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Biomedical subjects

T K Lee

Publications and source records attributed to T K Lee.

At least 37 records · Page 2Linked to original sources

Two cases of steakhouse syndrome associated with nutcracker esophagus.

The most common type of esophageal food-related foreign body is the meat bolus, which is frequently associated with underlying esophageal stenosis. Herein, we report two cases of meat bolus impaction associated with nutcracker esophagus. In the first case, the 63-year-old male patient had chest discomfort and swallowing difficulty after ingestion of butcher's meat. In the second case, the 55-year-old male patient had complained of swallowing difficulty after ingestion of chicken. In both cases, no pathologic findings were observed endoscopically after removal of the esophageal meat bolus. We performed esophageal manometry, which showed very high amplitudes of esophageal pressure in the mid- and distal esophagus. These findings were consistent with nutcracker esophagus. These cases show that esophageal motility disorder may be the cause of esophageal foreign body impaction, and esophageal manometry should be performed for evaluation of the cause of foreign body, especially in an endoscopically normal patient.

Deglutition Disorders↗

Anesthesiology Point of Care project.

We are developing a dynamic prototype visual communication system for the operating room environs. This has classically been viewed as an isolated and impenetrable workplace. All medical experiences and all teaching remain in a one to one closed loop with no recall or subsequent sharing for the training and education of other colleagues. The "Anesthesia Point of Care" (APOC) concept embraces the sharing of, recording of, and presentation of various physiological and pharmacological events so that real time memory can be shared at a later time for the edification of other colleagues who were not present at the time of the primary learning event. In addition it also provides a remarkably rapid tool for fellow faculty to respond to obvious stress and crisis events that can be broadcast instantly at the time of happening. Finally, it also serves as an efficient and effective means of paging and general communication throughout the daily routines among various healthcare providers in anesthesiology who work as a team unit; these include the staff, residents, CRNAs, physician assistants, and technicians. This system offers a unique opportunity to eventually develop future advanced ideas that can include training exercises, presurgical evaluations, surgical scheduling and improvements in efficiency based upon earlier than expected case completion or conversely later than expected case completion and even as a unique window to development of improved billing itemization and coordination.

Academic Medical Centers↗

A guided simulated annealing method for crystallography.

A new optimization algorithm, the guided simulated annealing method, for use in X-ray crystallographic studies is presented. In the traditional simulated annealing method, the search for the global minimum of a cost function is only determined by the ratio of energy change to the temperature. This method designs a new quality function to guide the search for a minimum. Using a multiresolution process, the method is much more efficient in finding the global minimum than the traditional method. Results for two large molecules, isoleucinomycin (C(60)H(102)N(6)O(18)) and an alkyl calix (C(72)H(112)O(8). 4C(2)H(6)O), with different space groups are reported.

Journal Article↗

Lignification induced by pseudomonads harboring avirulent genes on Arabidopsis.

The responses of Arabidopsis thaliana ecotypes to the bacterial pathogen Pseudomonas syringae pv. maculicola 4326 (Psm4326) harboring cloned avirulence genes avrB and avrRpt2 from P. syringae pv. glycinea were examined. Psm4326 containing avirulent genes, avrB and avrRpt2 induced lignification and peroxidase activities in the bacteria infiltrated leaves of Col-O only and not in Mt-O, Bla-2 and Po-1. However, Arabidopsis ecotypes infiltrated with Psm4326 harboring with and without avirulent genes all showed differential induction of mRNA for peroxidase gene and lignin accumulation up to 24 h after infiltration. Only avrB gene in Col-O showed strong corelationship between peroxidase mRNA expression as well as lignification gradually up to 36 h after infiltration. These results extend previous observations that avirulence genes from pathogens of one host plant can be recognized by non-host plants and provide the genetic framework for analysis of the plant-specific response to the bacterial avirulent gene products in A. thaliana.

Arabidopsis↗

Gene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells.

For gene therapy to be effective in cancers, it is necessary to deliver therapeutic genes into cells with high specificity and efficiency. In this study, we examined the in vitro and in vivo gene delivery efficiency of a new, growth receptor-mediated gene transfer system in hepatocellular carcinoma (HCC). The effects of transfection of wild-type p53 using this system were also studied. The system consisted of a ligand oligopeptide for epidermal growth factor receptor (EGFR) recognition, a polypeptide for DNA binding, and an endosome-releasing oligopeptide for endosomolysis. Two human HCC cell lines and a normal liver cell line were used, and pCMV-beta-galactosidase (beta-gal) was used as a reporter gene. Both HCC cell lines had strong expression of EGFR and the in vitro transfer efficiency peaked at day 5 at about 50%. This finding was in contrast to the normal liver cell line, which had weak EGFR expression and less than 1% transfer efficiency throughout. For in vivo gene transfer in tumors produced by inoculating HCC cells in nude mice and with the vector-beta-gal gene complex injected peritumorally, beta-gal expression was detected within the tumors at 12 hr, peaked at day 5 involving about 50% of the tumor cells and persisted at 2 weeks. Using this vector system, transfection of wild-type p53 into Huh-7 cells that had mutated p53 resulted in significant growth inhibition of cancer cells accompanied by a decreased G2/M phase and increased p53 protein. In conclusion, this receptor-mediated gene transfer system appears to work specifically in HCC cells with high efficiency, and may be promising in delivering apoptotic and other genes into HCC cells.

Antineoplastic Agents↗

Intracellular glutathione regulates taurocholate transport in HepG2 cells.

The hepatic organic anion transporter 1, Oatp1, was recently demonstrated to function as a GSH exchanger, indicating that hepatic uptake of drugs and xenobiotics may be sensitive to intracellular GSH levels. The present study characterized taurocholate uptake and efflux mechanisms in HepG2 cells and the effects of intracellular GSH on these transport processes. Taurocholate uptake into HepG2 cells was Na(+)-independent, saturable ( K(m) = 82 +/- 16 microM), and was cis-inhibited by bromosulfophthalein and some bile acids. Intracellular GSH depletion inhibited 3H-taurocholate uptake, and, conversely, the release of GSH from HepG2 cells was stimulated in the presence of extracellular taurocholate and other bile acids, consistent with a role for intracellular GSH in stimulating organic anion uptake. Interestingly, efflux of 3H-taurocholate from HepG2 cells was also sensitive to intracellular GSH concentration: efflux was inhibited in cells with lower intracellular GSH and stimulated in cells with higher GSH. RT-PCR analysis revealed that OATP-A, OATP-D, OATP-E, OATP-8, MRP1, MRP2, and MRP3 are expressed in HepG2 cells but that their expression is not altered by the maneuvers used to lower or raise intracellular GSH. These results provide direct evidence that intracellular GSH levels modulate both uptake and efflux of taurocholate and suggest that GSH plays a regulatory role in the hepatobiliary transport of potentially toxic organic compounds.

Anion Transport Proteins↗

Correlations between peripheral differential leukocyte counts and carotid atherosclerosis in non-smokers.

Substantial evidence clearly indicates the immuno-inflammatory nature of atherosclerosis and the important roles of monocytes and other leukocytes in atherogenesis. The relationship between atherosclerosis and the peripheral monocyte count, however, has been equivocal and uncertain so far. One possible reason may be an opposing effect of different major risk factors of atherosclerosis on the monocyte count, e.g. smoking increases the monocyte count while hypercholesterolemia is accompanied by a lower monocyte count. Since smoking is well shown to increase leukocyte counts prominently in weeks, our study included only non-smokers who participated in a health check program at our hospital from 1996 to 1998 and had received a carotid duplex study with extra payment. Our results revealed the followings: In male non-smokers (n=571), the presence of carotid atherosclerosis was associated with significant increases in the counts of all leukocyte, neutrophil, and monocyte (P<0.005,<0.001 and <0.05, respectively), and, after adjustments for age and body mass index, there were significant positive links between these three leukocyte counts and the severity of carotid atherosclerosis, judged by either the sum score of all carotid plaques or the score of the most severe carotid plaque. On the contrary, in female non-smokers (n=614), there was no significant link between differential leukocyte counts and either the presence or severity of carotid atherosclerosis. These results are compatible with recently recognized sex differences in the mechanism and pathophysiology of atherosclerosis, and together with relevant results in the literature, suggest that monocytes and neutrophils are the main types of leukocytes involved in atherosclerosis.

Adult↗

Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C beta4 mutant mice.

Long-term depression (LTD) at parallel fibre-Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase Cbetas (PLCbetas). PLCbetas consist of four isoforms (PLCbeta1-4) among which PLCbeta4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLCbeta4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre-Purkinje cell synapses and voltage-gated Ca2+ channel currents appeared normal. The mGluR1-mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1-mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLCbeta4 mutant mice. Wild-type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLCbeta4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLCbeta4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response.

Animals↗

Mongolian spots with involvement of the temporal area.

A Chinese baby girl was born after an uncomplicated pregnancy and a normal spontaneous vaginal delivery to a gravida 2, para 1, 32-year-old mother at 37 weeks' gestation. Neither parent had a history of alcohol or drug ingestion. There was no history of consanguinity. The Apgar scores were 7 at 1 min and 9 at 5 min. Her birth weight was 5 lb 14 oz and her length was 46 cm. At birth, she was noted to have grayish areas on the face and lower back. The infant was seen at 3 months of age because of persistent regurgitations. On average, she regurgitated 7-8 times a day. Physical examination showed that the infant was not in distress. Her weight was 6 lb 4 oz and length 47 cm. She had a Mongolian spot measuring 0.8 x 1.2 cm in the left temporal area (Fig. 1) and another Mongolian spot measuring 4 cm in diameter in the lumbar area. The Mongolian spots were grayish in color and the pigmentation was uniform in intensity. The rest of the examination was essentially normal. The infant was diagnosed to have Mongolian spots and gastroesophageal reflux. The latter was treated with postural therapy, thickened feedings, and metoclopramide 0.35 mg q.i.d. The infant was seen again at 4 months of age for a reassessment. There was no noticeable change in shape, size, or color of the Mongolian spots.

Female↗

Regional cerebral blood flow changes in patients with intractable obsessive compulsive disorders treated by limbic leukotomy.

The object of this study is to assess the changes in regional cerebral blood flow (rCBF) following stereotactic limbic leukotomy in patients with medically intractable Obsessive-Compulsive Disorder (OCD). Technetium-99-Hexa Methyl Propylene Amine Oxime (99mTc-HMPAO) Single Photon Emission Computed Tomography (SPECT) data obtained before and after limbic leukotomy were subjected to image fusion with MRI images. Eight samples were obtained from healthy voluteers. After localization of the ROI (Region Of Interest) in anatomical area, rCBF measurements were obtained by METLAB. The results of this study show a change of rCBF following limbic leukotomy in intractable OCD. Postoperative 99mTc-HMPAO SPECT findings implicate the medial frontal cortex, cingulate and striatum, which culd be linked to limbic leukotomy that blocks the functional connection of corticolimbic loop.

Adult↗

HUman MicroNucleus project: international database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei.

Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 per thousand and the interquartile range was between 3 and 12 per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.

Adolescent↗

Controlling biofilm and microbial contamination in dental unit waterlines.

Despite the fact that the ADA had set the goal of less than 200 colony-forming units per milliliter of unfiltered output water from dental unit waterlines to be achieved voluntarily by the year 2000, there is much confusion and resistance within the profession with regard to waterlines. Many in the profession are still wondering what the most effective means are to predictably achieve the goal. It is a well-established fact that bacterial biofilm can readily form within dental unit waterlines and degrade the microbial quality of the water in dental units regardless of the water source. These biofilms are primarily formed by various microcolonies of bacteria that attach to surfaces over time within the waterlines. An increasing number of medically compromised and immunocompromised patients being treated in dental offices and increased public awareness have brought about renewed interest in this issue. There are generally four categories of products that are available to address this issue: independent water systems, sterile water delivery systems, filtration, and chemical treatment protocols. A recent study at the University of California at Los Angeles demonstrates that the Ultra chemical treatment protocol can be an effective means of controlling biofilm in dental unit waterlines.

Alkalies↗

DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1.

We investigated the expression and deletion of DLC-1 (frequently deleted in liver cancer gene), first reported in 1998 and having a high homology with rat p122RhoGAP in hepatocellular carcinoma (HCC). Six (20%) of 30 human HCC samples and 2 (40%) of 5 HCC cell lines were found to have no detectable DLC-1 expression by reverse transcription-PCR. Homozygous DLC-1 deletion was detected by Southern blotting in two of six HCC samples and in both HCC cell lines with no DLC-1 expression. Transfection of DLC-1 into 5 HCC cell lines (two with DLC-1 deletion and three with intact DLC-1) showed significant growth inhibition in these two HCC cell lines with deleted DLC-1 with both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays but not in three other HCC cell lines with intact DLC-1. Our findings suggest that DLC-1 may play an important role in hepatocarcinogenesis.

Blotting, Southern↗

Modification of cardiovascular response of adenosine A2 receptor agonist by adenylate cyclase in the spinal cord of rats.

This study was performed to investigate the influence of spinal adenosine A2 receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by adenylate cyclase or guanylate cyclase. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. Injection (i.t.) of adenosine A2 receptor agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 3 nmol) produced a dose dependent decrease of BP and HR. Pretreatment with adenylate cyclase inhibitor, MDL-12,330, attenuated the depressor and bradycardiac effects of CPCA (2 nmol), but not with guanylate cyclase inhibitor, LY-83,583. These results suggest that adenosine A2 receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that the depressor and bradycardiac actions are mediated by adenylate cyclase.

Adenosine↗

Micronuclei in lymphocytes of prostate cancer patients undergoing radiation therapy.

To further verify the applicability of the micronucleus (MN) assay in biodosimetry, we measured the MN yield in cytokinesis-blocked (CB) peripheral blood lymphocytes (PBL) of eight prostate cancer (PC) patients. These patients had no previous chemotherapy or radiotherapy (xRT). They were treated with standardized schemes of fractionated pelvic xRT. Before xRT, and at one random time-point during the course of xRT, blood samples were collected from each patient for the following purposes: (1) to verify the relationship between the MN yield in PBL and the estimated equivalent (EQ) total-body absorbed dose; and (2) to evaluate the individual differences of ex vivo radiation dose-response (1-4 Gy) relationship of MN yield in PBL before xRT. The number of xRT fractions, cumulative tumor dose, and EQ total-body absorbed doses of these patients represented a wide range. We found in PBL of these patients that (1) MN yield (Y) increased linearly with the estimated EQ total-body absorbed dose as Y=14.6+9.2D (R(2)=0.7, p=0.007); the distributions of MN yield were overdispersed; the ratio of relative increment of MN yield per 1000 binucleated (BN) PBL ranged from 0.9 to 8.2 (median: 4.1) folds above that of the respective baseline levels; and (2) before xRT, the MN yields also increased linearly with the ex vivo radiation dose; at each radiation dose level, the distributions of MN yield were overdispersed in most patients. In two of the three patients with xRT-induced early side effects (cystitis, diarrhea), the MN yield in PBL induced by ex vivo irradiation before xRT was significantly higher than in the other patients without xRT-induced side effects. These findings suggest that MN yields in CB PBL can be used as an in vivo biodosimeter. Since the differences in individual ex vivo radiation dose-response relationship of MN yield in PBL before xRT appeared to be significant, our preliminary results also suggest that it may be possible to identify individual intrinsic radiosensitivity before the start of xRT.

Aged↗

Broad-spectrum sunscreen use and the development of new nevi in white children: A randomized controlled trial.

CONTEXT: High nevus density is a risk factor for cutaneous malignant melanoma. Melanocytic nevi originate in childhood and are largely caused by solar exposure. OBJECTIVE: To determine whether use of broad-spectrum, high-sun protection factor (SPF) sunscreen attenuates development of nevi in white children. DESIGN: Randomized trial conducted June 1993 to May 1996. SETTING AND PARTICIPANTS: A total of 458 Vancouver, British Columbia, schoolchildren in grades 1 and 4 were randomized in 1993. After exclusion of nonwhite children and those lost to follow-up or with missing data, 309 children remained for analysis. Each child's nevi were enumerated at the start and end of the study in 1996. INTERVENTION: Parents of children randomly assigned to the treatment group (n=222) received a supply of SPF 30 broad-spectrum sunscreen with directions to apply it to exposed sites when the child was expected to be in the sun for 30 minutes or more. Children randomly assigned to the control group (n=236) received no sunscreen and were given no advice about sunscreen use. MAIN OUTCOME MEASURE: Number of new nevi acquired during the 3 years of the study, compared between treatment and control groups. RESULTS: Children in the sunscreen group developed fewer nevi than did children in the control group (median counts, 24 vs 28; P=.048). A significant interaction was detected between freckling and study group, indicating that sunscreen use was much more important for children with freckles than for children without. Modeling of the data suggests that freckled children assigned to a broad-spectrum sunscreen intervention would develop 30% to 40% fewer new nevi than freckled children assigned to the control group. CONCLUSIONS: Our data indicate that broad-spectrum sunscreens may attenuate the number of nevi in white children, especially if they have freckles. JAMA. 2000.

Child↗