Bringing intellectual inquiry to the bedside.
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Clinical Nursing Research↗
Biomedical subjects
S Russell
Publications and source records attributed to S Russell.
In vivo expression of murine platelet glycoprotein Ibalpha.
We have performed a systematic in vivo evaluation of gene expression for the glycoprotein (GP) Ibalpha subunit of the murine platelet adhesion receptor, GP Ib-IX-V. This study is warranted by in vitro observations of human GP Ibalpha expression in cells of nonhematopoietic lineage and reports of regulation of the GP Ibalpha gene by cytokines. However, an in vivo role for a GP Ib-IX-V receptor has not been established beyond that described for normal megakaryocyte/platelet physiology and hemostasis. Our Northern analysis of mouse organs showed high levels of GP Ibalpha mRNA in bone marrow with a similar expression pattern recapitulated in mice containing a luciferase transgene under the control of the murine GP Ibalpha promoter. Consistently high levels of luciferase activity were observed in the two hematopoietic organs of mice, bone marrow (1,400 relative light units/microg of protein [RLUs]) and spleen (500 RLUs). Reproducible, but low-levels of luciferase activity were observed in heart, aorta, and lung (30 to 60 RLUs). Among circulating blood cells, the luciferase activity was exclusively localized in platelets. No increase in GP Ibalpha mRNA or luciferase activity was observed after treatment of mice with lipopolysaccharides (LPS) or tumor necrosis factor-alpha (TNF-alpha). We conclude the murine GP Ibalpha promoter supports a high level of gene expression in megakaryocytes and can express heterologous proteins allowing an in vivo manipulation of platelet-specific proteins in the unique environment of a blood platelet.
Animals↗
Retroviral vector targeting to melanoma cells by single-chain antibody incorporation in envelope.
Two strategies for targeting recombinant retroviruses to melanoma cells were compared. One was to extend the tropism of an ecotropic envelope to human melanoma cells, the other was to enhance the tropism of an amphotropic envelope for melanoma cells. Chimeric retroviral envelopes, incorporating a single-chain antibody (ScFv) directed against high-molecular-weight melanoma-associated antigen (HMWMAA) at the amino terminus are correctly processed and incorporated into virions. ScFv-ecotropic envelope chimeras allow specific, but low-titer, targeting of HMWMAA-positive cells, when co-expressed with ecotropic envelopes. ScFv-amphotropic envelope chimeras bind specifically to HMWMAA-positive cells and allow preferential infection at high titer.
Amino Acid Sequence↗
Microlaparoscopic tubal ligation under local anesthesia.
Local anesthesia to perform laparoscopic tubal ligation is of increased interest due to potential safety and cost benefits. We performed tubal ligation using microlaparoscopic techniques with local anesthesia and continuous intravenous sedation in 16 women desiring sterilization. Operating and recovery times and patient satisfaction were recorded and compared with values for 30 similar women undergoing microlaparoscopic tubal ligation under general anesthesia. Mean +/- SD operating and recovery times for local and general anesthesia were 29.3+/- 8.1 versus 33.6 +/- 11.1 minutes, and 83.9 +/- 59.4 versus 114.5 +/- 69.8 minutes, respectively. Patient satisfaction was high. The potential for cost savings when performed in an outpatient or clinic setting is significant.
Adult↗
Syndactyly, micrognathia and skeletal anomalies: a new syndrome?
We report a fetus with micrognathia, cleft palate, polysyndactyly, brachycephaly and proximal radial hypoplasia. We believe the abnormalities represent a new syndrome not previously described.
Abnormalities, Multiple↗
The Drosophila SOX-domain protein Dichaete is required for the development of the central nervous system midline.
SOX-domain proteins are a class of developmentally important transcriptional regulators related to the mammalian testis determining factor SRY. In common with other SOX-domain genes, the Drosophila Dichaete gene has a dynamic expression profile in the developing central nervous system, including cells of the ventral midline. We find defects in the differentiation of midline glia and concomitant axonal defects in Dichaete mutants that are rescued by driving Dichaete expression in the midline. Since Dichaete is required for the correct specification or differentiation of midline glia, we have used the ventral midline as a model system to study SOX gene function in vivo and demonstrate a genetic interaction between Dichaete and the POU domain gene ventral veinless. In mammals, a protein related to Dichaete, SOX2, also interacts with POU transcription factors. The midline phenotypes of Dichaete mutations are rescued by expression of mouse SOX2. Our data suggest that SOX gene structure, function and interactions have been conserved during evolution.
Alleles↗
Detectable levels of serum aflatoxin B1-albumin adducts in the United Kingdom population: implications for aflatoxin-B1 exposure in the United Kingdom.
This study aimed to estimate aflatoxin B1 (AFB1) exposure in the United Kingdom population by measuring levels of serum AFB1-albumin (alb), using immunoassay and high-performance liquid chromatography (HPLC) with fluorescence detection. A self-questionnaire on dietary habits from 104 volunteers (47 men and 57 women) in York was completed, and blood samples were collected. Serum alb was extracted, and AFB1-lysine (lys), the digest product of AFB1-alb, was isolated and measured. A sensitive ELISA (detection limit, approximately 1.4 pg of AFB1-lys) was developed. A good correlation was found between calibration of ELISA results and scintillation counting, for rats dosed with [3H]AFB1 (r = 0.972; P < 0.001). This ELISA was subsequently used to analyze human serum alb. For United Kingdom human sera, the mean adduct levels were 29.3 +/- 14.8 pg AFB1-lys equivalents (eq) mg albumin (males) and 26.9 +/- 14.4 pg AFB1-lys eq/mg alb (females). Confirmation of the ELISA data was sought using reversed-phase HPLC with fluorescence detection. HPLC chromatograms of digested York serum alb were compared to digested serum alb for humans from Qidong County, People's Republic of China, and from AFB1-dosed rats. These all gave similar HPLC profiles. Each sample contained fluorescent material that coeluted with and just before the AFB1-lys standard. Fluorescent fractions were found to be inhibitory in a separate anti-AFB1-lys ELISA, indicating that these earlier fluorescent peaks contained AFB1 residues. Our results suggest that measurable internal AFB1 exposure may be occurring in some United Kingdom individuals, albeit at lower levels than those seen for areas with high AFB1 exposure. The source of this exposure may reflect the known difficulties in accurately monitoring regulated imported foodstuffs and/or the lack of regulations on other potentially contaminated imports. However, no positive correlations were found between our AFB1-lys measurements and any dietary questionnaire information. Animal studies, as well as human studies, have been important in developing exposure and internal adduct relationships in humans. Based on this literature, our AFB1-alb data indicate a mean daily exposure of 3 microg of AFB1 and a mean internal dose in liver DNA of 5.9 adducts/10(7) nucleotides. We believe this may be an overestimate of the AFB1 exposure level in the United Kingdom, and further studies are needed to accurately relate external dose and internal AFB1 biomarkers in humans.
Adolescent↗
Outcome and clinical course of prenatally diagnosed cerebral ventriculomegaly.
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Child↗
Functional bioinformatics: the cellular response database.
Biological Scientists function in an increasingly data rich environment. The emerging field of bioinformatics is attempting to insure that this flow of information can be structured to support the generation of significant biological hypothesis and ultimately new knowledge. To date, most of the current databases have focused on protein and nucleic acid sequence information as the principle type of data stored for further interpretation. In this paper, we describe the Cellular Response Database. This database stores functional information regarding the changes of cellular gene expression associated with various stimuli, and supports queries linking cell types, expressed genes, and inducers. The database is designed to support information-intensive queries to aid in the determination of biological function, and is flexible enough to allow the storage of a broad range of experimental data such as cytotoxicity data, immunoassays of target gene protein expression, and others.
Cell Physiological Phenomena↗
Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis.
BACKGROUND: Squamous cell carcinoma (SCC) with histologically contiguous actinic keratosis has long been thought of as a tumor with minimal risk for metastasis. The objective of this study was to determine if contiguous actinic keratosis is present in the original tumors of metastatic cutaneous SCC and to describe the histologic features of these tumors. METHODS: The primary lesions of 22 patients with metastatic cutaneous SCC were examined using light microscopy. RESULTS: Contiguous actinic keratosis was present histologically in 44% of the original lesions of cutaneous SCC that metastasized. The average tumor thickness was 6.6 mm. Greater than 66% of the tumors were well or moderately differentiated. The skin adjacent to the tumors showed solar degeneration in almost all instances. CONCLUSIONS: The histologic presence of contiguous actinic keratosis is not a useful predictor of the metastatic behavior of cutaneous SCC. Increased tumor thickness and depth of invasion are the most consistent histopathologic features of cutaneous SCC that metastasize.
Carcinoma, Squamous Cell↗
Clinical dosimetry using MOSFETs.
PURPOSE: The use of metal oxide-silicon field effect transistors (MOSFETs) as clinical dosimeters is demonstrated for a number of patients with targets at different clinical sites. METHODS AND MATERIALS: Commercially available MOSFETs were characterized for energy response, angular dependency of response, and effect of accumulated dose on sensitivity and some inherent properties of MOSFETs. The doses determined both by thermoluminescence dosimetry (TLD) and MOSFETs in clinical situation were evaluated and compared to expected doses determined by calculation. RESULTS: It was observed that a standard calibration of 0.01 Gy/mV gave MOSFET determined doses which agreed with expected doses to within 5% at the 95% confidence limit for photon beams from 6 to 25 MV and electron beams from 5 to 14 MeV. An energy-dependent variation in response of up to 28% was observed between two orientations of a MOSFET. The MOSFET doses compared very well with the doses estimated by TLDs, and the patients tolerated MOSFETs very well. A standard deviation of 3.9% between expected dose and MOSFET determined dose was observed, while for TLDs the standard deviation was 5.1%. The advantages and disadvantages of using MOSFETs for clinical dosimetry are discussed in detail. CONCLUSION: It was concluded that MOSFETs can be used as clinical dosimeters and can be a good alternative to TLDs. However, they have limitations under certain clinical situations.
Calibration↗
Re: Allantoic cysts of the umbilical cord in trisomy 21.
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Adult↗
Cloning of the murine platelet glycoprotein Ibalpha gene highlighting species-specific platelet adhesion.
We report the sequence of a 2,779 base pari genomic DNA fragment containing the mouse glycoprotein (GP) Ibalpha gene. Similar to its human counterpart, the mouse GP Ibalpha gene contains a single exon encoding a 734-residue GP Ibalpha precursor polypeptide. Comparative analysis between human and mouse polypeptides reveals a 75% sequence similarity between the amino-terminal domain of each polypeptide. However, there is sequence divergence within a short linear sequence of the amino-terminal domain previously implicated in human GP Ibalpha as critical for the binding of human von Willebrand factor (vWF). Mouse and human primary sequences diverge through their extracytoplasmic macroglycopeptide domains reducing the overall sequence similarity to 70%. The transmembrane and cytoplasmic sequences are highly conserved in both species with 59 identical residues among the 62 comprising the carboxyl-terminus of each polypeptide. The species-specific interaction between human GP Ibalpha and vWF was demonstrated in a model flow system monitoring the ability of surface-bound human vWF to capture from flowing blood normal mouse platelets or transgenic mouse platelets expressing the human GP Ibalpha subunit. The results further define the structural elements necessary for the interaction of human vWF and platelets.
Amino Acid Sequence↗
Erythemally effective and actinic irradiance from a tungsten halogen lamp.
A protocol for assessment of biological hazard from ultraviolet radiation sources was developed. The protocol utilized both a ultraviolet radiation spectroradiometer and a broadband ultraviolet radiation meter for the determination of the erythemally effective irradiance and the actinic irradiance. A 250 W tungsten halogen lamp operating at 9.5 A was tested with this protocol. It was found that the erythemally effective irradiance varied from 41 microW cm(-2) at 10 cm to 1.5 microW cm(-2) at 50 cm. In the same range of distances, the actinic irradiance decreased from 23 to 0.5 microW cm(-2). The irradiance from the source was uniform within 30 degrees about the line perpendicular to the axis of the filament. Using the recommendation of the Australian radiation protection agency, the National Health and Medical Research Council, the maximum allowable exposure time at the distance of 50 cm in the direction perpendicular to the axis of the filament was about 33.3 minutes.
Erythema↗
User fee policies to promote health service access for the poor: a wolf in sheep's clothing?
An international survey of health service user fee and exemption policies in 26 low- and middle-income countries assessed whether user fee policies were supported by measures that protect the poor. In particular, it explored whether governments were introducing a package of supportive measures to promote service improvements that benefit disadvantaged groups and tackle differential ability to pay through an effective series of exemptions. The results show that many countries lack policies that promote access for disadvantaged groups within user fee systems and quality improvements such as revenue retention at the health care facility and expenditure guidelines for local managers. More significant policy failures were identified for exemptions: 27 percent of countries had no policy to exempt the poor; in contrast, health workers were exempted in 50 percent of countries. Even when an official policy to exempt the poor existed, there were numerous informational, administrative, economic, and political constraints to effective implementation of these exemptions. The authors argue that user fee policy should be developed more cautiously and in a more informed environment. Fees are likely to exacerbate existing inequities in health care financing unless exemptions policy can effectively reach those unable to pay.
Africa↗
The Paediatric Cochlear Implant Program at the Hospital for Sick Children, Toronto.
Ontario has a province-wide program for provision of cochlear implants. Toronto's Hospital for Sick Children is one of three designated centres that service the paediatric population. This cochlear implant program was established in 1989. Since that time, 37 children (as of May 1996) have been provided with cochlear implants. The program also services Ontario residents who were implanted elsewhere. In the following, we provide a detailed description of the program, including the processes through which children are selected as candidates, the follow-up studies that we carry out, and the roles of various health care professionals involved. We present a demographic survey of our patient population to date, and discuss some of the important issues relating to candidacy.
Child, Preschool↗
Overview of the Native American Cancer Conference III. Risk factors, outreach and intervention strategies.
BACKGROUND: Based on the lack of published information regarding Native Americans and cancer and the success of previous meetings, the Network for Cancer Control Research among American Indian and Alaska Native Populations (NCCR-AIANP) and the Native Hawaiian and American Samoan Cancer Research Network determined there was sufficient need to have annual national Native American cancer conferences. METHODS: The NCCR-AIANP, the Native Hawaiian and American Samoan Cancer Research Network, and the AMC Native American Cancer Research Program collaborated to organize the third national Native American cancer conference, "Native American Cancer Conference III: Risk Factors, Outreach and Intervention Strategies." RESULTS: The conference was held in Seattle, Washington, June 16-19, 1995. It provided a forum for scientific discussion and dissemination of information related to cancer prevention and control. CONCLUSIONS: Conference participants benefited from the topics presented and the diversity of the audience members. There continues to be a need to share what is happening in cancer research with this unique population and to address new issues of concern. A cancer conference seems to be a useful mechanism to provide such an opportunity.
American Samoa↗