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Biomedical subjects

R Clarke

Publications and source records attributed to R Clarke.

At least 199 records · Page 11Linked to original sources
PubMed1990

Nasal airflow in inspiration and expiration.

Inspiratory and expiratory airflow rates were measured in 30 subjects during quiet respiration (at a pressure gradient of 150 Pa) and at peak flow rates. For low flow rates airflow rate was greater for inspiration than for expiration. Conversely at peak flow rates flow was greatest during expiration. Thus there was a reversal in the phase relationship between inspiration and expiration as flow rate increased. It was also found that peak inspiratory flow rate correlated better with values for nasal resistance than did peak expiratory flow rate. Flow rate measured by rhinomanometry during quiet respiration was more sensitive to physiologically induced changes in nasal resistance than was peak flow rate. The findings are discussed with reference to previous work on the physiology of nasal airflow.

Adolescent↗
PubMed1990

The process of malignant progression in human breast cancer.

Malignant progression in breast cancer represents the processes through which localized, hormone-dependent tumor cells become resistant to endocrine manipulations and metastasize to sites distant from the primary tumor. By selection in ovariectomized athymic nude mice, we have isolated a variant (MIII) of the hormone-dependent, poorly invasive, human breast cancer cell line MCF-7. MIII cells have lost their absolute requirement for estrogen to form proliferating tumors in nude mice. Furthermore, these tumors are significantly more invasive than the parental MCF-7 cell line. MIII cells retain some responsivity to estrogens and antiestrogens, indicating that they have progressed to a hormone-independent but hormone-esponsive phenotype. In an attempt to determine the nature of this process, we have compared the phenotype of MIII cells with that of other MCF-7 variants. These comparisons strongly suggest that the factors contributing to perturbations in antiestrogen sensitivity, hormone-dependent growth, metastatic potential and tumorigenicity are essentially independent of each other and acquired in a random manner. Loss of estrogen receptor expression and overexpression of EGF receptors tend to occur later in the process of malignant progression.

Animals↗
PubMed1990

Aspergillar osteomyelitis of the acetabulum. A case report and review of the literature.

An unusual case of primary osteomyelitis of the acetabulum caused by Aspergillus flavus in a presumed immunocompetent adult is presented. Review of the literature found 25 additional cases of aspergillar osteomyelitis, which occurred predominantly in hosts with either inborn or acquired immune defects. There were notable differences between the adult and the pediatric cases in causation, clinical presentation, and treatment regimens. In children, the underlying cause was usually severe immunocompromise; among adults, the majority of cases occurred in hosts presumed to be immunocompetent. In all but one case, the children were treated with antifungal chemotherapy alone, whereas the adult patients nearly always received surgical debridement in conjunction with chemotherapy.

Acetabulum↗
PubMed1990

An evaluation of an anticoagulant clinic.

Patient comprehension of the risks of anticoagulation, tablet recognition skills and knowledge of complications of warfarin therapy were evaluated in 160 patients attending the anticoagulant clinic in a central Dublin teaching hospital group. Potential complications from over- and under- dosage with warfarin were unknown to 119 (74%) and 97 (60%) patients respectively. 1, 3 and 5 mg tablets could not be identified by 40 (25%), 55 (34%) and 60 (37%) patients respectively. The current prescribed dose could not be recollected by 31 (19%) patients. Haemorrhagic complications occurred in 23 (14%) subjects over one year, four of whom required hospital admission and two blood transfusions. No thromboembolic episodes were noted. This study reveals a widespread lack of understanding of anticoagulation and its potential complications in patients receiving warfarin therapy and has led to a critical reappraisal of patient education, patterns of referral and supervision of such individuals in our clinic.

Female↗
PubMed1989

Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo.

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.

Animals↗
PubMed1989

Postmortem cerebrospinal fluid pleocytosis.

We show that postmortem cerebrospinal fluid (CSF) pleocytosis is a common event. Postmortem cerebrospinal or ventricular fluid was obtained from children and adults. The cells were counted and morphologically characterized using several histochemical markers. Infants exhibit a brisk postmortem CSF pleocytosis. Sudden infant death cases have relatively high CSF counts. Typeable cells are mononuclear and consist of approximately 60%-70% lymphocytes and 20%-40% macrophages. When postmortem duration is greater than 12 h, the cells become vacuolated and cannot be identified. The etiology of these findings requires further study.

Adolescent↗
PubMed1989

A reappraisal of protein turnover values in neonates fed human milk or formula.

We investigated the effect of human milk feeding on the nitrogen metabolism of appropriate-for-gestational age infants of birth weight 1.5-2.0 kg. Eight infants received pooled mature human milk. The remaining 20 were divided into two equal groups, who received one of two low-protein, milk-based formulae. The formulae were identical in composition except for the protein source, which was either casein- or whey-predominant. The three diet groups received similar total nitrogen (390 mg N.kg-1.d-1) and energy (500 kJ.kg-1.d-1) intakes. The human-milk-fed group, however, received a significantly higher intake of nonprotein and urea nitrogen and a significantly lower true protein nitrogen. Nitrogen metabolism was studied using a modified constant infusion of [15N]glycine, mixed with the feeding every 2-3 h. Urine was collected in approximately 3-h aliquots and analysed for total ammonia and urea nitrogen. Excretion of the 15N label was measured in urinary urea and ammonia. No differences were seen between the three diet groups in total [15N]urea or [15N]ammonia urinary excretion. However, the concentration of 15N in urinary urea in the human-milk-fed group was lower than in the two formula-fed groups. This reduction in concentration appeared due to a higher dietary intake of urea among the human-milk-fed group, and the consequent dilution of the label in the urine. As a result, protein turnover rates calculated from the [15N]urea end product were artificially raised in the milk-fed group, and were significantly higher than those in the formula groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗
PubMed1989

Regulation of breast cancer cells by hormones and growth factors: effects on proliferation and basement membrane invasiveness.

The current understanding of the regulation of breast cancer cell proliferation and invasiveness by hormones and growth factors is reviewed. It has been shown that polypeptide growth factors are involved in hormone-independent breast cancer, and are sometimes oestrogen-regulated in hormone-responsive models. Basement-membrane invasiveness, relating to the metastatic potential of these cells, is also stimulated by oestrogen in hormone-dependent models, elevated in hormone-independent models, and is growth factor sensitive. Further understanding of the differential effects of growth factors on breast cancer cell proliferation and invasiveness should facilitate better therapeutic exploitation of regulation at this level.

Animals↗
PubMed1989

The effects of a constitutive expression of transforming growth factor-alpha on the growth of MCF-7 human breast cancer cells in vitro and in vivo.

It has been suggested that transforming growth factor-alpha (TGF-alpha) is a mitogenic autocrine growth factor for human breast cancer cells, responsible for mediating the mitogenic effects of 17 beta-estradiol (E2) in responsive cells. To test this hypothesis we have introduced eukaryotic expression vectors directing the expression of TGF-alpha mRNA into E2-responsive MCF-7 human breast cancer cells. Transfected cells produce levels of TGF-alpha equivalent to or greater than those produced by both E2-stimulated MCF-7 cells and hormone-independent MDA-MB-231 cells. One transfected clone (H8) secretes sufficient TGF-alpha to fully down-regulate EGF-R expression. However, both of the transfected clones that constitutively secrete elevated levels of TGF-alpha (A8 and H8) respond to E2 stimulation in vitro by increasing the rate of cellular proliferation and inducing PGR synthesis. The basal proliferative capacity of H8 and A8 cells is equivalent to that of the parental cells and to cells transfected only with the G418 (neomycin) resistance gene. Furthermore, the TGF-alpha cDNA-transfected clones do not form tumors in ovariectomized athymic nude mice without E2 supplementation. Thus, the precise role of TGF-alpha in mediating either the in vivo or the in vitro mitogenic effects of E2 in MCF-7 human breast cancer cells remains unclear. While TGF-alpha expression may be essential, it is not sufficient alone to induce the fully E2-independent phenotype. Thus, TGF-alpha may function in combination with other E2-induced growth factors to control breast cancer proliferation and tumorigenesis.

Breast Neoplasms↗
PubMed1989

The inter-relationships between ovarian-independent growth, tumorigenicity, invasiveness and antioestrogen resistance in the malignant progression of human breast cancer.

Among the processes contributing to the progressive acquisition of the highly malignant phenotype in breast cancer are ovarian-independent growth, antioestrogen resistance and increased metastatic potential. We have previously observed that increased invasiveness and development of ovarian-independent growth occur independently. In an attempt to define the inter-relationships between these processes further, we have compared the phenotypes of ovarian-independent, invasive and antioestrogen-resistant sublines of the ovarian-dependent human breast cancer cell line MCF-7. Cells acquiring ovarian-independent growth can retain sensitivity to anti-oestrogens. One clone of MCF-7 cells selected for stable antioestrogen resistance has become non-tumorigenic but its invasive potential remains unaltered. Thus, acquisition of some characteristics of the progressed phenotype can occur independently. This phenomenon of independent parameters in phenotypic progression could partly explain the considerable intra- and intertumour heterogeneity characteristic of breast tumours.

Animals↗
PubMed1989

Regulation of human breast cancer by secreted growth factors.

Laboratory evidence is presented that estrogens are able to induce the production of numerous growth factors which can act in an autocrine or paracrine fashion in estrogen dependent breast cancer. Estrogen independent tumors can produce these same growth factors constitutively and so escape the need for estrogen stimulation. Growth inhibitory factors such as TGF-beta can also be controlled by estrogens and antiestrogens. It is unclear at present, however, how much of the cytostatic effect of antiestrogens in vivo is explained by the production of growth inhibitors. The overall control of breast cancer growth is mediated by the combined effects of these growth stimulatory and inhibitory factors in both breast stroma and epithelium. Interruption of the action of growth factors and the use of growth inhibitors may provide opportunities for new approaches to the treatment of breast cancer.

Breast Neoplasms↗
PubMed1989

Endocrine therapy of human breast cancer cells: the role of secreted polypeptide growth factors.

Endocrine therapy is an important modality in the treatment of breast cancer. However, the precise molecular mechanisms underlying the growth inhibitory effect of endocrine therapy are unknown. Recently, it has been shown that breast cancer cells express and secrete polypeptide growth factors that can regulate the growth of the cells through autocrine and/or paracrine pathways. These growth factors are thought to be involved in the response to endocrine therapy. Three different mechanisms have been suggested: (1) stimulation of growth inhibitory peptides; (2) repression of mitogenic peptides; and (3) stimulation of mitogenic growth factors in cells overexpressing the corresponding receptor. This article reviews the scientific evidence on which these hypotheses are based.

Breast Neoplasms↗