Determinants involved in regulating the proportion of edited apolipoprotein B RNAs.

Editing the apolipoprotein B (apoB) RNA involves deamination of cytidine by the catalytic subunit, APOBEC-1, as a component of an editosome. A tripartite sequence (editing motif) is essential for editosome assembly and site-specific editing. Current theory for the regulation of apoB RNA editing proposes that APOBEC-1 is rate limiting in cells and determines the proportion of edited apoB mRNAs.

Overexpression of APOBEC-1 results in mooring sequence-dependent promiscuous RNA editing.

Apolipoprotein B (apoB) RNA editing involves site-specific deamination of a cytidine to a uridine. A mooring sequence, a spacer region, and a regulator region are components of the apoB RNA editing motif of which only the mooring sequence is both necessary and sufficient for editosome assembly and editing. The catalytic component of the editosome is APOBEC-1.

Phase II trial of 5-fluorouracil, folinic acid, and N,N1,N11-triethylenethiophosphoramide (thiotepa) in patients with advanced breast cancer.

A total of 35 women with advanced, metastatic breast cancer were treated with combination chemotherapy consisting of folinic acid 500 mg/m2 over 2 hours administered with 600 mg/m2 of 5FU at the midpoint of the folinic acid infusion weekly for 6 weeks, plus 60 mg/m2 of thiotepa on day 1 and day 28. The cycle was repeated every 8 weeks. Patients were evaluated for toxicity weekly.

Rotated object identification with and without orientation cues.

The time to name two-dimensional line drawings of objects increases linearly for object rotations between 0 degrees and 120 degrees from the upright. Several theories attribute these effects of orientation to finding the top or the top-bottom axis of objects. By this account, prior knowledge of the location of the top or the top-bottom axis of objects should diminish effects of object orientation when they are named.

Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma.

Purpose: This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered.

Patients And Methods: A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 micrograms/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle.

The efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte macrophage colony-stimulating factor in permitting the administration of higher doses of cyclophosphamide in a doxorubicin-cyclophosphamide combination. An NSABP pilot study in patients with metastatic or high-risk primary breast cancer. National Surgical Adjuvant Breast and Bowel Project.

Colony-stimulating factors (CSFs) shorten the duration of myelosuppression following chemotherapy and, thus, allow the administration of higher doses. This study evaluates the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in allowing administration of high-dose cyclophosphamide in combination with doxorubicin. Ninety women with metastatic, locally advanced, or high-risk (> or = 10 positive nodes) breast cancer and no prior anthracycline treatment were given doxorubicin (60 mg/m2) with progressively increased doses of cyclophosphamide (1,200 mg/m2, 1,800 mg/m2, and 2,400 mg/m2).

Inefficacy of low-dose continuous oral etoposide in non-small cell lung cancer.

Etoposide is more active in small cell lung cancer when given over 5 days than as a single injection. To examine this concept further, we designed this Phase II study in NSCLC using continuous low-dose oral etoposide. We enrolled 19 patients with measurable disease and the standard eligibility criteria.

High-dose chlorambucil and dexamethasone for relapsed non-Hodgkin's lymphomas.

Twenty patients with relapsed or refractory non-Hodgkin's lymphoma were treated with high-dose chlorambucil (14 mg/m2 every 6 hours for 6 doses) and dexamethasone (40 mg/day for 5 days). There was a 45% response rate with 17% complete responses. The median duration of complete response was 7 months.

Long-term intravenous hydroxyurea infusions in patients with advanced cancer. A phase I trial.

Background: Hydroxyurea is an S-phase specific drug. Constant exposure of tumor cells with a low S-phase fraction to the agent may result in improved cell kill. Because of its short half-life, a continuous intravenous infusion may result in better tumor exposure than intake by mouth.

Residual mediastinal mass after treatment of Hodgkin's disease: a decision analysis.

A residual mediastinal mass after completion of initial treatment for Hodgkin's disease is a frequent clinical problem. Investigators have suggested three possible approaches to this important problem: 1) observation, 2) additional diagnostic tests with subsequent action based upon test results, or 3) immediate treatment for high-risk patients. The method of decision analysis was applied to determine the optimal management for residual mediastinal abnormalities following treatment of Hodgkin's disease with combined modalities of MOPP chemotherapy and radiation therapy.

Phase I study of toremifene in patients with advanced cancer.

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted.

Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally.

Correlation of lactate and pH in human skeletal muscle after exercise by 1H NMR.

We have made in vivo 1H NMR measurements of the time course of pH and lactate in human skeletal muscle after exercise. Spectra were obtained in a 4.7-T 30-cm bore Bruker Biospec spectrometer with a 2.

Quantitation of metabolites by 1H NMR.

In this report we describe the three factors that need to be measured when quantitating an edited resonance relative to an internal standard using a surface coil. These factors are necessary by virtue of the water, fat suppressing, and localization schemes used in studing a 1H metabolite. First, use of semi-selective pulses requires amplitude correction of the edited and reference resonances.

GM-CSF in the treatment of Felty syndrome.

Many therapeutic agents have been tried with variable success in the treatment of Felty neutropenia, but the reports are anecdotal. We now describe the second trial of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), in a splenectomized, infected patient with Felty syndrome.

New hormonal approaches to the treatment of breast cancer.

From this data we can draw several conclusions. Although many new hormonal agents have been developed, there has not been significant improvement in tumor response to single agents over the past several decades. By applying knowledge of tumor ER and PR patient populations can be selected which will have a higher response rate to a given hormonal agent.

Keratoacanthoma necessitating metacarpal amputation.

Keratoacanthoma is usually considered a benign self-limiting lesion. First described in 1888 by Hutchinson, it most commonly involves the face and hands. It is usually controlled by complete soft tissue excision.

Monomethylated cap structures facilitate RNA export from the nucleus.

RNA export from the nucleus has been analyzed in Xenopus oocytes. U1 snRNAs made by RNA polymerase II were exported into the cytoplasm, while U1 snRNAs synthesized by RNA polymerase III, and therefore with a different cap structure, remained in the nucleus. Export of the polymerase II-transcribed RNAs was inhibited by the cap analog m7GpppG.

The trimethylguanosine cap structure of U1 snRNA is a component of a bipartite nuclear targeting signal.

The ability of series of U1 snRNAs and U6 snRNAs to migrate into the nucleus of Xenopus oocytes after injection into the cytoplasm was analyzed. The U snRNAs were made either by injecting U snRNA genes into the nucleus of oocytes or, synthetically, by T7 RNA polymerase, incorporating a variety of cap structures. The results indicate that nuclear targeting of U1 snRNA requires both a trimethylguanosine cap structure and binding of at least one common U snRNP protein.

Comparative study of virion structure, protein composition and genomic DNA of three ascovirus isolates.

The virions of three ascoviruses isolated from the noctuids Heliothis zea, Spodoptera frugiperda and Trichoplusia ni were compared with respect to their size and structure, protein composition and the size and relatedness of their DNAs. The virions of the isolates from H. zea (HAV) and T.

Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer.

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%).

Multiple domains of U1 snRNA, including U1 specific protein binding sites, are required for splicing.

Domains of U1 snRNA which are functionally important have been identified using a splicing complementation assay in Xenopus oocytes. Mutations in, and deletions of, all three of the hairpin loop structures near the 5' end of the RNA are strongly deleterious. Similarly, mutation of the Sm binding site abolishes complementation activity.