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Biomedical subjects

T Chen

Publications and source records attributed to T Chen.

At least 73 records · Page 4Linked to original sources
PubMed2001

Comparison of hprt and lacI mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminofluorene-treated Big Blue rats.

N-Hydroxy-2-acetylaminofluorene (N-OH-AAF) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene. In this study, transgenic Big Blue(R) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues. Male rats were given one, two, or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals, and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing. Mutant frequencies were measured in the spleen lymphocyte hprt gene, and lacI mutant frequencies were determined in the liver and spleen lymphocytes. At 6 weeks after beginning the dosing, the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 x 10(-6) compared with 3.2 x 10(-6) in control animals. Also at 6 weeks, rats given one, two, or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6, 155.6, and 406.8 x 10(-6), respectively, compared with a control frequency of 25.7 x 10(-6); rats given four doses had lacI mutant frequencies in spleen lymphocytes of 55.8 x 10(-6) compared with a control frequency of 20.4 x 10(-6). Additional rats were evaluated for DNA adduct formation in the liver, spleen lymphocytes, and bone marrow by (32)P-postlabeling. Adduct analysis was conducted 1 day after one, two, and four treatments with N-OH-AAF, 5 days after one treatment, and 9 days after two treatments. N-(Deoxyguanosin-8-yl)-2-aminofluorene was the major DNA adduct identified in all the tissues examined. Adduct concentrations increased with total dose to maximum values in samples taken 1 day after two doses, and remained essentially the same after four doses. In samples taken after four doses, adduct levels were 103, 28, and 7 fmol/microg of DNA in liver, spleen lymphocytes, and bone marrow, respectively. The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat. Environ. Mol. Mutagen. 37:195-202, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene.

In a previous study, we found that treating transgenic Big Blue rats with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene (N-OH-AAF) produced the same major DNA adduct in the target liver and the nontarget spleen lymphocytes and bone marrow cells, induced lacI mutants in the liver, and induced much lower frequencies of lacI and hprt mutants in spleen lymphocytes. In the present study, sequence analysis was conducted on lacI DNA and hprt cDNA from the mutants, to determine the mutational specificity of N-OH-AAF in the rat. All the mutation spectra from N-OH-AAF-treated rats differed significantly from corresponding mutation profiles from untreated animals (P = 0.02 to P < 0.0001). Although there were similarities among the mutational patterns derived from N-OH-AAF-treated rats (e.g., G:C --> T:A transversion was the most common mutation in all mutation sets), there were significant differences in the patterns of basepair substitution and frameshift mutation between the liver and spleen lymphocyte lacI mutants (P = 0.02) and between the spleen lymphocyte lacI and hprt mutants (P = 0.04). Also, multiplex PCR analysis of genomic DNA from the hprt mutants indicated that 12% of mutants from treated rats had major deletions in the hprt gene; no corresponding incidence of large deletions was evident among lacI mutations. All the mutation profiles reflect the general mutational specificity of the major DNA adduct formed by N-OH-AAF. The differences between N-OH-AAF mutation in the endogenous gene and transgene can be partially explained by the structures of the two genes. The tissue-specificity of the mutation spectra may contribute to targeting tumor formation to the liver. Environ. Mol. Mutagen. 37:203-214, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

Beneficial effect of intracellular trehalose on the membrane integrity of dried mammalian cells.

Recently, there has been much interest in using trehalose and other small carbohydrates to preserve mammalian cells in the dried state as an alternative to cryopreservation. Here, we report on the successful preservation of plasma membrane integrity after drying, as a first step toward full preservation of mammalian cells. Trehalose was introduced into cells using a genetically engineered version of alpha-hemolysin, a pore-forming protein; the cells were then dried and stored for weeks at different temperatures with approximately 90% recovery of the intact plasma membrane. We show that protection of the plasma membrane by internal trehalose is dose dependent and estimate the amount of internal trehalose required for adequate protection to be approximately 10(10) molecules/cell. In addition, a minimal amount of water (approximately 15 wt%) appears to be necessary. These results show that a key component of mammalian cells can be preserved in a dried state for weeks under mild conditions (-20 degrees C and 5% relative humidity) and thereby suggest new approaches to preserving mammalian cells.

3T3 Cells↗
PubMed2001

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung.

OBJECTIVE: We retrospectively assessed and compared the usefulness of 11C-methionine (MET)-PET with that of 18F-FDG-PET for the differentiation between benign lesions and malignant tumors of the lung. METHODS: We examined 101 patients with a suspected lung tumor including 79 patients with primary lung cancer and 22 patients with benign lesions. One hundred and forty PET studies (46 studies with MET-PET and 94 studies with FDG-PET) were performed. Both MET-PET and FDG-PET were performed on 39 patients. The MET-PET was performed 15 minutes after the administration of 67-740 MBq of MET, and FDG-PET 45 minutes after the administration of 30-437 MBq of FDG. The results were then evaluated by the standardized uptake value (SUV). RESULTS: The MET uptake in lung cancer was 3.69+/-1.22 (n = 37) which was significantly higher than that in benign lesions 1.81+/-1.04 (n = 9) (p < 0.001). The sensitivity, specificity and accuracy of MET-PET were 83.8%, 88.9% and 84.8%, respectively, when 2.66 of SUV was used as the cutoff value. The FDG uptake in lung cancer was 5.94+/-2.89 (n = 75) and was also significantly larger than that in benign lesions 2.46+/-1.01 (n = 19) (p < 0.001). The sensitivity, specificity and accuracy of FDG-PET were 81.3%, 78.9% and 80.9%, respectively (cutoff = 3.20). The MET uptake in the lesions correlated significantly with FDG uptake (r = 0.71, p < 0.001). According to an ROC analysis, the area under the curve for MET-PET (area = 0. 833) was higher than that for FDG-PET (area = 0.828), but the difference was not statistically significant. Furthermore, the combined use of MET-PET and FDG-PET did not improve the diagnostic ability. CONCLUSIONS: In conclusion, both MET-PET and FDG-PET were considered to be equally useful for the differential diagnosis of lung tumors. Furthermore, MET uptake in lung lesions was found to correlate significantly with FDG uptake.

Adult↗
PubMed2001

Docetaxel followed by hormone therapy after failure of definitive treatments for clinically localized/locally advanced prostate cancer: preliminary results.

An increasingly important issue in the management of prostate cancer is the occurrence of biochemical failure (ie, increasing serum prostate-specific antigen [PSA] levels) in patients with clinically localized prostate cancer who initially underwent definitive treatments with curative intent (prostatectomy and/or radiation therapy). This pilot trial evaluated chemotherapy followed by hormone therapy for a defined period in patients with biochemical (and possibly clinical) recurrence after initial local therapies for localized/locally advanced prostate cancer. Patients who developed increasing PSA > 4 ng/mL after initial prostatectomy and/or radiation therapy received docetaxel, 70 mg/m(2) every 3 weeks for up to 6 courses, followed by 4 months of total androgen suppression (using a luteinizing hormone-releasing hormone agonist plus bicalutamide, 50 mg/d) and 8 months of peripheral androgen blockade (using finasteride, 5 mg/d, plus bicalutamide, 50 mg/d). Twenty-seven patients have enrolled to date, 23 of whom received four or six cycles of docetaxel before hormonal therapies. Seventeen (74%) of 23 patients who completed four to six cycles of chemotherapy had a > or =40% decrease in PSA, and 16 (89%) of 18 patients who completed 4 months of total androgen suppression achieved PSA values of < or =0.1. The most common hematologic toxicity was grade (3/4) neutropenia; grade 3 nonhematologic toxicities were rare, and no grade 4 nonhematologic toxicities were reported. Thus, the preliminary results suggest that docetaxel before hormonal therapy includes a PSA response in many prostate cancer patients with biochemical failure after definitive local therapies.

Adenocarcinoma↗
PubMed2001

Dynamics of aluminum speciation in forest-well drainage waters from the Rhode River watershed, Maryland.

This paper reports an investigation of the dynamics of aluminum (Al) speciation in the forest-well waters from study site 110 of the Rhode River watershed, a representative sub-unit of Chesapeake Bay. Seasonal changes of Al speciation are evaluated by a modified MINEQL computer model using chemical equilibrium calculation. It was found that Al-F and Al-Org complexes were the dominate forms, whereas toxic forms of Al3+ and Al-OH were not significant. This indicates that Al toxicity is not very serious in the Rhode River area due to the high concentrations of fluoride and organic materials, even though sometimes pH is very low (approximately 4). Increased H+ or some other associated factors may be responsible for the decline in fish and amphibian population on the watershed.

Acid Rain↗
PubMed2001

Unified stabilization approach to principal and minor components extraction algorithms.

Principal component and minor component extractions provide powerful techniques in many information processing fields. There have been proposed a number of algorithms for principal and minor component (or subspace) extraction, which have different dynamical behaviors. In this paper, we give rigorous stability analysis of these algorithms, obtaining a unified insight view on the dynamical behaviors of various algorithms.

Algorithms↗
PubMed2001

Aromatase and COX-2 expression in human breast cancers.

We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen.

Adipocytes↗
PubMed2001

Combinatorial screening for enzyme-mediated coupling. Tyrosinase-catalyzed coupling to create protein--chitosan conjugates.

In nature, tyrosinase-generated o-quinones are commonly involved in processes that lead to functional biomaterials. These biomaterials are chemically complex and have been difficult to analyze. Furthermore, the cascade of reactions involving o-quinones is poorly understood, and it has been difficult to mimic ex vivo for materials processing. We report the use of a combinatorial approach to learn how tyrosinase and low molecular weight phenolic precursors can be used to generate biologically active protein-polysaccharide conjugates. Specifically, we screened various phenolic coupling precursors and various reaction conditions for the coupling of proteins onto the polysaccharide chitosan. Several natural phenols were identified as appropriate precursors for the coupling of polyhistidine tagged organophosphorus hydrolase (His-OPH) onto chitosan films. OPH activity was retained upon coupling and subsequent studies indicated that the histidine tag was not necessary for coupling. Using conditions identified for His-OPH coupling, we observed that various biologically active proteins (cytochrome c, OPH, and His-CAT) could be coupled onto chitosan films. The glycosylated protein horseradish peroxidase was not effectively coupled onto chitosan under the conditions studied. In all cases studied, we observed that coupling required a phenolic precursor, suggesting that tyrosinase is unable to couple by reaction with surface tyrosyl residues of the target protein. In conclusion, this study illustrates a combinatorial approach for the "discovery" of conditions to couple biologically active proteins onto chitosan through natural, quinone-based processes.

Biocompatible Materials↗
PubMed2001

Atrichia caused by mutations in the vitamin D receptor gene is a phenocopy of generalized atrichia caused by mutations in the hairless gene.

Generalized atrichia with papules is a rare disorder characterized by loss of hair shortly after birth and development of cutaneous cysts. Mutations in the hairless gene (HR) cause this phenotype in both mouse and human. Here we present a case of atrichia with papules in a patient with a normal HAIRLESS gene but with mutations in both alleles of the VITAMIN D RECEPTOR. The patient exhibited vitamin D resistant rickets, which was confirmed by an absent response of her fibroblasts to 1,25-dihydroxyvitamin D3 in vitro. Similar to individuals with HAIRLESS mutations, her skin showed an absence of normal hair follicles and the presence of follicular remnants and cysts. The cyst epithelium contained keratin-15- and keratin-17-positive cells suggesting derivation from the hair follicle bulge and the presence of epithelial stem cells. Although hair loss has been reported in association with hereditary vitamin D resistant rickets, we now characterize this alopecia as clinically and pathologically indistinguishable from generalized atrichia with papules, which was previously thought to be caused only by mutations in HAIRLESS. These findings suggest that VDR and HR, which are both zinc finger proteins, may be in the same genetic pathway that controls postnatal cycling of the hair follicle.

Alopecia↗
PubMed2001

Cytomegalovirus infection and non-neutropenic fever after autologous stem cell transplantation: high rates of reactivation in patients with multiple myeloma and lymphoma.

In a retrospective study, we examined the association between cytomegalovirus (CMV) infection and non-neutropenic fever immediately following autologous peripheral blood stem cell transplantation for a variety of haematological malignancies and solid tumours. Sixty non-neutropenic febrile episodes (41 in CMV-seropositive and 19 in CMV-seronegative patients) were evaluated. CMV reactivation, documented by CMV antigenaemia, was detected in 16 out of 41 (39%) seropositive patients compared with 0 out of 19 seronegative patients. In 12 of these 16 patients, CMV infection was considered the sole cause of fever. Thirteen patients had maximum antigenaemia levels > 5 cells/slide. Specific antiviral treatment led to the resolution of the fever in all, but two, patients, who developed fatal CMV pneumonia. Patients with multiple myeloma and lymphoma, possibly owing to a combination of disease-related characteristics and prior immunosuppressive treatment, had high rates of CMV reactivation and may require more frequent diagnostic evaluation and prompt therapeutic intervention.

Adult↗
PubMed2001

A randomized clinical trial comparing the efficacy of mandibular implant-supported overdentures and conventional dentures in diabetic patients. Part IV: Comparisons of dietary intake.

STATEMENT OF PROBLEM: It is unclear whether the replacement of conventional mandibular dentures with implant-supported overdentures alters the diet and thus improves the nutritional intake of edentulous persons. PURPOSE: The purpose of this study was to compare the pretreatment and posttreatment diets of edentulous diabetic patients who received new dentures with either a conventional complete mandibular denture (CD) or a mandibular implant-supported overdenture (IOD). MATERIAL AND METHODS: New dentures were made for 89 edentulous diabetic patients with acceptable metabolic control without insulin (NIT) or with insulin (IT). A randomized approach was used to assign 37 patients a mandibular CD and 52 patients a mandibular IOD supported by 2 cylindrical implants. Of the 89 patients, 58 submitted a dietary log for 7 consecutive days before treatment (PT) and 6 months after treatment completion (PTC). An average daily intake of 28 essential nutrients was determined for each patient at each time interval. Separate 2 x 2 x 2 repeated analysis of variance (ANOVA) tests were performed for each nutrient to compare the means of the 2 denture groups (CD and IOD), 2 diabetic groups (NIT and IT), and 2 time intervals (PT and PTC). The intakes were also compared with the recommended daily allowance (RDA). RESULTS: ANOVAs for all 28 nutritional variables showed no main effect for either denture type or diabetic treatment. Time effects were seen for magnesium, potassium, copper, and monounsaturated fats. The PTC mean intake of the total sample (N = 58) decreased for all 3 minerals and increased for monounsaturated fats with study dentures. Post hoc tests showed the differences between PT and PTC means to be statistically significant for only magnesium (P=.043) and potassium (P=.015). The percentage of patients with PT intake 25% or more below the RDA ranged from 33% to 85% in the CD group and from 24% to 100% in the IOD group for the same 11 nutrients. PTC fiber intake deficiency was noted in almost all participants. Carbohydrate consumption was markedly lower than that recommended by the American Diabetic Association. CONCLUSION: As is often the case with elderly groups, this group of edentulous diabetic patients showed highly comprised nutritional intakes of fiber, vitamins, and minerals. The replacement of old dentures with new dentures that included either a mandibular CD or IOD did not alter patient diets such that the patients improved their nutritional intakes of essential micronutrients and macronutrients.

Aged↗
PubMed2001

A dynamic programming approach to de novo peptide sequencing via tandem mass spectrometry.

Tandem mass spectrometry fragments a large number of molecules of the same peptide sequence into charged molecules of prefix and suffix peptide subsequences and then measures mass/charge ratios of these ions. The de novo peptide sequencing problem is to reconstruct the peptide sequence from a given tandem mass spectral data of k ions. By implicitly transforming the spectral data into an NC-spectrum graph G (V, E) where /V/ = 2k + 2, we can solve this problem in O(/V//E/) time and O(/V/2) space using dynamic programming. For an ideal noise-free spectrum with only b- and y-ions, we improve the algorithm to O(/V/ + /E/) time and O(/V/) space. Our approach can be further used to discover a modified amino acid in O(/V//E/) time. The algorithms have been implemented and tested on experimental data.

Algorithms↗
PubMed2001

Algorithms for identifying protein cross-links via tandem mass spectrometry.

Cross-linking technology combined with tandem mass spectrometry (MS-MS) is a powerful method that provides a rapid solution to the discovery of protein-protein interactions and protein structures. We studied the problem of detecting cross-linked peptides and cross-linked amino acids from tandem mass spectral data. Our method consists of two steps: the first step finds two protein subsequences whose mass sum equals a given mass measured from the mass spectrometry; and the second step finds the best cross-linked amino acids in these two peptide sequences that are optimally correlated to a given tandem mass spectrum. We designed fast and space-efficient algorithms for these two steps and implemented and tested them on experimental data of cross-linked hemoglobin proteins. An interchain cross-link between two beta subunits was found in two tandem mass spectra. The length of the cross-linker (7.7 A) is very close to the actual distance (8.18 A) obtained from the molecular structure in PDB.

Algorithms↗
PubMed2001

Spinal intramedullary cysticercosis in a five-year-old child: case report and review of the literature.

Spinal intramedullary cysticercosis is rare and usually afflicts adults. We report the case of a 5-year-old Mexican girl with back pain who had a complex thoracic spinal intramedullary mass on magnetic resonance imaging and a positive immunoblot for Taenia solium. Surgery revealed a cystic mass containing a cysticercus. Cysticercosis should be suspected as the cause of an intramedullary spinal mass in a patient from an endemic area.

Anti-Bacterial Agents↗
PubMed2001

Cloning of the Streptococcus mutans gene encoding glucan binding protein B and analysis of genetic diversity and protein production in clinical isolates.

Streptococcus mutans, the primary etiological agent of dental caries, produces several activities that promote its accumulation within the dental biofilm. These include glucosyltransferases, their glucan products, and proteins that bind glucan. At least three glucan binding proteins have been identified, and GbpB, the protein characterized in this study, appears to be novel. The gbpB gene was cloned and the predicted protein sequence contained several unusual features and shared extensive homology with a putative peptidoglycan hydrolase from group B streptococcus. Examination of gbpB genes from clinical isolates of S. mutans revealed that DNA polymorphisms, and hence amino acid changes, were limited to the central region of the gene, suggesting functional conservation within the amino and carboxy termini of the protein. The GbpB produced by clinical isolates and laboratory strains showed various distributions between cells and culture medium, and amounts of protein produced by individual strains correlated positively with their ability to grow as biofilms in an in vitro assay.

Amino Acid Sequence↗