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N Warren

Publications and source records attributed to N Warren.

53 records · Page 3Linked to original sources

A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells.

The Epstein-Barr viral (EBV) genome of approximately equal to 170 kilobase pairs (kbp) is maintained as a plasmid in human B lymphoblasts transformed by the virus. We have identified a cis-acting element within 1.8 kbp of the viral genome that allows recombinant plasmids carrying it to be selected at high frequency and maintained as plasmids in cells latently infected by EBV. This functional element(s) requires a segment of DNA at least 800 bp and at most 1800 bp long, which contains a family of 30-bp tandem repeats at one end. Since this region confers efficient stable replication only to plasmids transfected into cells containing EBV genomes, its function probably requires trans-acting products encoded elsewhere in the viral genome.

DNA Replication↗

Isolation of Physarum DNA segments that support autonomous replication in yeast.

Hybrid plasmids containint the bacterial resistance-transfer factor pBR322 and the yeast leu2+ gene have been used to isolate DNA fragments of Physarum that are capable of initiating DNA replication in a yeast host. Five of forty hybrid plasmids containint Physarum sequences transform leu2- yeast to Leu+ at high frequency. The resulting Leu+ transformants are characterized by phenotypic instability. Supercoiled plasmid molecules containing pBR322 sequences can be detected in the transformed yeast, indicating that the transforming DNA replicates autonomously. Plasmid DNA isolated from Leu+ yeast can transform leuB bacteria. The hybrid plasmid recovered from the Leu+ bacterial transformants is identical to the original plasmid, indicating structural integrity is maintained during passage through the yeast host. These hybrid plasmids containing Physarum sequences have the same characteristics as those containing autonomously replicating yeast chromosomal sequences. As the temporal sequence of DNA replication is particularly accessible to study in Physarum plasmodia, the functional significance of these segments should be amenable to study.

Base Sequence↗

Temperature-sensitive mutants of Physarum polycephalum: viability, growth, and nuclear replication.

Using a selfing strain of Physarum polycephalum that forms haploid plasmodia, we have isolated temperature-sensitive growth mutants in two ways. The negative selectant, netropsin, was used to enrich for temperature-sensitive mutants among a population of mutagenized amoebae, and, separately, a nonselective screening method was used to isolate plasmodial temperature-sensitive mutants among clonal plasmodia derived from mutagenized amoebae. Complementation in heterokaryons was used to sort the mutants into nine functional groups. When transferred to the restrictive temperature, two mutants immediately lysed, whereas the remainder slowed or stopped growing. Of the two lytic mutants, one affected both amoebae and plasmodia, and the other affected plasmodia alone. The growth-defective mutants were examined for protein and deoxyribonucleic acid synthesis and for aberrations in mitotic behavior. One mutant may be defective in both protein and deoxyribonucleic acid synthesis, and another only in deoxyribonucleic acid synthesis. The latter shows a striking reduction in the frequency of postmitotic reconstruction nuclei at the restrictive temperature. We believe that this mutant, MA67, is affected in a step in the nuclear replication cycle occurring late in G2. Execution of this step is necessary for both mitosis and chromosome replication.

Cell Nucleus↗

Three-peaked chemiluminescent response of human peripheral blood leukocytes following stimulation with phytohaemagglutinin (PHA).

Luminol-enhanced chemiluminescence (CL) was used to examine the response of various leukocyte populations following stimulation with a crude extract of Phaseolus vulgaris, namely phytohaemagglutinin (PHA-C). Populations stimulated included a human peripheral mixed leukocyte preparation (MLP), and purified preparations of lymphocytes, monocytes and polymorphonuclear leukocytes (PMNL). Mouse peritoneal exudate cells and the lymphocytic cells lines Molt #4 and Daudi were also stimulated. Following stimulation, a characteristic three-peaked chemiluminescent response was obtained from the MLP population. Little or no response was obtained from the purified lymphocytes. Monocytes produced a sharp peak corresponding to the second peak of the MLP response and PMNL produced a broad peak corresponding to the third peak of the MLP response. Mouse peritoneal exudate cells containing lymphocytes and monocytes/macrophages showed a two-peaked stimulation which corresponded to the first two peaks of the MLP response. Molt #4 and Daudi showed no chemiluminescence if stimulated individually, but if added to a MLP substantial enhancement of the first and second peaks was observed. These results indicate some form of lymphocyte/monocyte interaction leading to enhanced CL following PHA-C stimulation.

Animals↗

Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells.

Epstein-Barr virus (EBV) infects human B lymphocytes, transforming the infected cells into dividing blasts that can proliferate indefinitely. The viral genome of 172 kilobase pairs (kbp) is a plasmid in most transformed cells. We have identified a region of EBV DNA, termed oriP (nucleotides 7,333-9,109 of strain B95-8), which acts in cis to permit linked DNAs to replicate as plasmids in cells containing EBV DNA. We have postulated the existence of a trans-acting gene allowing oriP function. Here we report that this gene lies in a 2.6-kbp region of the viral genome (nucleotides 107, 567-110, 176) which encodes the EBNA-1 antigen. We show that circular DNAs containing oriP, the EBNA-1 gene and a selectable marker replicate autonomously in cells derived from at least four developmental lineages and from at least three species. We also find that the one-third of the EBNA-1 gene repetitive in sequence is not essential for the trans-acting function that EBNA-1 gives oriP.

Animals↗

The economic and social consequences of work-related musculoskeletal disorders: the Connecticut Upper-Extremity Surveillance Project (CUSP).

A population-based telephone survey was conducted in Connecticut to determine the social and economic impact of work-related musculoskeletal disorders (WRMSDs). Only 10.6% of cases had filed for workers' compensation. Respondents had spent an average of $489 annually out-of-pocket. Only 21% of individuals who had had medical visits or procedures reported having them paid for by workers' compensation. The WRMSD cases reported much higher levels of difficulty in daily tasks rated by the activities of daily living (ADL) scale, with odds ratios (ORs) ranging from 8.2 (child care) to 35.2 (bathing). The cases were significantly more likely to have moved for financial reasons (OR = 2.41), including having lost a home (OR = 3.44). The cases were also significantly more likely to have lost a car due to finances (OR = 2.45), more likely to have been divorced (OR = 1.91), and less likely to have been promoted (OR = 0.45). The study supports significant externalization of costs for WRMSD out of the workers' compensation system and a substantial social and economic impact on workers.

Activities of Daily Living↗

Challenges faced by the HIV health services planning council in Oakland, California, 1991-1994.

This study reports the findings of a case study of the health services planning council established in the Oakland, California, eligible metropolitan area (the Oakland EMA) under Title I of the Ryan White Comprehensive AIDS Resources Emergency Act of 1990 (the CARE Act). We gathered primary data through observation of planning council meetings, examination of documentary evidence, and in-depth interviews with key participants. An important finding of this study was the inconsistency observed between the rational, linear planning model embedded in the CARE Act legislation and the politicized, emergent, and, at times, chaotic planning process actually observed in the Oakland EMA. The primary reasons for this inconsistency included confusion among council members about the planning council's responsibilities and authority, as well as its relationship with the local health department; limitations on administrative support at the local level; reluctance of program administrators at the federal level to provide advice concerning development of the council; allegations of conflict of interest among members of the council; pre-existing societal tensions and divisions; concerns about the representativeness of the council's membership; competition among providers of services for funding; conflicting demands for services by persons affected by HIV disease; disagreements between the council and providers of services over policies and procedures for administering the services contracts; and concerns about the council's involvement in the selection of specific agencies for funding, its lapses in compliance with rules of order, and its failure to accurately record minutes of all of its meetings. Despite the challenges faced by the Oakland planning council, it was able to meet its Title I obligations, which resulted in significant increases in the availability of medical and social services for persons affected by HIV disease. However, dealing with the confusion and conflicts described above consumed a considerable amount of the planning council's time and energy and eventually required a complete reorganization of the council to assure its stability and the legitimacy of the Title I program at the local level. Medical Subject Headings (MeSH): health planning councils; health planning organizations; health care coalitions; organization and administration; organizational innovation; models, organizational.

California↗

Ambiguities in office-related injury: the poverty of present approaches.

This is a straightforward entry into the fray over the association of upper extremity disorders with the modern workplace. The authors point out that successful intervention and prevention efforts are underway around the world, despite the continuing debate on theory.

Arm Injuries↗