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Biomedical subjects

S F Chen

Publications and source records attributed to S F Chen.

122 records · Page 7Linked to original sources
PubMed1984

Transport of deoxycoformycin in human erythrocytes. Measurement by adenosine deaminase titration and radioisotope assays.

The assay of residual adenosine deaminase (ADA) activity was used as a sensitive measure of the transport of deoxycoformycin (dCF) into human erythrocytes. Contrary to prior reports from this laboratory, the inactivation of intraerythrocytic ADA by dCF was linear rather than log-linear, with time. Linear inactivation rates were also seen when erythrocytes were preloaded with a 5-fold excess of calf intestinal ADA. The uptake of tritium-labeled dCF molecules and the rate of inactivation of ADA molecules showed an approximate 1:1 stoichiometry. The nucleoside transport inhibitors, 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR) and dipyridamole, and the permeant, uridine, inhibited dCF transport with Ki values of 35 nM, 45 nM, and 340 microM respectively. The affinity of dCF for the nucleoside transporter was low with a Ki of approximately 10 mM for the inhibition of adenosine influx.

Adenosine Deaminase Inhibitors↗
PubMed1984

Release of polyunsaturated fatty acids from phospholipids and alteration of brain membrane integrity by oxygen-derived free radicals.

We studied the effects of oxygen-derived free radicals on the ultrastructure of brain cortical slices and the release of fatty acids from phospholipids of crude synaptosomes. Xanthine oxidase, hypoxanthine, and ADP-Fe3+, a free-radical-generating system, caused swelling of cellular processes and mitochondria. The oxygen-derived free radicals also caused the rapid release and accumulation of endogenous polyunsaturated fatty acids (PUFA) from membrane phospholipids as determined by high-performance liquid chromatography (HPLC). Furthermore, [3H]-arachidonic acid was also rapidly released from prelabeled phospholipids concomitant with a decrease in radioactivity in various phospholipid fractions. The radioactivities of neutral lipids including diacylglycerols were unchanged by free radicals. These data indicate that the activation of phospholipase A2 and the release of PUFA may have overt effect on membrane integrity and the subsequent development of cellular injury and brain edema.

Animals↗
PubMed1982

Effects of the chiral isomers of erythro- and threo-9-(2-hydroxy-3-nonyl)adenine on purine metabolism in sarcoma 180 cells.

The effects of the chiral isomers of erythro- and threo-9-(2-hydroxy-3-nonyl)adenines (EHNA and THNA) on purine metabolism in Sarcoma 180 cells have been determined. At concentrations of 10-80 microM [10- to 1000-fold greater than their Ki values with adenosine deaminase (ADA)], all isomers inhibited purine salvage and biosynthesis de novo. Although (+)-EHNA, the most potent ADA inhibitor, exerted the greatest effects, there was no direct correlation between the potency of ADA inhibition and the secondary effects on purine metabolism, e.g. (+)-EHNA is about 2-fold more inhibitory than (-)-EHNA in blocking purine base incorporation but about 250-fold more potent as an inhibitor of ADA (Ki of (+)-EHNA = 2 nM; Ki of (-)-EHNA = 500 nM [Bessodes et al., Biochem. Pharmac. 31, 879 (1982)]). All the isomers inhibited the incorporation of radiolabeled purine bases (adenine, guanine and hypoxanthine) and nucleosides (guanosine and inosine) into acid-soluble nucleotides and of glycine into 5'-phosphoribosyl-formylglycineamide. Unlike the results of Henderson et al. [Biochem. Pharmac. 26, 1967 (1977)] with Ehrlich ascites cells, the incorporation of adenosine into nucleotides was only slightly inhibited in Sarcoma 180 cells. (+)-EHNA did not inhibit the activities of 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase, purine phosphoribosyltransferases or nucleotide kinases in cell extracts. Accumulation of PRPP was inhibited only under conditions that fostered rapid synthesis.

Adenine↗
PubMedDate not supplied

Chemotherapy of mammary carcinomas arising in ras transgenic mice.

Transgenic female mice carrying the V-Ha-ras transgene linked to the MMTV promoter, which developed mammary carcinomas, were treated with selected cancer chemotherapy drugs. Agents were administered i.p. on a daily x 9 schedule when mice developed tumors that were 50-100 mg in size. Drugs which are clinically effective against breast cancer were quite efficacious in the transgenic model at their maximum tolerated dose. Doxorubicin produced excellent responses in tumor-bearing transgenic mice, with several mammary carcinomas undergoing tumor shrinkage. Two anthrapyrazoles, DuP 937 and DuP 941, novel anticancer drugs with phase 2 activity against breast cancer, were as effective as doxorubicin in the oncomice. Mitoxantrone, a synthetic agent with some properties similar to the anthracyclines, also had antitumor activity, but not as pronounced as obtained with doxorubicin or the anthrapyrazoles. Cisplatin, a drug with limited use in human breast cancer, only caused modest antitumor responses. A computerized data analysis method based on the area under the tumor growth curve was developed to better quantitate the data and provide statistical information. This quantitative analysis confirmed the high statistical significance of the activity of doxorubicin or the anthrapyrazoles in the ras transgenic model, and defined an excellent dose response relationship for each drug tested. Our results suggest that the ras transgenic model may be useful for identifying drugs that have efficacy for breast cancer in women.

Animals↗
PubMedDate not supplied

Pyrrolo[2,3-d]pyrimidine nucleosides: synthesis and antitumor activity of 7-substituted 7-deaza-2'-deoxyadenosines.

A one step synthesis, using the nucleoside 7-iodo-2'-deoxytubercidin (2b) in a Pd(0)/Cu(I)-catalyzed cross coupling reaction furnished a series of 7-alkynyl-2'-deoxytubercidin derivatives. The 7-iodo-, 7-chloro- or 7-bromo 2'-deoxytubercidins 2b-d as well as certain 7-alkynyl derivatives show significant activity against several tumor cell lines, with 7-iodo-2'-deoxytubercidin (2b) as the most effective compound.

Animals↗
PubMedDate not supplied

A study of primary- and re-infection with hepatitis C virus in blood transfusion recipients.

A nested polymerase chain reaction was used to assess viraemia in blood transfusion recipients with no serological evidence of hepatitis C virus (HCV) infection (naive recipients) and in recipients with prior or existing HCV infection (infected recipients), who were transfused with HCV-positive blood. In 10 hepatitis cases in naive recipients, defined as primary infection, nine showed clinical hepatitis, and one was sub-clinical; the time between transfusion and elevation of alanine aminotransferase (ALT) levels was 15-60 days (37.9 +/- 13.9). All 10 naive recipients showed abnormal ALT, and 10/10 and 7/10 were persistently positive for anti-HCV and HCV-RNA, respectively, for more than 1 year. Similarly, in five cases in previously infected recipients, defined as re-infection, 4/5 showed clinical hepatitis, the time to elevation of ALT was 30-46 days (34.8 +/- 6.4), and 5/5 and 3/5 were persistently positive for anti-HCV and HCV-RNA, respectively, for more than 1 year. All five infected recipients showed abnormal ALT. In conclusion, there was no significant difference (P = 0.05) in the frequency of the markers of infection resulting from primary or re-infection with HCV, suggesting that primary infection fails to induce a protective immune response.

Alanine Transaminase↗