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Biomedical subjects

Young Kim

Publications and source records attributed to Young Kim.

33 records · Page 2Linked to original sources

Numerical deconvolution of cDNA microarray signal: simulation study.

A computational model for simulation of the cDNA microarray experiments has been created. The simulation allows one to foresee the statistical properties of replicated experiments without actually performing them. We introduce a new concept, the so-called bio-weight, which allows for reconciliation between conflicting meanings of biological and statistical significance in microarray experiments. It is shown that, for a small sample size, the bio-weight is a more powerful criterion of the presence of a signal in microarray data as compared to the standard approach based on t test. Joint simulation of microarray and quantitative PCR data shows that the genes recovered by using the bio-weight have better chances to be confirmed by PCR than those obtained by the t test technique. We also employ extreme value considerations to derive plausible cutoff levels for hypothesis testing.

Cell Line, Tumor↗

Two cases of post transplant lymphoproliferative disorder in lung transplant recipients.

Post-transplant lymphoproliferative disease (PTLD) is a serious, often fatal complication after solid organ transplantation. The incidence of PTLD is greater among heart (2 approximately 13%), lung (12%) and heart/lung (5 approximately 9%) transplant recipients than among liver (2%), renal (1 approximately 3%) and bone marrow (1 approximately 2%) transplants recipients. The difference in the incidence of PTLD may be partly attributed to the higher dose of immunosuppressant therapy used for heart and lung transplantation. The Epstein-Barr virus (EBV) infection status of the donor and recipient before a transplant, and high dose of immunosuppressive drugs are considered major risk factors. Recently, 2 cases of PTLD in a single lung and a heart-lung transplantation recipient were encountered. Both patients presented with multiple pulmonary nodules in the transplanted lung, which developed 6 months and 2 years after the transplantation, respectively. Following a transthoracic lung biopsy for diagnostic confirmation, one patient underwent chemotherapy for PTLD and the other conservative care for an accompanying viral infection. Both patients showed rapid clinical deterioration, without response to treatment, and then rapidly succumbed. Herein, our experiences are reported, with a review of the literature.

Adult↗

Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: modulation of apoptosis, proliferation, and fractal dimension.

OBJECTIVES: Emerging evidence implicates the SNAIL family of transcriptional repressors in cancer development; however, the role of SNAIL in colorectal cancer has not been established. To investigate the importance of SNAIL in colorectal carcinogenesis, we examined the phenotypic and cellular consequences of SNAIL down-regulation in the MIN mouse. METHODS: Twenty-eight male MIN mice were randomized to treatment with an antisense phosphorodiamidate morpholino oligomer (AS-PMO) to SNAIL, saline, or a scrambled sequence control for 6 weeks. Tumors were scored and the molecular/cellular effects of anti-SNAIL treatment were evaluated through immunohistochemical analysis of the uninvolved intestinal mucosa for SNAIL and E-cadherin levels along with rates of apoptosis and proliferation. Furthermore, microarchitectural alterations were determined through measurement of fractal dimension. RESULTS: In the uninvolved mucosa, SNAIL AS-PMO treatment moderately decreased SNAIL protein when compared with saline-treated animals (immunohistochemistry scores 3.0 +/- 0.8 versus 2.1 +/- 0.6, respectively; P=0.01) with a concomitant increase in E-cadherin expression (1.8 +/- 0.6 versus 2.4 +/- 0.5; P < 0.05). Anti-SNAIL PMO, but not scramble control, resulted in a significant decrease in both total tumor number and incidence of tumors >2 mm (22% and 54%, respectively; P < 0.05). Furthermore, this was accompanied by an increased apoptosis rate (2-fold), decreased proliferation (3-fold), and normalization of the fractal dimension in the uninvolved intestinal mucosa. CONCLUSIONS: We show, for the first time, that SNAIL overexpression is important in intestinal tumorigenesis. While this PMO regimen afforded modest SNAIL suppression and hence tumor reduction, this provides compelling evidence for the role of SNAIL overexpression in colonic neoplasia.

Animals↗

On the nature of cardiovascular activation at an arousal from sleep.

STUDY OBJECTIVES: The intent of the study was to explore the nature and function of the cardiovascular activation response that occurs at an arousal from sleep. DESIGN: Four experiments were conducted. The first compared the pattern of physiologic response to orienting and startle stimuli and arousal from sleep. The second and third measured the amplitude of the cardiovascular arousal response as a function of the trait of fearfulness and the threat value of the arousing stimulus, respectively. The final experiment assessed the effect of arousal duration. SETTING: The experiments were conducted in the sleep laboratory of the Department of Psychology, University of Melbourne. PARTICIPANTS: A total of 42 (24 women and 18 men) healthy individuals between the ages of 18 and 24 participated in the experiments. INTERVENTIONS: The experiments manipulated the stimuli to which participants were exposed (orienting and startle stimuli and arousal from sleep), the threat value of stimuli used to arouse participants from sleep, and individual differences in fearfulness. MEASUREMENTS AND RESULTS: The major dependent variables were heart rate, blood pressure, and a measure of peripheral vasoconstriction (digital pulse volume). In addition, in the first study, the galvanic skin response and orbicularis oculi electromyographic activity were measured. Experiment 1 showed that the pattern of physiologic response at an arousal from sleep differed, with a substantially larger cardiovascular component, from responses to orienting and startle stimuli. Experiments 2a and 2b indicated that the magnitude of the cardiovascular response at an arousal was unrelated to either individual differences in fearfulness or differences in the threat value of arousing stimuli. The final experiment showed that the cardiovascular response at an arousal was not a return to waking levels of activity but, rather, was a transient activation response. CONCLUSIONS: The study supported the view that the cardiovascular activation response at an arousal from sleep is a transient, reflex-like response that is different from the response that occurs during normal wakefulness.

Adult↗

Effects of ankle exercise combined with deep breathing on blood flow velocity in the femoral vein.

Ankle exercises are commonly used to facilitate venous return in the lower extremity and to prevent deep vein thrombosis. Moreover, the respiratory cycle affects venous return. This study examined the effects of ankle exercise combined with deep breathing on the blood flow velocity in the femoral vein. Twenty healthy males (mean age 21.3 years), who had no medical history of lower extremity disease, were recruited for this study. The blood flow velocity in the femoral vein was measured while performing four exercise protocols: quiet breathing while resting (QR), deep breathing (DB), ankle exercise with quiet breathing (AQB), and ankle exercising combined with deep breathing (ADB). Using a Doppler ultrasound with an 8 MHz probe, peak blood flow velocities were collected for a 20 second period at the start of the inspiration phase in each protocol, three times. There were statistically significant differences in the peak blood flow velocity in the femoral vein with the four protocols (p lt 0.001). The mean (SD) peak blood flow velocity in the femoral vein was as follows: QR 10.1 (4.2) cm/sec, DB 15.5 (3.9) cm/sec, AQB 20.7 (6.6) cm/sec, and ADB 26.5 (9.4) cm/sec. Post hoc analyses revealed significant differences between each of the four protocols (p(adj) lt 0.01). The mean peak blood flow velocity in the femoral vein was greatest with the ADB protocol, which implies that the ADB protocol may be useful to prevent the blood stasis in patients at risk of deep vein thrombosis.

Adult↗

Phase I trial of docetaxel, carboplatin, and gemcitabine as first-line therapy for patients with high-risk epithelial tumors of müllerian origin.

OBJECTIVES: The aim of this study was to assess the feasibility of combining docetaxel, carboplatin, and gemcitabine (DoCaGem) as first-line treatment of ovarian and other müllerian origin tumors. METHODS: Four dose levels were planned for this phase I trial. Treatment consisted of carboplatin on day 1 only, docetaxel on days 1 and 8, and gemcitabine on days 1 and 8, every 21 days. RESULTS: Nineteen patients were enrolled, of whom 18 were evaluable for toxicity. The first 5 patients enrolled at dose level I (carboplatin AUC 5, 30 mg/m(2) docetaxel, 800 mg/m(2) gemcitabine) experienced no dose-limiting toxicity. At dose level II, 4/4 evaluable patients experienced significant bone marrow suppression that required dose reduction and/or dose delay. Further dose escalation was not attempted, and 9 additional patients were enrolled in dose level I. Of the 67 cycles administered on dose level I, day 8 treatment could not be administered due to bone marrow suppression in 16 cycles (24%), and prolongation of the cycle length from day 22 to day 29 was required in 13 cycles (19%). There were no episodes of febrile neutropenia in evaluable patients and no treatment-related deaths. Grade 3 nonhematologic toxicity (fatigue) occurred in 1 cycle. Response was determined in the 14 evaluable patients who tolerated 4 or more cycles of therapy, with 11 obtaining a complete clinical response and 3 obtaining a partial clinical response. CONCLUSIONS: The DoCaGem regimen is highly active, but myelosuppression at dose level I prevents full dose delivery. Other strategies to combine these three active agents are reasonable to explore.

Adult↗

Development and evaluation of an automated stainer for acid-fast bacilli.

The current strategy for the control of tuberculosis (TB) relies on early diagnosis, and smear microscopy is an essential component of the laboratory diagnosis of TB in most countries with a high prevalence of the disease. However, even simple smear microscopy examination is far from satisfactory because staining results can vary among individual technicians. In an effort to minimize variations in manual staining procedures, we developed an automated stainer for AFB and evaluated its usefulness in comparison with manual staining. The key feature of our automated stainer is a heating apparatus required for fixation and carbol-fuchsin staining. After smear slides are placed into the machine, the entire staining process is fully automated, from fixation to final washing and drying. With the automated methods, five slides can be fixed and stained in 21 min at consistent high quality. Using sputum samples from 91 TB patients, the staining results of the automated stainer were compared blindly with those of manual staining. The concordance rate between the two methods was 94.5%. In addition, there was no significant difference in the rate of detection of AFB in the sputum samples. Although further optimization of the auto staining procedures is required, the results indicate that the automated AFB stainer developed in this study looks promising for use in clinical mycobacteriology laboratory in order to minimize personal variation during AFB staining.

Equipment Design↗

Kinetic and inhibition studies for the aerobic cometabolism of 1,1,1-trichloroethane, 1,1-dichloroethylene, and 1,1-dichloroethane by a butane-grown mixed culture.

Batch kinetic and inhibition studies were performed for the aerobic cometabolism of 1,1,1-trichloroethane (1,1,1-TCA), 1,1-dichloroethylene (1,1-DCE), and 1,1-dichloroethane (1,1-DCA) by a butane-grown mixed culture. These chlorinated aliphatic hydrocarbons (CAHs) are often found together as cocontaminants in groundwater. The maximum degradation rates (k(max)) and half-saturation coefficients (K(s)) were determined in single compound kinetic tests. The highest k(max) was obtained for butane (2.6 micromol/mg TSS/h) followed by 1,1-DCE (1.3 micromol/mg TSS/h), 1,1-DCA (0.49 micromol/mg TSS/h), and 1,1,1-TCA (0.19 micromol/mg TSS/h), while the order of K(s) from the highest to lowest was 1,1-DCA (19 microM), butane (19 microM), 1,1,1-TCA (12 microM) and 1,1-DCE (1.5 microM). The inhibition types were determined using direct linear plots, while inhibition coefficients (K(ic) and K(iu)) were estimated by nonlinear least squares regression (NLSR) fits to the kinetic model of the identified inhibition type. Two different inhibition types were observed among the compounds. Competitive inhibition among CAHs was indicated from direct linear plots, and the CAHs also competitively inhibited butane utilization. 1,1-DCE was a stronger inhibitor than the other CAHs. Mixed inhibition of 1,1,1-TCA, 1,1-DCA, and 1,1-DCE transformations by butane was observed. Thus, both competitive and mixed inhibitions are important in cometabolism of CAHs by this butane culture. For competitive inhibition between CAHs, the ratio of the K(s) values was a reasonable indicator of competitive inhibition observed. Butane was a strong inhibitor of CAH transformation, having a much lower inhibition coefficient than the K(s) value of butane, while the CAHs were weak inhibitors of butane utilization. Model simulations of reactor systems where both the growth substrate and the CAHs are present indicate that reactor performance is significantly affected by inhibition type and inhibition coefficients. Thus, determining inhibition type and measuring inhibition coefficients is important in designing CAH treatment systems.

Bacteria, Aerobic↗

A combined method for determining inhibition type, kinetic parameters, and inhibition coefficients for aerobic cometabolism of 1,1,1-trichloroethane by a butane-grown mixed culture.

A combined method for determining inhibition type, kinetic parameters, and inhibition coefficients is developed and presented. The method was validated by applying it to data obtained from batch kinetics of the aerobic cometabolism of 1,1,1-trichloroethane (1,1,1-TCA) by a butane-grown mixed culture. The maximum degradation rates (k(max)) and half-saturation coefficients (K(s)) were independently determined in single compound tests, and compared with those obtained from inhibition tests. The inhibition type was determined using direct linear plots at various substrate and inhibitor concentrations. Kinetic parameters (k(max) and K(s)) and inhibition coefficients (K(ic) and K(iu)) were determined by nonlinear least squares regression (NLSR) fits of the inhibition model determined from the direct linear plots. Initial guesses of the kinetic parameters for NLSR were determined from linearized inhibition equations that were derived from the correlations between apparent maximum degradation rates (k(app)(max)) and/or the apparent half-saturation coefficient (K(app)(s)) and the k(max), K(s), and inhibitor concentration (I(L)) for each inhibition equation. Two different inhibition types were indicated from the direct linear plots: competitive inhibition of 1,1,1-TCA on butane degradation, and mixed inhibition of 1,1,1-TCA transformation by butane. Good agreement was achieved between independently measured k(max) and K(s) values and those obtained from both NLSR and the linearized inhibition equations. The initial guesses of all the kinetic parameters determined from linear plots were in the range of the values estimated from NLSR analysis. Overall the results show that use of the direct linear plot method to identify the inhibition type, coupled with initial guesses from linearized plots for NLSR analysis, results in an accurate method for determining inhibition types and coefficients. Detailed studies with pure cultures and purified enzymes are needed to further demonstrate the utility of this method.

Acetylene↗

Utility of (His)6 tag for purification and refolding of proplasmepsin-2 and mutants with altered activation properties.

Plasmepsin-2 is a malarial aspartic proteinase that has been implicated in the initial steps of hemoglobin degradation in parasites and thus represents an attractive antimalarial target. Escherichia coli expressed proplasmepsin-2 is capable of activation at acidic pH by autocatalytic cleavage of the pro part region, which results in products of different length. We designed a 10-amino-acid deletion in the pro part region that allows faster generation of homogeneous enzyme upon activation. Incorporation of a (His)6 tag onto the N-terminus of the pro part enables on-column refolding of proplasmepsin-2 and simplifies proenzyme purification and pro part separation after activation. The proposed purification procedure results in highly pure and easily crystallizable enzyme.

Animals↗

Sharks: a potential source of antiangiogenic factors and tumor treatments.

Since angiogenesis is a key feature of tumor growth, inhibiting this process is one way to treat cancer. Cartilage is a natural source of material with strong antiangiogenic activity. This report reviews knowledge of the anticancer properties of shark cartilage and clinical information on drugs such as neovastat and squalamine. Because their entire endoskeleton is composed of cartilage, sharks are thought to be an ideal source of angiogenic and tumor growth inhibitors. Shark cartilage extract has shown antiangiogenic and antitumor activities in animals and humans. The oral administration of cartilage extract was efficacious in reducing angiogenesis. Purified antiangiogenic factors from shark cartilage, such as U-995 and neovastat (AE-941), also showed antiangiogenic and antitumor activity. AE-941 is under phase III clinical investigation. Squalamine, a low molecular weight aminosterol, showed strong antitumor activity when combined with chemotherapeutic materials. The angiogenic tissue inhibitor of metalloprotease 3 (TIMP-3) and tumor suppressor protein (snm23) genes from shark cartilage were cloned and characterized.

Journal Article↗

The effects of normal aging on sleep spindle and K-complex production.

OBJECTIVES: Despite a relatively large body of literature describing the characteristics of sleep spindles and K-complexes in young adults, relatively little research has been conducted in older individuals. The general consensus from the few studies that have addressed this issue is that there is a progressive decrease in the number of spindles and K-complexes with age, although there is large intra-individual variation. Whether or not these changes are an inevitable consequence of the aging process can be addressed by studying healthy older adults who provide an example of the effects of age independently from those of disease. METHODS: Fourteen young adults (mean age=21.4+/-2.5 years) and 20 older adults (mean age=75.5+/-6.3 years) participated in the study. All subjects were neurologically and medically healthy and were not taking any medications with a known effect on the central nervous system or sleep. For each subject, a number of characteristics were determined including the number, density (SS/min), amplitude and frequency of all spindles as well as the number and density of K-complexes (KC/min). RESULTS: Spindle number, density and duration as well as K-complex number and density were all significantly lower in the elderly compared to the young adults. The EEG frequency within the spindles was significantly higher in the elderly, although the absolute difference was less than 0.5 Hz. Multiple regression analysis indicated that spindle duration and K-complex density were able to predict over 90% of the variance in age. CONCLUSIONS: The age-related decrease in sleep spindle and K-complex density is consistent with previous reports and may be interpreted as an age-related alteration of thalamocortical regulatory mechanisms.

Adult↗

Dust mite, cockroach, cat, and dog allergen concentrations in homes of asthmatic children in the northeastern United States: impact of socioeconomic factors and population density.

Home exposures to aeroallergens are an important environmental factor in allergic sensitization and in the development and exacerbation of asthma. We assessed variations in home concentrations of dust mite, cockroach, cat, and dog allergens in dust collected in the main living areas of asthmatics' homes by family income, mother's education, dwelling type, population density, household population density, and ethnicity in Connecticut and south-central Massachusetts. Dust samples were collected at the time of home interview in 999 homes as part of an ongoing longitudinal birth cohort study of 1,002 infants and their asthmatic siblings. The analysis employed lower and upper cut points for group 1 dust mite (> or = 2.0 microg/g and > or = 10 microg/g), cockroach (> or = 1.0 U/g and > or = 4.0 U/g), cat (> or = 1.0 microg/g and > or = 8.0 ug/g), and dog (> or = 2.0 microg/g and > or = 10.0 microg/g) allergens. Subject residences were geocoded to assess population density from the U.S. Census, and multiple logistic regression was used to control for confounding. The portion of homes at the lower cut point for dust mite, cockroach, cat, and dog allergens were 46.9%, 24.9%, 42.2%, and 35.6%, respectively; the upper cut point for each of the allergens was reached in 22.4%, 13.4%, 21.0%, and 22.9% of the homes, respectively. In all, 86.0% of the homes had at least one allergen at the lower cut point, and 58.0% had at least one allergen at the upper cut point. Forty-nine percent of the homes had two or more allergens at the lower cut point, and 19.7% had two or more allergens at the upper cut point. Higher education of the mother, higher household income, living in a single-family home in a less densely populated area with fewer people per room, and being a white household were associated with elevated dust mite, cat, and dog allergens and low cockroach allergen. In contrast, low income, living in a multifamily home in a high population density area with a higher occupancy rate per room, and being a Hispanic or black household were associated with elevated cockroach allergens and low concentrations of dust mite, cat, and dog allergens. Although the presence of an individual allergen is more likely associated with one or more socioeconomic or ethnic factors, most homes typically have multiple allergen burdens in excess of concentrations thought to be associated with sensitization and exacerbation of asthma. Mite and cockroach allergens have distinct and opposite associations with socioeconomic factors and population density.

Adolescent↗

Anesthetic care in developing countries: equipment and techniques.

Various organizations have been formed to provide short-term surgical services in developing countries. In these countries, the ability to provide effective anesthetic care requires the team to transport most of the equipment necessary to provide perioperative care for various surgical procedures. We review the basic supplies necessary to provide such care and discuss some of the issues related to the anesthesia machines, techniques, and monitoring in developing countries. Suggestions and options for preoperative assessment, intraoperative anesthetic care, and postoperative care, including pain management, are provided.

Anesthesia↗

Push-pull tests for assessing in situ aerobic cometabolism.

Three types of single-well push-pull tests were developed for use in assessing the feasibility of in situ aerobic cometabolism of chlorinated aliphatic hydrocarbons (CAHs). These included transport tests, biostimulation tests, and activity tests. Transport tests are conducted to evaluate the mobility of solutes used in subsequent tests. These included bromide or chloride (conservative tracers), propane (growth substrate), ethylene, propylene (CAH surrogates), dissolved oxygen (electron acceptor), and nitrate (a minor nutrient). Tests were conducted at an experimental wellfield of Oregon State University. At this site, extraction phase breakthrough curves for all solutes were similar, indicating apparent conservative transport of the dissolved gases and nitrate prior to biostimulation. Biostimulation tests were conducted to stimulate propane-utilizing activity of indigenous microorganisms and consisted of sequential injections of site ground water containing dissolved propane and oxygen. Biostimulation was detected by the increase in rates of propane and oxygen utilization after each injection. Activity tests were conducted to quantify rates of substrate utilization and to confirm that CAH-transforming activity had likely been stimulated. In particular, the transformation of injected CAH surrogates ethylene and propylene to the cometabolic byproducts ethylene oxide and propylene oxide provided evidence that activity of the monooxygenase enzyme system, responsible for aerobic cometabolic transformations of CAHs, had likely also been stimulated. Estimated zero-order transformation rates decreased in the order propane > ethylene > propylene. The series of push-pull tests developed and field tested in this study should prove useful for conducting rapid, low-cost feasibility assessments for in situ aerobic cometabolism of CAHs.

Bacteria, Aerobic↗