lee
Publications and source records attributed to K Lee.
Advancing the science of symptom management.
UNLABELLED: Since the publication of the original Symptom Management Model (Larson et al. 1994), faculty and students at the University of California, San Francisco (UCSF) School of Nursing Centre for System Management have tested this model in research studies and expanded the model through collegial discussions and seminars. AIM: In this paper, we describe the evidence-based revised conceptual model, the three dimensions of the model, and the areas where further research is needed. BACKGROUND/RATIONALE: The experience of symptoms, minor to severe, prompts millions of patients to visit their healthcare providers each year. Symptoms not only create distress, but also disrupt social functioning. The management of symptoms and their resulting outcomes often become the responsibility of the patient and his or her family members. Healthcare providers have difficulty developing symptom management strategies that can be applied across acute and home-care settings because few models of symptom management have been tested empirically. To date, the majority of research on symptoms was directed toward studying a single symptom, such as pain or fatigue, or toward evaluating associated symptoms, such as depression and sleep disturbance. While this approach has advanced our understanding of some symptoms, we offer a generic symptom management model to provide direction for selecting clinical interventions, informing research, and bridging an array of symptoms associated with a variety of diseases and conditions. Finally, a broadly-based symptom management model allows the integration of science from other fields.
Holistic Nursing↗
Modified Hodge and EDTA-disk synergy tests to screen metallo-beta-lactamase-producing strains of Pseudomonas and Acinetobacter species.
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Acinetobacter↗
Intrahepatic amino acid and glucose metabolism in a D-galactosamine-induced rat liver failure model.
A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D-galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid-supplemented Eagle minimal essential medium containing 3% wt/vol bovine serum albumin and oxygenated with 95% O(2)/5% CO(2). Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to alpha-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function.
Amino Acids↗
Neonatal intensive care unit outbreak caused by a strain of Klebsiella oxytoca resistant to aztreonam due to overproduction of chromosomal beta-lactamase.
Klebsiella oxytoca strains resistant to both aztreonam and ceftriaxone were isolated from six neonates in a neonatal intensive care unit and water reservoirs of two humidifiers attached to the neonatal incubators. These isolates were assumed to be of the same clone because they were characterized by the same antimicrobial susceptibility and pulsed field gel electrophoresis patterns. It was established that the drug resistance was attributed to overproduction of chromosomally encoded Kl beta-lactamase. It was determined that an isolate (K. oxytoca H1) contained a high enzyme concentration (27microg/100microg of protein in enzyme extracts), at least 27 times higher than the control K. oxytoca N1. It was also demonstrated that isolates had a point mutation in the - 35 concensus region of the promotor gene of bla(OXY-2)leading to enzyme overproduction. Outbreaks caused by K1 hyperproducers have not previously been described.
Aztreonam↗
Pancreatitis secondary to Ascaris lumbricoides infestation.
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Albendazole↗
Attractiveness of facial averageness and symmetry in non-western cultures: in search of biologically based standards of beauty.
Averageness and symmetry are attractive in Western faces and are good candidates for biologically based standards of beauty. A hallmark of such standards is that they are shared across cultures. We examined whether facial averageness and symmetry are attractive in non-Western cultures. Increasing the averageness of individual faces, by warping those faces towards an averaged composite of the same race and sex, increased the attractiveness of both Chinese (experiment 1) and Japanese (experiment 2) faces, for Chinese and Japanese participants, respectively. Decreasing averageness by moving the faces away from an average shape decreased attractiveness. We also manipulated the symmetry of Japanese faces by blending each original face with its mirror image to create perfectly symmetric versions. Japanese raters preferred the perfectly symmetric versions to the original faces (experiment 2). These findings show that preferences for facial averageness and symmetry are not restricted to Western cultures, consistent with the view that they are biologically based. Interestingly, it made little difference whether averageness was manipulated by using own-race or other-race averaged composites and there was no preference for own-race averaged composites over other-race or mixed-race composites (experiment 1). We discuss the implications of these results for understanding what makes average faces attractive. We also discuss some limitations of our studies, and consider other lines of converging evidence that may help determine whether preferences for average and symmetric faces are biologically based.
Adolescent↗
Psychological and physical distress of sheltered battered women.
We explored the physical and psychological distress of sheltered battered women. A convenience sample of 50 ethnically diverse women was obtained from women who had resided in two shelters for at least 21 days. Participants had experienced multiple traumatic events (8.1+/-4.6); however, only 19 (38.8%) of the participants were diagnosed with posttraumatic stress disorder (PTSD). When we analyzed biopsychosocial variables, we saw beneficial effects of support (financial, social, spiritual). These findings reinforce the need to enhance the resources of battered women, to help them identify existing opportunities, and to fortify self-caring strategies that give them strength.
Adult↗
G156A MGMT-transduced human mesenchymal stem cells can be selectively enriched by O6-benzylguanine and BCNU.
Human bone marrow-derived mesenchymal stem cells (hMSCs) are being investigated for a potential therapeutic role as hematopoietic support cells following chemo-radiotherapy and as vehicles of gene delivery. Although hMSCs can be safely infused into humans and experimental animals, there is limited evidence regarding their engraftment and proliferation in vivo. We developed a drug resistance gene transfer strategy to mark and selectively enrich marked hMSCs using chemotherapy. We have determined that hMSCs are markedly sensitized to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vitro when pretreated with O(6)-benzylguanine (BG) resulting in a more than four-fold decrease in BCNU IC(90). The MFG retroviral vector encoding a bicistronic transcript for green fluorescent protein (GFP) and mutant (G156A)-methylguanine methyltransferase (G156A-MGMT), which encodes O(6)-alkylguanine-DNA alkyltransferase (AGT), conferring, BG plus BCNU resistance, transduced a high percentage of hMSCs. Transduced hMSCs had high expression of GFP and AGT and became significantly resistant to BG and BCNU. Furthermore, the proportion of GFP expressing transduced hMSCs increased from 32 +/- 14% to 70 +/- 14% following BG and BCNU treatment in vitro. Intravenously infused hMSCs were detected in NOD-SCID mice 8 weeks later by PCR analysis but could not be recultured from the bone marrow. GFP-expressing hMSCs inoculated into subcutaneous wounds in nonobese diabetic-severe combined immunodeficient (NOD-SCID) mouse could be recultured at a low frequency, but enriched by BG and BCNU treatment from 0.05 +/- 0.03% to 0.55 +/- 0.4 (p = 0.028, Welch t-test). Our results indicate that hMSCs are sensitive to BG and BCNU, predicting significant toxicity to the hematopoietic microenvironment with this therapy. G156A-MGMT is a powerful selectable gene for a second marker gene in hMSCs. Drug resistance gene transfer into hMSCs may allow in vivo enrichment of hMSCs when MSC homing and engraftment into target tissues is optimized.
Animals↗
Sequential activities of phosphoinositide 3-kinase, PKB/Aakt, and Rab7 during macropinosome formation in Dictyostelium.
Macropinocytosis plays an important role in the internalization of antigens by dendritic cells and is the route of entry for many bacterial pathogens; however, little is known about the molecular mechanisms that regulate the formation or maturation of macropinosomes. Like dendritic cells, Dictyostelium amoebae are active in macropinocytosis, and various proteins have been identified that contribute to this process. As described here, microscopic analysis of null mutants have revealed that the class I phosphoinositide 3-kinases, PIK1 and PIK2, and the downstream effector protein kinase B (PKB/Akt) are important in regulating completion of macropinocytosis. Although actin-rich membrane protrusions form in these cell lines, they recede without forming macropinosomes. Imaging of cells expressing green fluorescent protein (GFP) fused to the pleckstrin homology domain (PH) of PKB (GFP-PHPKB) indicates that D3 phosphoinositides are enriched in the forming macropinocytic cup and remain associated with newly formed macropinosomes for <1 minute. A fusion protein, consisting of GFP fused to an F-actin binding domain, overlaps with GFP-PHPKB in the timing of association with forming macropinosomes. Although macropinocytosis is reduced in cells expressing dominant negative Rab7, microscopic imaging studies reveal that GFP-Rab7 associates only with formed macropinosomes at approximately the time that F-actin and D3 phosphoinositide levels decrease. These results support a model in which F-actin modulating proteins and vesicle trafficking proteins coordinately regulate the formation and maturation of macropinosomes.
1-Phosphatidylinositol 4-Kinase↗
Strengthening user participation through health sector reform in Colombia: a study of institutional change and social representation.
The challenge of achieving community participation as a component of health sector reform is especially great in low- and middle-income countries where there is limited experience of community participation in social policy making. This paper concentrates on the social representations of different actors at different levels of the health care system in Colombia that may hinder or enable effective implementation of the participatory policy. The study took place in Cali, Colombia and focused on two institutional mechanisms created by the state to channel citizen participation into the health sector, i.e. user associations and customer service offices. This is a case study with multiple sources of evidence using a combination of quantitative and qualitative social science methods. The analysis of respondents' representations revealed a range of practical concerns and considerable degree of scepticism among public and private sector institutions, consumer groups and individual citizens about user participation. Although participation in Colombia has been introduced on political, managerial and ethical grounds, this study has found that health care users do not yet have a meaningful seat around the table of decision-making bodies.
Attitude to Health↗
Genetic approaches to studying protein synthesis: effects of mutations at Psi516 and A535 in Escherichia coli 16S rRNA.
A genetic system for the study of ribosomal RNA function and structure was developed. First, the ribosome binding sequence of the chloramphenicol acetyltransferase gene and the message binding sequence of 16S ribosomal RNA were randomly mutated and alternative highly functional sequences were selected and characterized. From this set of mutants, a single clone was chosen and subjected to a second round of mutagenesis to optimize the specificity of the system. In the resulting system, plasmid-encoded ribosomes efficiently and exclusively translate specific mRNA containing the appropriate ribosome binding sequences. This system allows facile isolation and analysis of mutations that would normally be lethal and allows direct selection of rRNA mutants with predetermined levels of ribosome function. The system was used to examine the effects of mutations at the sole pseudouridine (Psi) in Escherichia coli 16S rRNA which is located at position 516 of the conserved 530 loop. The nucleotide opposite Psi516 in the hairpin, A535, was also mutated. The data show that a pyrimidine (Psi or C) is required at position 516, while substitutions at position 535 reduce ribosome function by < 50%. A requirement for base pair formation between Psi516 and A535 was not indicated.
Escherichia coli↗
Effects of adrenergic agonists on glycogenolysis in primary cultures of glycogen body cells and telencephalon astrocytes of the chick.
The glycogen body (GB) is at the dorsal area of the lumbosacral spinal cord in birds and is composed of uniform cells that are characterized by high-glycogen storage. Previous morphological and embryological examinations suggest that the GB is derived from the neuroepithelium and contains many blood vessels and a few nerve fibers. However, the function of the GB and role of the glycogen are unknown. Mammalian astrocytes are major sites for glycogen stores in the central nervous system. The metabolic features of astrocytes have been defined by using cultured cells. As a first step toward investigating the function of GB, we established primary culture of chicken GB cells and telencephalon astrocytes. The cultured GB cells maintained high glycogen content and glial fibrillary acidic protein (GFAP) in the cytoplasm. The glycogen content of GB cells significantly increased with the glucose concentration in the medium. The effects of adrenergic agonists on glycogenolysis were different between GB cells and telencephalon astrocytes. The telencephalon astrocytes shared similar characteristics of glycogenolysis with mouse astrocytes, which are mainly affected by beta adrenergic receptor. Although GB cells were affected by noradrenalin (both alpha and beta adrenergic agonist), they were not affected by beta adrenergic agonist. These results showed that cultured GB cells were considered as one lineage of astrocytes because of their reactivity to antibody against GFAP; however, the metabolic features of GB cells were different from those of telencephalon astrocytes.
Adrenergic Agonists↗
Regulation of progesterone receptors and decidualization in uterine stroma of the estrogen receptor-alpha knockout mouse.
Regulation of progesterone receptor (PR) in uterine stroma (endometrial stroma plus myometrium) by estrogen was investigated in estrogen receptor-alpha (ERalpha) knockout (alphaERKO) mice. 17 beta-Estradiol (E(2)) increased PR levels in uterine stroma of ovariectomized alphaERKO mice, and ICI 182 780 (ICI) inhibited this E(2)-induced PR expression. Estrogen receptor-beta(ER beta) was detected in both uterine epithelium and stroma of wild-type and alphaERKO mice by immunohistochemistry. In organ cultures of alphaERKO uterus, both E(2) and diethylstilbestrol induced stromal PR, and ICI inhibited this induction. These findings suggest that estrogen induces stromal PR via ERbeta in alphaERKO uterus. However, this process is not mediated exclusively by ERbeta+, because in ERbeta knockout mice, which express ERalpha, PR was up-regulated by E(2) in uterine stroma. In both wild-type and alphaERKO mice, progesterone and mechanical traumatization were essential and sufficient to induce decidual cells, even though E(2) and ERalpha were also required for increase in uterine weight. Progesterone receptor was strongly expressed in decidual cells in alphaERKO mice, and ICI did not inhibit decidualization or PR expression. This study suggests that up-regulation of PR in endometrial stroma is mediated through at least three mechanisms: 1) classical estrogen signaling through ERalpha, 2) estrogen signaling through ERbeta, and 3) as a result of mechanical stimulation plus progesterone, which induces stromal cells to differentiate into decidual cells. Each of these pathways can function independently of the others.
Animals↗
Multiple organ dysfunction: baseline and serial component scores.
OBJECTIVE: The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology. The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU. DESIGN: Prospective observational cohort study. SETTING: Sixteen Canadian ICUs. PATIENTS: A total of 1,200 patients were mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter. The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores. In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality. When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality. After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality. After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 1.5; serial RR, 1.4); respiratory (baseline RR, 1.4; serial RR, 1.4); renal (baseline RR, 1.3; serial RR, 1.5); and central nervous system (baseline RR, 1.6; serial RR, 1.7). We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems. Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 1.1 [0.9-1.4]; week 2 onward: RR, 1.9 [1.5-2.4]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 1.2 [1.0-1.5]; week 2 onward: RR, 1.7 [1.4-2.1]). The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1-3: RR, 0.9 [0.7-1.1]; week 4 onward: RR, 1.4 [1.0-2.0]). CONCLUSIONS: Organ dysfunction scores describe physiology at ICU admission and during ICU stay. Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS.
APACHE↗
Molecular modeling approach to understanding the mode of action of L-nucleosides as antiviral agents.
A series of unnatural L-nucleosides such as 3TC, FTC and L-FMAU have been found to be potent antiviral agents. The mode of action of L-nucleosides has been found to be similar to that of D-nucleosides as antiviral agents, despite their unnatural stereochemistry, that is, nucleotide formation by kinases followed by interaction with the reverse transcriptase (RT) of HIV or DNA polymerase. To date, the mode of action of nucleoside inhibitors at the molecular level with respect to the active conformations of the 5'-triphosphates as well as the interaction with the RT is not known. Recently, the X-ray crystal structure of the RT-DNA-dTTP catalytic complex has been reported. Computer modeling has been performed for several pairs of D- and L-nucleoside inhibitors using the HIV-1 RT model and crystal coordinate data from a subset of the protein surrounding the deoxynucleoside triphosphate (dNTP) binding pocket region. Results from our modeling studies of D-/L-zidovudine, D-/L-3TC, D-/L-dideoxycytosine triphosphates, dTTP and dCTP show that their binding energies correlate with the reported 50% effective concentrations. Modeling results are also discussed with respect to favorable conformations of each inhibitor at the dNTP site in the polymerization process. Additionally, the clinically important M184V mutation, which confers resistance against 3TC and FTC, was studied with our modeling system. The binding energy patterns of nucleoside inhibitors at the M184V mutation site correlate with the reported antiviral data.
Antiviral Agents↗
Selection of specific endophytic bacterial genotypes by plants in response to soil contamination.
Plant-bacterial combinations can increase contaminant degradation in the rhizosphere, but the role played by indigenous root-associated bacteria during plant growth in contaminated soils is unclear. The purpose of this study was to determine if plants had the ability to selectively enhance the prevalence of endophytes containing pollutant catabolic genes in unrelated environments contaminated with different pollutants. At petroleum hydrocarbon contaminated sites, two genes encoding hydrocarbon degradation, alkane monooxygenase (alkB) and naphthalene dioxygenase (ndoB), were two and four times more prevalent in bacteria extracted from the root interior (endophytic) than from the bulk soil and sediment, respectively. In field sites contaminated with nitroaromatics, two genes encoding nitrotoluene degradation, 2-nitrotoluene reductase (ntdAa) and nitrotoluene monooxygenase (ntnM), were 7 to 14 times more prevalent in endophytic bacteria. The addition of petroleum to sediment doubled the prevalence of ndoB-positive endophytes in Scirpus pungens, indicating that the numbers of endophytes containing catabolic genotypes were dependent on the presence and concentration of contaminants. Similarly, the numbers of alkB- or ndoB-positive endophytes in Festuca arundinacea were correlated with the concentration of creosote in the soil but not with the numbers of alkB- or ndoB-positive bacteria in the bulk soil. Our results indicate that the enrichment of catabolic genotypes in the root interior is both plant and contaminant dependent.
Bacteria↗
Ontogeny of Th1 memory responses against a Brucella abortus conjugate.
Protective immune responses to intracellular pathogens such as Brucella abortus are characteristically Th1-like. Recently we demonstrated that heat-killed B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKBA-OVA), but not B. abortus alone, can alter the antigen-specific cytokine profile from Th2- to Th1-like. In this report we study the ability of a single injection of B. abortus to switch a Th2 to a Th1 response in immature mice. One-day- and 1-week-old mice were given a single injection of B. abortus in the absence or presence of OVA, and at maturity mice were challenged with an allergenic preparation, OVA with alum (OVA-A). B. abortus given without OVA did not diminish the subsequent Th2 response in either age group. In contrast, mice receiving a single injection of B. abortus-OVA at the age of 1 week, but not those injected at the age of 1 day, had reversal of the ratio of OVA-specific Th1 to Th2 cells and decreased immunoglobulin E levels after allergen challenge as adults. Within 6 h both 1-day- and 1-week-old mice expressed interleukin-12 p40 mRNA following either B. abortus or B. abortus-OVA administration. However, only the 1-week-old mice exhibited increased expression of gamma interferon (IFN-gamma) mRNA. The absence of the early IFN-gamma response in 1-day-old mice may explain their inability to generate a Th1 memory response. These results suggest that at early stages of immune development, responses to intracellular bacteria may be Th2- rather than Th1-like. Furthermore, they suggest that the first encounter with antigen evokes either a Th1- or a Th2-like response which becomes imprinted, so that subsequent memory responses conform to the original Th bias. This has implications for protection against infectious agents and development of allergic responses.
Aging↗