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Biomedical subjects

H Lee

Publications and source records attributed to H Lee.

At least 415 records · Page 23Linked to original sources
PubMed1998

Diagnostic criteria for essential tremor: a population perspective.

BACKGROUND: Prevalence estimates vary 2750-fold among the 20 studies of essential tremor (ET). It is not clear how the choice of diagnostic criteria affects research results. OBJECTIVE: To determine the impact of alternative sets of diagnostic criteria on the diagnosis of ET. METHODS: As part of the Washington Heights-Inwood Genetic Study of ET (WHIGET), a population-based study of ET, 285 subjects who include 36 case subjects with probable or definite ET, 34 case subjects with possible ET, and 215 normal subjects were interviewed and examined. All diagnoses in WHIGET were assigned by 2 neurologists. Ten of the 20 published prevalence studies of ET provided diagnostic criteria for ET. Criteria differed in terms of requirements for the distribution, duration, and severity of tremor. These 10 sets of criteria were then each separately applied to the subjects in the WHIGET cohort to determine their impact on the diagnosis of ET. RESULTS: Depending on which diagnostic criteria were applied to the WHIGET cohort, the proportion of WHIGET case subjects with definite or probable ET who would have been diagnosed as having ET was as low as 14% and the proportion of WHIGET normal subjects who would have been diagnosed as having ET was as high as 51%. Diagnostic criteria that included a positive family history of ET or a lengthy duration of tremor would have classified many WHIGET case subjects with ET as normal, whereas criteria that did not specify a minimal tremor severity would have classified many WHIGET normal subjects as having ET. CONCLUSIONS: Alternative sets of diagnostic criteria for ET greatly impact on the diagnosis of ET. For population-based studies, information on tremor type and severity rather than family history should be included in diagnostic criteria.

Adolescent↗
PubMed1998

The structure and function of yeast xylose (aldose) reductases.

Yeast xylose (aldose) reductases are members of the aldo-keto reductase family of enzymes which are widely distributed in a variety of other organisms. In yeasts, these enzymes catalyse the first step of xylose metabolism where xylose is converted to xylitol. In the past 16 years, xylose reductases from yeasts able to ferment or utilize xylose have been isolated and studied mainly because of their importance in xylose bioconversions. In recent years, genes encoding xylose reductases from several yeasts have been cloned and sequenced. A comparison of the primary sequences of yeast xylose reductases with the much better characterized human aldose reductase and human aldehyde reductase reveals that the yeast enzymes are hybrids between aldo-keto reductases and the short chain dehydrogenases/reductases families of enzymes. Why this is so and its evolutionary significance is presently not known. This short review will critically examine the structure and function information that can be gleaned from the sequence comparison. Several interesting questions arise from the sequence comparison and these can provide fruitful areas for further investigations.

Aldehyde Reductase↗
PubMed1998

Correlation between the amounts of polycyclic aromatic hydrocarbons and mutagenicity of airborne particulate samples from Taichung City, Taiwan.

Taichung is the largest city in the central part of Taiwan, and its air pollution problems are similar to those in other large cities around the world. To evaluate the potential of the air pollution and identify major pollutant sources in this city, 181 airborne particulate samples were collected biweekly from seven locations around Taichung over an entire year. The mutagenicity of acetone extracts of the air samples was evaluated using the Salmonella/microsomal test with Salmonella typhimurium TA98 in the presence and absence of S9 mixtures. The air samples from September 1994 showed the highest direct and indirect mutagenicity among the 12 months, whereas those from October and June had the lowest direct and indirect mutagenicity, respectively. To elucidate the correlation between mutagenicity and polycyclic aromatic hydrocarbons (PAHs), high-performance liquid chromatography was used to determine the amount of each of 10 PAHs in the air samples. Among the 10 PAHs, the monthly average amount of B[g,h,i]P in the samples was the highest, followed by B[a]FA, B[a]P, and B[k]FA. Linear regression analysis showed a positive correlation between monthly average total amounts of PAHs and indirect mutagenicity. The monthly average amount of B[g,h,i]P was correlated more with indirect mutagenicity than with other PAHs. B[g,h,i]P is an indicator PAH emitted from both diesel and gasoline engine exhaust. Thus, we suggest that mobile air pollutant sources in Taichung City may be more significant than stationary ones. Moreover, B[g,h,i]P seems to act as a mutagenicity indicator compound in air samples from Taichung City.

Air Pollutants↗
PubMed1998

Expression of gonadotropin-releasing hormone (GnRH) and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells.

The purpose of this study was to determine the production of gonadotropin-releasing hormone (GnRH), the co-occurrence of GnRH receptors in prostate cancer cells, and the effect of GnRH on prostate cancer cell proliferation. Four human prostate cancer cell lines were studied. LNCaP is an androgen sensitive prostate cancer cell line, DU-145 and PC-3 are androgen resistant, and TSU-Pr1 is uncharacterized. The expression of GnRH and GnRH receptor mRNAs were assessed by in situ hybridization and the effect of exogenous GnRH on proliferation of prostate cancer cells was measured by thymidine incorporation assay. GnRH mRNA expression, determined by in situ hybridization, was found in 83.48% of the LNCaP, 89.7% of the TSU-Pr1, 86.2% of the PC-3 and 95.3% of the DU-145. Signals of GnRH receptor mRNA were detected in more than 95% of the cells of all four cell lines. The proliferation of the prostate cancer cells grown in media supplemented with peptide hormone lacking charcoal-stripped serum was significantly (P < 0.05) suppressed. No significant effect of GnRH on the proliferation of all four prostate cancer cells was observed. In summary, prostate cancer cells produced GnRH and its receptors, and exogenous GnRH treatment did not affect the prostate cancer cell proliferation. The existence of GnRH and GnRH receptor mRNA in the same cell suggests that the role of GnRH produced by prostate cancer cells would be autocrine.

Cell Division↗
PubMed1998

Gastric bypass operation for obesity.

Gastric bypass is considered by many to be the gold standard for surgical treatment of obesity. Gastric bypass was a natural evolution from gastric operations that were used for the treatment of peptic ulcer disease. Gastric bypass, first described in 1967, has undergone many modifications. It presently exists as a hybrid operation. Gastric bypass operation has been extensively scrutinized and evaluated against other operations for the treatment of obesity. Co-morbidities due to severe obesity are usually ameliorated or arrested after the weight loss from gastric bypass. Gastric bypass operation is now being performed with a perioperative morbidity of less than 10%. The average percentage excess weight loss with gastric bypass is 70%. The success rate, defined as 50% excess weight loss after at least 2 years of follow-up, is 85%. The metabolic deficiencies of gastric bypass are controllable with supplemental intake. This report with special references to the Fobi pouch operation, a modification of gastric bypass done by the author, presents the evolution, modifications, risk, outcome, and future trends of gastric bypass for treatment of obesity.

Adult↗
PubMed1998

Involvement of Brca2 in DNA repair.

Abnormalities precipitated by a targeted truncation in the murine gene Brca2 define its involvement in DNA repair. In culture, cells harboring truncated Brca2 exhibit a proliferative impediment that worsens with successive passages. Arrest in the G1 and G2/M phases is accompanied by elevated p53 and p21 expression. Increased sensitivity to genotoxic agents, particularly ultraviolet light and methylmethanesulfonate, shows that Brca2 function is essential for the ability to survive DNA damage. But checkpoint activation and apoptotic mechanisms are largely unaffected, thereby implicating Brca2 in repair. This is substantiated by the spontaneous accumulation of chromosomal abnormalities, including breaks and aberrant chromatid exchanges. These findings define a function of Brca2 in DNA repair, whose loss precipitates replicative failure, mutagen sensitivity, and genetic instability reminiscent of Bloom syndrome and Fanconi anemia.

Animals↗
PubMed1998

Osmotin, a plant antifungal protein, subverts signal transduction to enhance fungal cell susceptibility.

The plant pathogenesis-related protein osmotin is an antifungal cytotoxic agent that causes rapid cell death in the yeast S. cerevisiae. We show here that osmotin uses a signal transduction pathway to weaken defensive cell wall barriers and increase its cytotoxic efficacy. The pathway activated by osmotin includes the regulatory elements of the mating pheromone response STE4, STE18, STE20, STE5, STE11, STE7, FUS3, KSS1, and STE12. Neither the pheromone receptor nor its associated G protein alpha subunit GPA1 are required for osmotin action. However, mutation of SST2, a negative regulator of G alpha proteins, resulted in supersensitivity to osmotin. Phosphorylation of STE7 was rapidly stimulated by osmotin preceding any changes in cell vitality or morphology. These results demonstrate that osmotin subverts target cell signal transduction as part of its mechanism of action.

Antifungal Agents↗
PubMed1998

Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus.

At a position equivalent to the gene encoding the saimiri transforming protein (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) contains a distinct open reading frame called K1. Although KSHV and HVS are related members of the rhadinovirus subgroup of gamma herpesviruses, K1 and STP exhibit no similarity in amino acid sequence or in structural organization. Since STP is required for the oncogenic potential of HVS, we investigated the functional consequence of K1 expression. Expression of the K1 gene in rodent fibroblasts produced morphologic changes and focus formation indicative of transformation. A recombinant herpesvirus in which the STP oncogene of HVS was replaced with K1, immortalized primary T lymphocytes to IL-2 independent growth and induced lymphoma in common marmosets. These results demonstrate the transforming potential of the K1 gene of KSHV.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Formation of spheroidal aggregates of hepatocytes on biodegradable polymers under continuous-flow bioreactor conditions.

Our laboratory has investigated heterotopic hepatocyte transplantation on biodegradable polymer matrices as an experimental treatment for end-stage liver disease. One of the limitations has been survival of sufficient cell mass after transplantation. We hypothesize that in vitro conditioning of cells within polymer matrices prior to implantation may increase hepatocyte survival and function. In this preliminary study we investigated the effect of continuous flow on hepatocytes and sinusoidal endothelial cells on poly-L-lactic acid (PLLA) discs in vitro. Highly porous PLLA discs were manufactured measuring 18 mm diameter by 1 mm thickness using previously described techniques. Hepatocytes were isolated from adult, male Lewis rats (200-300 g) using a two-step collagenase digestion. Sinusoidal endothelial cells were isolated using a two-step collagenase digestion, differential sedimentation, Percoll gradient centrifugation, and selective adherence. PLLA discs were seeded with hepatocytes alone or with co-cultures of hepatocytes and sinusoidal endothelial cells. Seeded discs were then secured within a flow bioreactor chamber and exposed to continuous flow of culture media at a rate of 20 ml/minute through the chamber. Seeded discs placed in static culture conditions served as controls. Specimens seeded with only hepatocytes were harvested at 24 hours, 48 hours, and 168 hours after seeding. Co-culture specimens were harvested after 168 hours. Specimens were viewed under phase-contrast microscopy and then formalin-fixed and prepared for histologic sectioning. Sections were stained with Hematoxylin and Eosin and then analyzed with light microscopy. Hepatocytes under flow conditions formed spheroidal aggregates of cells of 50 to 200 microns in diameter by 24 hours in culture. Hepatocytes in static conditions showed decreased aggregation of cells and spheroid formation was absent. Co-cultured specimens under flow also showed spheroid formation with endothelial cells lining the outside of hepatocyte spheroids. Co-cultured specimens in static culture showed no spheroid formation and no organization between sinusoidal endothelial cells and hepatocytes. These results suggest that continuous flow increases organization of hepatocytes cultured within biodegradable polymer matrices.

Animals↗
PubMed1998

Changes in binge drinking and related problems among American college students between 1993 and 1997. Results of the Harvard School of Public Health College Alcohol Study.

In 1997, the Harvard School of Public Health College Alcohol Study resurveyed colleges that participated in a 1993 study. The findings revealed little change in binge drinking: a slight decrease in percentage of binge drinkers and slight increases in percentages of abstainers and frequent binge drinkers. Two of 5 students were binge drinkers (42.7%); 1 in 5 (19.0%) was an abstainer, and 1 in 5 was a frequent binge drinker (20.7%). As was true in 1993, 4 of 5 residents of fraternities or sororities were binge drinkers (81.1%). Asian students showed a greater increase and White students a greater decrease in binge drinking from 1993 to 1997, compared with all other students. Among students who drank alcohol, increases in frequency of drinking; drunkenness; drinking to get drunk; and alcohol-related problems, including drinking and driving, were reported. Binge drinkers in both 1993 and 1997 were at increased risk of alcohol-related problems, and nonbingers at colleges with high binge drinking rates had increased risks of encountering secondhand effects of binge drinking.

Adolescent↗
PubMed1998

Characterization of the carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in cooking aerosols under domestic conditions.

Lung cancer in women is the leading cause of cancer death in Taiwan. Most Chinese women are non-smokers and 60% of female lung cancer patients have adenocarcinomas. Epidemiological data indicate that the incidence of lung cancer among Chinese women may be correlated with cooking fumes. However, the carcinogenic compound(s) in cooking fume aerosols is not defined. In the present study, the cooking aerosols from Chinese stir-frying of fish were prepared under domestic conditions. To determine the mutagenic compounds in the cooking aerosol, mutagens were purified by two steps of high-performance liquid chromatography (HPLC), and their mutagenicity was monitored with Salmonella typhimurium TA98. The mutagen was eluted as a single peak. The chemical structure of the mutagenic fraction of cooking aerosol from frying of fish was characterized by UV spectra and electrospray mass spectrometry. The bacterial indirect-acting mutagenic compound in the cooking aerosol extract was determined to be 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). An amount of 0.25 ng MeIQx/g of meat per min was estimated based on the mutagenic response. These data indicated that significant amounts of MeIQx (268.1 ng/Chinese dish of frying fish) were present in cooking aerosol in a short time. Chinese women spend approximately 1 h preparing meals everyday, thus, they may be exposed to significant amounts of MeIQx from cooking aerosols in the kitchen.

Aerosols↗
PubMed1998

Amphetamines in hair by enzyme-linked immunosorbent assay.

Human hair was collected from the occipital crown region of the head from several subjects; these hair samples were presumptively positive for amphetamines by a previously evaluated immunoassay. Hair was washed briefly with methanol to remove external contamination, then extracted with hot methanol for 2 h to recover the drugs. The extracts were evaporated to dryness, reconstituted in buffer, and analyzed using a new enzyme-linked immunosorbent assay (ELISA) technique adapted for the detection of amphetamines in hair. Gas chromatography-mass spectrometry was used as the reference technique. Cross-reactivity of several related compounds was evaluated by equating the inverse of the ligand concentration at 50% antibody binding to the affinity constant for each compound. The ratio of a compound's affinity constant to that for d-methamphetamine was used to derive percent crossreactivity. These experiments yielded values of 30.8% for d-amphetamine, 7.4% for I-methamphetamine, 4.3% for phentermine, 2.9% for I-amphetamine, and <1% for ephedrine, methylenedioxyamphetamine, and methylenedioxymethamphetamine. Cross-reactivity of unrelated compounds was found to be non-existent. The optimum cutoff concentration was determined by receiver operating characteristic curve analysis to be 300 pg/mg and the observed limit of detection was 60 pg/mg. Intra-assay precision at 300 pg/mg was 3.3% (coefficient of variation, CV), and the interassay CV was 10.5%. The sensitivity and specificity of the method were 83% and 92%, respectively.

Amphetamine-Related Disorders↗
PubMed1998

Creatine synthesis and transport systems in the male rat reproductive tract.

Previous studies from this laboratory showed that high levels of guanidinoacetate methyltransferase are present in mouse testis and epididymis, whereas guanidinoacetate methyltransferase mRNA and protein are not detected in seminal vesicles where large amounts of creatine (Cr) and phosphocreatine are found (Lee et al., Biol Reprod 1994; 50:152-162). To further investigate the origin(s) of Cr in the male reproductive tract, the expression patterns of the three enzymes and a transporter involved in Cr metabolism were examined with rat reproductive tissues. Western blot analysis showed that expression of L-arginine:glycine amidinotransferase was limited to the kidney. On the other hand, high levels of the mRNAs for both guanidinoacetate methyltransferase and Sadenosylhomocysteine hydrolase were expressed in the testis and epididymis as well as the liver and kidney. Cr transporter mRNA was highly expressed in the seminal vesicle and vas deferens. These results suggest that the source of Cr in the male reproductive tract varies depending on the tissue; in the testes and epididymides, Cr is synthesized from guanidinoacetate, while in the seminal vesicles, Cr is transported from blood. Previous and present findings suggest the importance of Cr metabolism and/or transport for reproductive functions.

Adenosylhomocysteinase↗
PubMed1998

HOS1, a genetic locus involved in cold-responsive gene expression in arabidopsis.

Low-temperature stress induces the expression of a variety of genes in plants. However, the signal transduction pathway(s) that activates gene expression under cold stress is poorly understood. Mutants defective in cold signaling should facilitate molecular analysis of plant responses to low temperature and eventually lead to the identification and cloning of a cold stress receptor(s) and intracellular signaling components. In this study, we characterize a plant mutant affected in its response to low temperatures. The Arabidopsis hos1-1 mutation identified by luciferase imaging causes superinduction of cold-responsive genes, such as RD29A, COR47, COR15A, KIN1, and ADH. Although these genes are also induced by abscisic acid, high salt, or polyethylene glycol in addition to cold, the hos1-1 mutation only enhances their expression under cold stress. Genetic analysis revealed that hos1-1 is a single recessive mutation in a nuclear gene. Our studies using the firefly luciferase reporter gene under the control of the cold-responsive RD29A promoter have indicated that cold-responsive genes can be induced by temperatures as high as 19 degrees C in hos1-1 plants. In contrast, wild-type plants do not express the luciferase reporter at 10 degrees C or higher. Compared with the wild type, hos1-1 plants are l ess cold hardy. Nonetheless, after 2 days of cold acclimation, hos1-1 plants acquired the same degree of freezing tolerance as did the wild type. The hos1-1 plants flowered earlier than did the wild-type plants and appeared constitutively vernalized. Taken together, our findings show that the HOS1 locus is an important negative regulator of cold signal transduction in plant cells and that it plays critical roles in controlling gene expression under cold stress, freezing tolerance, and flowering time.

Arabidopsis↗
PubMed1998

In vivo assay of protein-protein interactions in Hin-mediated DNA inversion.

In order to form the catalytic nucleoprotein complex called the invertasome in the Hin-mediated DNA inversion reaction, interactions of the DNA-binding proteins Hin and Fis are required. Assays for these protein-protein interactions have been exploited with protein cross-linkers in vitro. In this study, an in vivo assay system that probes protein-protein interactions was developed. The formation of a DNA loop generated by protein interactions resulted in transcriptional repression of an artificially designed operon, which in turn increased the chance of survival of Escherichia coli host cells in a streptomycin-containing medium. Using this system, we were able to assay the Hin-Hin interaction that results in the pairing of the two recombination sites and protein interactions that result in the formation of the invertasome. This assay system also led us to find that an individual Hin dimer bound on a recombination site can form a stable complex with Fis bound on the recombinational enhancer; this finding has never been observed in in vitro studies. Possible pathways toward the formation of the invertasome are discussed based on the assay results for a previously reported Hin mutant.

Bacterial Proteins↗