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Biomedical subjects

S Nicholson

Publications and source records attributed to S Nicholson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Analysis of DNA adducts by accelerator mass spectrometry in human breast tissue after administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene.

Epidemiological evidence has suggested an association between meat consumption and the risk of breast cancer. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, has been implicated in the aetiology of breast cancer and has been shown to induce tumour formation in rodent mammary glands. In addition, polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P) which has also been shown to induce tumour formation at a number of sites in rodents including the breast, are produced during the cooking of meat through the pyrolysis of fats. The aim of this study was to examine the bioavailability of these compounds to human breast tissue and their ability to bind to DNA to form DNA adducts. Patients undergoing breast surgery at York District Hospital were orally administered prior to surgery a capsule containing 20microg of 14C PhIP (182kBq, specific activity 2.05GBq/mmol) or 5microg of 14C B[a]P (36kBq, specific activity 1.81GBq/mmol). At surgery, normal and tumour breast tissue was resected and tissue concentrations of carcinogen measured by liquid scintillation counting and DNA adduct levels by accelerator mass spectrometry (AMS) were subsequently determined. It was found that both 14C PhIP and 14C B[a]P were able to reach the target organ where they had the ability to form DNA adducts. The level of adducts ranged from 26.22-477.35 and 6.61-208. 38 adducts/10(12) nucleotides following administration of 14C PhIP and 14C B[a]P, respectively, with no significant difference observed between levels in normal or tumour tissue. In addition, the data obtained in this study were comparable to adduct levels previously found in colon samples following administration of the same compounds to individuals undergoing colorectal surgery. This is the first report that these two carcinogens bind to human breast DNA after administration of a defined low dose.

Aged↗
PubMed2000

The Child-Friendly Healthcare Initiative (CFHI): Healthcare provision in accordance with the UN Convention on the Rights of the Child. Child Advocacy International. Department of Child and Adolescent Health and Development of the World Health Organization (WHO). Royal College of Nursing (UK). Royal College of Paediatrics and Child Health (UK). United Nations Children's Fund (UNICEF).

OBJECTIVE: Although modern medical technology and treatment regimens in well-resourced countries have improved the survival of sick or injured children, most of the world's families do not have access to adequate health care. Many hospitals in poorly resourced countries do not have basic water and sanitation, a reliable electricity supply, or even minimal security. The staff, both clinical and nonclinical, are often underpaid and sometimes undervalued by their communities. In many countries there continues to be minimal, if any, pain control, and the indiscriminate use of powerful antibiotics leads to a proliferation of multiresistant pathogens. Even in well-resourced countries, advances in health care have not always been accompanied by commensurate attention to the child's wider well-being and sufficient concerns about their anxieties, fears, and suffering. In accordance with the United Nations Convention on the Rights of the Child,(1) the proposals set out in this article aim to develop a system of care that will focus on the physical, psychological, and emotional well-being of children attending health care facilities, particularly as inpatients. DESIGN OF THE PROGRAM: To develop in consultation with local health care professionals and international organizations, globally applicable standards that will help to ensure that practices in hospitals and health centers everywhere respect children's rights, not only to survival and avoidance of morbidity, but also to their protection from unnecessary suffering and their informed participation in treatment. Child Advocacy International will liase closely with the Department of Child and Adolescent Health and Development of the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) in the implementation of the pilot scheme in 6 countries. In hospitals providing maternity and newborn infant care, the program will be closely linked with the Baby Friendly Hospital Initiative of WHO/UNICEF that aims to strengthen support for breastfeeding. United Nations Children's Fund, United Nations Convention on the Rights of the Child, child protection, breastfeeding, pain control, palliative care, child abuse.

Child↗
PubMed1999

The kinesin light chain gene: its mapping and exclusion in mouse and human forms of inherited motor neuron degeneration.

The underlying genetic cause is known for only 10-20% of familial motor neuron disease (MND). Thus the genes involved in the aetiology of 80-90% of familial MND remain to be determined, and animal models are powerful tools for undertaking this task. We have mapped a heritable form of motor neuron degeneration in the mouse to a region that has homology to human chromosome 14q32.1-qter. This region contains the kinesin light chain gene (KLC1), which is a candidate for involvement in motor neuron degeneration because of its function in the motor-protein kinesin, and its neuronal expression. To investigate the role of KLC1 in a mouse motor neuron degeneration mutant that we are studying, we have identified mouse Klc1 gene sequences and mapped them with respect to our mutant locus. We have also investigated KLC1 in human patients with familial MND. Based on recombination and the absence of mutations in the coding region of KLC1, this gene can be excluded as a candidate gene in our mouse mutation and, where we have investigated, it is normal in human familial MND.

Animals↗
PubMed1999

Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase.

The two genetically established antimicrobial mechanisms of macrophages are production of reactive oxygen intermediates by phagocyte oxidase (phox) and reactive nitrogen intermediates by inducible nitric oxide synthase (NOS2). Mice doubly deficient in both enzymes (gp91(phox-/-)/NOS2(-/-)) formed massive abscesses containing commensal organisms, mostly enteric bacteria, even when reared under specific pathogen-free conditions with antibiotics. Neither parental strain showed such infections. Thus, phox and NOS2 appear to compensate for each other's deficiency in providing resistance to indigenous bacteria, and no other pathway does so fully. Macrophages from gp91(phox-/-)/NOS2(-/-) mice could not kill virulent Listeria. Their killing of S. typhimurium, E. coli, and attenuated Listeria was markedly diminished but demonstrable, establishing the existence of a mechanism of macrophage antibacterial activity independent of phox and NOS2.

Abscess↗
PubMed1998

Use of a reduced-carbohydrate, modified-fat enteral formula for improving metabolic control and clinical outcomes in long-term care residents with type 2 diabetes: results of a pilot trial.

Physiologic responses of 30 enterally-fed long-term care residents with type 2 diabetes receiving total nutrition support via either a disease-specific (reduced-carbohydrate, modified-fat) formula or a standard high-carbohydrate formula for 3 mo were compared. Objectives of the study included evaluating metabolic response (glycemic control and lipids) and clinical outcomes. Thirty-four subjects requiring total enteral nutrition support by tube were enrolled in this prospectively randomized, double-blind, controlled, parallel group 3-mo pilot trial. Thirty were evaluable in that they completed 4 wk. Twenty-seven completed all 12 wk. The groups were well-matched for physiologic and demographic parameters at baseline. Fasting serum glucose and capillary (fingerstick) glucose values demonstrated better control in the disease-specific formula-fed group. Serum lipid profiles of this group were similar to or better than those of the standard formula-fed group. The amount of insulin administered to insulin-using subjects in the disease-specific formula-fed group was consistently less than before initiation of the formula, whereas the amount administered was consistently higher in the group fed the standard formula. Overall, subjects randomized to the disease-specific formula experienced better numerical biochemical control and better clinical outcomes when expressed on a numerical and percentage basis. These included surrogate markers of diabetes control such as serum glucose and glycohemoglobin, as well as clinical outcomes such as incidence of infections and pressure ulcers. These findings confirm that the disease-specific formula provides better glycemic control, poses no risk to lipoprotein metabolism, and provides for better clinical outcomes.

Aged↗
PubMed1998

CSF-1 and interferon-gamma act synergistically to promote differentiation of FDC-P1 cells into macrophages.

FDC-P1 cells expressing the wildtype CSF-1 receptor, FDwtfms, differentiate into macrophages during incubation with CSF-1. This response is amplified in the presence of interferon-gamma. Cells expressing the 807F mutant receptor, 807F cells, proliferate in response to CSF-1 and do not differentiate. However, in response to CSF-1 and interferon-gamma they differentiate as well. CSF-1 causes the activation of STAT proteins in FDwtfms cells, but not in 807F cells. Cellular differentiation correlates with a sustained activation of STAT1 and STAT3 in response to interferon-gamma over at least 40 hours. However, interferon-gamma alone did not cause differentiation of cells expressing either receptor. Other defects in response to CSF-1 of the 807F cells, such as lack of PLC gamma 2 activation, were not complemented by co-incubation of the cells with CSF-1 and interferon-gamma. It appears that a combination of signaling pathways are activated by CSF-1 and interferon-gamma which caused the shift of response from proliferation to differentiation in the 807F cells and an enhanced differentiation in the FDwtfms cells.

Animals↗
PubMed1997

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood.

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.

Administration, Oral↗
PubMed1996

Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis.

The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2.

Amino Acid Sequence↗
PubMed1995

'Stupid calves'.

Explore the source record for details and available documents.

Animals↗
PubMed1995

The expression of emotional distress in old English prose and verse.

The Old English elegies and Alfred's translation of De Consolatione Philosophiae were examined for the presence of abstract nouns denoting adverse mood states. Large numbers of these nouns were discovered and grouped into five categories. This counters the arguments of those who believe the Anglo-Saxons expressed negative emotions chiefly in somatic terms.

Affective Symptoms↗
PubMed1994

Comparison of radioligand assay and immunostaining for epidermal growth factor receptor in human breast cancer.

Epidermal growth factor (EGF) receptor status is a useful prognostic indicator in women with breast cancer. Lack of standardization and correlation of methodology for the detection of EGF receptor has hampered its further evaluation. EGF receptor status was ascertained by immunohistochemistry and radioligand assay in 120 breast cancers. Of 52 tumours negative for EGF receptor on radioligand assay, 47 were negative on immunohistochemistry and, of 68 tumours positive for the receptor on assay, 52 were positive on immunohistochemistry. If the more widely evaluated radioligand assay is assumed to be the 'gold standard', immunohistochemistry has a sensitivity of 81 per cent and a specificity of 91 per cent.

Biomarkers, Tumor↗
PubMed1994

Semantic and episodic relations are experimentally dissociable and stochastically independent.

Subjects who studied DOG-BEER and WINE-SWEATER were more likely to recall BEER cued by DOG if they used interactive imagery rather than separate imagery, but the two groups showed no difference in recall of BEER cued by WINE. Recall of BEER cued by WINE was enhanced if BEER and "alcoholic beverages" had been presented before the list was studied, but recall of BEER cued by DOG was unaffected. We conclude that there are two independent types of relation: An episodic relation records the joint occurrence of previously unrelated words; a semantic relation reflects events in one's prior life. The value of a semantic relation is enhanced if the target item is primed in its family; the value of an episodic cue is enhanced by processes that directly encode the occurrence of the two items as a unique event in the life of the subject.

Humans↗