Search PubMed⌕ Search

Biomedical subjects

R B Weiss

Publications and source records attributed to R B Weiss.

At least 109 records · Page 6Linked to original sources

Cytosine photoproduct-DNA glycosylase in Escherichia coli and cultured human cells.

Ultraviolet irradiation of DNA produces a variety of pyrimidine base damages. The activities of Escherichia coli endonuclease III and a human lymphoblast endonuclease that incises ultraviolet-irradiated DNA at modified cytosine moieties were compared. Both the bacterial and human enzymes release this cytosine photoproduct as a free base. These glycosylase activities are linear with times of reaction, quantities of enzyme, and irradiation dosages of the substrates. Both enzyme activities are similarly inhibited by the addition of monovalent and divalent cations. Analysis by DNA sequencing identified loci of endonucleolytic incision as cytosines. These are neither cyclobutane pyrimidine dimers, 6-(1,2-dihydro-2-oxo-4-pyrimidinyl)-5-methyl-2,4(1H,3H)-pyrimidinediones, nor apyrimidinic sites. This cytosine photoproduct is separable from unmodified cytosine by high-performance liquid chromatography. This separation should facilitate identification of this modified cytosine and elucidation of its biological significance.

Base Sequence↗

A human endonuclease incises ultraviolet-irradiated DNA at cytosines and oxidized DNA at thymines.

Both ultraviolet irradiation and oxidation of DNA produce a variety of pyrimidine base damages. A human endonuclease recognizes such altered bases on these DNA substrates. This human endonuclease incises ultraviolet-irradiated DNA exclusively at sites of photochemically modified cytosines. The precise sites of incision by the human enzyme were determined by DNA sequencing. Chemically oxidized DNA was incised exclusively at thymine loci. The degree of enzymic cleavage at cytosine photoproducts was identical at each site. However, the extent of incision at selected oxidized thymine residues varied within the DNA sequence. These results indicate that the distribution of thymine oxidative modifications is influenced by the neighboring DNA bases.

Base Sequence↗

Testicular relapse in adult acute lymphocytic leukemia: a case report and literature review.

In the pediatric age group, acute lymphocytic leukemia (ALL) may involve the testicles during complete remission of the disease in the marrow. We report a case of testicular involvement with ALL in an adult and review 11 cases of this phenomenon reported previously, to draw attention to the fact that it can occur at any age. Recognition of this fact is important, because testicular involvement may be the first manifestation of systemic relapse. The treatment of choice is irradiation to both testicles and combination chemotherapy.

Adult↗

Arterial thrombosis associated with adjuvant chemotherapy for breast carcinoma: a Cancer and Leukemia Group B Study.

PURPOSE: Multiagent chemotherapy and chemohormonal therapy for breast cancer are associated with an increased risk for venous thromboembolic complications. We observed instances of arterial thrombosis in two studies of breast cancer involving multiagent chemotherapy for stages II and III disease. Our purpose in this study was to determine the incidence of this complication and whether it appeared to be related to the chemotherapy or was a random event. PATIENTS AND METHODS: Episodes of arterial thrombotic events were identified from record reviews of 1,014 assessable patients with breast cancer entered on two Cancer and Leukemia Group B protocols. Details of the kind of arterial event, when it occurred, the outcome, and the occurrence of metastases were analyzed. RESULTS: Thirteen (1.3%) patients had an arterial thrombosis: six (5.3%) of 113 patients with stage III disease and seven (0.8%) of 901 patients with stage II disease. Four of these patients had a peripheral arterial thrombosis and nine had strokes (four were fatal). All these events occurred while the patients were receiving adjuvant chemotherapy. Only one additional arterial event (a stroke approximately four years later) has occurred in this patient group after chemotherapy was completed. CONCLUSION: Arterial thrombosis is also associated with multiagent chemotherapy in patients with breast cancer. The mechanism is unknown.

Aged↗

Wavelength dependence of DNA incision by a human ultraviolet endonuclease.

The wavelength dependence of an ultraviolet irradiation of the DNA substrate for a human endonuclease was determined. Sites of DNA incision for all UVB and UVC wavelengths examined were at cytosines which were neither cyclobutane pyrimidine dimers nor 6-4'-(pyrimidin-2-one)pyrimidines. The optimal wavelengths for formation of these cytosine photoproducts were between 270 and 295 nm. This human endonuclease therefore has a similar ultraviolet substrate specificity to endonuclease III.

Base Sequence↗

E. coli ribosomes re-phase on retroviral frameshift signals at rates ranging from 2 to 50 percent.

Many retroviruses express gag-pol or gag-pro-pol polypeptides by coupling their translation from overlapping reading frames with -1 ribosomal frameshifts. Here, we show that the well-known ribosomal frameshift signals found in retroviral mRNA will provoke Escherichia coli ribosomes to shift frame in the same manner as their eukaryotic counterparts. Ribosomes of E. coli respond in vivo to both the tandem slippery codons present at the retroviral frameshift site and the 3' flanking sequence. Slight alteration of the mouse mammary tumor virus gag-pro frameshift site from A-AAA-AAC to A-AAA-AAG boosts the level of frameshifting in E. coli to over 50%. This suggests that A-AAA-AAG, and its slippery relatives, may be utilized by E. coli genes as sites of high-level ribosomal frameshifting. This observed conservation of response to retroviral frameshift signals affords new avenues to dissect the mechanism of ribosomal frameshifting evoked by these mRNA sequences.

Base Sequence↗

Mitoxantrone: its development and role in clinical practice.

Mitoxantrone is an antitumor agent that was synthesized to try to develop a doxorubicinlike drug with a better therapeutic index. It has clinical activity for acute leukemias, breast carcinoma, non-Hodgkin's lymphoma, and ovarian cancers. There is some lack of cross-resistance to the anthracyclines. Its spectrum of toxicity is advantageous in that it causes less alopecia and can be administered for a slightly longer time than doxorubicin. For selected patients, mitoxantrone can be useful as a substitute for doxorubicin, but doxorubicin will remain the more widely used drug.

Antineoplastic Combined Chemotherapy Protocols↗

Mutants of translational components that alter reading frame by two steps forward or one step back.

External suppressors, sufS, of a -1 frameshift mutant cause ribosomes to shift into the -1 frame when reading the sequence CAG GGA GUG. The resulting product is not Gln-Gly-Val but Gln-Gly-Ser with Ser being encoded by the underlined AGU. The alleles investigated are approximately 2% efficient in causing frameshifting. Two other suppressors, hopR and hopE of the same -1 frameshift mutant, cause some ribosomes reading the sequence GUG UG to decode a single amino acid, Val, from the five nucleotides. The possibility is considered that peptidyl-tRNA(Val) dissociates from the mRNA, but re-pairs in a triplet manner after the mRNA slips forward by two bases.

Amino Acid Sequence↗

Eosinophilia associated with adult T-cell leukemia/lymphoma.

Eosinophilia is associated with a number of disorders including malignancies. A patient is described who had eosinophilia associated with adult T-cell leukemia/lymphoma (ATL) induced by human T-lymphotropic virus type I (HTLV-I). Both tissue and peripheral blood eosinophilia and high titers of HTLV-I antibody were present. The eosinophilia was most likely caused by the malignant cells producing one or more lymphokines. The patient has achieved a durable complete remission from combination chemotherapy. Because durable remissions in ATL are rare with any known therapy and eosinophilia has not previously been associated with ATL, it is possible that the tumor in this patient was derived from a T-cell subset not usually transformed by HTLV-I. ATL is another malignancy now known to cause eosinophilia.

Adult↗

Phase I and clinical pharmacology study of intravenous flavone acetic acid (NSC 347512).

We have conducted a Phase I and pharmacological study of flavone acetic acid, one of a series of novel flavonoids. The drug was administered i.v. weekly for 4 weeks, with a 2-week rest and then repeated. Flavone acetic acid was given initially in a 1-h infusion, but at the 3900-mg/m2 dose level, the infusion time was lengthened to 3 h. A total of 31 patients were treated with 9 different dose levels, ranging from 330 to 6400 mg/m2. Dose-limiting toxicity was acute hypotension that began after about one-third of each drug dose had been infused and rarely lasted more than a few minutes after the infusion was discontinued. In addition, subjective fatigue and asthenia causing unacceptable patient discomfort was dose limiting. A significant side effect noted that was not dose limiting was diarrhea during the infusion. This drug exhibited nonlinear pharmacokinetic behavior. Plasma levels exceeded 300 micrograms/ml during the infusion at the maximally tolerated dose. After the infusion ended the principal half-life was about 2 h. In 24-h urine collections 27% of the flavone acetic acid dose was recovered as intact drug and an additional 37% was recovered as a metabolite. The maximally tolerated dose determined in this study is 6400 mg/m2 given i.v. over 3 h.

Adult↗

Toxicity comparisons between two chemotherapy regimens as adjuvant or salvage treatment in nonseminomatous testicular cancer.

The Testicular Cancer Intergroup Study was initiated to evaluate the efficacy of adjuvant chemotherapy in Stage II and salvage therapy in Stage I nonseminomatous testicular carcinoma. Chemotherapy regimens of cisplatin, vinblastine, and bleomycin (PVB) or the same drugs plus cyclophosphamide and dactinomycin (VAB) were used at institution or cooperative group preference. A comparison of the toxicities of these two regimens shows that VAB caused significantly more mucosal, dermatologic, and otologic toxicity than PVB, and PVB caused more leucopenia. Both regimens were equally effective in controlling cancer. Either regimen could be used as chemotherapy in testicular cancer, and the decision about which one to use could be based on their differences in toxicity and degree of patient convenience.

Antineoplastic Combined Chemotherapy Protocols↗

Enhancement of natural killer activity in human peripheral blood by flavone acetic acid.

Natural killer cell activity and interferon (IFN) production were measured in 6 patients receiving flavone acetic acid for treatment of cancer. Natural killer cell activity was significantly increased in 3 of 6 patients receiving 6.4 g of flavone acetic acid/m2 by 3-hour iv infusion. Analysis of cell surface markers failed to reveal significant changes in any cell population. There was no evidence of induction of IFN-gamma, but 3 of 4 patients tested had evidence of induction of type I IFN, as measured in a virus neutralization assay.

Adult↗

Reading frame switch caused by base-pair formation between the 3' end of 16S rRNA and the mRNA during elongation of protein synthesis in Escherichia coli.

Watson-Crick base pairing is shown to occur between the mRNA and nucleotides near the 3' end of 16S rRNA during the elongation phase of protein synthesis in Escherichia coli. This base-pairing is similar to the mRNA-rRNA interaction formed during initiation of protein synthesis between the Shine and Dalgarno (S-D) nucleotides of ribosome binding sites and their complements in the 1540-1535 region of 16S rRNA. mRNA-rRNA hybrid formation during elongation had been postulated to explain the dependence of an efficient ribosomal frameshift on S-D nucleotides precisely spaced 5' on the mRNA from the frameshift site. Here we show that disruption of the postulated base pairs by single nucleotide substitutions, either in the S-D sequence required for shifting or in nucleotide 1538 of 16S rRNA, decrease the amount of shifting, and that this defect is corrected by restoring complementary base pairing. This result implies that the 3' end of 16S rRNA scans the mRNA very close to the decoding sites during elongation.

Bacterial Proteins↗

Phase II trial of 4'-deoxydoxorubicin (DxDx) in non-small cell lung cancer: a Cancer and Leukemia Group B Trial.

Eighty-seven patients with histologically or cytologically proven non-small-cell carcinoma of the lung were treated with 4'-deoxydoxorubicin (DxDx) 30 mg/m2 every 3 weeks. Three responses (4%), all partial, were observed. All responses occurred in patients with large-cell anaplastic lung cancer and none in squamous or adenocarcinoma histologies (P less than 0.01). The durations of partial response for these three responders were 70, 198+ and 209+ days. The side effects noted were predominantly neutropenia, anemia, and weight loss. In three patients, declines in cardiac ejection fraction of 7%, 12%, and 23% occurred after cumulative drug doses of 150 mg/m2, 150 mg/m2, and 233 mg/m2, respectively. 4'-Deoxydoxorubicin had little activity in non-small-cell lung cancer at the dose used in this study.

Carcinoma, Non-Small-Cell Lung↗

Procarbazine hypersensitivity manifested as a fixed drug eruption.

A case of a previously unrecognized form of hypersensitivity to procarbazine characterized by a nonpigmented fixed drug eruption is reported. Despite skin testing, association of the skin lesion to procarbazine could be determined only by drug rechallenge. Various aspects of procarbazine hypersensitivity reactions as well as the pathogenesis and importance of the fixed drug eruption are discussed.

Adult↗