Biomedical subjects

H Lee

Publications and source records attributed to H Lee.

At least 199 records · Page 11Linked to original sources

PubMed2001

Msx homeobox genes inhibit differentiation through upregulation of cyclin D1.

During development, patterning and morphogenesis of tissues are intimately coordinated through control of cellular proliferation and differentiation. We describe a mechanism by which vertebrate Msx homeobox genes inhibit cellular differentiation by regulation of the cell cycle. We show that misexpression of Msx1 via retroviral gene transfer inhibits differentiation of multiple mesenchymal and epithelial progenitor cell types in culture. This activity of Msx1 is associated with its ability to upregulate cyclin D1 expression and Cdk4 activity, while Msx1 has minimal effects on cellular proliferation. Transgenic mice that express Msx1 under the control of the mouse mammary tumor virus long terminal repeat (MMTV LTR) display impaired differentiation of the mammary epithelium during pregnancy, which is accompanied by elevated levels of cyclin D1 expression. We propose that Msx1 gene expression maintains cyclin D1 expression and prevents exit from the cell cycle, thereby inhibiting terminal differentiation of progenitor cells. Our model provides a framework for reconciling the mutant phenotypes of Msx and other homeobox genes with their functions as regulators of cellular proliferation and differentiation during embryogenesis.

Animals↗

PubMed2001

Telomere associations in interphase nuclei: possible role in maintenance of interphase chromosome topology.

The relative sizes of individual telomeres in cultured human cells under conditions of cell cycling, replicative quiescence, cell transformation and immortalization were determined using quantitative fluorescence in situ hybridization (Q-FISH) with a telomere-specific peptide nucleic acid (PNA) probe. Results obtained from analysis of telomere length profiles (TLPs), which display the distribution of relative telomere lengths for individual cells, confirmed telomere length heterogeneity at the single cell level and proportional shortening of telomere length during replicative aging of virus-transformed cells. TLPs also revealed that some telomeric ends of chromosomes are so closely juxtaposed within interphase nuclei that their fluorescent signals appear as a single spot. These telomeric associations (TAs) were far more prevalent in interphase nuclei of noncycling normal and virus-transformed cells than in their cycling counterparts. The number of interphase TAs per nucleus observed in late-passage E6/E7-transformed cells did not increase during progression to crisis, suggesting that telomere shortening does not increase the frequency of interphase TAs. Furthermore, interphase TAs were rarely observed in rapidly cycling, telomerase-positive, immortalized cells that exhibit somewhat shortened, but stabilized, telomere length through the activity of telomerase. Our overall results suggest that the number of interphase TAs is dependent more on whether or not cells are cycling than on telomere length, with TAs being most prominent in the nuclei of replicatively quiescent cells in which nonrandom (even preferred) chromosome spatial arrangements have been observed. We propose that interphase TAs may play a role in the generation and/or maintenance of nuclear architecture and chromosome positional stability in interphase nuclei, especially in cells with a prolonged G(1)/G(0) phase and possibly in terminally differentiated cells.

Cell Cycle↗

PubMed2001

Effect of dopamine on excretory urographic image quality and the prevention of contrast-induced nephropathy in dogs.

The effect of low dose dopamine on the excretory urographic image quality and contrast media-induced nephropathy in normal dogs (experiment 1) and the dogs with decreased renal function (experiment 2) were assessed. In experiment 2, decreased renal function was induced by gentamicin overdose. In each experiment, animals were divided into 3 groups. In group 1, only contrast medium (iohexol) was administered. In group 2, contrast medium plus intravenous fluid (0.9% saline) were administered. And in group 3, contrast medium plus intravenous fluid and low dose dopamine were administered. Investigated parameters included intrarenal resistive index (RI), serum BUN and creatinine concentrations, contrast medium elimination time and radiographic image quality. In experiment 1, RI of group I increased at 80 min after contrast medium administration (p<0.05), but RI of group 3 decreased at 48 and 72 hr (p<0.05). Serum BUN concentration of group 1 was higher than that of group 2 and 3 (p<0.05); in radiographic examination, contrast medium elimination time decreased in group 2 and 3, but image quality of group 2 was inferior to that of group 3. In experiment 2, image quality of group 3 only provided adequate visualization of renal structures. The formula of contrast medium plus low dose dopamine was found to provide good nephrogram and pyelogram image quality without supplemental contrast medium, and to protect renal tubules from prolonged exposure to concentrated contrast medium.

Animals↗

PubMed2001

Enzyme-linked immunosorbent assay for screening the plasma residues of tetracycline antibiotics in pigs.

The recommended therapeutic doses of three kinds of tetracyclines, oxytetracycline (OTC, withdrawal period, 10 days), chlortetracycline (CTC, withdrawal period, 5 days) and tetracycline (TC, withdrawal period, 5 days), were each administered to a group of 15 pigs. Blood was sampled before drug administration and during the withdrawal period. The concentration of tetracyclines in plasma, determined by semi-quantitative ELISA, was compared with that of internal standard (10 ppb as oxytetracycline). The absorbance ratio of internal standard to sample (B/Bs) was employed as an index to determine the tissue residues in pigs. All 45 plasma samples from nontreated pigs showed negative in the residue of any of three tetracycline antibiotics. OTC was detected in plasma of pigs treated until the 8th day, CTC until the 4th day, and TC was detected until the 3rd day of its withdrawal period. The present study showed that the semi-quantitative ELISA easily be adopted in predicting tissue residues for tetracycline antibiotics in live pigs.

Animals↗

PubMed2001

Prospective comparative evaluation of stapled versus transected silastic ring gastric bypass: 6-year follow-up.

BACKGROUND: The effect of transecting vs. stapling the stomach in continuity in the banded gastric bypass (GBP) operation was studied. METHOD: 50 patients, 25 in each group, were enrolled into a prospective study to determine if transecting the stomach vs. stapling it in continuity in performing GBP for obesity decreases the incidence of gastro-gastric fistula formation without increased morbidity. RESULTS: The patient profiles in the 2 groups were very similar. The peri-operative complications included 1 splenic capsular injury in each group, controlled without a splenectomy. There was 1 anastomotic leak in the stapled and 1 bleeding from the cut edge of the bypassed stomach in the transected group, both requiring re-operations in the immediate postoperative period. There was no peri-operative mortality. The percent follow-up after 6 years was 80% and 88% in the stapled and transected groups respectively. The incidence of late complications of solid food intolerance, ventral incisional hernia, cholelithiasis and small bowel obstruction was similar in both groups. There were 8 gastro-gastric fistulas in the stapled group and 1 in the transected group. The reduction in body mass index and percent excess weight loss (66%) were similar in both groups. CONCLUSION: The incidence of gastro-gastric fistula may be reduced in GBP procedures by transecting the stomach as opposed to stapling it in continuity, without an increase in morbidity or mortality or any loss in the effectiveness of the operation.

Adult↗

PubMed2001

Revision of failed gastric bypass to distal Roux-en-Y gastric bypass: a review of 65 cases.

BACKGROUND: No bariatric operation has been documented to effect adequate weight loss in all patients. Patients with inadequate weight loss or significant weight regain with an anatomically intact short-limb gastric bypass, of which the Fobi pouch operation (FPO) for obesity is a modification, are usually revised to a distal Roux-en-Y gastric bypass (DRYGBP) to enhance weight loss. METHOD: A retrospective review of the charts of all patients who had a revision to a DRYGBP at our Center during an 8-year period was carried out and the findings analyzed. RESULTS: 65 patients who had the FPO had a revision to the DRYGBP. Most were super obese patients who, even though they had lost significant weight, were still morbidly obese. Some were patients who had not lost adequate weight or <40% excess weight, and a small number were patients who requested more weight loss even though they had a BMI of < 35. 15 patients developed protein malnutrition requiring supplemental feeding. 6 required rerevision to short-limb gastric bypass. CONCLUSION: Revision of short-limb gastric bypass to DRYGBP usually enhances weight loss but at a cost of an increased incidence of protein malnutrition.

Adult↗

PubMed2001

Band erosion: incidence, etiology, management and outcome after banded vertical gastric bypass.

BACKGROUND: Prosthetic devices have been used in bariatric operations to control the outlet of the gastric pouch and thus maintain weight loss. A complication of these prostheses is erosion or migration into the gastric lumen. The transected banded vertical gastric bypass (TBVGBP) is one of the modifications of gastric bypass. This modification has a silastic ring placed around the pouch to form the stoma. METHOD: The records of patients with band erosion (BE) after this operation were reviewed, to determine the incidence, etiology, management and outcome during a 9-year period. RESULTS: From May 1992 through May 2001, 2,949 primary and secondary TBVGBP were performed through the Center for Surgical Treatment of Obesity, utilizing 3 hospitals. 48 patients (1.63%) were documented to have BE: 40 documented by us and 8 by subsequent treating surgeons or at other facilities. Presenting symptoms were weight regain (18), stenosis or obstruction (17), pain (9), bleeding (7), and 5 were incidental findings. Some patients presented with more than one symptom. 8 were treated expectantly with spontaneous extrusion of the band. 16 bands have been removed endoscopically in 14 patients. 26 patients had open surgical revision, with 12 having band removal only and 14 band removal and revision of either the gastroenterostomy with or without band replacement or conversion to a distal Roux-en-Y gastric bypass (DRYGBP). Two patients who had revision to DRYGBP were re-revised to a longer common limb because of protein malnutrition. Three patients who had revision of the gastroenterostomy with band removal and replacement developed leaks that were managed non-surgically. Two of these re-eroded and the band was removed endoscopically with a subsequent revision to a DRYGBP. There was no death due to BE. CONCLUSION: BE is an uncommon complication of TBVGBP. Infection, previous bariatric operations and surgical technique play a role in BE. BE is best managed by endoscopic removal but can be treated expectantly or by open surgical intervention. Band removal without replacement or revision to DRYGBP may result in weight regain.

Gastric Bypass↗

PubMed2001

Drinking levels, alcohol problems and secondhand effects in substance-free college residences: results of a national study.

OBJECTIVE: This study examines alcohol use, associated problems and secondhand effects among residents of substance-free and alcohol-free housing on U.S. college campuses. METHOD: In the spring of 1999, a nationally representative sample of students completed survey questionnaires regarding alcohol use and related behaviors. The responses of 2,555 (61.25% female) students living in different types of residences (substance-free, alcohol-free and unrestricted) at the 52 campuses at which these housing options existed were compared. RESULTS: Substance-free residences were not substance-free; however, residents drank less heavily and experienced fewer alcohol-related problems and secondhand effects than students living in unrestricted housing. They were less likely (three fifths) to engage in heavy episodic drinking. The difference between students in substance-free and unrestricted housing was greatest for students who had not been heavy episodic drinkers in high school and for those on campuses with lower overall levels of heavy episodic drinking. In contrast, students who lived in alcohol-free halls were no less likely to be heavily involved in alcohol use than were students in unrestricted housing. CONCLUSIONS: Residence in substance-free housing was associated with lower likelihood of heavy episodic drinking in college for students who were not heavy episodic drinkers in high school. Whether or not this is a causal relationship or a result of self-selection needs to be examined in a prospective study. These living arrangements are also associated with lower levels of secondhand effects. College administrators may want to consider offering or increasing their substance-free housing options as one possible method of decreasing heavy student drinking.

Adult↗

PubMed2001

Improving the rate of infectivity of Cryptosporidium parvum oocysts in cell culture using centrifugation.

Centrifugation was evaluated as a method to improve infectivity assays of Cryptosporidium parvum in cell culture using the focus detection method, an immunofluorescence-based method for detecting infectious C. parvum oocysts in vitro. Human ileocecal adenocarcinoma (HCT-8) cells were grown for 48 hr on 13-mm cover slips in 24-well microtiter plates and infected with bleach-treated C. parvum oocysts. Plates were centrifuged at 228 g for 10 min and incubated at 37 C for 5, 12, 18, 24, and 48 hr. Foci of infection were stained by immunofluorescence and enumerated using epifluorescent microscopy. Results were compared to noncentrifuged controls. Foci in centrifuged samples could be enumerated after 18 hr. According to most probable number (MPN) analysis, the number of infectious oocysts estimated at 48 hr (13,326 infectious oocysts) was reached by 18 hr in centrifuged samples. After 48 hr, there was no significant difference (P < 0.05) between centrifuged and noncentrifuged samples enumerated by number of foci or the MPN of infectious oocysts. Centrifugation may expedite detection during C. parvum infectivity assays. Furthermore, multiwell plate formats are more cost effective than traditional chamber slides.

Animals↗

PubMed2001

Enhancement of tumor oxygenation and radiation response by the allosteric effector of hemoglobin, RSR13.

Prior studies using pO(2) microelectrodes have shown that RSR13, an allosteric modifier of hemoglobin, increases tissue oxygenation in vivo. Recently, measurements of tissue oxygenation have been performed by many investigators using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). In this study, we tested the hypothesis that the BOLD MRI signal ratio in tumors will change after administration of RSR13. NCI-H460 human lung carcinoma cells were used as a xenograft in athymic nude mice. Mice with 1-cm(3) tumors in the flank were anesthetized and mounted on the MRI apparatus, and various doses of RSR13 were administered intraperitoneally (i.p.). MR images were then acquired at 10-min intervals for up to 60 min after injection. The effect of RSR13 on tumor response was studied using the same mouse xenograft model with tumor growth delay measurements. RSR13 increased the MRI signal ratio [Intensity(t)/Intensity(t = 0)] in a dose-dependent manner, with maximum increases occurring 30 min after RSR13 was administered. An RSR13 dose of 200 mg/kg proved to be optimum. Since the MRI signal ratio has been shown previously to be linearly related to tissue oxygenation, the changes in the MRI signal ratio can be attributed to changes in tumor oxygen levels. Using a 200-mg/kg dose of RSR13, with a 10-Gy dose of radiation administered to tumors 30 min later, enhancement of radiation-induced tumor growth delay by RSR13 was observed (enhancement factor = 2.8). Thus our MRI results support and verify the previously reported RSR13-induced increase in tumor oxygenation obtained using pO(2) microelectrodes. Based upon these results and other previous studies, the mechanism of enhancement of the effect of radiation by RSR13 probably involves an increase in tumor oxygenation.

Allosteric Regulation↗

PubMed2001

The generation and characterization of a radiation-resistant model system to study radioresistance in human breast cancer cells.

To systematically study the selection of radioresistant cells in clinically advanced breast cancer, a model system was generated by treating MDA-MB231 breast cancer cells with fractionated gamma radiation. A clonogenic assay of the surviving cell populations showed that 2-6 Gy per fraction resulted in a rapid selection of radioresistant populations, within three to five fractions. Irradiation with additional fractions after this initial increase did not increase the radioresistance of the surviving population significantly. Doses of 0.5 and 8 Gy per fraction were not effective in selecting radioresistant cells. To further determine the cause of the changes in radiosensitivity, 15 clones were isolated from the cell populations treated with 40 or 60 Gy with 2 or 4 Gy per fraction, respectively, and were analyzed for radiosensitivity. The average D(10) for these clones was 6.75 +/- 0.36 Gy, which was higher than that for the parental cell population (D(10) = 6.0 +/- 0.2 Gy). The operation of cell cycle checkpoints and the doubling time were similar for both the nonirradiated parental population and the isolated radioresistant subclones. In contrast, a decrease in the apoptotic potential was correlated (r = 0.7, P < 0.01) with increased survival after irradiation, suggesting that apoptosis is an important factor in determining radioresistance under our experimental conditions. We also isolated several subclones from the nonirradiated parental cell population and analyzed them to determine their radiosensitivity after fractionated irradiation. Ten fractions of 4 Gy (40 Gy in total) did not result in a significant increase in the radioresistance of these subclones compared to the irradiated cell populations. The possible mechanisms of the increased radioresistance after fractionated irradiation are discussed.

Apoptosis↗

PubMed2001

Fluorescence produced by transfection reagents can be confused with green fluorescent proteins in mammalian cells.

The Aequorea victoria green fluorescent protein (GFP) reporter system is a convenient way to monitor gene expression and other cellular functions in mammalian cells. To study gene expression, a GFP-fusion plasmid construct is often transfected into mammalian cells using a variety of methods including calcium phosphate- and liposome-based DNA transfer. Subsequently, the expression of GFP-fusion protein is monitored by fluorescence microscopy or flow cytometry. Here, we report that certain transfection reagents can produce fluorescence that can be detected in a wide range of wavelengths, which can be confused with GFP-fusion protein. The fluorescence false positives can be a problem, particularly when the GFP expression levels are low. To improve the GFP-based detection or screening methods, it is imperative to include an appropriate negative control and to detect GFP using a narrow-wavelength emission filter corresponding to the emission spectrum around the GFP peak.

Animals↗

PubMed2001

Physiological characteristics of nationally competitive female road cyclists and demands of competition.

There are few published data describing female cyclists and the studies available are difficult to interpret because of the classification of athletes. In this review, cyclists are referred to as either internationally competitive (International Cycling Union world rankings provided when available) or nationally competitive. Based on the limited data available it appears that the age, height, body mass (BM) and body composition of women cyclists who have been selected to the US and Australian National Road Cycling Teams from 1980 to 2000 are fairly similar. Female cyclists who have become internationally competitive are generally between 21 to 28 years of age, 162 to 174 cm, 55.4 to 58.8 kg and 38 to 51 mm (sum of 7 skinfolds) corresponding to 7 to 12% body fat. The lower BM and percentage body fat are traits unique to the most competitive women. Internationally competitive women cyclists also possess a slightly superior ability to produce a high absolute power output for a fixed time period and a noticeably greater ability to produce power output relative to BM. In Women's World Cup races, successful women (top 20 places) spend more time >7.5 W/kg (11 +/- 2 vs 7 +/- 2%, p < 0.01) and less time <0.75 W/kg (24 +/- 4 vs 29 +/- 3%, p = 0.05) compared with non-top 20 placed riders. Additionally, cyclists in the top 20 produced higher average power (3.6 +/- 0.4 vs 3.1 +/- 0.1 W/kg, p = 0.01). Unlike professional men's road cycling, the physiological characteristics of internationally competitive female road cyclists and the demands of women's cycling competition are poorly understood.

Adult↗

PubMed2001

MICA polymorphism is associated with type 1 diabetes in the Korean population.

OBJECTIVE: Recent studies have demonstrated that MICA (major histocompatibility complex class I chain-related genes) on the short arm of the chromosome 6 are associated with susceptibility to various autoimmune diseases in Caucasians. The aim of our study was to investigate the role of MICA in type 1 diabetes susceptibility independent of the HLA DR-DQ polymorphism in genetically distinct Koreans. RESEARCH DESIGN AND METHODS: A total of 119 patients selected from Korean Seoul type 1 diabetes registry and 134 nondiabetic unrelated control subjects were typed for exon 5 polymorphism of MICA in addition to HLA DR-DQ typing. A total of 52 simplex families of type 1 diabetes were also studied. RESULTS: The MICA microsatellite allele consisting of six repetitions of GCT/AGC (A6) was present at a significantly lower frequency in the diabetic patient group (Pc < 0.01; Pc = P value after Bonferroni correction) than in the control population. The MICA microsatellite allele consisting of four repetitions (A4) was present at a higher frequency in diabetic patients (P < 0.05). This deviated distribution was not changed even after controlling for the HLA DRB1-DQB1 haplotype. Transmission/disequilibrium test revealed significant deviation of transmission for alleles at the A6 polymorphism within the MICA gene (P < 0.05). CONCLUSIONS: We could assess that the MICA gene might be associated with type 1 diabetes transracially independent of the HLA gene.

Adolescent↗

PubMed2001

A case of glaucoma associated with Sturge-Weber syndrome and Nevus of Ota.

The Sturge-Weber syndrome consists of a unilateral port-wine hemangioma of the skin along the trigeminal distribution and is accompanied by an ipsilateral leptomeningeal angioma. Glaucoma is present in approximately half of the cases. The Nevus of Ota is a melanocytic pigmentary disorder, most commonly involving the area innervated by the trigeminal nerve. Elevated intraocular pressure, with or without glaucomatous damage, is observed in 10% of the cases. We report the first case of glaucoma associated with Sturge-Weber syndrome and Nevus of Ota in Korea.

Antihypertensive Agents↗

PubMed2001

Modulation of H2 histamine receptor-mediated cAMP generation and granulocytic differentiation by extracellular nucleotides via activation of protein kinase C.

Extracellular ATP exerts a variety of biological actions through several kinds of P2 receptor in HL-60 promyelocytes. We show that stimulation of P2Y2 receptors with ATP and analogs resulted in the inhibition of a subsequently histamine-induced cAMP production and functional differentiation. Treatment of the cells with phorbol 12-myristate 13-acetate also blocked the histamine-mediated cAMP generation just as ATP did. Incubation of the cells with the protein kinase C inhibitor bisindolylmaleimide (GF109203X) abolished the inhibitory effects of extracellular nucleotides, suggesting that protein kinase C may act as an inter-regulator between two receptors. However, ATP did not affect the binding affinity or total binding of [3H]histamine to membrane receptors; it also did not heterologously desensitize H2 receptors. The ATP treatment synergistically elevated the cAMP levels induced directly by forskolin or indirectly by G protein activation after cholera toxin treatment. This indicates that the site of the protein kinase C action is not the G protein or effector enzyme. Co-stimulation of the cells with nucleotides and histamine inhibited histamine-mediated granulocytic differentiation, which was evaluated by looking at the extent of N-formyl-methionyl-leucyl-phenylalanine responses. Taken together, the results demonstrate that extracellular nucleotides are negatively involved in the modulation of histamine signaling via activation of protein kinase C, probably by inhibiting coupling between receptor and G protein.

Adenosine Triphosphate↗

PubMed2001

Extracellular polymeric substances in relation to nutrient removal from a sequencing batch biofilm reactor.

Experimental investigations were performed to determine the possibility of simultaneous biological nitrogen and phosphorus removal during various biofilm processes in conjunction with biofilm characterisation, especially extracellular polymeric substance (EPS). Since biologial nitrogen removal requires an alternating exposure of anaerobic-anoxic-oxic conditions in the bulk liquid that surrounds the biofilm growth media, a sequencing batch reactor (SBR)-type operation was used. Various materials including expanded clay, polystyrene, polyurethane, and acrylic materials were used as the biofilm growth support medium. Simultaneous nitrogen and phosphorus removal was possible with SBR, but it was postulated that nutrient removal efficiencies varied with film thickness. Thinner biofilm promoted nitrification and phosphorus removal, but thicker biofilm enhanced denitrification and reduced phosphorus removal. EPS contents were similar regardless of support media types or biofilm configuration, but EPS contents gradually increased as the film growth continued after backwashing. EPS contents were increased with increased nitrogen removal, but it was difficult to define its relation with phosphorus removal. In addition, suspended solids removal was correlated well with the EPS content in the biofilms.

Biofilms↗

PubMed2001

Mutational study of the role of tyrosine-49 in the Saccharomyces cerevisiae xylose reductase.

The xyl1 gene encoding xylose reductase was cloned from Saccharomyces cerevisiae and expressed in Escherichia coli. The purified enzyme readily carried out xylose reduction in vitro. It prefers NADPH as the co-enzyme by about 80-fold over NADH. Compared to the native enzyme purified from S. cerevisiae (Kuhn et al., 1995), the recombinant xylose reductase displayed slightly higher (about two-fold) affinities (K(m)) for the substrate (xylose) and co-factor (NADPH), as well as a 3.9-fold faster turnover number (K(cat)) and 7.4-fold greater catalytic efficiency (K(cat)/K(m)). The reason for the apparent discrepancies in kinetic constants between the recombinant and native S. cerevisiae xylose reductases is not known. Replacement of Tyr49 by Phe in the recombinant enzyme led to greater than 98% loss of activity, suggesting that this residue plays a critical role in catalysis. Intrinsic enzyme fluorescence spectroscopic analysis showed that the wild-type and the Y49F variant both bound the co-enzyme NADPH with similar affinity. This supports the view that Tyr49 is involved in interaction with the substrate and not the co-factor during catalysis.

Aldehyde Reductase↗