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Biomedical subjects

S Simpson

Publications and source records attributed to S Simpson.

At least 55 records · Page 3Linked to original sources

Hantavirus pulmonary syndrome: clinical, diagnostic, and virologic aspects.

Hantavirus pulmonary syndrome is an acute pneumonitis with a high mortality rate that is caused by a newly recognized hantavirus. Four Corners virus (also known as Muerto Canyon virus and Sin Nombre virus) is enzootic among deer mice (Peromyscus maniculatus). Incidental transmission to humans can result in a disease characterized by rapidly progressive respiratory insufficiency, diffuse noncardiogenic pulmonary edema, vascular volume contraction with hemoconcentration, lactic acidosis, depressed cardiac output, and cardiac dysrhythmias preterminally. The onset of pulmonary edema is preceded by a prodrome of fever and severe myalgias. Characteristic laboratory abnormalities include thrombocytopenia, leukocytosis with prevalent immature myeloid cells, and the presence of immunoblastic lymphocytes in the peripheral blood. Agent-specific diagnosis is based on the detection of Four Corners virus-specific antibodies in serum by Western blot assays and the detection of Four Corners virus RNA in peripheral blood mononuclear cells by the reverse transcriptase-polymerase chain reaction. Effective treatment depends on the rapid institution of intensive care support.

Adolescent

Scores on profile of mood states of college football players from nonscholarship and scholarship programs.

Scores on the Profile of Mood States of football players from three small football programs (ns = 85, 71, and 91) were compared. Scores of athletes from the two nonscholarship programs did not conform to the "iceberg profile," differing mainly on Anger. These same players differed significantly from the scholarship athletes at a major college on all mood states. Mean total mood scores fell between those for major college scholarship athletes and high school athletes. Means for players associated with the small scholarship program more closely resembled means of major college athletes on both the individual mood states and the total mood score. The results supported the hypothesis that nonscholarship collegiate athletes differ in significant ways from those receiving scholarships.

Adult

JCAHO standards: options and opportunities.

The 1994 Joint Commission on Accreditation of Healthcare Organizations (JCAHO) standards focus on the hospital as a system. Chapters of the manual are configured around major patient care functions and organizational structures. JCAHO envisions that if these functions are performing well, quality outcomes will result. The standards are written in a generic fashion, which gives hospitals maximum opportunity to develop programs of standards compliance within the resources and capabilities of their organization. Nurse managers have an opportunity to facilitate creative methods to meet standards' compliance.

Guidelines as Topic

Unit-based shared governance can work!

The Nurse Executive Council at a 540-bed community teaching health center planned and implemented Shared Governance in a 10-bed Medical Intensive Care Unit (MICU). Paid time was provided for nurses to take part in one of four councils. After a pilot year resulting in satisfaction with job autonomy and input into decision-making, staff reaffirmed their commitment to shared governance as a permanent "way of life" in the MICU. During the second year, patient care assistants and unit clerks were integrated into the Councils and staff began serving as consultants to other units and institutions.

Decision Making, Organizational

A Burkitt lymphoma cell line with integrated Epstein-Barr virus at a stable chromosome modification site.

Fluorescence in situ hybridization (FISH), Southern, and slot blotting were used to detect Epstein-Barr virus (EBV) DNA and RNA sequences in a Burkitt's lymphoma (BL) cell line derived from a North American patient (NAB-2). FISH analysis after hybridization with a BamHI "V" region of EBV showed that NAB-2 cells have EBV genome integrated at a single site on the short arm of chromosome 2(p13). Single hybridization signals were detected at homologous sites on both chromatoids and nuclei. Furthermore, hybridization of intact nuclei without formamide denaturation and heat allowed the detection of single specific viral RNA transcripts visible as "tracks" or "traces." Southern blot analysis confirmed the integration of EBV genome into the host DNA. Quantification of slot blot hybridization revealed that NAB-2 cells have on average one copy of EBV per cell. Virus insertion into chromosomal DNA caused a stable modification site expressed as a distinctive achromatic region adjacent to the band 2p13. The chromatid lesion at the site of EBV integration involving a recombinogenic and fragile site may have contributed to the development of the NAB-2 BL.

Blotting, Southern

A multifunctional prokaryotic protein expression system: overproduction, affinity purification, and selective detection.

A series of plasmid vectors, pRSET A, B, and C, have been developed for high-level protein expression in prokaryotes and have been characterized. Based upon the T7 RNA polymerase-driven pET system, the pRSET vectors encode recombinant proteins as fusions with a multifunctional leader peptide containing a hexahistidyl sequence for purification on Ni(2+)-affinity resins, a tyrosine residue for radioiodination, and an enterokinase proteolytic cleavage site for leader peptide removal. Monoclonal antibodies (MAbs) to two epitopes on the leader peptide, which also contains amino acids 1-12 of the T7 gene 10 major capsid protein, were developed and provide for universal immunological detection of pRSET-expressed fusion proteins. Subcloning of protein-encoding DNA is facilitated by an 11-site polylinker which is offset for all three ribosomal reading frames, and an f1(+) origin of DNA replication permits single-stranded DNA synthesis for site-directed mutagenesis protocols. Representative fusion proteins overexpressed in Escherichia coli were successfully purified under both denaturing and nondenaturing conditions by single-step Ni2+ affinity chromatography. Purification was independent of recombinant protein solubility in sonicated or freeze-thawed E. coli lysates. Isolation of MAbs for selective recognition of either of two leader peptide epitopes was demonstrated by immunoprecipitation, but this selectivity was less evident under conditions for Western blotting. In combining the utility of T7 RNA polymerase-directed expression with several recent advances in protein purification and detection, the pRSET vectors will serve as a powerful resource for a variety of studies in protein biochemistry.

Amino Acid Sequence

A study of the Huntington's disease associated trinucleotide repeat in the Scottish population.

Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.

Adult

Skin-to-skin contact beginning in the delivery room for Colombian mothers and their preterm infants.

To determine if the transition to extrauterine life is facilitated by skin-to-skin contact, six relatively low risk preterm infants experienced six continuous hours of skin-to-skin contact on their mothers' chests beginning within 30 minutes of birth. Heart and respiratory rates and oxygen saturation remained within normal limits and all infant temperatures rose rapidly to thermoneutral range. Two infants developed grunting respirations by the time skin-to-skin contact began, but the grunting disappeared with warm, humidified oxygen and continuous skin-to-skin contact. All infants were fully breastfeeding and ready for discharge by 24-48 hours postbirth. Early skin-to-skin contact was safe and seemed beneficial for these relatively low risk preterm infants.

Colombia

Overexpression of wild-type p53 alters growth and differentiation of normal human keratinocytes but not human papillomavirus-expressing cell lines.

To examine whether the tumor suppressor gene p53 influences epidermal differentiation, primary cultures of human foreskin keratinocytes and six human papillomavirus (HPV)-positive cell lines were infected with recombinant retroviruses encoding wild-type p53. Overexpression of p53 in organotypic cultures of normal keratinocytes decreased their growth rate and induced premature cell flattening and involucrin expression, a marker of squamous differentiation. However, overexpression of p53 inhibited or delayed production of other epidermal proteins, keratin 10, profilaggrin, and keratinocyte transglutaminase. Furthermore, levels of endogenous cellular p53 dramatically decreased during epidermal differentiation, suggesting that down-regulation of p53 permits complete expression of specific epidermal proteins. Three HPV-immortalized keratinocyte cell lines and three HPV-positive cervical carcinoma-derived cell lines expressed significantly less (< 3-fold) p53 protein than normal keratinocytes. Up-regulation of wild-type p53 (> 5-fold) by retrovirus infection did not significantly inhibit growth or restore normal epithelial differentiation in any line. Thus, overexpression of wild-type p53 can either induce or inhibit expression of specific epidermal proteins in normal keratinocytes but does not reverse immortality or aberrant differentiation of HPV-immortalized or carcinoma-derived cell lines.

Cell Differentiation

Comparative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines.

The pathogenesis of cervical human papillomavirus (HPV) infection is influenced by the host's immune response. This response depends upon secretion of specific lymphokines to recruit and activate immune cells at the site of infection. To examine whether cervical cells enhance immune-responsiveness, secretion of lymphokines by cultures of normal cervical cells, HPV-immortalized cervical lines, and carcinoma lines was compared. Normal cervical cells constitutively secreted interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte macrophage colony stimulating factor. Lymphokines were also produced by exo- and endocervical epithelia in vivo. In contrast, four cervical cell lines immortalized by HPV DNAs and three carcinoma lines secreted selected lymphokines at significantly reduced levels. Interferon-gamma induced major histocompatibility class I and II proteins and intercellular adhesion molecule-I in normal cells, but results in immortal or carcinoma lines were variable. These results suggest that cervical epithelial cells have the potential to influence inflammation and immunity in the cervical mucosa. Furthermore, decreased expression of lymphokines and histocompatibility molecules by HPV-immortalized cervical cells suggests that similar alterations might accompany persistent HPV infections in vivo.

Carcinoma

HIV and associated cutaneous diseases.

HIV infections manifest a wide spectrum of dermatologic diseases. These can be classified and described as primary bacterial infections, fungal infections, associated cutaneous disorders, and hypersensitivity reactions. The presentation of each disease can be clearly identified, and current preferred medical therapies recommended for each disorder.

Diagnosis, Differential

Leukoregulin and gamma-interferon inhibit human papillomavirus type 16 gene transcription in human papillomavirus-immortalized human cervical cells.

The human papillomavirus (HPV) transforming genes E6 and E7 are retained and expressed in the majority of cervical cancers implying an important role for these proteins in maintenance of the malignant phenotype. Leukoregulin (LR) and recombinant gamma-interferon (r-IFN-gamma), lymphokines secreted by immune cells present in regressing HPV infections, inhibited transcription of E6/E7 RNAs in several human cervical epithelial cell lines immortalized by recombinant HPV-16, -18, and -33 DNAs. r-IFN alpha was not effective. Reduction in E6/E7 RNA expression was accompanied by inhibition of cell proliferation coincident with an increase in epidermal transglutaminase activity, a marker of squamous differentiation. LR and r-IFN gamma enhanced transcription of class 1 cell surface histocompatibility antigens (HLA) and r-IFN gamma additionally induced HLA class 2 expression. HPV-immortalized cells developed partial resistance to the growth inhibitory effects of lymphokines after malignant transformation or extended propagation in culture. This is the first demonstration that LR and r-IFN gamma selectively inhibit transcription of HPV-transforming genes and suggests a molecular mechanism by which these lymphokines participate in regression of premalignant cells.

Blotting, Northern

Wheat germ agglutinin inhibits the C5a receptor interaction: implications for receptor microheterogeneity and ligand binding site.

Wheat germ agglutinin (WGA) has been shown to inhibit the interaction of C5a with the C5a receptor on both polymorphonuclear neutrophils (PMNs) and the histiocytic cell line U937. The level of inhibition with isolated receptor preparations is 100%, and on intact cells 10 to 20% of the receptor population appear to retain their ability to bind C5a in the presence of WGA. In contrast, this lectin completely inhibits the C5a-mediated degranulation of PMN primary and secondary granules, suggesting that the population of C5a receptors responsible for mediating degranulation is also recognized by WGA. More than 50% of the receptors appear to be blocked before an effect on degranulation occurs. This inhibition by WGA does not appear to be due to down-regulation of C5a receptors from the cell surface, excessive aggregation of receptor sites, or interaction of WGA with the carbohydrate portion of the C5a molecule. The inhibition is reversed by N-acetylglucosamine but not by sialic acid. This effect appears to be specific for WGA because various other lectins do not inhibit the C5a receptor interaction. That the inhibition by WGA is due to direct binding of the lectin to N-acetylglucosamine residues on the C5a receptor is strongly supported by the ability of the cross-linked C5a-receptor complex to bind to and be specifically eluted from a WGA-Affigel affinity matrix. These observations are consistent with hypothesis that the population of C5a receptors on leukocytes exhibits microheterogeneity with respect to structure (carbohydrate content) and/or function.

Binding Sites

Inhaled histamine increases the rate of absorption of sodium cromoglycate from the lung.

Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/- 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways.

Adolescent

A single base deletion in the 5' noncoding region of Theiler's virus attenuates neurovirulence.

Viral chimeras have been constructed through in vitro manipulations of the infectious cDNA clones of two prototypes of Theiler's murine encephalomyelitis virus: (i) the virulent GDVII strain and (ii) the less virulent BeAn and VL strains. Previous studies have suggested that the phenotypic differences in virulence between the BeAn and GDVII strains map to both the 5' noncoding and the coat protein regions of these viral genomes. It is shown here that attenuation mapped to the 5' noncoding region is due, at least in part, to an inadvertent deletion resulting from a cloning artifact of one C nucleotide out of four between positions 876 and 879 in the BeAn sequences. The in vitro growth characteristics in BHK-21 cells, however, do not reflect the large differences in neurovirulence between chimeras that are identical except for the deleted C. Another chimera with a mutation at position 877 and a deletion at 976 is also attenuated. The wild-type sequences from the less virulent strains BeAn and VL between nucleotides 1 and 933, in an otherwise GDVII chimera, do not attenuate virulence. Sequences of the 500 nucleotides of the 5' noncoding region proximal to the translation initiation codon were obtained for nine additional Theiler's virus strains. The attenuating deletions are discussed in the context of these sequences and the proposed secondary structures for the 5' noncoding region.

Animals

Osteomyelitis of the calcaneum.

We reviewed 52 cases of osteomyelitis of the calcaneum. The clinical symptoms and signs were well defined, but different and less dramatic than those of long-bone osteomyelitis. Blood cultures were positive in 41% of cases and tissue cultures in 91%. Routine haematological tests were of little value, and radiological changes were often delayed, and were absent in 12%. With early diagnosis, treatment with antibiotics alone was usually effective, but complications and chronic disease were more likely if there was delay. Early diagnosis is the key to successful treatment. We describe a new physical sign and consider that diagnosis is almost always possible by clinical methods.

Adolescent

Methicillin resistant Staphylococcus aureus and its implications for nursing practice: a literature review.

The subject of methicillin-resistant Staphylococcus aureus (MRSA) and its implications for nursing practice are reviewed. Resistance of Staphylococcus aureus to antibiotics, and the emergence and incidence of MRSA both in the United Kingdom and abroad, are examined. Modes of transmission of MRSA by transfer of affected patients and, specifically, cross infection by staff are reviewed with methods to prevent cross infection, including screening of staff, handwashing techniques, barrier and cohort nursing, being examined. The costs of an MRSA outbreak, both financially and psychologically, to staff and patients are discussed. Guidelines for the control of epidemic MRSA are explained in the context of the above topics, and all areas are related to improving nursing practice.

Cross Infection