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S Simpson

Publications and source records attributed to S Simpson.

At least 109 records · Page 6Linked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Recombinant retroviruses encoding human papillomavirus type 18 E6 and E7 genes stimulate proliferation and delay differentiation of human keratinocytes early after infection.

Human papillomavirus (HPV) DNAs are detected in most genital dysplasias and cancers, suggesting that these viruses perturb epithelial growth and differentiation. The E6 and E7 genes of HPV type 18 induce immortality in keratinocytes cultured from genital tract epithelia, and the immortal cell lines display aberrant squamous differentiation. To examine whether the E6 and E7 proteins directly alter keratinocyte growth and differentiation, high-titer recombinant retroviruses were constructed for efficient transfer and expression of HPV-18 genes E6, E6* and E7 in cultures of normal human keratinocytes. Infection with retroviruses encoding E6 and E7 stimulated cell proliferation, reduced the requirement for bovine pituitary extract and induced immortality. E6 and E7 also delayed but did not prevent the onset of terminal squamous differentiation. The magnitude of effects on growth and differentiation of cultured cells was directly related to levels of E7 protein expression. Thus, expression of the HPV-18 E6 and E7 genes stimulates cell proliferation and delays differentiation of keratinocytes in vitro.

Blotting, Southern↗
PubMed1992

A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells.

The human erbB-2 oncogene encodes a tyrosine kinase receptor. A ligand for the erbB-2 receptor (gp30), with an apparent molecular weight of 30,000, was reported to modulate the growth of cells overexpressing erbB-2. Whereas low concentrations of gp30 induced proliferation of these cells, higher concentrations inhibited their growth. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells AU-565 and MDA-MB-453 (which overexpress erbB-2) and MCF-7 cells (which express low levels of this protooncogene). Ligand concentrations that inhibited growth in cells overexpressing erbB-2 induced apparent differentiation of cells with a more mature phenotype, i.e., with characteristics such as inhibited cell growth, altered cytoplasmic and nuclear morphology, and increased synthesis of milk components (casein and lipids). No significant effect of the ligand was observed in the human breast cancer cell line MCF-7. Concomitant with the induction of differentiation in AU-565 and MDA-MB-453 cells, the erbB-2 protein was translocated from membrane to the cytoplasm and perinuclear sites. These findings indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is associated with an apparent induction of differentiation.

Breast Neoplasms↗
PubMed1992

Fine structure of cells in the young regenerating spinal cord of the lizard Anolis carolinensis after H3-thymidine administration.

H3-thymidine was injected in a single dose into adult lizards Anolis carolinensis during early stages of tail regeneration when the new tail measured in length 2-5 mm (about 3 weeks). Electron microscopic autoradiography revealed that in the regenerating spinal cord three different cell types were recognizable four hours post-injection. By far the most common type was the ependymal cell. Ependymal or roundish cells with clear electron-density or storing bundles of intermediate filaments were occasionally found. A second rarer, cell type devoid of intermediate filaments was a pale round cell, often highly labelled. This cell showed a very poor ultrastructural differentiation and probably represents the precursor of the few neurons and glial cells observed in older stages of regeneration. The third type was a neuroblast at different degrees of differentiation and did not uptake H3-thymidine revealing it was a post-mitotic cell. Despite the relatively advanced ultrastructural differentiation of these neurons, synapses were rarely seen after three weeks of SC regeneration in Anolis.

Animals↗
PubMed1991

Transforming growth factor beta 1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice.

While stimulating the growth of fibroblasts, transforming growth factor beta 1 (TGF-beta 1) inhibits the growth of various normal and malignant cell lines in vitro. We studied the effects of TGF-beta 1 in vivo. The level of TGF-beta 1 in serum was maximally elevated 2 h after injecting 1 muCi of 125I-TGF-beta 1 into the peritoneal cavity of nude mice. Five h after the i.p. administration of 10 micrograms of unlabeled TGF-beta 1, 20 ng/ml of TGF-beta-like material in serum were detected by a radioreceptor assay on A549 lung carcinoma cells. Trichloracetic acid-precipitable 125I-TGF-beta 1 was taken up by liver, spleen, lungs, kidneys, and tumor tissue but not by the brain. At doses exceeding 2 micrograms/day, TGF-beta 1 induced a generalized interstitial fibrosis and a cachexia, which was not mediated by elevated serum levels of tumor necrosis factor alpha as determined by Western blot analysis and enzyme-linked immunosorbent assay. A total of 200,000 cells of the estrogen receptor-negative human breast cancer line MDA-MB-231, which had been shown to be maximally growth inhibited in vitro by 40 pM TGF-beta 1 and to have high-affinity receptors (9, 11, 12), were injected into the mammary fat pad of each nude mouse. The duration of treatment was 16 days with ten animals in the control group and five animals in the treated groups. The dose ranged from 1 to 4 micrograms per animal daily. The treatment was started 24 h after the injection of the tumor cells. Tumor growth was not significantly affected at either nontoxic or toxic doses of TGF-beta 1. Thus, we have demonstrated that TGF-beta 1, apart from being a local growth factor, has systemic effects, such as cachexia and multiple fibrosis. Its role as an antitumor agent may be limited.

Animals↗
PubMed1991

Tissue culture conditions determine the effects of estrogen and growth factors on the anchorage independent growth of human breast cancer cell lines.

We determined the effects of epidermal growth factor, insulin-like-growth-factor-1 and estradiol on the anchorage independent growth of the estrogen receptor positive human breast cancer cell lines MCF7 and T-47D. In serum free conditions growth factors but not estrogen induced a dose dependent stimulation of growth in both cell lines. The ability of estrogen to induce colony formation of early passage MCF7 cells (less than 100) was strictly correlated to the concentration of sulfatase and charcoal treated calf serum (CCS) with a maximal effect at a concentration of 5% CCS and 10 nM estradiol. CCS alone had no stimulatory effect on the anchorage independent growth of early passage MCF7 cells, but increased colony formation in late passage (greater than 1000) MCF7 and T-47D cells. The growth of late passage MCF7 cells was inhibited by antiestrogen. Thus, the presence of serum components is necessary for the effect of estrogen but not for the effects of growth factors on the anchorage independent growth of estrogen receptor positive human breast cancer cell lines; after a prolonged period of tissue culture serum components switch their function from indirectly modulating estrogen effects to directly stimulating growth in the absence of estrogen.

Breast Neoplasms↗
PubMed1991

The clinical manifestation of mental disorder in Huntington's disease: a retrospective case record study of disease progression.

All cases (86) of Huntington's Disease presenting between 1970 and 1987 in the Grampian Health Board region were identified and a case note analysis of neurological and psychiatric syndromes carried out--the latter using the PSE syndrome check-list. The commonest syndromes were organic impairment, irritability, loss of interest and concentration and simple depression and these were often the presenting psychiatric syndromes. General anxiety, worrying and social unease occurred early, commonly before movement disorder and were associated with longer survival.

Anxiety Disorders↗
PubMed1991

Interstitial deletion of chromosome 13: prognosis and adult phenotype.

A de novo interstitial deletion of chromosome 13 (46,XY,del(13)(pter----q14.3::q22.3----qter] is described in a 22 year old man with severe mental retardation, poor language development, low set ears, hypertelorism, broad nasal bridge, short hands and fingers, and a history of swallowing disorder in childhood with subsequent dyspepsia. The dysmorphic features did not become evident until later childhood, supporting the view that karyotyping should be performed routinely in all children with developmental delay.

Abnormalities, Multiple↗
PubMed1991

Personality profile of nonscholarship college football players.

This paper presents a profile of the mood states of nonscholarship football players as measured by the Profile of Mood States inventory. Analysis suggests that these 120 athletes did not conform to the "iceberg profile" described for elite athletes, differing mainly in the areas of tension and anger. The athletes measured for this report indicated more anger than a sample of 60 football players attending an institution providing financial aid for participation in sports. Total mood scores were lower than those of college athletes on scholarship and high school athletes and nonathletes. Differences in mood states were also found between members of the offensive and defensive squads and between varsity and junior varsity players.

Achievement↗
PubMed1990

Regulation of C5a and formyl peptide receptor expression on human polymorphonuclear leukocytes.

Fluorescein conjugates of C5a (FL-C5a) and formyl methionine-leucine-phenylalanine-lysine (FL-FMLPL) have been used to determine how the expression of receptors for these peptides is regulated on human polymorphonuclear leukocytes (PMN). Video intensification microscopy showed that receptors for FL-C5a were homogeneously distributed on the surface of the PMN, but within minutes were mobilized into patches and internalized by the PMN. Internalization of C5a receptors was confirmed in studies in which external FL-C5a fluorescence was quenched by reducing the pH. A similar rapid internalization was observed with FL-FMLPL. This process was inhibited for both fluorescent ligands by monensin. Reexpression of C5a and formyl peptide receptors after internalization occurred with both receptors. By comparison, the rate of reexpression of formyl peptide receptors was much faster than that observed with C5a receptors with the half maximal reexpression time for each being 5 to 10 min and 18 to 60 min, respectively. C5a receptor reexpression was completely blocked by monensin suggesting receptor recycling, whereas monensin had little effect on FMLPL receptor reexpression. The reexpression of both receptors occurred in the presence of cycloheximide indicating that this process occurred independent of protein synthesis. Additional studies on formyl peptide receptor showed that when PMN were treated with ionomycin to fully mobilize the intracellular pool of FMLPL receptors, receptor reexpression failed to occur. These studies show that both C5a and formyl peptide receptors are internalized after binding ligand, but that their reexpression occurs through different mechanisms. C5a receptors appear to be recycled to the cell surface whereas formyl peptide receptors are reexpressed predominantly by translocation from an intracellular pool.

Cell Compartmentation↗
PubMed1990

Parkinsonism death rates by race, sex and geography: a 1980s update.

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups. The patterns were different from those reported during 1959-1961. Changing geographic patterns in mortality provide evidence for an environmental etiology for PD.

Cause of Death↗
PubMed1989

Herpes simplex virus induces a processing factor that stimulates poly(A) site usage.

Extracts from herpes simplex virus-infected cells and from mock-infected cells have been compared for their ability to process at RNA poly(A) sites in vitro. Nuclear extracts from infected cells contain an activity that increases processing efficiency specifically at a late herpes simplex virus poly(A) site. By contrast, a second virus poly(A) site is processed with equal efficiency by nuclear extracts from infected and mock-infected cells. Using precursor RNAs containing these two virus poly(A) sites in tandem, which allows ready detection of the processing factor, we show that this specific activity is heat labile. Analysis of RNAs produced by virus recombinants that contain the poly(A) site sequences in tandem also indicates that increased processing at the late virus poly(A) site occurs in vivo.

Base Sequence↗
PubMed1989

Linkage in a family with X-linked Charcot-Marie-Tooth disease.

The gene for the X-linked form of Charcot-Marie-Tooth disease (CMT Peroneal Muscular Atrophy, X-linked: McKusick No. 30280) has been shown in a single family to be linked to DXYS1 with a lod score of 4.55 at a recombination fraction of 0.03 and to PGK1 with a lod score of 3.34 at zero recombination. This is in agreement with previous work based on several families. Pooled data from this family and 7 previously reported families give a maximum lod score of 12.04 at theta max of 0.05 for linkage between CMTX and DXYS1 loci.

Charcot-Marie-Tooth Disease↗
PubMed1988

Components required for in vitro cleavage and polyadenylation of eukaryotic mRNA.

We have studied in vitro cleavage/polyadenylation of precursor RNA containing herpes simplex virus type 2 poly A site sequences and have analyzed four RNA/protein complexes which form during in vitro reactions. Two complexes, A and B, form extremely rapidly and are then progressively replaced by a third complex, C which is produced following cleavage and polyadenylation of precursor RNA. Substitution of ATP with cordycepin triphosphate prevents polyadenylation and the formation of complex C however a fourth complex, D results which contains cleaved RNA. A precursor RNA lacking GU-rich downstream sequences required for efficient cleavage/polyadenylation fails to form complex B and produces a markedly reduced amount of complex A. As these GU-rich sequences are required for efficient cleavage, this establishes a relationship between complex B formation and cleavage/polyadenylation of precursor RNA in vitro. The components required for in vitro RNA processing have been separated by fractionation of the nuclear extract on Q-Sepharose and Biorex 70 columns. A Q-Sepharose fraction forms complex B but does not process RNA. Addition of a Biorex 70 fraction restores cleavage activity at the poly A site but this fraction does not appear to contribute to complex formation. Moreover, in the absence of polyethylene glycol, precursor RNA is not cleaved and polyadenylated, however, complexes A and B readily form. Thus, while complex B is necessary for in vitro cleavage and polyadenylation, it may not contain all the components required for this processing.

Base Sequence↗