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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 343 records · Page 19Linked to original sources

Metabolic engineering.

Metabolic engineering is the science that combines systematic analysis of metabolic and other pathways with molecular biological techniques to improve cellular properties by designing and implementing rational genetic modifications. As such, metabolic engineering deals with the measurement of metabolic fluxes and elucidation of their control as determinants of metabolic function and cell physiology. A novel aspect of metabolic engineering is that it departs from the traditional reductionist paradigm of cellular metabolism, taking instead a holistic view. In this sense, metabolic engineering is well suited as a framework for the analysis of genome-wide differential gene expression data, in combination with data on protein content and in vivo metabolic fluxes. The insights of the integrated view of metabolism generated by metabolic engineering will have profound implications in biotechnological applications, as well as in devising rational strategies for target selection for screening candidate drugs or designing gene therapies. In this article we review basic concepts of metabolic engineering and provide examples of applications in the production of primary and secondary metabolites, improving cellular properties, and biomedical engineering.

Biomedical Engineering↗

Anterior cruciate ligament tears: MR imaging-based diagnosis in a pediatric population.

PURPOSE: To evaluate the diagnostic accuracy of primary and secondary magnetic resonance (MR) imaging findings of anterior cruciate ligament (ACL) tears in young patients with immature skeletal systems. MATERIALS AND METHODS: MR images obtained in 43 patients aged 5-16 years who underwent arthroscopy were retrospectively reviewed. Two reviewers evaluated primary findings (abnormal signal intensity, abnormal course as defined by Blumensaat angle, and discontinuity), secondary findings (bone bruise in lateral compartment, anterior tibial displacement, uncovering of posterior horn of lateral meniscus, posterior cruciate ligament line, and posterior cruciate angle), and meniscal and other ligamentous injuries. RESULTS: There were 19 ACL tears and 24 intact ACLs. Overall sensitivity and specificity of MR imaging in detecting ACL tears were 95% and 88%, respectively. Sensitivities of the primary findings were 94% for abnormal Blumensaat angle; 79%, abnormal signal intensity; and 21% discontinuity. The specificity of all primary findings was 88% or greater. The sensitivity and specificity of the secondary findings, respectively, were 68% and 88% for bone bruise; 63% and 92%, anterior tibial displacement; 42% and 96%, uncovered posterior horn of lateral meniscus; 68% and 92%, positive posterior cruciate line; and 74% and 71%, abnormal posterior cruciate angle. Fifteen (79%) patients had meniscal tears, and five (26%) had collateral ligament injuries. CONCLUSION: Primary and secondary findings of ACL tears in young patients have high specificity and are useful for diagnosis.

Adolescent↗

Safety and cost of hyperhydration for the prevention of hemorrhagic cystitis in bone marrow transplant recipients.

Hemorrhagic cystitis is a major cause of morbidity after bone marrow transplantation. Traditional methods of prevention have included mesna (2-mercaptoethane sodium sulfonate) and bladder irrigation. We report the use of hyperhydration as an alternative to these prophylactic measures. One hundred consecutive patients who underwent autologous or allogeneic bone marrow transplantation received high dose cyclophosphamide with hyperhydration using 5% dextrose normal saline at the rate of 250 ml/h and furosemide to maintain a urine output of >150 ml/h. Seventy-one of these patients also received high dose cyclophosphamide as mobilization chemotherapy. There were no episodes of hemorrhagic cystitis following mobilization chemotherapy. The incidence of hemorrhagic cystitis after transplant conditioning was 7% with 2 patients developing clinically significant hemorrhagic cystitis; one was a severe episode. The cost of hyperhydration was US$ 20 per course as opposed to US$ 1,500 per course for mesna, based on acquisition costs at our institution. We conclude that hyperhydration is a safe, inexpensive means of preventing hemorrhagic cystitis associated with high dose cyclophosphamide in bone marrow transplant recipients.

Adult↗

Random assignment and patient choice in a study of alternative pain relief for sickle cell disease.

This article presents two case examples in which women with sickle cell disease, when invited to participate in a nursing experiment, requested assignment to the experimental group. This experience stimulated the authors to explore the ethics of random assignment relative to equipoise, informed consent, patient choices, study validity, the clinician-patient relationship, patient support networks, and other issues. There is a need for in-depth discussion about random assignment and its implications within the nursing research and advanced practice communities.

Adult↗

Sources of midsleep awakenings in childbearing women.

Sleep disturbance is a complaint of childbearing women that has implications for perinatal health. A descriptive, longitudinal study examined the numbers and sources of midsleep awakenings in women prior to conception and during each trimester of pregnancy. A secondary analysis of data from a larger study of sleep during childbearing was performed for subjects (n = 25) who completed sleep diaries across the four measurement periods. There was a two-fold increase in the number of awakenings from pre-conception to the third trimester of pregnancy. Maintenance insomnia during pregnancy follows a pattern of prevalence that can be characterized by trimester. The predominant source of awakening during the first and third trimesters of pregnancy was due to the need to urinate. Parity and environmental circumstances can influence sources of awakenings. Nurses working with childbearing women can provide information and assistance with strategies to minimize or mitigate lengthy episodes of sleep disturbance.

Adult↗

Comparison of alternative sources of data on health service encounters.

OBJECTIVES: Due to the paucity and incompleteness of routine databases, many areas of health services research rely on the accuracy of individuals' recollections of health service encounters. The objective of this study is to explore differences between patient and physician recall of health care resource use by employing data from two randomized controlled trials. METHODS: Data on the frequency of use of community-based health services were reported by both patients and their general practitioners (GPs) at three-month intervals for the first year after randomization. Analysis compared the completeness of data collected, the level of agreement between GPs and patients and differences in the estimated cost of community services. Further analysis assessed the impact of patient characteristics on reporting. RESULTS: Data provided by GPs were less likely to be complete than patient data. There were significant differences between GPs and patients in their reported use of certain community services, particularly in relation to GP-patient contacts. However, this did not lead to significant differences in estimates of costs. Patient characteristics influenced the level of agreement with GPs, but not the proportion of forms completed. CONCLUSIONS: In research in which the use of community resources is a major component of costs, differential estimates of resource use may influence study results. Further research is required to identify optimal data collection methods for health service encounters. Where possible, studies should incorporate estimates of resource use from a variety of sources and conduct sensitivity analyses to assess the robustness of the results.

Adult↗

Sleep disturbances in children with human immunodeficiency virus infection.

OBJECTIVE: To describe the sleep patterns and level of fatigue in children and adolescents (6-18 years of age) with HIV infection, compared with ethnic-, gender-, and age-matched healthy children in the home setting. DESIGN: Descriptive, comparative. SETTING: Conducted in each child's home environment. STUDY PARTICIPANTS: Eighteen HIV-infected and 15 noninfected children completed the study. The Centers for Disease Control and Prevention HIV classifications for the 18 HIV-infected children were: A (n = 7), B (n = 6), and C (n = 5). METHODS: A symptom diary was developed using a previously validated fatigue assessment scale, modified for use with children. Content validity of the diary was established with a panel of 5 experts in child development and pediatric HIV disease. Children were asked to complete the diary each morning and evening for 3 days. Each child wore a wrist actigraph during the same period. RESULTS: The HIV-infected children had significantly more wake time after sleep onset, compared with noninfected children (13.55% vs 7. 47%). The HIV-infected children had more awakenings (25.33 vs 16.71) and were awake for longer periods (3.01 vs 1.01 minutes), compared with noninfected children. By parent report, 7 HIV-infected children napped and 2 noninfected children napped, indicating greater daytime fatigue in the HIV-infected children. HIV-infected children also reported a greater level of evening tiredness (2.47 vs 1.8). CONCLUSIONS: The findings from this study suggest that sleep disturbances occur in HIV-infected children, similar to findings previously described in HIV-infected adults. Additional research is necessary to characterize the nature and patterns of sleep disturbance and fatigue related to pediatric HIV-infection, to assess the impact these may have on daily activities, and to develop strategies to improve sleep for these children.

Adolescent↗

Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein.

OBJECTIVE: The mechanisms by which newborns are at increased risk for invasive bacterial infections have been incompletely defined. A central element of innate immunity to bacterial infection is the neutrophil-a cell that contains cytoplasmic granules replete with antibiotic proteins and peptides. The activity of adult neutrophils against gram-negative bacteria is believed to depend to a significant degree on the presence in neutrophil primary (azurophilic) granules of the 55-kDa bactericidal/permeability-increasing protein (BPI), which binds with high affinity to bacterial lipopolysaccharides and kills gram-negative bacteria. In light of the importance of BPI to antibacterial host defense and to investigate possible factors underlying the risk of neonatal bacterial infections, we determined the relative content of BPI in the neutrophils of adults and newborns. DESIGN: The cellular content of BPI was determined by Western blotting of neutrophils derived from full-term newborn cord blood (n = 21; mean gestational age: 38.6 weeks) and from adult peripheral blood (n = 22; mean age: 29 years). Extracellular levels of BPI in adult and newborn plasma were assessed by enzyme-linked immunosorbent assay. Neutrophil content of other azurophil granule markers also was assessed: myeloperoxidase by Western blotting and defensin peptides by acid-urea polyacrylamide gel electrophoresis and Coomassie staining. Acid extracts of newborn and adult neutrophils were analyzed for antibacterial activity against serum-resistant encapsulated isolate Escherichia coli K1/r. RESULTS: The neutrophils of newborns contain at least threefold to fourfold less BPI per cell than adult neutrophils (67 +/- 13 ng per 10(6) cells vs 234 +/- 27 ng per 10(6) cells). The relative BPI-deficiency of newborn neutrophils apparently was not attributable to perinatal stress-related degranulation of intracellular BPI stores because: 1) newborn and adult neutrophils contained nearly identical amounts of 2 microbicidal constituents derived from the same primary (azurophil) granule compartment as BPI (the enzyme myeloperoxidase as well as defensin peptides), and 2) levels of extracellular BPI in newborn plasma, measured by enzyme-linked immunosorbent assay, represent only approximately 2% of cellular BPI content. As predicted by their lower BPI content, newborn neutrophil acid extracts demonstrated significantly lower antibacterial activity against E coli K1/r than did adult neutrophil acid extracts. CONCLUSION: These data suggest that the neutrophils of newborns are selectively deficient in BPI, a central effector of antibacterial activity against gram-negative bacteria. BPI deficiency correlates with decreased antibacterial activity of newborn neutrophil extracts against serum-resistant E coli and could contribute to the increased incidence of gram-negative sepsis among newborns relative to healthy adults.neonatal sepsis, gram-negative bacteria, endotoxin, neutrophil, polymorphonuclear leukocyte, innate immunity, bactericidal/permeability-increasing protein, defensin, myeloperoxidase.

Adult↗

An attribution-emotion model of helping behavior.

To investigate the help-giving judgment of the attribution-emotion model further, data from five manifest variables of controllability, responsibility, anger, sympathy, and help-giving, were subjected to path analysis, which provided an easy interpretation of the model. Participants were 90 men and 81 women in an introductory psychology course.

Adult↗

Axenic cultivation and characterization of Giardia lamblia isolated from humans in Korea.

Inoculating of human fecal cysts to suckling Mongolian gerbils, two Giardia lamblia isolates, K1 and K2, were established as axenic cultures. Using this in vitro culture, both isolates were characterized as a "medium-rate grower" upon its growth pattern. These two Giardia isolates were grouped by using two genetic analysis. With genetic analysis of SSU-rDNA sequences, both K1 and K2 were found as members of Hopkins' group 1, despite some nucleotide differences noticed in K2 (5 differences/292 bases). The other genetic study used PCR-RFLP of the tim (triose phosphate isomerase) gene. Both of K1 and K2 were found to belong to Nash's group 2. Our results suggest that Nash's group 2 can not be a separate group, but a part of Hopkins' group 1.

Animals↗

[A case of pelvic aggressive angiomyxoma involving urinary bladder].

A 23-year-old man visited hospital with the complaints of hematuria and miction pain. Computed tomography and magnetic resonance imaging of the pelvis showed a large pelvic tumor contiguous to the urinary bladder. Resection of the tumor with partial cystectomy was performed on February, 1998. Histopathological examination showed that the tumor composed of angiomyxoma infiltrating into the urinary bladder. The patient is alive without recurrence of aggressive angiomyxoma 12 months after surgery. To our knowledge, this is the first report in the Japanese literature of aggressive angiomyxoma involving the urinary bladder. Awareness of this uncommon neoplasma is important in the diagnosis of pelvic tumor to prevent an extensive surgery.

Adult↗

Mechanisms related to [18F]fluorodeoxyglucose uptake of human colon cancers transplanted in nude mice.

UNLABELLED: [18F]Fluorodeoxyglucose ([18F]FDG), a glucose analogue, has been widely used for tumor imaging. To investigate the mechanisms related to [18F]FDG uptake by tumors, an experiment involving nude mice was performed. METHODS: Human colon cancer cell lines SNU-C2A, SNU-C4 and SNU-C5 were transplanted to nude mice. Using immunohistochemical staining and Western blot, the expression of glucose transporter (Glut) isoforms (Glut-1 through -5) in xenografted tumors was analyzed. For the analysis of messenger ribonucleic acid (mRNA) expression, reverse-transcription polymerase chain reaction and Northern blot were used and the enzyme activity of hexokinase in cancer tissues was measured by continuous spectrophotometric rate determination. RESULTS: [18F]FDG uptake in SNU-C4 and SNU-C5 cells was higher than in normal colon cells. Among these cells and xenografted tumors, SNU-C5 showed the highest level of [18F]FDG uptake, followed by SNU-C4 and SNU-C2A. An immunostaining experiment showed intense staining of Glut-1 in SNU-C5 tumors but somewhat faint staining in SNU-C4. SNU-C5 tumors also showed positive staining with Glut-3, although this was not the case with SNU-C2A and SNU-C4. Western blot analysis showed the expression of Glut-1 and Glut-3 in all tumors. Experiments involving Northern blot analysis and reverse-transcription polymerase chain reaction confirmed the overexpression of Glut-1 mRNA in all tumors, with the highest level in SNU-C5. The level of Glut-3 mRNA was also elevated in SNU-C5 tumors but not in SNU-C2A and SNU-C4. The enzyme activity of hexokinase did not vary among different tumors. CONCLUSION: Gluts, especially Glut-1, are responsible for [18F]FDG uptake in a nude mouse model of colon cancer rather than hexokinase activity. Increased numbers of glucose transporters at the plasma membrane of cancer cells is attributed to an increased level of transcripts of glucose transporter genes and may be a cause of increased [18F]FDG uptake, at least in colon cancer tumors.

Animals↗

Bombesin receptors inhibit G protein-coupled inwardly rectifying K+ channels expressed in Xenopus oocytes through a protein kinase C-dependent pathway.

Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled receptors has been shown to be important in postsynaptic inhibition in the central nervous system, there is also evidence to suggest that inhibition of GIRK channels by Gq-coupled receptors is involved in postsynaptic excitation. In the present study we addressed whether the Gq-coupled receptors of the bombesin family can couple to GIRK channels and examined the mechanism by which this process occurs. Different combinations of GIRK channel subunits (Kir3.1, Kir3.2, and Kir3.4) and bombesin receptors (BB1 and BB2) were expressed in Xenopus oocytes. In all combinations tested GIRK currents were reversibly inhibited upon application of the bombesin-related peptides, neuromedin B or gastrin-releasing peptide in a concentration-dependent manner. Incubation of oocytes in the phospholipase C inhibitor U73122 or the protein kinase C (PKC) inhibitors chelerythrine and staurosporine significantly reduced the inhibition of GIRK currents by neuromedin B, whereas the Ca2+ chelator, BAPTA-AM had no effect. The involvement of PKC was further demonstrated by direct inhibition of GIRK currents by the phorbol esters, phorbol-12,13-dibutyrate and phorbol-12-myristate-13-acetate. In contrast, the inactive phorbol ester 4alpha-phorbol and protein kinase A activators, forskolin and 8-bromo cAMP did not inhibit GIRK currents. At the single-channel level, direct activation of PKC using phorbol ester phorbol-12, 13-dibutyrate caused a dramatic reduction in open probability of GIRK channels due to an increase in duration of the interburst interval.

Animals↗

A 40-kDa NF1-like protein, not YY1, binds to the rat p53 promoter for transactivation in various rat organs.

Two recognition motifs of a 40-kDa NF1-like protein were previously identified in the rat p53 promoter. One is located between -296 and -312 (NF1-like element 1) and the other between -195 and -219 (NF1-like element 2). The latter one was also identified as a NF1/YY1 recognition motif in the human p53 promoter. NF1 or YY1 binds to the motif and regulates the expression of the human p53 gene in a tissue-specific manner. In this study, we investigated the binding protein for NF1-like element 2 in various rat tissues. Unlike the human p53 transcription, an NF1-like protein, not YY1, bound to the motif in every tested tissue: thymus, kidney, and spleen. In vitro transcription assay also confirmed that the NF1-like protein regulated the p53 transcription in rat spleen, although the human p53 transcription was regulated by YY1 in that organ. The molecular mass of the binding protein was determined to be 40 kDa, which was the same as that of the NF1-like protein identified in liver. Therefore, the 40-kDa NF1-like protein may be a universal transcription regulator for the rat p53 gene.

Animals↗

[Transfusion of platelet concentrates].

Although a number of research have been realized in the aim of decreasing the use of platelet concentrates, these blood products remain absolutely necessary for patients with therapeutic aplasia and for some surgical patients. After the description of the main rules of platelet transfusion procedures, we will discuss some controversial issues: threshold value for platelet transfusion, platelet doses, place of curative and prophylactic strategies, refractoriness to platelet transfusion, HLA alloimmunization. Then we will focus our review on the future alternatives for platelet transfusion.

Blood Donors↗

B7.1 is a quantitatively stronger costimulus than B7.2 in the activation of naive CD8+ TCR-transgenic T cells.

Using a TCR transgenic mouse bred onto a recombinase-activating gene-2-deficient background, we have examined the influence of B7.1 and B7.2 on activation of naive, CD8+ T cells in vitro. We found that B7.1 was a more potent costimulus than B7.2 for induction of proliferation and IL-2 production by naive CD8+ T cells. This difference appeared to be quantitative in nature, as determined using transfectants expressing various defined levels of B7.1 or B7.2, or using purified B7.1 or B7.2 fusion proteins. In contrast to the quantitative differences seen in stimulation of naive T cells, B7.1 and B7.2 were comparable in their ability to costimulate responses in T cells previously primed in vitro. In addition, primed, but not naive, T cells were capable of proliferating and producing IL-2 in response to a TCR stimulus alone, apparently in the absence of B7 costimulation. Lastly, we found that B7.1 and B7.2 were equivalently capable of driving differentiation of naive CD8+ T cells into an IL-4-producing phenotype when exogenous IL-4 was added to the primary culture or to an IFN-gamma-producing phenotype in the presence of IL-12. These results indicate that signals generated by B7.1 and B7.2 are qualitatively similar, but that B7.1 is quantitatively stronger than B7.2. Further, our results indicate that the activation state of the responding T cell may influence the efficiency with which the T cell can respond to a costimulatory signal provided by either B7.1 or B7.2.

Animals↗