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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 145 records · Page 8Linked to original sources

Oxygen transfer characteristics in a pilot scale surface aeration vessel with Simcar aerator.

The volumetric mass transfer coefficient, KLa, was determined by dynamic method in a surface aerated pilot scale squared vessel up to 0.531 m3 equipped with Simcar type impeller. Through surface aeration, the oxygen transfer characteristics were investigated with the variations of operating variables such as stirring speed, impeller diameter, liquid height and power input per liquid volume (P0/V). It was seen from the results of different oxygen concentration absorption that the dynamic method might lead to errors in KLa when air was used for absorption. To provide reliable KLa values measured by dynamic, the KLa data using pure oxygen were used and confirmed with feeding steady-state method (FSM). As expected, KLa depends on P0/V, impeller size and liquid height. However, for Simcar type impeller, the KLa shows linear dependency on P0/V in contrast to majority of correlations reported in the literature which shows KLa variation of (P0/V)0.65 for disk type impeller. Moreover, it was interesting to find that the bubble behaviors inside the vessel computed by computational fluid dynamics (CFD) could explain qualitatively the KLa changes with operating variables. For the purpose of scale-up procedures, the empirical correlations for predicting KLa were developed within +/- 2% accuracy.

Adsorption↗

Setting a local research agenda for women's health: The National Centers of Excellence in Women's Health.

Although women's health research expanded greatly in the past 10 years, significant gaps in knowledge remain. Prioritization and promotion of research will help assure continuing progress in closing such gaps and improving the health of women. Although a comprehensive agenda for the new millennium has been developed at the national level, the process for establishing a local research agenda is not well defined. The purpose of this study was to describe criteria for and barriers to establishing a local research agenda in women's health. A secondary aim was to describe mechanisms for identifying women's health researchers and for facilitating multidisciplinary research. Directors of Research at National Centers of Excellence in Women's Health (CoEs) (n = 18) were surveyed by mail for this information. The results indicate that the local research agenda should emphasize health issues that are prevalent in women, research that is likely to establish treatment, psychosocial/cultural factors, and quality of life issues. The process of setting a research agenda should include input from the communities served as well as from scientists. Critical evaluation of scientific strengths and weaknesses is an essential preliminary step in prioritizing research opportunities in order to implement and evaluate a research agenda in women's health.

Academic Medical Centers↗

Difluoromethylornithine is effective as both a preventive and therapeutic agent against the development of UV carcinogenesis in SKH hairless mice.

Targeting specific events associated with tumor development represents a rational approach to chemoprevention as well as therapeutic intervention. In this study the ability of difluoromethylornithine (DFMO) to inhibit UV-induced skin carcinogenesis when administered before or after the appearance of tumors was examined. SKH hairless mice were irradiated 3 times per week with 90 mJ/cm(2); this dose was increased by 10% weekly to a maximum of 175 mJ/cm(2). Mice supplied 0.4% DFMO in the drinking water continuously throughout the experiment had an average of 2.0 tumors/mouse (72% incidence) at 30 weeks while controls had an average of 8.2 tumors/mouse (100% incidence). DFMO started after 12 weeks of UV, a time prior to tumor appearance, yielded 3.6 tumors and 100% incidence at 30 weeks. Starting DFMO at 22 weeks, when an average of 2.5 tumors were present, caused regression of tumors for several weeks, followed by a slight rebound. The final tumor number at 30 weeks was 3.0 (96% incidence). Thus, DFMO has strong chemopreventive efficacy, as well as therapeutic activity, against UV-induced skin tumors. Histological and proliferative markers support this conclusion.

Animals↗

Multiple functions of the nonconserved N-terminal domain of yeast TATA-binding protein.

The TATA-binding protein (TBP) is composed of a highly conserved core domain sufficient for TATA-element binding and preinitiation complex formation as well as a highly divergent N-terminal region that is dispensable for yeast cell viability. In vitro, removal of the N-terminal region domain enhances TBP-TATA association and TBP dimerization. Here, we examine the effects of truncation of the N-terminal region in the context of yeast TBP mutants with specific defects in DNA binding and in interactions with various proteins. For a subset of mutations that disrupt DNA binding and the response to transcriptional activators, removal of the N-terminal domain rescues their transcriptional defects. By contrast, deletion of the N-terminal region is lethal in combination with mutations on a limited surface of TBP. Although this surface is important for interactions with TFIIA and Brf1, TBP interactions with these two factors do not appear to be responsible for this dependence on the N-terminal region. Our results suggest that the N-terminal region of TBP has at least two distinct functions in vivo. It inhibits the interaction of TBP with TATA elements, and it acts positively in combination with a specific region of the TBP core domain that presumably interacts with another protein(s).

DNA-Binding Proteins↗

Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea.

Antibiotic resistance in Helicobacter pylori varies according to geographical region. We studied the primary resistance rates among 652 H. pylori isolated from Korea in relation to collection date, disease presentation, age and gender. Resistance rates were 40.6% (metronidazole), 5.9% (clarithromycin), 5.3% (tetracycline), 0% (amoxycillin), 1.5% (furazolidone) and 1.5% (nitrofurantoin). Resistance to metronidazole and clarithromycin increased from 1994 to 1999 (from 33.3 to 47.7% and 4.8 to 7.7%, respectively), but the differences only reached significance when rates of metronidazole resistance in women were compared with those in men (48.6 versus 36.9%).

Adolescent↗

A prospective study of complications associated with cuffed, tunnelled haemodialysis catheters.

BACKGROUND: Despite the US Dialysis Outcome Quality Initiative )DOQI( guidelines, for various reasons, increasing numbers of end-stage renal disease patients are becoming dependent on cuffed haemodialysis catheters (HCs) for chronic haemodialysis access. Their use is complicated by frequent failure due to thrombosis and catheter-related sepsis. In our unit, all HCs are put in place by the radiology department. METHODS: In a prospective study we looked at the outcome of all HCs over a three-year period, during which time 573 consecutive HCs were placed in 336 patients. Each line was followed individually until it was removed or until the end of the study. RESULTS: In a survival analysis of those HCs removed following HC failure, HC half-life was 312 days and one-year HC survival was 47.5%. The most frequent indications for HC removal were non-function (36.6%), clinical suspicion of line sepsis (16.4%) and patient death (14.4%). Using a Cox proportional hazards model, catheter number in a given patient and the presence of diabetes mellitus were found to be independent predictors of HC failure. The total incidence of HC-related sepsis was 1.3 episodes/1000 catheter days. The probability of developing bacteraemic HC-related sepsis was 27.5% at one year. CONCLUSIONS: Less than half of the HCs were removed electively because of availability of a more permanent mode of renal replacement, thereby illustrating the level of dependence that has developed on them as permanent access. Consequently, their limitations (infection and malfunction) are placing an ever increasing burden on the healthcare services.

Catheters, Indwelling↗

Formation of cholesterol oxides in irradiated raw and cooked chicken meat during storage.

The objective of this study was to determine the effect of electron-beam irradiation on the oxidation of cholesterol in raw and cooked chicken meats with different packaging and storage times. Patties were prepared with skinless chicken breasts and legs. Half of the patties were used for raw meat study and the other half for cooked meat work. For cooked samples, patties were cooked in an electric oven to an internal temperature of 70 C. Raw and cooked meat patties were either aerobically or vacuum-packaged before irradiation. Irradiated patties were stored at 4 C up to 2 wk, and the amounts of cholesterol oxides in the patties were analyzed at 0, 7, and 14 d of storage. In raw chicken meat with vacuum packaging, 7beta-hydroxycholesterol and beta-epoxide were the only two cholesterol oxides present in significant amounts. In raw chicken meat with aerobic packaging, 7alpha-hydroxycholesterol and 7-keiocholesterol, which were not detected in vacuum-packaged raw chicken meat, were found. 7beta-Hydroxycholesterol in raw chicken meat was increased by irradiation and storage time, regardless of packaging. The kinds of cholesterol oxides found in cooked meat were basically the same as those found in raw chicken, but the levels in cooked meats at all storage time were higher than those of the raw meats. With vacuum packaging, irradiation had no consistent effect on the amount of beta-epoxide, 7alpha-hydroxycholesterol, or 7-ketocholesterol, but storage significantly influenced the amount of 7-ketocholesterol, 7beta-hydroxycholesterol, and total cholesterol oxides in cooked chicken meat. With aerobic packaging, irradiation significantly increased the formation of 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol, and 7-ketocholesterol in cooked meat stored for 0 and 7 d. After 14 d of storage, however, irradiation had minor effects on the formation of cholesterol oxides in aerobically packaged cooked chicken.

Animals↗

Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate.

This study was designed to establish a simple and reliable assay method that could be routinely used in the clinical laboratory setting using liquid extraction and high-performance liquid chromatography (HPLC). In addition, a case of potential interaction of grapefruit juice with sildenafil citrate is presented. The peaks of sildenafil (measured as sildenafil salt) and internal standard were identified with an ultraviolet detector at 230 nm and detection limit at 10 ng/mL. In a single elderly male patient, grapefruit juice increased the Cmax of sildenafil by 42% (1067.7 ng/mL to 1517.0 ng/mL) although AUC was not significantly altered (4082.9 ng x h/mL to 4171.9 ng x h/mL) by grapefruit juice. Sildenafil could be determined in a simple and reliable method using HPLC with liquid extraction. This case indicated that grapefruit juice might increase the Cmax of sildenafil without significant change in AUC. A further study with an appropriate number of subjects is needed before determining the degree of interaction between grapefruit juice and sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗

Intraosseous sacral myxopapillary ependymoma and the differential diagnosis of sacral tumors.

Although involvement of other regions of the spinal cord and brain stem is seen, myxopapillary ependymoma is most commonly found at the filum terminale or cauda equina. Less commonly, myxopapillary ependymoma may occur outside the central nervous system from direct metastatic extension of an intrathecal tumor, and rarely it may present as a primary tumor outside the thecal sac. The authors present a case of primary sacral myxopapillary ependymoma, which was first diagnosed as a chordoma. They then discuss the magnetic resonance imaging findings of this and other sacral tumors. Myxopapillary ependymoma should be considered in the differential diagnosis for a primary expansile sacral mass along with other lesions such as chordoma, aneurysmal bone cyst, and giant cell tumor.

Adult↗

Hepatitis B virus nucleic acids circulating in the blood: distinct patterns in HBs carriers with hepatocellular carcinoma.

Circulating nucleic acids in serum and plasma are common in a variety of disease conditions. Here, we focus (i) on our approach for the detection of various hepatitis B virus (HBV)-related nucleic acids in liver tissue and in serum, (ii) on the progression of the chronic HBV infection, (iii) on the relation of HBV-specific nucleic acids circulating in the blood of patients with hepatocellular carcinoma, and in general (iv) on the diagnostic potential of circulating HBV nucleic acids.

Amino Acid Sequence↗

The cost-effectiveness of fluoridating water supplies in New Zealand.

OBJECTIVE: Tooth decay has been substantially reduced in New Zealand, and the difference in caries rates between fluoridated and non-fluoridated areas has narrowed. We investigated whether it is cost-effective to fluoridate water supplies that are now non-fluoridated. METHODS: The net cost of fluoridation was based on the cost of fluoridating a water supply minus the averted costs of treating decay. A range of population sizes was considered. The main analysis was conducted from a societal perspective, using a real discount rate of 5%. Fluoridation was assumed to occur continuously between the years 2000 and 2030. Other assumptions were a Maori population proportion of 15%, no new decay after age 34, and no further dental cost savings after age 45. Information on averted decay in 4 to 12 year old New Zealand children (29,000 receiving fluoridated water and 47,000 receiving non-fluoridated water) was available; information on averted decay in adults was obtained from a study in the United States. Sensitivity analyses investigated the effects of varying the Maori population proportion, the discount rate, and the number of fluoride injection sites. RESULTS: Fluoridation was cost-saving (dental cost savings exceeded fluoridation costs) for communities above about a thousand people. The true break-even community size may be lower. For smaller communities, fluoridation may be considered cost-effective depending on the non-monetised value assigned to an averted decayed surface. CONCLUSIONS AND IMPLICATIONS: Fluoridation remains very cost-effective, and is particularly so for communities with high proportions of children, Maori, or people of low socio-economic status.

Adolescent↗

Paclitaxel-induced immune suppression is associated with NF-kappaB activation via conventional PKC isotypes in lipopolysaccharide-stimulated 70Z/3 pre-B lymphocyte tumor cells.

Paclitaxel, a potent antitumor agent, has been shown to be lipopolysaccharide (LPS) mimetic in mice, stimulating signaling pathways and gene expression indistinguishably from LPS. In the present study, we showed the intracellular signaling pathway of paclitaxel-induced nuclear factor-kappaB (NF-kappaB) activation and its suppressive effect on LPS-induced signaling in murine 70Z/3 pre-B cells. Stimulation of 70Z/3 cells with LPS for 30 min caused activation of NF-kappaB in the nuclei by detection of DNA-protein binding specific to NF-kappaB. Similarly, paclitaxel also produced a marked and dose-related NF-kappaB activation. However, pretreatment of cells with 10 microM paclitaxel for 18 h resulted in complete inhibition of LPS-mediated NF-kappaB activation. Interestingly, the activity of IkappaB kinase (IKK-beta), which plays an essential role in NF-kappaB activation through IkappaB phosphorylation, was largely enhanced in paclitaxel-treated cells, detected as IkappaBalpha phosphorylation. Because protein kinase C (PKC) is implicated in the activation of NF-kappaB via IKK-beta, the effect of paclitaxel on PKC activation was also measured. It was shown that NF-kappaB nuclear translocation and DNA binding in response to paclitaxel was completely blocked by the conventional PKC inhibitor, Gö 6976. Moreover, immunoblotting analysis with paclitaxel-treated cell extract demonstrated that the conventional PKC isotype PKC-alpha was found to be involved in the regulation of paclitaxel-induced NF-kappaB activation, as determined by electrophoretic mobility shift of PKC. Therefore, these data suggest that paclitaxel may activate IKK-beta via conventional PKC isotypes, resulting in NF-kappaB activation and, finally, desensitization of LPS-inducible signaling pathway in 70Z/3 pre-B cells.

Animals↗

Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy.

Whole-cell assays were implemented to search for efflux pump inhibitors (EPIs) of the three multidrug resistance efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN) that contribute to fluoroquinolone resistance in clinical isolates of Pseudomonas aeruginosa. Secondary assays were developed to identify lead compounds with exquisite activities as inhibitors. A broad-spectrum EPI which is active against all three known Mex efflux pumps from P. aeruginosa and their close Escherichia coli efflux pump homolog (AcrAB-TolC) was discovered. When this compound, MC-207,110, was used, the intrinsic resistance of P. aeruginosa to fluoroquinolones was decreased significantly (eightfold for levofloxacin). Acquired resistance due to the overexpression of efflux pumps was also decreased (32- to 64-fold reduction in the MIC of levofloxacin). Similarly, 32- to 64-fold reductions in MICs in the presence of MC-207,110 were observed for strains with overexpressed efflux pumps and various target mutations that confer resistance to levofloxacin (e.g., gyrA and parC). We also compared the frequencies of emergence of levofloxacin-resistant variants in the wild-type strain at four times the MIC of levofloxacin (1 microg/ml) when it was used either alone or in combination with EPI. In the case of levofloxacin alone, the frequency was approximately 10(-7) CFU/ml. In contrast, with an EPI, the frequency was below the level of detection (<10(-11)). In summary, we have demonstrated that inhibition of efflux pumps (i) decreased the level of intrinsic resistance significantly, (ii) reversed acquired resistance, and (iii) resulted in a decreased frequency of emergence of P. aeruginosa strains that are highly resistant to fluoroquinolones.

Anti-Infective Agents↗

Furazolidone- and nitrofurantoin-resistant Helicobacter pylori: prevalence and role of genes involved in metronidazole resistance.

The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant. rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection.

Anti-Infective Agents, Urinary↗

DNA sequence analysis of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant clinical Helicobacter pylori isolates.

We previously reported that inactivation of rdxA and/or frxA converted Helicobacter pylori from metronidazole sensitive to metronidazole resistant. To examine the individual roles of rdxA and frxA in the development of metronidazole resistance in H. pylori, we examined the status of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant H. pylori isolates obtained following unsuccessful therapy containing metronidazole. Arbitrary primed fingerprinting analyses revealed that the genotypes of 11 sensitive and resistant pairs of strains were essentially identical. Amino acid sequence identities of RdxA and FrxA from the 14 metronidazole-sensitive isolates ranged from 92 to 98% and 95 to 98%, respectively, compared to that of H. pylori J99 (MIC, 1 microg/ml). All strains with high-level metronidazole resistance (MICs, 128 microg/ml) contained premature truncation of both RdxA and FrxA caused by nonsense and/or frameshift mutations. Strains with intermediate resistance to metronidazole (MICs, 32 to 64 microg/ml) contained a single premature truncation and/or altered RdxA and FrxA caused by nonsense, frameshift, and unique missense mutations. The low-level metronidazole-resistant strains (MICs, 8 microg/ml) contained unique missense mutations in FrxA but no specific changes in RdxA. The results demonstrate that alterations in both the rdxA and frxA genes are required for moderate and high-level metronidazole resistance and that metronidazole resistance that develops during anti-H. pylori therapy containing metronidazole is most likely to involve a single sensitive strain infection rather than a coinfection with a metronidazole-resistant strain.

Amino Acid Sequence↗

2-Bromoethanesulfonate affects bacteria in a trichloroethene-dechlorinating culture.

Long-term exposure to 2-bromoethanesulfonate (BES), an agent known to inhibit methanogenesis, altered the bacterial community structure of an anaerobic enrichment culture that reductively dechlorinated trichloroethene (TCE). BES did not hinder the dechlorination of TCE or other chlorinated ethenes as previously reported, although different intermediates and end products were observed.

Alkanesulfonic Acids↗

Murine cytomegalovirus open reading frame M27 plays an important role in growth and virulence in mice.

Using a Tn3-based transposon mutagenesis approach, we have generated a pool of murine cytomegalovirus (MCMV) mutants. In this study, one of the mutants, RvM27, which contained the transposon sequence at open reading frame M27, was characterized both in tissue culture and in immunocompetent BALB/c mice and immunodeficient SCID mice. Our results suggest that the M27 carboxyl-terminal sequence is dispensable for viral replication in vitro. Compared to the wild-type strain and a rescued virus that restored the M27 region, RvM27 was attenuated in growth in both BALB/c and SCID mice that were intraperitoneally infected with the viruses. Specifically, the titers of RvM27 in the salivary glands, lungs, spleens, livers, and kidneys of the infected SCID mice at 21 days postinfection were 50- to 500-fold lower than those of the wild-type virus and the rescued virus. Moreover, the virulence of the mutant virus appeared to be attenuated, because no deaths occurred among SCID mice infected with RvM27 for up to 37 days postinfection, while all the animals infected with the wild-type and rescued viruses died within 27 days postinfection. Our observations provide the first direct evidence to suggest that a disruption of M27 expression results in reduced viral growth and attenuated viral virulence in vivo in infected animals. Moreover, these results suggest that M27 is a viral determinant required for optimal MCMV growth and virulence in vivo and provide insight into the functions of the M27 homologues found in other animal and human CMVs as well as in other betaherpesviruses.

3T3 Cells↗

Mature dendritic cells infected with canarypox virus elicit strong anti-human immunodeficiency virus CD8+ and CD4+ T-cell responses from chronically infected individuals.

Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8+ T-cell responses from chronically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-gamma) and beta-chemokines. Furthermore, canarypox virus-infected DCs were >30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8+ effector cells, although the presence of CD4+ T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-gamma-secreting CD4 helper responses from bulk as well as purified CD4+ T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8+ and CD4+ helper responses in vivo.

AIDS Vaccines↗