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Biomedical subjects

S Richardson

Publications and source records attributed to S Richardson.

At least 19 recordsLinked to original sources
PubMed1996

Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts.

Random high throughput sequencing of a human osteoclast cDNA library was employed to identify novel osteoclast-expressed genes. Of the 5475 ESTs obtained, approximately 4% encoded cathepsin K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare. In addition, ESTs for cathepsin K were absent or at low frequency in cDNA libraries from numerous other tissues and cells. In situ hybridization in osteoclastoma and osteophyte confirmed that cathepsin K mRNA was highly expressed selecively in osteoclasts; cathepsins S, L, and B were not detectable. Cathepsin K was not detected by in situ hybridization in a panel of other tissues. Western blot of human osteoclastoma or fetal rat humerus demonstrated bands of 38 and 27 kDa, consistent with sizes predicted for pro- and mature cathepsin K. Immunolocalization in osteoclastoma and osteophyte showed intense punctate staining of cathepsin K exclusively in osteoclasts, with a polar distribution that was more intense at the bone surface. The abundant expression of cathepsin K selectively in osteoclasts strongly suggests that it plays a specialized role in bone resorption. Furthermore, the data suggest that random sequencing of ESTs from cDNA libraries is a valuable approach for identifying novel cell-selective genes.

Amino Acid Sequence↗
PubMed1996

Gamma delta T lymphocyte regeneration after T lymphocyte-depleted bone marrow transplantation from mismatched family members or matched unrelated donors.

The recovery of gamma delta T lymphocytes was studied in 31 recipients of T cell-depleted allogeneic bone marrow (BMT) to determine if the dynamics of reconstitution could be related to graft-versus-host disease (GVHD) or other complications of marrow transplantation. Two distinct patterns of regeneration were apparent. In 12 patients, there was a progressive rise in both the percentage and the absolute number of peripheral blood gamma delta T cells over the first year post-transplantation, but these increases never breached levels found in 14 healthy donors. Each of the 19 remaining patients had abnormally high proportions and numbers of gamma delta T cells on at least two occasions following transplantation. The clinical factor that best explained these observations was the frequency of intercurrent infections. Of 19 patients with abnormally increased percentages and numbers of gamma delta T lymphocytes, 18 had one or more episodes of confirmed viral or fungal infection, contrasted with only two of 12 in the comparison group (P < 0.001). There was no significant association of gamma delta T cell recovery patterns with the presence of GVHD (P = 0.33). We conclude that the recovery of gamma delta T lymphocytes after marrow transplantation may vary. Supranormal levels of this T cell subset are associated with infection and may contribute significantly to cellular immune defenses against fungal or viral disease.

Adolescent↗
PubMed1996

Breastfeeding prevalence among six-week-old infants at University Hospital of the West Indies.

Eight-five (85) mothers attending postnatal and well baby clinics were interviewed at six weeks post-partum regarding breastfeeding. An overall prevalence of 98.8% at six weeks of age was seen, with an exclusive breastfeeding rate of 37.6%. Older maternal age and multiparity favoured exclusive breastfeeding. There was no significant association between pattern of breastfeeding (exclusive versus partial) and employment or union status. Breastfeeding was found to favour good weight gain in normal birthweight babies. Normal birthweight babies who were exclusively breastfed had a higher mean weight gain than the exclusively breastfed low birthweight infants, who in turn had better weight gain when partially breastfed.

Adolescent↗
PubMed1995

Polyadenylic-polyuridylic acid enhances the natural cell-mediated cytotoxicity in patients with breast cancer undergoing mastectomy.

BACKGROUND: Surgical procedures suppress host antitumor defense mechanisms, which may increase the risk of metastatic tumor dissemination. We have evaluated the effects of the biologic response modifier polyadenylic-polyuridylic acid (PAPU) on natural cytotoxicity in patients with breast cancer undergoing operation. METHODS: PAPU (150 mg) or placebo was given intravenously during the perioperative period (preoperative, days -1 and 0; postoperative, days 1, 3, 5, 7, and 14). The function (chromium release assay) and number (flow cytometry) of natural killer (NK) cells were measured before operation (days -2 and -1), on the day of operation (day 0), and after operation (days 1, 2, 4, 6, and 18). RESULTS: Surgical procedures suppressed NK cell cytotoxicity in the placebo group on postoperative days 1 (p < 0.001), 4, 6, and 18 (p < 0.05), whereas inhibition on postoperative day 2 failed to reach significance. PAPU abolished this immunosuppression after operation. The NK cell activity was elevated when compared with the control group; it was significant (p < 0.05) on postoperative days 1, 2, 4, 6, and 18. Surgical procedures also reduced circulating NK cell numbers during the first postoperative week in the placebo group; the decrease was statistically significant on day 4. The decrease in NK cell numbers in the PAPU group was insignificant. CONCLUSIONS: PAPU prevented the decrease in the circulating number and cytotoxic activity of NK cells that occurred after operation and enhanced NK cell cytotoxicity. This may have important implications for patients with cancer undergoing major operation.

Adult↗
PubMed1995

Production of genetically modified Epstein-Barr virus-specific cytotoxic T cells for adoptive transfer to patients at high risk of EBV-associated lymphoproliferative disease.

EBV-induced lymphoproliferative disease (EBV-LPD) is a disorder most commonly associated with the immunocompromise that follows allogeneic organ transplantation. In patients receiving T cell-depleted bone marrow from HLA-mismatched or HLA-matched unrelated donors, the incidence of EBV-LPD is particularly high, ranging from 5 to 30%. Administration of EBV-specific cytotoxic T lymphocytes may be one means of preventing and treating this disease. We now describe a method that allows the routine and timely preparation of large numbers of such cells to allow their safe administration to bone marrow transplant recipients. We also describe how these cells may be genetically marked before infusion, to determine their fate and disposition in vivo.

Adolescent↗
PubMed1995

Evaluation of two recombinant Maedi-visna virus proteins for use in an enzyme-linked immunosorbent assay for the detection of serum antibodies to ovine lentiviruses.

Defined segments of the gag polyprotein and transmembrane envelope glycoprotein from Maedi-visna virus were expressed as glutathione S-transferase fusion proteins in Escherichia coli and evaluated singly and in combination for use in an enzyme-linked immunosorbent assay (ELISA). Two hundred sixty field serum specimens from 15 sheep flocks were tested in parallel with recombinant and whole-virus antigens, and the relative sensitivities and specificities of the recombinant antigens were calculated. When the recombinant gag and transmembrane proteins were used in combination, a sensitivity of 97.4% and a specificity of 99.4% relative to whole-virus antigen were observed, indicating the utility of these proteins in diagnostic testing.

Animals↗
PubMed1994

Superoxide dismutase, catalase, and U78517F attenuate neuronal damage in gerbils with repeated brief ischemic insults.

Repeated ischemic insults at one hour intervals result in more severe neuronal damage than a single similar duration insult. The mechanism for the more severe damage with repetitive ischemia is not fully understood. We hypothesized that the prolonged reperfusion periods between the relatively short ischemic insults may result in a pronounced generation of oxygen free radicals (OFRs). In this study, we tested the protective effects of superoxide dismutase (SOD) and catalase (alone or in combination), and U78517F in a gerbil model of repetitive ischemia. Three episodes (two min each) of bilateral carotid occlusion were used at one hour intervals to produce repetitive ischemia. Superoxide dismutase and catalase were infused via osmotic pumps into the lateral ventricles. Two doses of U78517F were given three times per animal, one half hour prior to each occlusion. Neuronal damage was assessed 7 days later in several brain regions using the silver staining technique. The Mann-Whitney U test was used for statistical comparison. Superoxide dismutase showed significant protection in the hippocampus (CA4), striatum, thalamus and the medial geniculate nucleus (MGN). Catalase showed significant protection in the striatum, hippocampus, thalamus, and MGN and the substantia nigra reticulata. Combination of the two resulted in additional protection in the cerebral cortex. Compared to the controls, there was little protection in a dose of 3 mg/kg of U78517F. There was significant protection with a dose of 10 mg/kg in the hippocampus (CA4), striatum, thalamus, medial geniculate nucleus and the substantia nigra reticulata.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer.

1. The effects of essential fatty acids (gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines--interleukin (interleukin-1 beta, 2, 4 and 6), tumour necrosis factor-alpha and interferon-gamma--were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: tricylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1 beta levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-alpha by 73% (P = 0.040) and interferon-gamma by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.

Aged↗
PubMed1994

Evidence that verotoxins (Shiga-like toxins) from Escherichia coli bind to P blood group antigens of human erythrocytes in vitro.

The interaction of verotoxins (VTs) with human erythrocytes (RBCs) in vitro was investigated, with particular reference to the role of P blood group glycolipids that are structurally related to the known VT receptors. RBC binding of purified VT1, VT2, VT2c, and VT2e was detected by direct and indirect immunofluorescence. Glycolipids were extracted from defined RBCs, separated by thin-layer chromatography, and assessed for VT binding in an overlay assay by adding toxin and specific antibodies. All VTs bound to P1 phenotype (Pk, P, and P1 antigens) and P2 phenotype (Pk and P antigens) RBCs but not to p phenotype (lacking the Pk, P, and P1 antigens) RBCs. Binding of VT1 and VT2 was approximately 10-fold greater to P1 and the rare Pk2 (Pk antigen but no P1 or P antigen) phenotype cells than to P2 phenotype RBCs, whereas VT2e bound equally well to P1 and P2 phenotype cells. The VT1 and VT2 immunofluorescence results correlated with the detection of P1 and/or increased amounts of Pk (globotriaosylceramide) antigen; VT2e immunofluorescence correlated with the detection of P (globotetraosylceramide) antigen. The Pk band pattern and VT binding observed in the thin-layer chromatogram of human P1 and P phenotype RBC extracts varied from that of human kidney and Pk1 phenotype (Pk and P1 antigens) RBCs. We conclude that each VT binds to human RBCs in vitro by utilizing specific P blood group glycolipids as receptors. On P1 and P phenotype RBCs, the accessibility of the Pk antigen for VTs appeared to be restricted. The occurrence of VT-RBC binding in natural VT-producing Escherichia coli disease and its relevance for the pathophysiology of hemolytic uremic syndrome remain to be established.

Bacterial Toxins↗
PubMed1994

Survey of family physicians: what is their role in cancer patient care?

In 1993, a survey of randomly-selected family physicians in two regions of Ontario was conducted to assess their views on various aspects of supportive care of patients with cancer. A response rate of 71% was obtained. Results showed that physicians are using preventive and screening techniques in their practices. They are comfortable with most of their roles in supportive cancer care with the exceptions of conveying news of therapy failure and total coordination of care. There is significant dissatisfaction with certain aspects of the timing and content of the consultation letters received from the regional cancer centers. Finally, family physicians expressed the importance of their roles in palliative care.

Adult↗
PubMed1994

Leadership: a nursing perspective.

The Task Force for Collaborative Nursing Education Models was a successful collaboration involving female nurse administrators. The nature of leadership in the Task Force was studied as part of a larger research project examining the process of collaboration that evolved over the 40 months of its existence (October 1987-February 1991). A retrospective qualitative case study approach was used. Data were collected from an analysis of documents that had been generated by the group, and from 36 semi-structured interviews with the 28 Task Force members. Findings and conclusions about leadership were validated during a final group interview with eight selected members. Findings of this study support the following contentions: women lead differently than men, and leadership is a collective process rather than a specialized role assumed by a single person who influences the work of other group members. Leadership was also found to rotate among group members according to the issue being considered and the expertise of those present. These findings did not support the positivist theories of leadership prevalent in current nursing management text books.

Female↗
PubMed1994

A reactionist professional association: the Provisional Council of University Schools and Departments of Nursing, 1942-1948.

From its inception in 1942, the Canadian Association of University Schools of Nursing (CAUSN) has developed into the accrediting agency for university nursing programs and the national voice for its 30 member schools. The current research examines the creation in 1942 of the Provisional Council of University Schools and Departments of Nursing, the forerunner of the CAUSN. The research is historical in design. Primary and secondary data were collected and analyzed inductively. Primary data consisted of archival documents located in the Queen's University Archives, Kingston, Ontario and the Canadian Nurses Association (CNA) Archives, Ottawa, Ontario. Secondary data augmented and corroborated analysis of primary data and included published histories of the CAUSN and the CNA, as well as books and articles about the development of university nursing education in Canada. The impetus for the inception in 1942 of the Provisional Council of University Schools and Departments of Nursing originated with the CNA. The Provisional Council subsequently achieved none of its stated goals. Instead, it focused on its relationship with the CNA and contested the need for its own existance. The Provisional Council was a reactionist association that reflected the uncoordinated nature of university nursing education and the inability of university nursing educators to set aside parochial differences.

Accreditation↗
PubMed1993

Conditional independence models for epidemiological studies with covariate measurement error.

We construct a unifying representation of the structure of measurement error problems with particular reference to situations commonly encountered in epidemiological studies, and outline how estimation of the parameters of interest can be carried out in a Bayesian framework using Gibbs sampling. We show how this approach can be implemented for designs involving continuous measurement errors assessed through a validation substudy, and discuss our results on simulated data.

Analysis of Variance↗
PubMed1993

A Bayesian approach to measurement error problems in epidemiology using conditional independence models.

Risk factors used in epidemiology are often measured with error which can seriously affect the assessment of the relation between risk factors and disease outcome. In this paper, a Bayesian perspective on measurement error problems in epidemiology is taken and it is shown how the information available in this setting can be structured in terms of conditional independence models. The modeling of common designs used in the presence of measurement error (validation group, repeated measures, ancillary data) is described. The authors indicate how Bayesian estimation can be carried out in these settings using Gibbs sampling, a sampling technique which is being increasingly referred to in statistical and biomedical applications. The method is illustrated by analyzing a design with two measuring instruments and no validation group.

Bayes Theorem↗