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Biomedical subjects

L Pearson

Publications and source records attributed to L Pearson.

At least 19 recordsLinked to original sources
PubMed1995

Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.

The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1.

Animals↗
PubMed1995

A rationale for mouth care: the integration of theory with practice.

Mouth care is a commonly performed nursing procedure in which the aim is to ensure that patients' mouths are cared for. However, there is evidence that unless dental plaque is removed from the tooth surfaces and the gingival margin, the mouth is in danger of becoming unhealthy and, therefore, uncared for. It appears from the dental literature that the use of a toothbrush is one of the best and most widely used tools in the Western world for removing dental plaque (Addy, Slayne & Wade 1992), other methods being ineffective, dangerous, or poorly researched (Trenter-Roth & Creason 1986). However, a review of the nursing literature indicates that toothbrushes are not the tools of choice for mouth care by nurses (Howarth 1977, Harris 1980). Thus, there appears to be a gulf between the knowledge base from the dental literature and the reality of nursing practice resulting in 'mouth care' becoming a misleading misnomer. The aim in this paper is to present a rationale for mouth care based upon the dental literature and to apply such knowledge to nursing practice, especially in intensive therapy units (ITUs), so that nurses may be in a better position to provide 'mouth care' which lives up to its name.

Clinical Nursing Research↗
PubMed1994

Inhibition of prokaryotic and eukaryotic transcription by the 2:1 2,9-dimethyl-1,10-phenanthroline-cuprous complex, a ligand specific for open complexes.

The redox-stable, tetrahedral cuprous chelate of neocuproine (2,9-dimethyl-1,10-phenanthroline) binds to the single-stranded DNA formed in open complexes and is an effective inhibitor of eukaryotic and prokaryotic transcription. Despite the many kinetic and structural differences between prokaryotic and eukaryotic transcription systems, they are all similarly inhibited by neocuproine copper, suggesting that all open complexes may share a homologous structure.

Base Sequence↗
PubMed1994

Footprinting RNA-protein complexes following gel retardation assays: application to the R-17-procoat-RNA and tat--TAR interactions.

RNA-protein complexes isolated following a gel retardation assay can be footprinted within the gel matrix using the chemical nuclease activities of 4,7-dimethyl-, 5,6-dimethyl-, and 3,4,7,8-tetramethyl-1,10-phenanthroline-copper. These complexes are more reactive than 1,10-phenanthroline-copper but share its reaction preference for bulges and loops. The interaction of the coat protein of R-17 with its viral RNA target and tat- and tat-derived peptides with HIV TAR RNA have been studied. In both cases, the RNA sequence opposite a 2-3 nucleotide bulge are protected. Tat-derived peptides inhibit cleavage at sites which intact tat does not protect. These results are consistent with transcription studies which have suggested that truncation of tat increases nonspecific binding.

Amino Acid Sequence↗
PubMed1994

Allergies, upper respiratory tract infections, and asthma.

The aims of this study were (1) to quantify the prevalence of aeroallergen hypersensitivity in presentations for emergency treatment of asthma and (2) to determine the strength of association between viral upper respiratory tract infections (URTIs) and admission for treatment of asthma. A series of 209 asthmatic patients presenting to the Emergency Department (ED) of the Alfred Hospital over 6 months underwent skin prick testing and venipuncture for serum IgE and rye grass pollen (RGP) RAST. A case-control study of 38 asthmatic inpatients and 90 controls admitted for road trauma or endoscopy underwent nasopharyngeal aspiration for viral culture and immunofluorescence (IF). Eighty-four percent of ED asthmatic patients had one or more positive skin tests to common aeroallergens, 57% had a positive skin test, and 45% had a positive RAST to RGP. Viral cultures or IF studies were positive in 8 asthmatic patients and 2 controls. Asthmatic inpatients were 6 times more likely to have a viral URTI than were controls. It is concluded that aeroallergen hypersensitivity is present in most asthmatic patients presenting to the ED, and that there is a strong association between viral URTIs and admission for asthma.

Adolescent↗
PubMed1990

Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs.

A primary site of infection by human adenoviruses is lymphoid cells. However, analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported. The adenovirus early region 3 (ES) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens, thus preventing their cell surface expression with a resultant decrease in host immunologic destruction. To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells, both DNA binding and transfection analysis with the E3 promoter in both cell types were performed. These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts. Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B. Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif (L2) had minimal effects on promoter expression in HeLa cells, but resulted in dramatic decreases in expression by lymphoid cells. In contrast, mutagenesis of proximal NF-kappa B motif (L1) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small, but reproducible, increase in gene expression in lymphoid cells when coupled to the L2 mutation. Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenovirus Early Proteins↗
PubMed1990

Diverse soybean actin transcripts contain a large intron in the 5' untranslated leader: structural similarity to vertebrate muscle actin genes.

Plant actins are encoded by complex and highly divergent multigene families. Despite the general lack of intron conservation in animal, fungal and protist actin genes, evidence is presented which indicates that higher plant actin genes have an untranslated leader exon with structural similarity to that found in vertebrate actin genes. All functional higher plant actin genes sequenced to date contain a potential intron acceptor site in the 5' untranslated region 10 to 13 nucleotides upstream of the initiator ATG. A leader specific cDNA probe hybridized to sequences over 1.0 kbp upstream from the coding region confirming the presence of an upstream exon. Primer extension of mRNA with gene-specific oligonucleotides was used to analyze the 5' untranslated exon and leader intron from four divergent soybean actin genes, SAc3, 4, 6 and 7. The 5' ends of all four mRNAs are heterogeneous. The consensus promoter elements of the SAc7 actin promoter were identified. Gene specific primer extension sequencing of actin mRNAs indicated that splicing of the 5' leader intron occurred at the predicted acceptor site in SAc6 and SAc7. The SAc6 and SAc7 5' untranslated exons are small (88-111 nt) and the leader introns are relatively large (844-1496 nt). The presence of an intron within the 5' RNA leader and an intron which splits a glycine codon at position 152 in all plant actin genes and all vertebrate muscle actin genes suggests that these structures may have been conserved due to a functional role in actin expression. The 5' regions of these two soybean actin genes contain many unusual features including (CT) repeats and long stretches of pyrimidine-rich DNA. The possible roles of the upstream exon/intron and the C + T-rich regions are discussed.

Actins↗
PubMed1990

A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat.

Regulation of human immunodeficiency virus (HIV) gene expression is dependent on specific regulatory regions in the long terminal repeat. These regions include the enhancer, SP1, "TATA," and trans-activating (TAR) regions. In addition, viral regulatory proteins such as tat and rev are important in regulating HIV gene expression. The mechanism of tat activation remains the subject of investigation, but effects at both transcriptional and posttranscriptional levels seem likely. Previous mutagenesis of the tat protein revealed that the amino terminus, the cysteine-rich domain, and the basic domain were all required for complete tat activation. Mutants of other viral trans-acting regulatory proteins, including E1A, tax, and VM65, have been identified that were capable of antagonizing the activity of their corresponding wild-type proteins. We wished to determine whether mutants of the tat protein could be identified that exhibited a similar phenotype. One mutant (delta tat) that truncated the basic domain of tat resulted in a transdominant phenotype inhibiting tat-induced gene expression of the HIV long terminal repeat but not other viral promoters. This mutant exhibited its maximal phenotype in cotransfection experiments when present in an 8- to 30-fold molar excess over the wild-type tat gene. Trans-activation of the HIV long terminal repeat by delta tat was very defective at the DNA concentrations used in these experiments. RNase protection analysis indicated that this mutant decreased tat-induced steady-state mRNA levels of the HIV long terminal repeat. Second-site mutations of the delta tat gene in either the amino terminus or cysteine region eliminated the transdominant phenotype. In contrast to tat, which was localized predominantly to the nucleolus, delta tat was present in both the nucleus and cytoplasm, suggesting that it may inhibit tat function by preventing nucleolar localization. Transdominant mutants of tat may have a role in potentially inhibiting HIV gene expression.

Amino Acid Sequence↗
PubMed1990

Remitting, seronegative, symmetrical synovitis with pitting edema--13 additional cases.

The case histories of 13 elderly patients (8 men/5 women) with a relatively acute onset of a severe symmetrical synovitis affecting the flexor digitorum tendon sheaths and wrist joints with pitting edema of the dorsum of both hands are described. All were persistently seronegative for IgM rheumatoid factors and all went into complete remission without relapse. Asymptomatic residual flexion contractures of the fingers and wrists were a constant feature during remission. HLA-B7 was present in 15 of a total 23 reported cases (relative risk = 4.4). This condition, with its excellent prognosis, is differentiated from rheumatoid arthritis and polymyalgia rheumatica.

Aged↗
PubMed1989

Multiple transcriptional regulatory domains in the human immunodeficiency virus type 1 long terminal repeat are involved in basal and E1A/E1B-induced promoter activity.

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) is the site of activation of the HIV tat protein. However, additional transactivators, such as the adenovirus E1A and herpesvirus ICPO proteins, have also been shown to be capable of activating the HIV LTR. Analysis of adenovirus mutants indicated that complete transactivation of the HIV LTR was dependent on both the E1A and E1B proteins. To determine which regions of the HIV LTR were important for complete E1A/E1B activation, a variety of oligonucleotide-directed mutations in HIV transcriptional regulatory domains were assayed both in vivo and in vitro. S1 nuclease analysis of RNA prepared after transfection of these HIV constructs into HeLa cells infected with wild-type adenovirus indicated that the enhancer, SP1, TATA, and a portion of the transactivation-responsive element were each required for complete E1A/E1B-mediated activation of the HIV LTR. These same promoter elements were required for both basal and E1A/E1B-induced levels of transcription in in vitro transcription reactions performed with cellular extracts prepared from cells infected with dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. No mutations were found that reduced only E1A/E1B-induced expression without proportionally reducing basal levels of transcription, suggesting that E1A/E1B-mediated induction of the HIV LTR requires multiple promoter elements which are also required for basal transcriptional levels. Unlike activation by the tat protein, there was not a rigid dependence on maintenance of the transactivation-responsive stem base pairing for E1A/E1B-mediated activation either in vivo or in vitro, indicating that activation occurs by a mechanism distinct from that of tat induction.

Adenovirus Early Proteins↗
PubMed1989

Ethics and rehabilitation--how to develop your ethical awareness.

The professional responsibility of nurses is to help patients achieve an optimal quality of life. The ANA Code for Nurses (1976) mandates that nurses are advocates for patients. Some of the challenges that this mandate poses for nurses are addressed in this article. Interest in the unique issues of rehabilitation ethics is increasing, and nurses need to take the responsibility of obtaining training in ethics. Strategies to achieve this are discussed and an "Ethical Seminar Outline" is provided. This increase in ethical awareness will define to patients and the general public the nurse's professional role. It will also give nurses the tools they need to be the advocates the patients need in these complex times.

Awareness↗
PubMed1988

Functional domains required for tat-induced transcriptional activation of the HIV-1 long terminal repeat.

The transcriptional regulation of the human immunodeficiency virus (HIV) type I involves the interaction of both viral and cellular proteins. The viral protein tat is important in increasing the amount of viral steady-state mRNA and may also play a role in regulating the translational efficiency of viral mRNA. To identify distinct functional domains of tat, oligonucleotide-directed mutagenesis of the tat gene was performed. Point mutations of cysteine residues in three of the four Cys-X-X-Cys sequences in the tat protein resulted in a marked decrease in transcriptional activation of the HIV long terminal repeat. Point mutations which altered the basic C-domain of the protein also resulted in decreases in transcriptional activity, as did a series of mutations that repositioned either the N or C termini of the protein. Conservative mutations of other amino acids in the cysteine-rich or basic regions and in a series of proline residues in the N terminus of the molecule resulted in minimal changes in tat activation. These results suggest that several domains of tat protein are involved in transcriptional activation with the cysteine-rich domain being required for complete activity of the tat protein.

DNA Mutational Analysis↗
PubMed1985

Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome.

Eight elderly men and two elderly women presented with symmetrical polysynovitis of acute onset involving most of their appendicular joints and flexor digitorum tendons associated with pitting edema of the dorsum of both hands and both feet. Onset of seven of the ten cases could be pinpointed almost to the hour. Rheumatoid factors were absent from serum samples in all, and no radiologically evident erosions developed. Clinical and laboratory signs of inflammation and the edema disappeared gradually in each case. Treatment consisted of aspirin or other nonsteroidal anti-inflammatory drugs. Hydroxychloroquine, 200 to 400 mg/day, was given in six and gold therapy in two cases. Painless limitation of motion of the wrists and/or fingers persisted in all, although the patients were both unaware of and unhampered by this abnormality. Six of eight cases where typing was possible were positive for HLA-B7, CW7, and DQW2 (relative risk for B7, 9.5). Three cases of this syndrome were found in a consecutive series of 52 men diagnosed as having definite "rheumatoid arthritis," and thus represent a distinctive condition with an excellent prognosis.

Acute Disease↗
PubMed1985

The use of pNJ5000 as an intermediate vector for the genetic manipulation of Agrobacterium Ti-plasmids.

The use of broad-host-range plasmids derived from RP4 as intermediate vectors for the transfer of narrow-host-range recombinant plasmids from Escherichia coli to Agrobacterium tumefaciens as a preliminary to marker exchange is described. Recombinant plasmids having a ColE1 type origin were linked to the RP4 derivative. Cointegrate formation appeared to take place by RecA-independent, homologous recombination within a short piece of DNA derived from the beta-lactamase gene of Tn1/Tn3 carried by both vector components, so that it never disrupted the recombinant portion of the construction. pNJ5000 provides an unstable intermediate vector for use in marker exchange experiments, while its stable relative pNJ1020 provides a carrier for use in binary vector systems.

Cloning, Molecular↗