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Biomedical subjects

B Hardy

Publications and source records attributed to B Hardy.

At least 19 recordsLinked to original sources
PubMed2002

Association between gastric acid and mucin secretion in dyspeptic patients.

BACKGROUND AND AIMS: The maintenance of an intact gastric mucosa implies a balance between aggressive, such as acid, and protective factors such as mucin. We examined gastric aspirates to determine a possible correlation between gastric acid and mucin contents. METHODS: Gastric contents were aspirated at gastroscopy in 14 patients. Acid content was evaluated by titration, and mucin content by gel filtration. In 4 other patients these measurements were also performed for 1-hour basal gastric secretion, and after pentagastrin stimulation. Western blot and dot blot for mucin protein were performed with polyclonal antibodies to the protein of MUC 5AC and MUC 6. RESULTS: A positive correlation was demonstrated between acid and mucin content in 14 patients, r = 0.77. In 4 other patients mucin secretion, after pentagastrin injection, increased by 3-46 fold in comparison with basal secretion. A positive correlation was demonstrated between basal acid and mucin secretion, and stimulated acid and mucin secretion. In dot blot experiments, MUC 5AC had a significant higher dot blot intensity than MUC 6. CONCLUSIONS: There is a correlation between acid and mucin secretion rates. Secretagogue that causes acid secretion may also cause secretion of protective mucin.

Aged↗
PubMed2001

Effect of exogenous thyroid-stimulating hormone on thyroid papillary carcinoma cells in tissue culture.

BACKGROUND: To determine the prognostic value of thyroid suppression therapy in patients with thyroid carcinoma, we studied the effect of thyroid-stimulating hormone (TSH) on the morphology, proliferation rate, and the T3, T4 production rate of primary thyroid carcinoma cells in culture. METHODS: From August 1997 to February 1998 tissues were collected for immediate culture from 13 patients undergoing surgery for thyroid cancer. Cells were incubated for 48 h with TSH in different concentrations. T3 and T4 production was measured by radioimmunoassay; cell proliferation was measured in a radioactive counter. Morphology was determined by cytologic examination. RESULTS: Ten samples were eligible for analysis. Changes in TSH affected T3 and T4 levels. The proliferation rate was not influenced by TSH levels. CONCLUSIONS: Thyroid papillary carcinoma cells grown in culture maintain their T3 and T4 synthesis ability. This ability is TSH-dependent and correlates with TSH concentration. The morphology of the cells is also maintained. However, their proliferation is not TSH-dependent, placing the current postthyroidectomy treatment policy in question.

Carcinoma, Papillary↗
PubMed2001

Movement and change: independent sector domiciliary care providers between 1995 and 1999.

Promoting the development of a flourishing independent sector alongside good quality public services was a key objective of the community care reforms of the last decade. This paper charts some of the ways the independent domiciliary care sector is changing, as local authorities shift the balance of their provision toward independent sector providers and away from a reliance on in-house services. Two surveys of independent domiciliary care providers were carried out in 1995 and 1999. The aims of the studies were to describe the main features of provider organisations, such as size of business, client group and funding sources; to examine the nature of provider motivations and their past and future plans; to consider how local authorities manage the supply side of social care markets; and to examine the effects on providers of the development of the mixed economy. The first survey in 1995 was conducted in eight local authority areas, which by 1999 had increased to 11 because of the creation of three new unitary authorities. The findings are based on 261 postal surveys together with 111 interviews between the two studies. The research illustrates a domiciliary care market that is still relatively young with many small but growing businesses. There are considerable differences in the split between in-house and independent sector services in individual authorities and a common perception among independent providers that in-house services receive favourable treatment and conditions. Spot or call-off contracts continue to be the most common form of contract although there are moves toward greater levels of guaranteed service and more sophisticated patterns of contracting arrangements. There remains an ongoing need to share information between local authorities and independent providers so that good working relationships can develop with proven and competent providers.

Aged↗
PubMed2001

Treatment with BAT monoclonal antibody decreases tumor burden in a murine model of leukemia/lymphoma.

BAT is a monoclonal antibody produced against membranes of Daudi cells that induces anti-tumor activity in mice against a variety of solid murine and human tumors, mediated by its immune stimulatory properties on murine and human lymphocytes. The present study analyzes the effect of BAT on leukemia/lymphoma using the BCL1 model of leukemia/lymphoma in BALB/C mice. BAT antibody binds to BCL1 leukemia cells and recognizes a 48 kDa protein similar to the antigen on Daudi cells. Mice inoculated with leukemia cells were treated either by direct BAT injections or by adoptive transfer of lymphocytes from BAT-injected mice. Administration of BAT monoclonal antibody was either once, on day 14, or daily on days 10-13 post tumor inoculation. A single injection of BAT resulted in reduction of peripheral blood tumor cells, however additional injections further decreased the tumor cell number reaching a 95-fold reduction on day 20 post tumor inoculation. Anti-tumor effect was also obtained when animals were injected with splenocytes from BAT-treated donor mice. A significant prolongation of survival of BAT-treated mice was observed although with no cure. The results of this study indicate that BAT might be used for reducing the tumor burden in leukemia for immunotherapy and in combination with other treatment modalities.

Adoptive Transfer↗
PubMed2000

CD4+ T lymphocytes as a primary cellular target for BAT mAb stimulation.

BAT is a monoclonal antibody (mAb) produced against membranes of a human Burkitt lymphoma cell line (Daudi) that was selected for its ability to stimulate lymphocyte proliferation. BAT manifests anti-tumor properties in mice bearing a variety of murine tumors. BAT also induced regression of human tumors inoculated into SCID mice that had been engrafted with human lymphocytes. The anti-tumor activity of BAT was related to its immune stimulatory properties. Previous data indicated that T lymphocytes and NK cells mediate in vivo the anti-tumor activity. In order to define the primary target cell for BAT stimulatory activity, the in vitro stimulatory effect of BAT on purified lymphocyte subpopulations was investigated. Human CD4(+), CD8(+) T cells and CD56(+) NK cells were purified and their in vitro response to BAT was investigated. Results indicate that BAT selectively stimulated CD4(+) cells as assessed by proliferation and secretion of IFN-gamma. FACS analysis has also revealed a selective increase in BAT antigen on CD4(+) T cells that were cultured with BAT antibody. The effector cells that mediate BAT-induced tumor eradication may, however, be distinct from those that serve as the primary cellular target of the antibody. Cytokines such as IFN-gamma that are produced by CD4(+) cells may be involved in activation of additional cell types that may be involved in tumor destruction.

Animals↗
PubMed1999

Activation of lymphocytes by BAT and anti CTLA-4: comparison of binding to T and B cells.

In this study we compare the binding and immune stimulatory properties of BAT and anti CTLA-4 monoclonal antibodies (mAbs). Both antibodies were previously shown to manifest effective immune responses against tumor cells. We have described that BAT antibody, produced against Daudi, a B lymphoblastoid cell line, binds and activates T cells. In this paper we demonstrate that anti CTLA-4, produced against the T-cell activation determinant CTLA-4, binds also to B lymphoblastoid cell lines like Daudi and Raji. Both antibodies do not bind resting B cells. BAT binds resting T lymphocytes as well as activated T lymphocytes, whereas anti CTLA-4 binds only activated T cells. Competitive binding experiments indicate that the binding sites of BAT and anti CTLA-4 on activated T cells are distinct. We have studied the in vitro stimulatory effect of BAT and anti CTLA-4 on lymphocytes cultured with or without tumor cells. In contrast to BAT that increased the proliferation of lymphocytes that have been cultured with tumor cells, anti CTLA-4 did not synergize with tumor cells to enhance lymphocyte proliferation.

Abatacept↗
PubMed1999

Inter-agency services in England and The Netherlands. A comparative study of integrated care development and delivery.

In England and the Netherlands there is much comparable experience in developing and delivering integrated services, provided by different health care agencies to people with multiple care demands. The achievement of integrated care provision in such cases appears to be very difficult and laborious in both countries. This article may be considered a first step in exploring the reasons for this and in developing a framework that is not context specific, as a contribution to a more generally applicable analysis of obstacles to integration and the means for overcoming them. After analysing the English and Dutch health and social care systems and their development in recent decades, we conclude that basically there are clear system similarities which are hindering the integration of services, for instance the predominant complexity of the system with a lot of stakeholders having different roles, tasks, interests and power positions. We have identified common mechanisms that play a dominant role in both systems; not only the social, economic and political context, but also the local context, the legal context and funding streams. Other relevant factors are the procedural and structural arrangements at different system levels and the collaborative culture and tradition. The way these mechanisms work in practice, however, is different for England and the Netherlands, due to system differences. In the Netherlands for instance there is a clear emphasis on bargaining in the context of non-hierarchical structured networks, whilst in England hierarchies and the interplay between hierarchies, markets and networks play a more dominant role. In spite of the differences and problems in both countries we have found a similar recognition of interdependence and willingness to pursue integration of services for multi-problem patients.

Delivery of Health Care, Integrated↗
PubMed1999

Medication management: an exploratory study into the role of community mental health nurses.

The recent emphasis on community care for those with mental illness has changed working patterns and modified inter-professional role boundaries within multi-disciplinary teams. Clients with serious mental illness are usually prescribed medications, which have a wide range of side effects. However, it is uncertain who is responsible for monitoring clients for the side effects of their medications, ensuring clients' and carers' understandings of their prescribed medications and optimizing compliance with medication. This paper discusses the findings of the first phase of an ongoing study designed to assess the role of community mental health nurses (CMHNs) in managing clients' medication and the provision of appropriate continuing professional education. Our respondents were 14 CMHNs, seven of whom were preparing to undertake a pharmacology module as part of a higher education diploma, and seven who were to act as comparators. Data from questionnaires, interviews and clinical observations were triangulated. All respondents felt that issues surrounding clients' medication were not accorded a sufficiently high profile and that it was, in part, their responsibility to expand their roles to meet these unmet needs of clients. Administering and managing clients' medications were considered to be the main area of 'occupational territory' which distinguished CMHNs from social workers. However, the nurses felt that their practice was limited by lack of appropriate educational preparation.

Community Mental Health Services↗
PubMed1999

Assessing educational effectiveness: the impact of a specialist course on the delivery of care.

An exploratory study was undertaken in South Wales to assess the changes in clinical practice brought about by a specialized pharmacology module designed for Community Mental Health Nurses (CMHNs), in our institution. The respondents were the seven CMHNs who completed the course in 1997 and returned to clinical practice, and seven CMHN comparators, matched on the basis of work experience and location. In order to assess the impact of the module, the practice, attitudes and knowledge of the respondents were investigated before and after the course and 6 months later, using semistructured interviews, nonparticipant observation and questionnaires. The three data sets were analysed using the constant-comparative method, and relevant themes were identified and refined. While we obtained some objective measures of positive educational impact, these should be considered in relation to contextual and confounding variables. Both reported and observed behaviours indicated that the main benefit from the course was increased awareness and monitoring of the side-effects of medication. Respondents had not implemented change uniformly; several factors determined how they modified working practices, including service pressures and the support of colleagues.

Cohort Studies↗
PubMed1997

A lymphocyte-activating monoclonal antibody induces regression of human tumors in severe combined immunodeficient mice.

Monoclonal antibodies were raised against Daudi B-lymphoblastoid cell line membranes. An mAb (BAT) was selected for its ability to stimulate human and murine lymphocyte proliferation. BAT induced cytotoxicity in human and murine lymphocytes against natural killer cell-sensitive and -resistant tumor cell lines. A single intravenous administration of BAT to mice that had been inoculated with various murine tumors (e.g., B16 melanoma, 3LL carcinoma, and methylcholanthrene fibrosarcoma) resulted in striking antitumor effects as manifested by complete tumor regression and prolonged survival of the treated mice. BAT exhibited a diminished but significant antitumor effect in athymic nude mice, which are deficient in T lymphocytes, and in beige mice, which are deficient in NK cells. Furthermore, selective depletion of T or NK cells in mice reduced the response to the antitumor effect of BAT. These data indicate a dual role for T and NK cells in mediating the antitumor activity of BAT. We report here on the antitumor activity of BAT mAb on human tumor xenografts in mice. BAT demonstrated an antitumor effect in nude mice bearing human colon carcinoma (HT29) xenografts. It failed, however, to inhibit established lung metastases in severe combined immunodeficient (SCID) mice that had been inoculated (i.v.) with SK28 human melanoma. Engraftment of human lymphocytes into SCID mice bearing human melanoma xenografts rendered them responsive to the antitumor effect of BAT. The efficacy of BAT in the regression of human tumors by activation of human lymphocytes indicates its potential clinical use.

Animals↗
PubMed1997

Immune stimulatory and anti-tumor properties of anti-CD3 and BAT monoclonal antibodies: a comparative study.

A novel monoclonal antibody raised to Daudi cell membranes was found to exhibit immune stimulatory and anti-tumor properties. The activity of this antibody (BAT) which also binds T cells was compared to that of anti-CD3. Anti-CD3 reacts with the T cell receptor complex, induces cell proliferation, and cytolytic activity in vitro and also manifests in vivo anti-tumor effect against murine tumors. Comparison of the two antibodies demonstrates similar induction in vitro of splenocyte proliferation and cytolytic activity. Both BAT and anti-CD3 antibodies manifest anti-tumor activity in mice bearing B16 melanoma. They differ however in the timing of antibody administration post-tumor inoculation which is most effective in eliciting the anti-tumor effect. Whereas BAT is most effective when administered 10 to 14 days post-tumor inoculation, anti-CD3 is effective at an early time. Data also indicate that BAT synergises with tumor cells in eliciting cell proliferation in vitro. In contrast, this effect could not be demonstrated with anti-CD3. The properties of BAT may be of advantage in its potential clinical use.

Adjuvants, Immunologic↗
PubMed1996

Virtual conferences.

An interview with Barry Hardy, conducted in May and June 1996 by e-mail and on 12 June 1996 at a MOO site. The development of the Internet has provided the opportunity o f conducting meetings and conferences electronically. In this interview, Barry Hardy outlines the main principles involved in staging and attending a 'virtual meeting', and issues an invitation to the readers o f trends in CELL BIOLOGY to become involved in organizing the first international electronic cell-biology conference.

Interview↗
PubMed1995

Monoclonal antibodies against native ovarian tumor cells: specificity and characterization of the antigen. A preliminary report.

Monoclonal antibodies were prepared against native human ovarian carcinoma cells derived from the ascitic fluid of a patient (BH). One antibody, HC7R7, was selected on the basis of its binding to tumor BH cells, to other ovarian tumor cell lines (CAOV-3 and GZL-8), but not to the patient's fibroblasts. One hundred cell smears from ascitic and pleural effusions of tumor-suspected patients were immunostained with HC7R7. All serous ovarian carcinomas and half of the breast carcinomas stained positive with HC7R7; cells from noncancer ovarian aspirates were negative. Mesothelial cells were also stained with HC7R7. A correlation was noted between HC7R7 and OC-125 staining of ovarian tumor cells but not between HC7R7 and c-neu staining of breast tumor paraffin sections. The location of HC7R7-positive material in ovarian tumor cell lines (CAOV-3 and GZL-8) differed from that in the breast tumor cell line (MCF-7). CAOV-3 and GZL-8 showed membrane binding while, in MCF-7, not fully identified intracellular organelles were stained. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and immunoblots from membrane and cytosol fractions of GZL-8 and MCF-7 showed HC7R7 binding to three protein bands in the membrane fraction and to three other bands in the cytosol, all in the 29- to 68-kDa range. Two of the bands were glycoproteins. The only band that was different in the GZL-8 and MCF-7 cells was a 43-kDa glycoprotein, which was more pronounced in the MCF-7 cells. The possible significance of the new HC7R7 antibodies for detection and survey of ovarian malignancies is discussed.

Aged↗
PubMed1995

Activation of human lymphocytes by a monoclonal antibody to B lymphoblastoid cells; molecular mass and distribution of binding protein.

A novel monoclonal antibody (BAT) to the B-lymphoblastoid cell line activates murine lymphocytes and exhibits a striking antitumor activity in mice. In order to evaluate the potential use of this antibody against human cancer, we have investigated its immuno-stimulatory properties on human peripheral blood lymphocytes (PBL). Our findings demonstrate that BAT mAb induces proliferation and cytotoxicity in human PBL against natural-killer-cell-sensitive and natural-killer-cell-resistant tumor cell lines. Interleukin-2 at a low concentration synergizes with BAT mAb in eliciting these effects. BAT mAb binds to human peripheral T cells as revealed by a double-labelling technique using anti-CD3 and BAT mAb. The molecular mass of the antigen recognized by BAT mAb was 48-50 kDa under reducing and non-reducing conditions. This study provides a basis for future experiments to evaluate the use of BAT mAb in the immunotherapy of cancer.

Adjuvants, Immunologic↗