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Biomedical subjects

S Litwin

Publications and source records attributed to S Litwin.

117 records · Page 7Linked to original sources
PubMed1970

Molecular Recombination in T4 Bacteriophage Deoxyribonucleic Acid: III. Formation of Long Single Strands During Recombination.

Evidence was presented to support the hypothesis that long single strands appearing at late times (15 min after infection) are produced as a result of recombination and not as a continuous elongation during the replication process. The production of long strands does not depend on the multiplicity of infection, and the first long strands appear at the time when 20 to 50 phage equivalent units of deoxyribonucleic (DNA) are synthesized, and not earlier. The addition of chloramphenicol at 5 min, which prevents molecular recombination but allows replication of DNA, prevents the formation of long, single strands. Chloramphenicol added between 8 and 10 min after infection, a time at which molecular recombination is fully expressed and covalent repair of recombinant molecules is allowed, does not prevent formation of long single strands. Cutting of single-strand DNA with a limited amount of endonuclease I allows confirmation that the fast-sedimenting characteristic of intracellular denatured DNA is caused primarily by the length of the strands, and not by the formation of aggregates. The computer simulation of two recombination models indicates the feasibility of random breakage and rejoining of molecules in generating long concatenates.

Journal Article↗
PubMed1969

Interpretation of sucrose gradient sedimentation pattern of deoxyribonucleic acid fragments resulting from random breaks.

Mass distribution in a sucrose gradient of deoxyribonucleic acid (DNA) fragments arising as a result of random breaks is predicted by analytical means from which computer evaluations are plotted. The analytical results are compared with the results of verifying experiments: (i) a Monte Carlo computer experiment in which simulated molecules of DNA were individuals of unit length subjected to random "breaks" applied by a random number generator, and (ii) an in vitro experiment in which molecules of T4 DNA, highly labeled with (32)P, were stored in liquid nitrogen for variable periods of time during which a precisely known number of (32)P atoms decayed, causing single-stranded breaks. The distribution of sizes of the resulting fragments was measured in an alkaline sucrose gradient. The profiles obtained in this fashion were compared with the mathematical predictions. Both experiments agree with the analytical approach and thus permit the use of the graphs obtained from the latter as a means of determining the average number of random breaks in DNA from distributions obtained experimentally in a sucrose gradient. An example of the application of this procedure to a previously unresolved problem is provided in the case of DNA from ultraviolet-irradiated phage which undergoes a dose-dependent intracellular breakdown. The relationship between the number of lethal hits and the number of single-stranded breaks was not previously established. A comparison of the calculated number of nicks per strand of DNA with the known dose in phage-lethal hits reveals a relationship closely approximating one lethal hit to one single-stranded break.

Centrifugation, Density Gradient↗
PubMedDate not supplied

Differentiating large cell lymphoma from indolent small B-cell lymphoma in fine needle aspirates using p53, PCNA and transformed lymphocyte count.

OBJECTIVE: To determine the usefulness of proliferating cell nuclear antigen (PCNA), p53 protein expression and transformed lymphocyte count (TLC) as adjunctive tests to differentiate indolent small B-cell lymphoma from large cell lymphoma in fine needle aspiration biopsies. STUDY DESIGN: Aspirates of lymphoproliferative disorders from April 1993 to January 1997 were reviewed. The percentage of TLCs was determined on the Papanicolaou smear. The percentage and intensity of p53 and PCNA immunocytochemical staining was evaluated on cell block sections. These results were compared and correlated with the final diagnoses based on available morphology, flow cytometry and clinical history. RESULTS: There were 40 cases of non-Hodgkin's lymphoma and 12 reactive lymph nodes. Adequate cell blocks were available on 16 large cell lymphomas, 7 grade 1-2 follicular center cell lymphomas, 6 mucosal associated lymphoid tissue lymphomas, 2 small lymphocytic lymphomas and 2 mantle cell lymphomas. Average TLC and p53 nuclear staining was highest in large cell lymphomas (57% TLC and 24% p53), followed by grades 1 and 2 follicular lymphomas (14% TLC and 15% p53) and lowest in other indolent lymphomas (< 10% TLC and < 1% p53). Average PCNA staining was highest in large cell lymphomas (46%) and lowest in small lymphocytic lymphomas (7%); however, TLC was the best parameter for differentiating large cell lymphoma from indolent small B-cell lymphoma. CONCLUSION: TLC differentiated large cell lymphoma from indolent small B-cell lymphoma better than either p53 or PCNA alone or in combination. Significant overlap between categories limits usefulness of these immunocytochemical stains for differentiating these entities.

Biopsy, Needle↗
PubMedDate not supplied

Long-term survival results for patients with locally advanced, initially unresectable non-small cell lung cancer treated with aggressive concurrent chemoradiation.

PURPOSE: Patients with locally advanced, initially unresectable non-small cell lung cancer (NSCLC) have a median survival time of 9 to 11 months, a 2-year survival rate of 13%, and a long-term survival rate of 5% to 7% when treated with radical thoracic radiation alone. Because of the preclinical radiosensitizing capabilities of 5-fluorouracil and cisplatin and the therapeutic synergy of etoposide and cisplatin, we combined these agents with full-dose radical thoracic radiation to determine the feasibility and efficacy of this approach in locally advanced NSCLC. METHODS: Patients with clinical stage IIIb and bulky IIIa NSCLC and ECOG performance status 0 or 1 received 5-fluorouracil infusion (640-800 mg/m2/d CVI days 1-5, 29-34), cisplatin (20 mg/m2/d, days 1-5, 29-34), etoposide (50 mg/m2, days 1, 3, 5, 29, 31, 33) and concurrent thoracic radiation (60 Gy/2 Gy/d/30 Fx). Patients with adequate cytoreduction proceeded to surgical resection. RESULTS: From March 1987 to July 1990, 41 patients were enrolled on study; 40 are evaluable. The objective response rate was 90%. Thirteen patients (39%), five with clinical stage IIIb disease and eight with IIIa disease, underwent thoracotomy and resection; three proved to have pathological complete remissions. Ten of 77 chemotherapy courses were complicated by neutropenic fever. Grade 3 or 4 esophagitis occurred in 21 patients (52%). Cardiac ischemia or infarction occurred in two patients (5%). There were seven deaths in the first 6 months in the absence of disease progression. Two-year survival was 38%, 3-year survival 25%, and 4- to 5-year survival 18%. Six patients (15%) remain alive at the median follow-up time of 66 months (range, 64-84). CONCLUSIONS: Despite substantial early morbidity and mortality, concurrent, aggressive chemoradiation produced a long-term survival rate in locally advanced NSCLC comparable to other combined modality approaches. However toxicity, particularly esophagitis and postoperative complications, preclude the use of this regimen in phase III studies. Combined modality approaches for locally advanced, initially unresectable NSCLC have become standard; research must simultaneously focus on ways to enhance efficacy and reduce toxicity.

Antineoplastic Combined Chemotherapy Protocols↗