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Biomedical subjects

J Ellis

Publications and source records attributed to J Ellis.

At least 361 records · Page 20Linked to original sources
PubMedDate not supplied

Silencing of gene expression: implications for design of retrovirus vectors.

Transcriptional silencing of retroviruses poses a major obstacle to their use as gene therapy vectors. Silencing is most pronounced in stem cells which are desirable targets for therapeutic gene delivery. Many vector designs combat silencing through cis-modifications of retroviral vector sequences. These designs include mutations of known retroviral silencer elements, addition of positive regulatory elements and insulator elements to protect the transgene from negative position effects. Similar strategies are being applied to lentiviral vectors that readily infect non-dividing quiescent stem cells. Collectively these cis-modifications have significantly improved vector design but optimal expression may require additional intervention to escape completely the trans-factors that scan for foreign DNA, establish silencing in stem cells and maintain silencing in their progeny. Cytosine methylation of CpG sites was proposed to cause retroviral silencing over 20 years ago. However, several studies provide evidence that retrovirus silencing acts through methylase-independent mechanisms. We propose an alternative silencing mechanism initiated by a speculative stem cell-specific "somno-complex". Further understanding of retroviral silencing mechanisms will facilitate better gene therapy vector design and raise new strategies to block transcriptional silencing in transduced stem cells.

Chromatin↗
PubMedDate not supplied

Factors associated with the frequency of house calls by primary care physicians.

OBJECTIVE: To evaluate factors associated with the frequency of house calls by primary care physicians. DESIGN: A cross-sectional design with a self-administered mailed survey. SITTING/PARTICIPANTS: 751 primary care physicians who care for Medicaid patients in Virginia. RESULTS: Among 389 physician respondents (52%), regular house callers (n = 216) were compared with occasional house callers (n = 162). Among physician characteristics, specialty and practice duration were associated with house call frequency. Regular house callers also more often cited chronic illness (67% vs. 20%, p less than 0.01) and terminal illness (67% vs. 40%, p less than 0.01) as indications for house calls, compared with occasional house callers. Use of visiting nurses to substitute for physician house calls was less often considered appropriate by frequent house callers (7% vs. 24%, p less than 0.01), and regular house callers were less likely to report being "too busy" to make house calls (71% vs. 29%, p less than 0.01). Multivariate analysis confirmed the association of these attitudes with house call frequency. CONCLUSION: These data suggest that specific attitudes among primary care physicians are associated with house call frequency.

Adult↗
PubMedDate not supplied

Chromium(VI) and apparent phenotypic reversion in Salmonella TA100.

After treatment with potassium chromate at concentrations causing ultramicroscopic cellular lesions, a significant proportion (up to 75%) of TA100 colonies fail to replicate on fresh minimal plates containing biotin. This suggests that chromium(VI) may not always induce his- reversion to his+ in Salmonella TA100. The terms 'false' or phenotypic reversion have been used to distinguish such instances from 'true' or genotypic reversion, where progeny his+ cells readily grow on biotin replica plates. Results of the present study indicate that the majority of chromate-exposed colonies, initially scored as his-, are identifiable as his+ after 24 h culture on nutrient agar. Moreover, chromate exerts a cytostatic effect on TA100 since early colony development is suppressed at high chromate concentrations. A gradual chemical reduction of chromium(VI) ions by normal media compounds is probably responsible for the re-emergence of colony growth during prolonged incubation of test plates. Thus, temporary growth inhibition at high chromate concentration appears to be responsible for most of the non-replicating colonies detected in mutagenicity assays of chromium(VI).

Chromates↗
PubMedDate not supplied

Structure of equine corticotropin releasing factor.

A 41 amino acid peptide, probably identical in structure to human corticotropin releasing factor, was isolated from 70 equine hypothalami by methanol extraction, immunoaffinity chromatography and single step of reverse phase HPLC. The amino acid sequence was determined by gas phase sequence analysis. Probable carboxyl terminal amidation was demonstrated by similar retention times for equine and human corticotropin releasing factor on reverse phase HPLC at pH 8. The likely structure of equine corticotropin releasing factor is: Ser-Glu-Glu-Pro-Pro- Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg- Ala-Glu - Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. The purified peptide is equipotent with human corticotropin releasing factor in an in vitro bioassay and in a human plasma binding protein assay.

Amino Acid Sequence↗
PubMedDate not supplied

Comparison of platelet immunity in patients with SLE and with ITP.

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.

Adult↗
PubMedDate not supplied

Identification and chemical synthesis of a tandemly repeated immunogenic region of Plasmodium knowlesi circumsporozoite protein.

Complementary DNA clones that code for the immunogenic region of the Plasmodium knowlesi circumsporozoite protein were shown to contain a tandemly repeating 36-base pair unit. A synthetic dodecapeptide corresponding to the predicted reading frame of the repeating nucleotide unit behaved, in an immunoradiometric assay, identically with the native P. knowlesi circumsporozoite protein. The repeating 36-base pair unit occurred 12 times within the gene and accounts for at least one-third of the amino acid sequence of the surface antigen protein.

Amino Acid Sequence↗
PubMedDate not supplied

A behaviour management course for a group of mothers: the importance of the course setting for effective use of available resources.

Many patients experience difficulty in managing aspects of their young children's behaviour; and yet personnel with the psychological skills to resolve these problems are only available to a small proportion of parents, usually after a period of serious escalation of the difficulties. This article describes an attempt to make economical use of an educational psychologist's time by providing a short course for a volunteer group of mothers whose children attended a pre-school group. The educational orientation of the centre is shown to facilitate the transmission of the required skills and knowledge to the mothers, suggesting both a desirable form of organization for such centres and a specific activity which could profitably take place within them.

Behavior Therapy↗