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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 235 records · Page 13Linked to original sources

Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation.

Although caffeine has been suggested as an antioxidant at millimolar concentrations, little information is available about the antioxidant activity of caffeine and its metabolites at physiological concentrations. Antioxidant activity was measured by oxygen-radical absorbing capacity (ORAC) using 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator. The antioxidant ability was tested at 40 micromol/l by determining the level of thiobarbituric acid reactive substances (TBARS) and conjugated dienes produced from the oxidation of human low density lipoprotein (LDL) by 45 mmol/l AAPH. There was neither antioxidant activity nor protective ability present with caffeine, 1,7-dimethylxanthine, 3,7-dimethylxanthine, or 1, 3-dimethylxanthine at this micromolar concentration. The antioxidant activity was however significant with 1-methylxanthine (1-X) and 1-methyluric acid (1-U), the main metabolites of caffeine in humans. The relative ORAC values of Trolox, ascorbic acid, uric acid, 1-X, and 1-U were 1:0.47:0.86:0.58:0.81, respectively, on a molar basis. These compounds also significantly reduced the level of TBARS and conjugated dienes produced from the LDL peroxidation. The antioxidant effect of 1-X is equivalent to ascorbic acid and 1-U is to uric acid.

Antioxidants↗

Fabrication of a radiation bolus prosthesis for the maxillectomy patient.

Radiation therapy has been used in the treatment of numerous head and neck malignancies. Unfortunately, this treatment also causes complications by increasing the morbidity to the surrounding tissues. The fabrication of a tissue bolus prosthesis is recommended to compensate for the loss of tissue and to help distribute the radiation homogeneously to the tissues. This article describes the procedures necessary for making an impression and fabricating a tissue bolus prosthesis. This custom-made prosthesis is simple, efficient, and atraumatic for the patient. Use of a tissue bolus prosthesis allows the radiation oncologist to adequately irradiate the tissues.

Equipment Design↗

The density of the extinction probability of a time homogeneous linear birth and death process under the influence of randomly occurring disasters.

Under the influence of randomly occurring disasters, the eventual extinction probability, q, of a birth and death process, Z, is a random variable. In this paper, we obtain an integral expression for the probability density function g(x) of q under the assumption that the population process Z is a time homogeneous linear birth and death process and the disasters occur according to an arbitrary renewal process so that its interarrival times have a density. An example is provided to demonstrate how to evaluate the integral numerically.

Birth Rate↗

Expression of the human erythrocyte glucose transporter in transitional cell carcinoma of the bladder.

OBJECTIVES: It has previously been shown that glucose uptake and use is more prevalent in carcinomas than in normal cells and tissues. We hypothesized that human erythrocyte glucose transporter (Glut-1) expression is increased in bladder transitional cell carcinoma (TCC) and that the grade of expression might correlate with the degree of malignancy. METHODS: Immunostaining of Glut-1 protein was studied in normal bladder (5 cases), benign papilloma (10 cases), superficial tumor (48 cases), and invasive tumor (31 cases) tissue. The immunoreactivity grading system used was as follows: absence of immunoreactivity in tumor cell = 0; less than 10% of the tumor cells immunoreactive = 1+; 10% to 50% of the tumor cells immunoreactive = 2+; and greater than 50% of the tumor cells immunoreactive = 3+. RESULTS: Immunostaining of Glut-1 protein was not expressed in the normal bladder or benign papilloma samples, but it was expressed in 63.0% (46 of 73) of the TCC samples. In the pattern of expression of Glut-1 protein, superficial TCC was stained focally, but invasive TCC was stained diffusely in the tumor nests. The grade of Glut-1 protein expression increased more significantly in the invasive TCC than in the superficial TCC samples (P = 0.002) and more significantly in the high nuclear grade than in the low nuclear grade samples (P = 0.007). In the superficial TCC samples, the bladder tumor recurrence rate did not significantly correlate with Glut-1 protein expression (P = 0.40). CONCLUSIONS: Our results suggest that the Glut-1 protein is not expressed in normal bladder mucosa and benign lesions, that Glut-1 protein expression is strongly associated with neoplastic progression in bladder TCC, and that Glut-1 expression does not correlate with the recurrence rate in superficial bladder TCC.

Carcinoma, Transitional Cell↗

Long-term cardiac mortality following radiation therapy for Hodgkin's disease: analysis with the relative seriality model.

PURPOSE: (a) To assess the increased risk of death due to ischemic heart disease (IHD) in a group of patients treated for Hodgkin's disease (HD) with radiation therapy (RT) as the primary treatment. (b) To quantify the dose response of IHD using a biophysical model. MATERIALS AND METHODS: Patient material consisted of 157 patients diagnosed for HD between 1972 and 1985 who received RT as the primary treatment at Radiumhemmet, Karolinska Hospital. The general population formed the control group. The RT treatments were reconstructed based on the individual treatment data and simulator films. Individual clinical and dosimetrical data were analyzed with the relative seriality model. The material was also analyzed grouping the material according to dose-volume constraints. RESULTS: Of the 157 patients, 13 (8.3%) died due to IHD. The standardized mortality ratio (SMR) was 5.0 (95% CI, 2.7-8.6). Analysis of dose-volume histograms (DVH) showed an increasing risk with increasing dose to a larger volume fraction. The observed individual clinical complication data could not be modeled unambiguously. The group analysis resulted in the dose-response parameters: D(50)=71 Gy, gamma=0.96 and s=1.0. CONCLUSIONS: A significantly increased risk of death due to IHD following RT for HD was found. The risk was found to increase with higher dose and larger volume fraction irradiated.

Adolescent↗

Characteristics of lung cancer in Korea, 1997.

The high proportion of smokers and the incidence of advanced, unresectable lung cancer in Korea were examined to aid the development of a national anti-smoking program and the early detection of lung cancer. Koreans are a single racial group with a high smoking rate among men and a contrastingly low smoking rate among women. This report documents a retrospective investigation conducted by The Korean Academy of Tuberculosis and Respiratory Disease into the characteristics of all lung cancers diagnosed between 1 January 1997 and 31 December 1997 in Korea. Among the 3794 patients included in this study, 76.8% were smokers and, in particular, 89.8% of the males were smokers. Squamous cell carcinoma was the most frequent type of lung cancer encountered (44.7%), followed by adenocarcinoma (27.9%). The smoking rate in the case of adenocarcinoma was significantly lower than that found in both squamous cell carcinoma and small cell cancer. The most common symptom was a cough. Only 7.2% of patients were asymptomatic. Bronchoscopic biopsy has a primary role in the diagnosis of squamous cell carcinoma and small cell cancer, but percutaneous needle biopsy has a more important role in the case of adenocarcinoma. Two-thirds of the nonsmall cell lung cancer patients were detected in the unresectable advanced stages (IIIB and IV). In contrast to other countries, squamous cell carcinoma is still the most frequent type of lung cancer in Korea. The high proportion of smokers and the incidence of advanced, unresectable lung cancer at diagnosis have urged development of a national anti-smoking program to promote the cessation of smoking and the early detection of lung cancer.

Adult↗

Cholinergic modulation of synaptic transmission and plasticity in entorhinal cortex and hippocampus of the rat.

Effects of cholinergic agents on synaptic transmission and plasticity were examined in entorhinal cortex and hippocampus. Bath application of carbachol (0.25-0.75 microM) induced transient depression of field potential responses in all cases tested (24/24 in layer III of medial entorhinal cortex slices and 24/24 in CA1 of hippocampal slices; 11.0+/-1.9% and 7.8+/-2.5%, respectively) and long-lasting potentiation in some cases (4/24 in entorhinal cortex and 12/24 in hippocampus; 33.7+/-3.7% and 32.1+/-9.9%, respectively, in successful cases). Carbachol (0.5 microM) induced transient depression, but not long-lasting potentiation, of N-methyl-D-aspartate receptor-mediated responses in entorhinal cortex. At 5 microM, carbachol induced transient depression only (55. 9+/-4.7% in entorhinal cortex and 41.4+/-2.9% in hippocampus), which was blocked by atropine. Paired-pulse facilitation was not altered during carbachol-induced potentiation but enhanced during carbachol-induced depression. These results suggest that the underlying mechanisms of carbachol-induced depression and potentiation are decreased transmitter release and selective enhancement of non-N-methyl-D-aspartate receptor-mediated responses, respectively. Long-term potentiation could be induced in the presence of 10 microM atropine by theta burst stimulation. The magnitude was significantly lower (15.2+/-5.2%, n=9) compared with control (37.2+/-6.1%, n=8) in entorhinal cortex, however. These results demonstrate similar, but not identical, cholinergic modulation of synaptic transmission and plasticity in entorhinal cortex and hippocampus.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Antiherpetic activities of acidic protein bound polysacchride isolated from Ganoderma lucidum alone and in combinations with interferons.

To investigate antiherpetic activity, an acidic protein bound polysaccharide (APBP) was isolated from carpophores of Ganoderma lucidum. This brownish APBP was isolated from water soluble substances of the carpophores by activity-guided isolation method. APBP was tested for its antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay in tissue culture. APBP showed potent antiviral activity against HSV-1 and HSV-2 in Vero cells at its 50% effective concentration (EC(50)) of 300 and 440 microg/ml, respectively. APBP had no cytotoxicity on Vero cells at a concentration of 1x10(4) microg/ml. APBP exhibited a potent antiviral activity with selectivity index (SI) of more than 22.73. The combined antiherpetic effects of APBP with protein antiviral agents, interferon alpha (IFN alpha) and interferon gamma (IFN gamma), were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of APBP with IFN alpha on HSV-1 and HSV-2 showed more potent synergistic effects with CI values of 0.30-0.62 for 50-90% effective levels than those of APBP with IFN gamma with CI values of 0.65-1.10. These results suggest the possibility of developing APBP as a new antiherpetic agent.

Animals↗

Interstitial colocalization of two cervid satellite DNAs involved in the genesis of the Indian muntjac karyotype.

A number of repetitive DNA clones were generated from PCR amplifications of Indian muntjac genomic DNA using primer sequences derived from a white tailed deer satellite II DNA sequence. One clone (Mmv-0.7) was characterized and shown to be a cervid satellite II DNA clone. Multiple colored FISH studies with cervid satellite I (C5) and this satellite II clone (Mmv-0.7) to Chinese muntjac metaphase chromosomes localized both satellite DNAs at the pericentromeric regions of all chromosomes except for chromosome 3 and the Y chromosome, whereas chromosome 3 exhibited pericentromeric satellite II DNA only. Where distinguishable, the pericentromeric satellite II signals appeared terminally oriented with respect to satellite I. Six pairs of Chinese muntjac autosomes had interstitial satellite I sites with four of these autosomal pairs (chromosomes 1, 2 and two other smaller autosomal pairs) also exhibiting interstitial satellite II signals. An interstitial site on the X chromosome was found to have satellite II signals. For the Indian muntjac chromosomes, FISH studies revealed a pericentromeric hybridization for satellites I and II as well as 27 distinct interstitial hybridization sites, each having at least one of the satellite DNAs. These data were used to more precisely define the chromosome fusion-associated breakpoints that presumably led to the formation of the present-day Indian muntjac karyotype. It further hints at the possibility that the Indian muntjac karyotype may have evolved directly from a 2n = 70 ancestral karyotype rather than from an intermediate 2n = 46 Chinese muntjac-like karyotype.

Animals↗

Genetic evaluation of pervasive developmental disorders: the terminal 22q13 deletion syndrome may represent a recognizable phenotype.

The evaluation of mental retardation is always a challenge to clinicians. The recognition of specific physical or behavioral characteristics can vastly improve diagnostic yield. Several genetic disorders have been identified to have certain behavioral characteristics, such as Williams syndrome, Smith-Magenis syndrome, and the velocardiofacial syndrome (VCFS). The deletion affecting the chromosome 22q in the most distal band (22q13) appears to define yet another neurobehavioral phenotype. In addition to our report, there are about 17 other cases published of this particular deletion syndrome. We describe three children who share features of developmental delay and pervasive behaviors in addition to normal to advanced growth patterns. Results of cytogenetic analysis suggest that the 3 patients share a deletion affecting the terminal 22q13 region. Two were found to have a cryptic deletion, in the third it was detected by conventional cytogenetics. The cryptic deletions were demonstrated using fluorescent in situ hybridization (FISH), where the control probe for the DiGeorge/VCFS region was deleted. While there remain gaps in our understanding of this particular deletion syndrome, we propose that patients with normal or advanced growth, significantly delayed speech, deviant development and pervasive behaviors, with minor facial dysmorphism, be screened for this deletion.

Autistic Disorder↗

Establishment and characterization of seven human renal cell carcinoma cell lines.

OBJECTIVE: To establish human renal cell carcinoma (RCC) cell lines, and to investigate the cell phenotypes and molecular characteristics of human RCC cell lines and their corresponding tumour tissues. MATERIALS AND METHODS: Seven human RCC cell lines from pathologically proven RCCs were established. The histopathology of the primary tumours, in vitro growth characteristics and status of tumour suppressor genes, mismatch repair genes and microsatellite instability (MSI) were examined in cell lines and their corresponding tumour tissues. Five of the cell lines were derived from clear cells (SNU-228, -267, -328, -349, and -1272), one from granular cells (SNU-482), and one from mixed clear and granular cell types (SNU-333). The mutational status was compared for von Hippel-Lindau (VHL), p53, TGF-beta type II receptor (TGF-betaRII), hMSH2, and hMLH1 genes in the cell lines and their corresponding tumour tissues. The MSI status of the cell lines was determined by screening for adenine repeat sequences, e.g. BAT-25, BAT-26, and BAT-40. RESULTS: All lines showed different doubling times and were confirmed by DNA fingerprinting analysis to be unique. Contamination by mycoplasma or bacteria was excluded. In two cell lines (SNU-349 and -1272) and their tumour tissues, mutations in the VHL gene were found. The SNU-267 line had a frameshift mutation in the p53 gene. A missense mutation of the TGF-betaRII gene was detected in the SNU-1272 line and the corresponding tissue. Analysis of the repeat sequences showed one cell line (SNU-349) to have MSI and the other six to have microsatellite stability. As MSI is a hallmark of the inactivation of mismatch repair genes, the presence of hMSH2 and hMLH1 mutations was investigated in all seven cell lines. An inactivating homozygous single base-pair deletion of the hMLH1 gene was found only in the SNU-349 cell line and corresponding tissue. Moreover, a frameshift mutation within an 8-bp polyadenine repeat present in the hMSH3 coding region was found only in the MSI cell line and tumour tissue. CONCLUSION: These newly established RCC cell lines should provide a useful in vitro model for studies related to human RCC. The SNU-349 cell line should be especially useful for studies of MSI and mismatch repair-defective RCCs.

Aged↗

Clinical pharmacokinetic and in vitro combination studies of nolatrexed dihydrochloride (AG337, Thymitaq) and paclitaxel.

A clinical study of nolatrexed dihydrochloride (AG337, Thymitaq) in combination with paclitaxel was performed. The aims were to optimize the schedule of administration and determine any pharmacokinetic (PK) interactions between the two drugs. In vitro combination studies were performed to assist with schedule optimization. Three patients were entered on each of three different schedules of administration of the two drugs: (1) paclitaxel 0-3 h, nolatrexed 24-144 h; (2) nolatrexed 0-120 h, paclitaxel 48-51 h; (3) nolatrexed 0-120 h, paclitaxel 126-129 h. Paclitaxel was administered at a dose of 80 mg m(-2) over 3 h and nolatrexed at a dose of 500 mg m(-2) day(-1) as a 120-h continuous intravenous infusion. Plasma concentrations of both drugs were determined by high performance liquid chromatography. In vitro growth inhibition studies using corresponding schedules were performed using two head and neck cancer cell lines. In both HNX14C and HNX22B cell lines, synergistic growth inhibition was observed on schedule 2, whereas schedules 1 and 3 demonstrated antagonistic effects. In the clinical study, there was no effect of schedule on the pharmacokinetics of nolatrexed. However, patients on schedules 1 and 3 had a higher clearance of paclitaxel (322-520 ml min(-1) m(-2)) than those on schedule 2 (165-238 ml min(-1) m(-2)). Peak plasma concentrations (1.66-1.93 vs. 0.86-1.32 microM) and areas under the curve (392-565 vs. 180-291 microM min(-1)) of paclitaxel were correspondingly higher on schedule 2. The pharmacokinetic interaction was confirmed by studies with human liver microsomes, nolatrexed being an inhibitor of the major routes of metabolism of paclitaxel. Toxicity was not schedule-dependent. Nolatrexed and paclitaxel may be safely given together when administered sequentially at the doses used in this study. Studies in vitro suggest some synergy, however, due to a pharmacokinetic interaction, paclitaxel doses should be reduced when administered during nolatrexed infusion.

Adult↗

Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells.

The objective of this study is to determine if a non-immunogenic Dunning's rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-beta1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta1 (TGF-beta1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta1 reduced from 70 to 10 pg per 2x10(4) cells and the rate of in vitro 3H-thymidine incorporation increased 3-5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P< or =0.05) for cells transfected with TGF-beta1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-beta1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta1 is down-regulated.

Animals↗

Leisure time physical activity in Australian women: relationship with well being and symptoms.

This paper explores the association between moderate levels of physical activity (PA) and health benefits in well being and symptoms such as tiredness, back pain, and constipation. Participants in the Australian Longitudinal Study on Women's Health, 14,502 young women (ages 18-23 years), 13,609 middle-age women (45-50 years), and 11,421 older women (ages 70-75 years), answered questions about vigorous and less vigorous exercise (used to determine a physical activity score), well being (SF-36), symptoms, and medical conditions. There were significant associations between the PA score and SF-36 in each cohort. Odds ratios (OR) for a range of symptoms and conditions were lower for women who reported low to moderate activity than for sedentary women, for example, for young women or for constipation = 0.76 (CI, 0.65-0.89), for middle-age women or for tiredness = 0.70 (0.63-0.78). There was no threshold of PA at which health benefits increased significantly. Although cross-sectional, the findings suggest that low-to-moderate levels of exercise are associated with a range of health benefits for women of all ages. These preliminary findings will be followed up during the longitudinal study.

Adolescent↗

Psychological stress may induce increased humoral and decreased cellular immunity.

Stress alters immune function and affects different immune cell populations in different ways. The authors examined whether psychological stress has different effects on the production of macrophage, T-helper 1(Th1) cell, and T-helper 2(Th2) cell-derived cytokines. Forty-two college students were recruited and their blood was sampled on the day they were to take a stressful academic examination and again 4 weeks after the examination. The stress from the academic examination significantly increased IL-1 beta, IL-6, and IL-10 and decreased IFN-gamma production. These findings suggest that examination stress may increase Th2 cell-mediated humoral immunity and macrophage activities and may decrease Th1 cell-mediated cellular immunity.

Adult↗

Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home.

OBJECTIVE: To describe the use of zanamivir during an influenza A outbreak. POPULATION: Residents of a 176-bed long-term-care facility for the elderly in Newmarket, Ontario, Canada, 90% of whom received influenza vaccine in the fall of 1998. OUTBREAK: When respiratory illness due to influenza A was confirmed, infection control measures and amantadine prophylaxis were initiated. Despite these measures, transmission of influenza A continued. INTERVENTION: Zanamivir inhalations, 10 mg daily for prophylaxis and 10 mg twice daily for treatment of influenza. RESULTS: There were 13 definite and 66 probable outbreak-associated cases of influenza A. Twelve (15%) cases developed pneumonia, 7 (9%) were hospitalized, and 2 (2.6%) died. All 12 culture-positive cases yielded influenza A/Sydney/H3N2/05/97-like virus, a 1998/99 vaccine component. The three isolates obtained prior to the initiation of amantadine were amantadine-susceptible; all nine obtained after prophylaxis was instituted were amantadine-resistant. One hundred twenty-nine (92%) of 140 residents who were offered zanamivir accepted it and were able to attempt inhalations. Of these 129, 78% (100) had no difficulty in complying with inhalations. Difficulty with inhalations was associated with decreased functional and mental status. Fifteen (58%) of 26 residents fully dependent in activities of daily living had difficulty compared to 14 (14%) of 100 others (P<.001). Twenty-two (45%) of 49 residents not oriented to person, place, or time had difficulty compared to 7 (10%) of 77 others (P<.001). In the 2 weeks after zanamivir prophylaxis, only 2 new cases of respiratory illness occurred, neither confirmed as influenza. No side effects were identified in 128 zanamivir-treated residents. CONCLUSION: A minority of nursing home residents have difficulty following instructions for zanamivir inhalations. Zanamivir was well tolerated, and its use was temporally associated with termination of an outbreak that amantadine had failed to control.

Activities of Daily Living↗

Saccharomyces cerevisiae BUB2 prevents mitotic exit in response to both spindle and kinetochore damage.

The spindle assembly checkpoint-mediated mitotic arrest depends on proteins that signal the presence of one or more unattached kinetochores and prevents the onset of anaphase in the presence of kinetochore or spindle damage. In the presence of either damage, bub2 cells initiate a preanaphase delay but do not maintain it. Inappropriate sister chromatid separation in nocodazole-treated bub2 cells is prevented when mitotic exit is blocked using a conditional tem1(c) mutant, indicating that the preanaphase failure in bub2 cells is a consequence of events downstream of TEM1 in the mitotic exit pathway. Using a conditional bub2(tsd) mutant, we demonstrate that the continuous presence of Bub2 protein is required for maintaining spindle damage-induced arrest. BUB2 is not required to maintain a DNA damage checkpoint arrest, revealing a specificity for spindle assembly checkpoint function. In a yeast two-hybrid assay and in vitro, Bub2 protein interacts with the septin protein Cdc3, which is essential for cytokinesis. These data support the view that the spindle assembly checkpoint encompasses regulation of distinct mitotic steps, including a MAD2-directed block to anaphase initiation and a BUB2-directed block to TEM1-dependent exit.

Cell Cycle↗