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Biomedical subjects

C Lu

Publications and source records attributed to C Lu.

At least 289 records · Page 16Linked to original sources
PubMed1984

Lymphoma presenting as an abdominal mass involving an ectopic spleen.

We recently evaluated a patient with a huge asymptomatic abdominal mass which eventually proved to be an ectopic spleen. Pathology revealed a well-differentiated lymphoma involving the entire spleen and hilar nodes. Before her operation, a series of radiographic procedures was carried out which demonstrated the nature of the mass. The radiographic findings and diagnostic modalities used to establish the diagnosis form the basis of this report.

Aged↗
PubMed1983

The 1-nitropyrene reductase of Salmonella typhimurium.

We have devised a sensitive fluorimetric assay to monitor the conversion of 1-nitropyrene to 1-aminopyrene. Application of this assay to extracts of Salmonella typhimurium strains TA98 and TA100 (which are sensitive to the mutagenic and lethal effects of 1-nitropyrene) has shown that these bacteria contain 'nitropyrene reductase' activity at the low level of 10(-11) mol/min/mg protein. NADPH and NADH serve equally well as reducing agents. The nitropyrene reductase activity of strain TA100 F50 (a mutant resistant to 1-nitropyrene) was found to be considerably lower.

Aminopyrine↗
PubMed1983

Identification of the epsilon-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: a fidelity subunit for DNA replication.

Based on extensive genetic and biochemical studies, the multisubunit DNA polymerase III holoenzyme is considered responsible for the chain-elongation stage in replication of the genome of Escherichia coli and is thus expected to be the major determinant of fidelity as well. Previous experiments have shown that two mutations conferring a very high mutation rate on E. coli, mutD5 and dnaQ49, decrease severely the 3' leads to 5' exonucleolytic editing activity of the polymerase III holoenzyme. To identify more precisely the nature of these mutations, we have carried out genetic mapping and complementation experiments. From these studies and experiments by others, we conclude that the most potent general mutator mutations in E. coli occur in a single gene, dnaQ. To define further the role of the dnaQ gene, we have used two-dimensional gel electrophoresis to compare the labeled dnaQ gene product with purified polymerase III holoenzyme. The dnaQ product comigrates with the epsilon-subunit, a 25-kilodalton protein of the polymerase III "core" enzyme. We conclude that the epsilon-subunit of polymerase III holoenzyme has a special role in defining the accuracy of DNA replication, probably through control of the 3' leads to 5' exonuclease activity.

DNA Polymerase III↗
PubMed1983

Mutator strains of Escherichia coli, mutD and dnaQ, with defective exonucleolytic editing by DNA polymerase III holoenzyme.

The closely linked mutD and dnaQ mutations confer a vastly increased mutation rate on Escherichia coli and thus might define a gene with a central role in the fidelity of DNA replication. To look for the biochemical function of the mutD gene product, we have measured the 3' leads to 5' exonucleolytic editing activity of polymerase III holoenzyme from mutD5 and dnaQ49 mutants. The editing activities of the mutant enzymes are defective compared to wild type, as judged by two assays: (i) decreased excision of a terminal mispaired base from a copolymer substrate and (ii) turnover of dTTP to dTMP during replication with a phage G4 DNA template. Thus, the mutD (dnaQ) gene product is likely to control the editing (proofreading) capacity of polymerase III holoenzyme.

Base Sequence↗
PubMed1982

Site-specific DNA condensation and pairing mediated by the int protein of bacteriophage lambda.

The int protein of bacteriophage lambda catalyzes the site-specific integrative recombination that inserts lambda DNA into the host chromosome. The attachment site region of lambda DNA required for this reaction spans 230 base pairs and includes four separable binding sites for int protein. We have used the electron microscope to determine the functional consequences of the interaction of int with its multiple binding sites. We find that int condenses a 230-base pair segment of DNA into a compact structure about 14 nm in diameter; the condensed region includes all of the four binding sites for int. Condensed segments will form paired structures between attachments sites. We suggest that a sequential cooperative interaction between bound int molecules provides for a distinct reactive DNA conformation and for pairing between substrate sites.

Bacteriophage lambda↗
PubMed1982

Bronchogenic carcinoma located in the aortic window. The importance of the primary lesion as a determinant of survival.

Thirty-four patients with an aortic window lesion were carefully staged with gallium scans and mediastinoscopy according to the TNM classification system for carcinoma of the lung. All were in Stage III. Twenty-five patients had non-oat cell carcinomas (15 squamous cell, eight adeno-, two large cell) and nine had oat cell carcinomas. Quantitative ventilation-perfusion lung scans were particularly helpful in verifying the subaortic location of the tumor by showing a less than 20% interference with pulmonary blood flow or ventilation secondary to left mainstem bronchus or pulmonary artery invasion. Decision for resectability in 13 Stage III M0 patients was based on the length of the uninvolved proximal left main pulmonary artery seen on pulmonary arteriogram. Eight patients (seven non-oat cell and one oat cell) had resection after radiation and prior to chemotherapy (after two cycles of chemotherapy and prior to radiation therapy for the oat cell) with a resultant survival rate better than those of M0 and M1 non-oat cell or oat cell patients without resection. The survival rates of nine non-oat cell M0 patients, nine non-oat cell M1 patients, and eight oat cell patients, all without resection, were not statistically different. This similarity in survival rates is explained by the observation that 38% of the non-oat cell M1, 71% of the non-oat cell M0, and 63% of the oat cell patients died from complications of their primary tumor. Patients with aortic window lesions, irrespective of their histology, have an extremely poor prognosis due to the high incidence of lethal complications of their primary tumor. Complete resection when feasible, as judged by pulmonary arteriography, provides the best control of the primary tumor and, as a consequence, gives longer survival.

Adenocarcinoma↗
PubMed1981

Erythema annulare centrifugum associated with ascariasis.

Erythema annulare centrifugum (EAC) is a figurate erythema that has been associated with man diverse entities. A case of EAC was related to infestation by the nematode, Ascaris lumbricoides. A careful examination of the patient did not define an immunologic basis for EAC. Results of lymphocyte stimulation tests of the patient showed an immune response to A lumbricoides extracts but not to A suum extracts. This finding is of practical importance, since most laboratoires use A suum extracts in routine skin and serologic tests for human ascariasis.

Anthelmintics↗
PubMed1981

Amaranth suppresses the mutagenicity of 2-acetylaminofluorene by lowering the concentration of NADPH in top agar.

Addition of 1 mg amaranth (FD&C Red No. 2) to the top agar of Salmonella/S9 assay plates decreased the yield of revertants induced by 20 micrograms 2-acetylaminofluorene (AAF) by over 50% and additional amaranth completely eliminated the mutagenic response. Similar suppression of AAF mutagenicity was seen with sulfonazo III, another azo dye. The suppressive effect of amaranth was greatest at low S9 concentrations and decreased as the amount of S9 was increased. When N-hydroxyacetylaminofluorene (N-OH-AAF) was used as mutagen, amaranth had little or no effect on either the number of revertants obtained or the S9 optimum. Similarly, 1-naphthylamine-4-sulfonic acid (a reduction product of amaranth) did not significantly affect the mutagenicity of AAF. The rate of metabolism of [14C]AAF by the S9 preparations was shown to be markedly decreased by amaranth, as were the levels of both the phenolic metabolites and of N-OH-AAF. Thus, it appeared that amaranth acts by blocking the conversion of AAF to N-OH-AAF and that this effect is caused by the amaranth itself and not by its constituent amines. Further experiments indicated that amaranth greatly decreased the levels of NADPH formed in reaction mixtures comparable to S0 mix in top agar and that such reaction mixtures also metabolized amaranth to colourless compounds. It appears likely that in top agar, NADPH reacts with amaranth at a fast enough rate to limit severely the level of the reduced co-factor (which must be formed from NADPH+ by the action of endogenous glucose-6-phosphate dehydrogenase) and thus decreases the rate of activation of mutagens by other NADPH-dependent processes.

2-Acetylaminofluorene↗
PubMed1981

Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium.

1-Nitropyrene is slowly reduced by intact cells of Salmonella typhimurium to yield 1-aminopyrene and N-acetyl-1-aminopyrene plus six unidentified minor products. When the bacteria are exposed to tritiated 1-nitropyrene, increasing amounts of radioactivity become bound to DNA as the nitropyrene is metabolized. Enzymatic hydrolysis of the labelled DNA yields low molecular weight labelled compounds which probably represent nucleoside adducts formed by the reaction of nitropyrene metabolites with DNA. Results with appropriate mutant strains indicate that bacterial nitroreductases are involved in activating nitropyrene to a reactive intermediate that binds to DNA and that nitropyrene adducts in DNA are subject to excision repair.

Biotransformation↗
PubMed1979

Inhibition of hepatic drug metabolism by norethindrone.

In order to assess the effect of norethindrone on hepatic drug metabolism in man, hepatic N-demethylation of aminopyrine was studied by means of the aminopyrine breath test (ABT) in 7 healthy women during two menstrual cycles. Aminopyrine metabolic clearance rates were also studied in 3 women. The women were examined at the ends of the first, second, and third weeks before starting progestogen therapy and at the same times during a second menstrual cycle during which they took norethindrone, 350 microgram/day. The ABT was 5.1 +/- 1.9% (mean +/- SD) during the three control weeks and lower (p less than 0.001) during the three weeks on norethindrone, 3.9 +/- 0.9%. Aminopyrine metabolic clearance rate also fell during norethindrone therapy. The data suggest that progestogens inhibit hepatic microsomal function.

Adult↗
PubMed1979

Action of nitrofurans on E. coli: mutation and induction and repair of daughter-strand gaps in DNA.

The antibacterial and mutagenic potency of 9 nitrofurans in "treat and plate" experiments varied over almost 5 orders of magnitude. The relative toxicities were as follows: FANFT greater than AF2 greater than ANFT greather than furazolidone greater than furagin greater than nitrofurantoin greater than nitrofurazone greater than methylnitrofuroate greater than nitrofuroic acid. In general, mutagenic activity paralleled toxicity. The compounds at concentrations corresponding to their LD50's, induced mutations at frequencies which ranged from 2.5/10(6) survivors for FANFT to 130/10(6) survivors for furagin (NF416). The observed differences in antibacterial and mutagenic activity are unlikely to be due to lack of activation of the weaker agents since the two most potent agents were reduced somewhat more slowly than many of the less active agents. The relative sensitivities to the antibacterial effects of AF2 of strains WP2, WP2 uvrA, CM561 (lexA) and CM571 (recA) were 1 : 1.6 : 3 : 7 and to nitrofurazone 1 : 1 : 25 : 50. The wvrA strain was 6--7-fold more mutable with both these agents than was WP2. No increase over the spontaneous mutation frequency was observed when recA or lexA strains were exposed to either AF2 or nitrofurazone in these experiments. When wild-type of wvrA bacteria containing nitrofuran-induced lesions replicated their DNA in drug-free medium in the presence of [3H]thymidine for 5 min, the label was found in low molecular weight DNA indicating that daughter-strand gaps were formed. During subsequent incubation in nonradioactive medium the molecular weight of the DNA increased to the control value. A recA strain (which was very sensitive to the lethal effects of AF2 and nitrofurazone) lacked the ability to repair daughter-strand gaps caused by nitrofuran-induced lesions.

DNA Repair↗