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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 163 records · Page 9Linked to original sources
PubMed1995

Analysis of feline dual lymphocyte populations observed by flow cytometry.

Two discrete lymphocyte populations were observed commonly on flow cytometric analysis (FCM) of feline lymphocyte subsets. The identity of these populations as small and large lymphocytes was established by correlating data from FCM with that from peripheral blood films. Dual lymphocyte populations were more likely to be seen in feline immunodeficiency virus-positive (FIV(-)+ ve) cats but their occurrence was not affected by health status, age, gender or breed. FIV(-)+ ve cats had a significantly higher proportion of large lymphocytes than FIV-negative (FIV(-)- ve) cats. However, FIV(-)+ ve cats had significantly fewer small lymphocytes than FIV(-)- ve cats but similar numbers of large lymphocytes. Lymphocyte subset analysis revealed that small lymphocytes had a greater proportion of CD4+ cells than large lymphocytes, regardless of the FIV or health status of the cat. In FIV(-)- ve cats, small lymphocytes had a greater proportion of Pan T + lymphocytes than large lymphocytes, but the converse was seen in FIV(-)+ ve cats. The proportion of CD8 + cells was higher in small lymphocytes than large lymphocytes in well FIV(-)- ve cats but this distinction was not seen in sick FIV(-)- ve cats or FIV(-)+ ve cats of any health status. Regardless of health status, FIV(-)+ ve cats had a lower absolute count of small lymphocytes which were T cells (due to lower numbers of both CD4 + and CD8 + cells) than FIV(-)- ve cats. The numbers of small B cells were similar for both FIV(-)+ ve and FIV(-)- ve cats. However, there were no differences between FIV(-)+ ve and FIV(-)- ve cats in the absolute values of any subset of the large lymphocytes, which suggested that FIV may affect only small lymphocytes. Statistically, the inclusion or exclusion of the large lymphocyte population for routine lymphocyte subset analysis did not affect the overall results. However, because there were significant differences in subset distribution between small and large lymphocytes, analysis of both groups should be included in studies examining the role of lymphocytes in disease.

Animals↗
PubMed1995

Expression of the BCL-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas.

Although expression of the bcl-2 protein has been investigated in a number of non-haematological malignancies, little is known of its distribution in premalignant lesions. Expression of bcl-2 was investigated immunohistochemically in archival biopsies of normal (n = 8) and dysplastic bronchial epithelium (n = 56) and in 31 bronchial resection margins and their corresponding carcinomas. All dysplasias had lost the prominent basal staining pattern seen in histologically normal epithelium. Two were negative and six had occasional basal positive cells. In 37 cases up to 66% of the epithelial cells throughout the full epithelial thickness were bcl-2 positive with weak to moderate staining intensity. In 11 cases, all severe dysplasias, strong expression was observed in > 90% of the epithelial cells. Four patterns of bcl-2 expression in dysplasias were identified and an increasingly aberrant pattern of bcl-2 expression correlated with an increasing grade of dysplasia (Spearman's rank correlation, P < or = 0.0001). Sixty-five per cent of the carcinomas contained bcl-2-positive cells. Patients with non-small-cell lung carcinomas (n = 27) in which > 50% of the tumour cells were bcl-2 positive showed a survival advantage compared with those with 0-25% bcl-2-positive cells (P = 0.02). No correlation was found between p53 expression (Walker et al., 1994) and bcl-2 expression in dysplasias or carcinomas.

Bronchi↗
PubMed1995

Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections.

The lung is continuously exposed to infectious and non-infectious agents causing cell activation. Activated cells in the lung such as antigen-presenting cells which harbour HIV may favour this organ as a site for virus production. To test this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV-infected patients and healthy controls were obtained and the activation of the cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA-1. The HIV-infected individuals were subdivided into 'lung symptomatic' or 'lung asymptomatic' patients, depending on the presence or absence of secondary lung diseases besides HIV. All HIV-infected individuals demonstrated a decreased number of CD4+ lymphocytes in blood; however, normal numbers of these cells were found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and BAL was higher in lymphocytes from HIV-infected patients compared with controls. The activation state was highest in the lung symptomatic group. Lung symptomatic patients and lung asymptomatic patients with extrapulmonary infections had increased levels of free virus in plasma. Four out of four individuals without or with only low amounts of cell-free HIV in plasma belonged to the symptom-free subgroup. These results suggest that microorganisms other than HIV may promote viral replication via antigen-driven accumulation and activation of CD4+ cells in the lung or other organs, and thus may be responsible for the loss of helper T cells and the progression of the disease.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Thick bone section preparation using a silicon-rubber-based sealant.

A method has been developed, using a silicon-rubber-based sealant, which allows 2-3-mm-thick specimens to be maintained in a protected fluid environment for a number of months, without risk of dehydration. Following this, the specimen can be retrieved, stained, embedded and sectioned further. For example, 2-mm-thick sections of fixed unstained bone are easily examined by means of epi-illuminated polarized light and fluorescence microscopies using either conventional or confocal optics. The method could easily be extended to other tissues, for example brain tissue.

Bone and Bones↗
PubMed1995

Analysis of leucocytes and lymphocyte subsets in cats with naturally-occurring cryptococcosis but differing feline immunodeficiency virus status.

Although cryptococcosis is a well-characterised disease of cats, the factors predisposing individuals to infection are unknown. As an indication of the immune status of an individual, lymphocyte subsets can be analysed. Reference ranges for feline lymphocyte subsets (Pan T+, CD4+, CD8+ and B cells) were established using a rapid whole blood technique and flow cytometry. There were no effects of age or sex on lymphocyte subset values. The numbers of circulating leucocytes and lymphocyte subsets were determined in FIV-positive and FIV-negative cats with cryptococcosis and compared with a group of healthy control cats. There were only minor differences in the numbers of lymphocyte subsets among the subgroups of cats examined in the study and the predisposition to cryptococcosis in cats could not be explained by deficiencies in lymphocyte subsets. There was a tendency for FIV-negative cats with cryptococcosis to have reduced numbers of circulating CD4+ cells and lower CD4:CD8 ratios compared with normal cats, although the interpretation of this finding was complicated by the wide reference range for normal cats. The extent to which this is the cause of the fungal infection was not determined. The only difference in leucocyte or lymphocytes subset values between FIV-negative cats with cryptococcosis and FIV-positive cats with cryptococcosis was that the CD4+ percentage was lower in the FIV-positive cats. The absolute CD4+ count was similar however, in FIV-positive and FIV-negative cryptococcosis cases. On the basis of this and other available information, the categorisation of cryptococcosis as a disease defining the AIDS phase of FIV infection may be incorrect.

Animals↗
PubMed1995

T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provocation in atopic asthma.

Increasing evidence suggests a role for activated T cells and cytokines in the regulation of eosinophilic inflammation in asthma. In this study, we investigated the distribution of leukocytes, lymphocytes, their activation state, and the cytokine profile in BAL from 10 atopic asthmatics with positive skin prick tests and elevated specific IgE levels to birch or grass pollen. Using segmental allergen challenge, 250 PNU of the appropriate allergen or saline were instilled into different segments, which were lavaged 10 min (10 min) and 18 h (18 h) after allergen challenge or 18 h after saline challenge (C). In peripheral blood the number of neutrophils and activated IL-2R+/CD4+ T cells increased significantly 18 h after allergen provocation; there was no change in eosinophils, other leukocytes, or lymphocyte subsets. In contrast, numbers of eosinophils, neutrophils, and IL-2R+/CD4+ T cells increased significantly in BAL samples at 18 h. The numbers of neutrophils and eosinophils were not significantly different in the lavage performed at 10 min and at C. Analysis of cytokines in concentrated BAL fluid revealed significantly increased levels of IL-5, IL-2, IL-1, TNF-alpha, IL-6, IL-8, and GM-CSF, but not of IL-4 and IFN-gamma at 18 h compared with those at C and at 10 min. The correlation between IL-5 levels, eosinophil numbers, and activated T cells supports a role for T-cell-derived IL-5 in causing tissue eosinophilia in allergic asthma.

Adult↗
PubMed1995

Estrogen stimulation and tamoxifen inhibition of leiomyoma cell growth in vitro and in vivo.

Uterine leiomyomas (fibroids) are the most common gynecological neoplasms and may be associated with significant morbidity. Recently, we described a rat model (Eker rat) of fibroid development in which reproductive tract leiomyomas develop spontaneously with high frequency. The present studies describe the estrogen and antiestrogen responsiveness of an Eker rat leiomyoma-derived cell line in vitro and a nude mouse xenograft system in vivo. In this cell line, estradiol stimulated growth in estrogen-depleted medium, whereas the nonsteroidal antiestrogen tamoxifen maximally inhibited cell proliferation in medium containing 10% charcoal-stripped serum. Proliferation was also decreased by the biologically active tamoxifen metabolite 4-hydroxytamoxifen; the metabolite was more effective than the parent compound in exerting this growth inhibition. Compared to placebo-treated controls, estradiol increased the size of tumors that developed in a nude mouse xenograft system, whereas tamoxifen increased tumor latency and decreased tumor size. This study of leiomyoma cells in a well defined system suggests that antiestrogens may prove efficacious in the treatment of this clinically important neoplasm.

Animals↗
PubMed1995

Rodent model of reproductive tract leiomyomata. Establishment and characterization of tumor-derived cell lines.

Uterine myometrial tumors are the most commonly found gynecological neoplasm in women. The underlying causes of uterine leiomyomata are poorly understood, a result in part of the absence of a good animal model system in which to study these tumors. This report describes a novel rat model (Eker rat) in which spontaneous gynecological smooth muscle tumors arise with a high frequency. Leiomyomas are the predominant reproductive tract tumor that arise in these animals, although leiomyosarcomas have also been observed. Cell lines have been established from both the benign and malignant lesions. All of the lines express smooth muscle-specific actin, and leiomyoma-derived cell lines express desmin. Two of the cell lines are tumorigenic in nude mice, and the lines are variable for expression of estrogen and progesterone receptors. These lines are the first rodent tumor-derived lines to be established from leiomyomata and are the only lines available from a hereditary form of these tumors. Together with Eker rats that spontaneously develop leiomyomata, they constitute an in vitro/in vivo model system for gaining insights into the mechanism of transformation of uterine smooth muscle cells and the role of steroid hormones and hormone receptors in myometrial tumorigenesis.

Actins↗
PubMed1995

When to wean: whose advice do mothers find helpful?

A survey of the weaning practice of first-time mothers shows that the health visitor is the most used and useful source of advice, but infant behaviour remains the main influence on parents' practice. Caroline Walker suggests that official guidelines may be too rigid to reflect the diversity of individual infant's needs as experienced by their carers, and that a more flexible approach may be needed if professionals' credibility is not to suffer.

Community Health Nursing↗
PubMed1995

Rodent model of reproductive tract leiomyomata. Clinical and pathological features.

Mesenchymal tumors of the lower reproductive tract of women are poorly understood at the molecular level as a result in part of the lack of relevant animal models. The present study describes a novel model of gynecological smooth muscle tumors in which these neoplasms arise in Eker rats as part of a familial cancer syndrome. The tumors develop as a result of a germline mutation in the tuberous sclerosis 2 (TSC2) gene, and predisposition to tumor development is inherited in an autosomal dominant fashion. Uterine and/or cervical tumors arise spontaneously as single or multicentric neoplasms and increase in incidence with increasing age. The tumors were classified into three phenotypic variants of leiomyoma/leiomyosarcoma and into stromal cervicovaginal tumors on the basis of cytological and histological features and immunostaining patterns for smooth muscle actin and desmin. Tumors histologically identical to the typical human myometrial leiomyoma arose, as did a subset of atypical leiomyomas having an epithelioid phenotype. Eker rats were found to develop both benign and malignant smooth muscle tumors. The high spontaneous incidence of smooth muscle tumors of uterus and cervix in this rodent model provides a unique opportunity to study the molecular mechanisms underlying the development of these clinically important gynecological neoplasms.

Animals↗
PubMed1994

Wilms' tumor suppressor gene expression in rat and human mesothelioma.

Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors.

Aged↗
PubMed1994

Cellular and immunological markers of allergic and intrinsic bronchial asthma.

Based on a growing body of evidence, allergic as well as intrinsic bronchial asthma have recently been defined as chronic persistent inflammatory disorders. Agreement has been reached that asthma can no longer be equated with bronchospasm only, and that the absence of reversibility of airflow obstruction does not exclude bronchial asthma. Bronchial hyperreactivity, on the other hand, although common to the vast majority of asthmatics, is not specific for bronchial asthma and provocation tests to measure bronchial hyperreactivity are not suited for routine monitoring of bronchial asthma. The clinical features of asthma are related to cellular as well as to soluble parameters of bronchial inflammation. Therefore, means of assessing and monitoring asthmatic inflammation have been investigated. Since eosinophils, T lymphocytes, mast cells, macrophages, neutrophils, epithelial cells, and structural cells, as well as various proinflammatory mediators and proteins, have been implicated in the pathogenesis of bronchial asthma, it has been anticipated that several of these cells or mediators might be either diagnostic of bronchial asthma or could serve as markers to monitor the underlying bronchial inflammation. Currently there is no diagnostic marker of bronchial asthma, which, on its own, either confirms or excludes bronchial asthma with appropriate sensitivity and specificity. Clinically the most reliable feature of bronchial asthma that seems to be related closely to the symptomatology still is the presence of eosinophils in peripheral blood, and especially in sputum. Eosinophil-derived products, particularly eosinophil granule proteins, have been investigated as markers of eosinophil participation in the pathogenesis of asthma and, comparable to eosinophil numbers themselves, are possible predictors of impending exacerbations of allergic, as well as intrinsic bronchial asthma. However, clinically their precise value in diagnosing and monitoring of bronchial asthma has not been documented convincingly and requires further investigation. Increasing data suggest that the regulation of eosinophilia is largely conveyed by interleukin-5 (IL-5) released from activated T-helper lymphocytes and possibly other cells. Therefore, T-lymphocyte activation, and especially assessment of systemic and local IL-5 levels, might be of diagnostic value and possibly useful in monitoring of inflammation in bronchial asthma in the future. A possible role and future applications for other markers of inflammation not related to eosinophils in monitoring or diagnosing bronchial asthma need to be established.

Adult↗
PubMed1994

Characteristics of two cell lines derived from a histologically undifferentiated bronchial carcinoma expressing neuroendocrine markers.

This study investigates the characteristics of two human cell lines--1PT and 1PT VARIANT A--both derived from the same histologically undifferentiated, neuroendocrine positive, non-small cell lung carcinoma (NSCLC) and capable of growth in unsupplemented serum-free minimum essential medium. In stationary culture, the cells of both lines grew both attached to a plastic substratum and in suspension; the 1PT VARIANT A line formed three-dimensional clusters of loosely adherent cells. The cell lines differed in their DNA content, the 1PT having 1.44 times and the 1PT VARIANT A having 2.39 times the normal human diploid DNA content. Chromosome counts supported this observation, the ploidy of the 1PT and VARIANT A lines being 1.11 and 1.64, respectively. On transmission electron microscopy the cells of both lines had dense core granules and immature desmosomes, whereas only the 1PT VARIANT A line had mucin granules. Both lines formed, in nude mice, tumors that, like the original tumor from which they were derived, were histologically undifferentiated and showed local invasion. The original tumor and both lines had demonstrable neuroendocrine markers. Cytokeratins were apparent in the tumor but not the cell lines, and neurofilaments were present in the cell lines only. Staining for epithelial membrane antigen, neural cell adhesion molecule, and desmoplakin differentiated between the two lines. These lines provide a useful model for the investigation of the biology of the neuroendocrine positive subgroup of NSCLC, which is clinically important because of the possible responsiveness of these tumors to chemotherapy.

Animals↗
PubMed1994

Pulmonary function, activated T cells, peripheral blood eosinophilia, and serum activity for eosinophil survival in vitro: a longitudinal study in bronchial asthma.

A close correlation among the number of activated, peripheral blood T helper cells, eosinophilia, and airflow obstruction has been reported in patients with asthma. To test these cross-sectional data we performed a prospective, longitudinal study investigating the relationships among T-cell activation in peripheral blood, eosinophilia, forced expiratory volume in 1 second (FEV1), and serum activity toward eosinophil survival in 20 individuals with asthma over a period of 21 days after admission to a clinic located 1560 m above sea level. During the study, maintenance treatment with inhaled beta 2-agonists and theophylline was unchanged. Five patients had also been taking inhaled corticosteroids, and this was also not changed during the study period. According to the changes in pulmonary function observed at the end of the study, patients were divided into three groups: twelve patients whose pulmonary function improved by more than 10% from baseline (group I), four patients whose pulmonary function deteriorated by more than 10% from baseline necessitating therapeutic intervention (group II), and four patients with no change in FEV1 (< 10% from baseline) (group III). Activation of T cells as determined by interleukin-2 receptor expression, number of eosinophils, and serum activity toward eosinophil survival in vitro declined in group I; whereas FEV1 increased. The decrease in FEV1 in group II was associated with an increase in interleukin-2 receptor-positive T cells, number of eosinophils, and serum activity. In group III FEV1, interleukin-2 receptor expression on T cells, the number of peripheral blood eosinophils, and the measured serum activity for eosinophil survival in vitro did not change significantly from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Analysis of leucocytes and lymphocyte subsets for different clinical stages of naturally acquired feline immunodeficiency virus infection.

We report alterations in leucocytes numbers and lymphocyte subset percentages, determined by flow cytometry, for three observed and previously defined clinical stages (asymptomatic carrier (AC), AIDS-related complex (ARC) and AIDS) of naturally occurring FIV infection. Unstaged FIV-positive cats had significantly lower numbers of total leucocytes (WCC) and neutrophils, lower percentages of PanT+ and CD4+, lower CD4:CD8 ratio and a higher percentage of B cells compared with unstaged FIV-negative cats. When FIV-positive cats were separated into clinical stages and compared with matched FIV-negative cats, AC FIV-positive cats had a significantly lower WCC, lower absolute numbers of neutrophils and lymphocytes, lower percentages of CD4+ and CD8+ cells, lower CD4:CD8 ratios and a higher percentage of B cells than healthy FIV-negative cats. ARC FIV-positive cats had lower percentages of PanT+ and CD4+ cells, lower CD4:CD8 ratios and higher percentages of B cells than matched FIV-negative cats. FIV-positive cats with AIDS had significantly lower percentages of CD4+ cells than matched FIV-negative cats. Comparisons among the three observed clinical stages of FIV-positive cats showed that AC FIV-positive cats had significantly lower WCC, significantly lower absolute numbers of neutrophils and a significantly lower percentage of CD8+ cells than ARC FIV-positive cats. AIDS FIV-positive cats had a significantly lower percentage of B cells than AC or ARC FIV-positive cats. FIV-positive cats had a similar leucocyte response to illness as FIV-negative cats but had consistently lower percentages of CD4+ lymphocytes. Thus, in the staging of FIV, a rise in the percentage of CD8+ lymphocytes could be used to distinguish between AC and ARC and a fall in the percentage of B lymphocytes could distinguish AIDS from AC and ARC.

Animals↗
PubMed1994

Healthy alliance? The relevance of health professionals to housing management.

British public policy now relies on the development of 'healthy alliances' to meet the care, support and servicing needs of people with health problems and mobility difficulties. Such alliances are not, however, new; notably, housing policy is frequently used as a health intervention. This paper examines the character and effectiveness of the resulting alliance between health professionals and housing managers, and considers its future prospects.

Health Personnel↗