Search PubMed⌕ Search

Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 343 records · Page 19Linked to original sources
PubMed1995

MRI assessment of the blood-brain barrier in a hamster model of scrapie.

Magnetic resonance (MR) imaging in combination with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement was used to investigate the integrity of the blood-brain barrier in a hamster model of scrapie (263K) during the clinical phase of the disease. The post Gd-DTPA images of the infected hamster brain showed marked enhancement, which was not present in control animals. These results suggest that blood-brain barrier function is disrupted in the clinically-affected animal.

Animals↗
PubMed1995

Vincristine and oral etoposide in refractory multiple myeloma.

A total of 15 patients with refractory multiple myeloma (MM; 4 primary unresponsive and 11 relapsed and resistant to re-induction/salvage therapy) received i.v. vincristine on day 1 and oral etoposide daily for 4 days, the treatment being repeated at 3-weekly intervals. The patients were re-assessed after three cycles of chemotherapy, and non-responders received no further therapy. There was no complete or partial response. A minimal response was seen in two patients, and two others showed stable disease. None of the responses was sustained, and all patients eventually had progressive disease. It is concluded that combination chemotherapy with vincristine and oral etoposide given by this schedule is unlikely to be of any value in refractory myeloma.

Administration, Oral↗
PubMed1995

Elevation of striatal and accumbal preproenkephalin, preprotachykinin and preprodynorphin mRNA abundance subsequent to N-methyl-D-aspartate receptor blockade with MK-801.

The effect of N-methyl-D-aspartate (NMDA) receptor blockade on the expression of preproenkephalin (PPE), preprotachykinin (PPT) and preprodynorphin (PPD) mRNAs in the caudate-putamen and nucleus accumbens was assessed with the non-competitive NMDA receptor antagonist MK-801. Administration of MK-801 once daily for 7 consecutive days increased the abundance of all three neuropeptide mRNAs in the caudate-putamen (CPU) and nucleus accumbens (NAc). (1) PPE mRNA abundance was increased in the anterior CPU (26%) as well as dorsal and ventral CPU (46% and 39%, respectively) but was unaffected in the NAc. (2) PPT mRNA was increased in the NAc (33%), anterior CPU (27%), dorsal CPU (43%) and ventral CPU (67%). In the ventral CPU, PPT mRNA abundance doubled when the dose of MK-801 increased two-fold (from 67% to 119% above control). (3) PPD mRNA was elevated in dorsal and ventral regions of the CPU (49% and 24%, respectively) and in anterior CPU (50%). In the NAc PPD mRNA was increased only at the higher dose (0.1 mg/kg) of MK-801. Cellular analysis of the distribution of grains per cell shows that increases are due to increased accumulation of mRNA by previously expressing cells of the CPU and NAc. These observations demonstrate that NMDA receptor activity plays a significant role in the regulation of neuropeptide expression in the caudate-putamen and accumbens of the rat brain.

Animals↗
PubMed1995

A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor.

The cyclic nucleotide-gated channel from rod photoreceptors is composed of two distinct subunits (alpha and beta). The properties of the alpha subunit, which can form functional channels by itself, are modified by coexpression with a homologous polypeptide, designated the beta subunit. However, the alpha subunit from rod photoreceptor membranes copurifies with a 240 kDa protein that is significantly larger than this putative beta subunit. We now demonstrate by peptide sequencing and by cloning and functional expression of cDNA that the 240 kDa protein represents the complete beta subunit with an unusual bipartite structure. The N-terminal part is essentially identical to a glutamic acid-rich protein (GARP), whereas the C-terminal part is highly homologous to the previously cloned human "beta subunit." Expression of the complete beta subunit in HEK 293 cells results in a polypeptide with the same apparent molecular weight as the 240 kDa protein of the native rod channel. Coexpression of the alpha subunit with the full-length beta subunit yields hetero-oligomeric channels with properties characteristic of the native channel.

Amino Acid Sequence↗
PubMed1995

Antitumor activity of three mouse mammary cancer cell lines after interferon-gamma gene transfection.

BACKGROUND: The antitumor effects of three mouse mammary tumors transfected to express interferon-gamma were evaluated. METHODS: Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected with highly efficient viral vectors. Wild type or transfected tumor cells were injected subcutaneously into Balb/c mice. Animals were observed for tumor growth and the induction of immunologic memory. RESULTS: A significant decrease occurred in the size of all transfected tumors, EMT6 1.9 cm2, DA3 1.7, and 410 1.8 compared with nontransfected control tumors with a mean size of 4 cm2 on day 30. To further test the development of immunity, animals were injected with either nontransfected or transfected tumors and challenged with nontransfected tumor. Animals immunized with transfected tumor cells had significantly smaller tumors, EMT6 2.5 cm2, DA3 3.1, and 410 2.4 compared with controls with a mean size of 4 cm2. No specific splenocyte cytotoxicity was shown. Expression of major histocompatibility complex class I antigens was enhanced in the 410 and DA3 tumor lines. CONCLUSIONS: Significant antitumor effects were observed after interferon-gamma gene transfection of three mouse mammary cancer cell lines. Up-regulation of major histocompatibility complex class I antigen expression is a partial explanation of these findings. These results provide preliminary studies for gene therapy of human breast cancer.

Animals↗
PubMed1995

Characterisation of Legionella pneumophila antigen in urine of guinea pigs and humans with Legionnaires' disease.

To study and develop the urinary antigen detection assay, urine was obtained from aerosol infected guinea pigs. The appearance of Legionella pneumophila antigen in guinea pig urine was then compared with that detected in urine from human Legionnaires' Disease (LD) cases. This study demonstrated that the antigen expressed in the experimental model of LD was of identical molecular weight, reacted almost identically in an ELISA based assay and in Western blots with the antigen found in human urine. The guinea pig urine can therefore be used as a reliable, consistent and controllable source of antigen for use in the urinary antigen assay.

Animals↗
PubMed1995

Incidence and spread of Haemophilus influenzae on an Antarctic base determined using the polymerase chain reaction.

A PCR-based method of detecting Haemophilus influenzae in cultures inoculated from throat swabs was evaluated using samples from groups of laboratory staff and medical students and then applied to samples originating from the closed human community of an Antarctic research station. Suitable PCR primers to an H. influenzae gene (ompP2) were used to amplify the gene from DNA preparations made from mixed growth on chocolate agar with added vancomycin. PCR product was reamplified and subjected to restriction endonuclease digestion to allow temporal and spatial mapping of strains over an 8-month period. Eleven different strains of H. influenzae were detected. One particular strain was detected in a third of the base members.

Adult↗
PubMed1995

A possible screening test for inherited p53-related defects based on the apoptotic response of peripheral blood lymphocytes to DNA damage.

The cellular response, in terms of cell cycle arrest(s) and apoptosis, to radiation-induced DNA damage was studied. Experiments were performed on both mitogen-stimulated and resting peripheral blood lymphocytes (PBLs) from normal and cancer-prone (C-P) individuals. The C-P individuals comprised three patients carrying germline p53 mutations and three members of two families apparently without such mutations, but with an inherited defect which results in p53 deregulation as shown by high levels of stabilised p53 protein in normal tissues. Interestingly, mitogen-stimulated PBL, from both normal and C-P individuals failed to demonstrate a G1 arrest after gamma radiation. However, a clear difference was seen in the apoptotic response to DNA damage, of PBL from normal and C-P individuals; PBLs from C-P individuals with inherited p53-related defects had a reduced apoptotic response (P = 0.0003). There was a wide margin of separation, with no overlap between the two groups, supporting the possibility of using this altered apoptotic response as a screening test. This simple and rapid procedure could be used to identify those individuals in a C-P family who carry germline p53-related defects. The method appears to detect both individuals with p53 mutations and those apparently without mutations but with other p53-related defects.

Adult↗
PubMed1995

Women's experiences of rheumatoid arthritis.

This paper is based on findings drawn from research undertaken within a qualitative framework of analysis. The purpose of the research was to explore women's experiences of rheumatoid arthritis. Three areas of concern to the women are identified and discussed in the light of relevant literature. They are as follows: seeking help, searching for meaning and uncertainty about symptoms. A major theoretical concern of both authors is to demonstrate the importance of placing patients' personal accounts of their experiences and understandings at the centre of nursing interest and practice. It is argued that there is a need to develop research studies of how patients experience disease, in order to develop a basis for good practice.

Arthritis, Rheumatoid↗
PubMed1995

Registered nurses' experiences of mentoring undergraduate nursing students.

This paper describes a research study undertaken by the first author, which explored and analysed registered nurses' experiences of mentoring undergraduate nursing students within a single health authority in England. The study design was qualitative and data were collected through semi-structured interviews with 12 mentors. The findings of the study indicate that mentoring undergraduate nursing students is a complex and skilled activity, requiring educational preparation, support and recognition. The potential for mentoring to further the personal and professional development of mentors is highlighted.

Education, Nursing↗
PubMed1995

The implementation of Project 2000 in the community: a new perspective on the community nurse's role.

This paper considers some of the initiatives taken by community nurses in England in implementing Project 2000 placements. The data were obtained during an English National Board funded study in two phases. The first phase involved a series of exploratory interviews, a postal questionnaire survey, and semi-structured interviews with 15 managers. In phase two, one Project 2000 demonstration district was studied in depth by means of interviews complemented by small-scale questionnaire studies. Community nurses had confronted a number of difficulties in implementing Project 2000. Among the most serious of these were shortage of time, poor communication with the colleges of nursing and lack of preparation. As a consequence, community nurses took what they saw as independent approaches to students' placements. Many set their own aims and objectives for placements and produced written guidelines and teaching plans for students. Many also asserted the importance of their role in the assessment of students' practical work.

Attitude of Health Personnel↗
PubMed1995

Parallels and contradictions in the theory and practice of action research and nursing.

This paper draws on the authors' experiences of nursing in general and of action research projects. Parallels will be drawn between, on the one hand, the relationship between the practice and theory of nursing and, on the other band, the relationship between the practice and theory of action research. Difficulties common to nursing and action research will be identified (e.g. between the implementation of the theory of nursing and of action research). Over- simplification, non-specificity of issues and gaps in theory are frequent but inevitable problems that hinder theoretical applications. Similarly, comparisons will be made between the problems associated with the translation of nursing practice into theory and the difficulties in transposing the experience of research into theory. The complexities of practice, whether nursing or research, and the evolutionary nature of experience inescapably give rise to dilemmas when analysing theory and practice. The concepts of theory and practice when conceived as a dichotomy present a useful overview of issues. We argue that, through a discussion of the core themes of action research, including 'knowledge in action' and 'self and group reflection', consideration should also be given to a symbiotic and complementary analysis of theory and practice. We observe that many contradictions exist within the theory and practice of action research and of nursing, and that these need to be addressed to promote theoretical and practical advances. Action research offers theoretical and practical insights that contribute to the current debate on the reciprocal relationship between theory and practice.

Diffusion of Innovation↗
PubMed1995

The critical glycosylation site of human transferrin receptor contains a high-mannose oligosaccharide.

The human transferrin receptor (TfR) contains three N-linked oligosaccharides and glycosylation is required for the proper folding and function of the molecule. Earlier studies demonstrated that the oligosaccharide at Asn-727 is vital for the production of fully active TfR. The oligosaccharide(s) present at this site have been analysed using a combination of site-directed mutagenesis and chemical analysis. Wild-type TfR and mutants containing only the Asn-727 site or missing all three sites were transfected into mouse 3T3 cells and receptors were analysed by endo-N-acetylglucosaminidase H (Endo-H) digestion, SDS-PAGE and immunoblotting. These studies suggested that the Asn-727 site contains high-mannose or Endo-H-sensitive hybrid oligosaccharides. Glycosylation of Asn-727 found in the TfR purified from human placentae was analysed by high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) and mass spectrometry following tryptic digestion, peptide purification via reverse-phase high-performance liquid chromatography (RP-HPLC) and peptide sequencing. HPAE-PAD showed the presence of a series of high-mannose oligosaccharides. Mass spectrometry confirmed these observations, but also showed the presence of an 80 Da anionic moiety on a fraction of the oligosaccharides.

3T3 Cells↗
PubMed1995

Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life.

Two hundred children were followed from birth through 2 years of age with nasopharyngeal cultures to determine the normal colonization pattern of nontypeable Haemophilus influenzae. Forty-four percent of the children were colonized on one or more occasions; the acquisition rate was greatest in the first year. Monthly prevalence rates were 11%. Colonization with the initial strain persisted 1-5 months (median, 2). Children carried 1 predominant strain at a time but became colonized with up to 7 different strains (mean, 2.2). Children colonized with a single strain for < or = 2 months produced a greater nasopharyngeal secretory IgA to nontypeable H. influenzae response than did children colonized with different strains (log 2.35 +/- 0.68 vs. 1.89 +/- 0.25 U of P6 secretory IgA/ng/mL of total secretory IgA, P < .01). The duration of colonization with a strain and acquisition of a new strain may be affected in part by the local production of specific secretory IgA.

Aging↗
PubMed1995

Experimental Legionnaires' disease in SCID-Beige mice reconstituted with human leucocytes.

A new small animal model of experimental Legionnaires' disease is described in which the reconstitution of SCID-Beige mice with human peripheral blood leucocytes permits the in-vivo growth of Legionella pneumophila in the lungs of aerosol-challenged mice. Following infection, viable bacterial counts within the lungs of mice increased from 10(5) cfu/lung at the time of inoculation to a maximum of 10(10) cfu/lung by 48 h post-inoculation. Two types of disease were detected in the lungs of infected SCID-Beige mice. An acute exudative bronchiolitis and bronchopneumonia were seen in the most severely affected mice and, in the less severely affected mice, lesions of subacute or chronic disease were seen with thickening of alveolar walls and consolidation of lung tissue. Human cells did not appear to be involved directly in the pathology but were required for the establishment of infection. Immunohistological staining of lung tissue revealed substantial amounts of bacterial antigen distributed in a pattern similar to that seen in human Legionnaires' disease.

Aerosols↗
PubMed1995

A re-evaluation of the role of alpha 2-adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat.

1. The acute behavioural effects of the alpha2-adrenoceptor antagonists, yohimbine, idazoxan and delequamine (RS-15385-197) were compared in two tests of exploratory behaviour in the rat, operated in tandem. These were the elevated X-maze test (5 min) and a modified holeboard test (12 min), which comprised a holeboard arena with a small roof in one corner as a 'refuge'. Rats were first placed into this corner, thus enabling measurements of initial emergence latency and the number of forays. The experiments were always done with a concomitant vehicle control group, with 10-12 rats per group, and with the treatment blinded. 2. In order to validate the tests, the effects of representatives of four classes of psychoactive agents were examined, viz. picrotoxin (anxiogenic), chlordiazepoxide (anxiolytic), (+)-amphetamine (stimulant) and diphenhydramine (sedative). The modified holeboard tended to be more sensitive than the measurement of total arm entries in the elevated X-maze at detecting drug effects on exploratory behaviour, but unlike the X-maze it could not clearly identify each class of agent. Thus, picrotoxin (5 mg kg(-1), i.p.) reduced total arm entries and open arm exploration in the X-maze (P<0.02) and suppressed most measures of activity in the holeboard (P<0.05); chlordiazepoxide (7.5 mg kg(-1), i.p.) increased total arm entries and open arm exploration (P<0.02) in the X-maze, without clear-cut effects in the holeboard; (+)-amphetamine (1 mg kg(-1), i.p.) had no significant effects in the X-maze, but increased most holeboard activities (P<0.05), and diphenhydramine (30 mg kg(-1), i.p.) reduced total arm entries in the X-maze (P<0.002) and hole exploration in the holeboard (P<0.05).

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1995

RS-45041-190: a selective, high-affinity ligand for I2 imidazoline receptors.

1. RS-45041-190 (4-chloro-2-(imidazolin-2-yl)isoindoline) showed high affinity for I2 imidazoline receptors labelled by [3H]-idazoxan in rat (pKi = 8.66 +/- 0.09), rabbit (pKi = 9.37 +/- 0.07), dog (pKi = 9.32 +/- 0.18) and baboon kidney (pKi = 8.85 +/- 0.12), but had very low affinity for alpha 2-adrenoceptors in rat cerebral cortex (pKi = 5.7 +/- 0.09). 2. RS-45041-190 showed low affinity for other adrenoceptors, dopamine, 5-hydroxytryptamine, and muscarinic receptors and dihydropyridine binding sites (selectivity ratio > 1000). 3. RS-45041-190 showed moderate potency for the inhibition of monoamine oxidase A in vitro (pIC50 = 6.12), but had much lower potency for monoamine oxidase B (pIC50 = 4.47), neither of which equated with its affinity for I2 receptors. 4. RS-45041-190 (0.001 to 3 mg kg-1, i.v. and 1 ng-50 micrograms i.c.v.) had only small, transient effects on blood pressure and heart rate in anaesthetized rats. In conscious rats, RS-45041-190 had no effect on body core temperature or tail skin temperature (1 mg kg-1, s.c.) or on activity or rotarod performance (10 mg kg-1, i.p.). There were also no effects on barbiturate sleeping time in mice after doses of 1-10 mg kg-1, i.p. 5. RS-45041-190 (10 and 25 mg kg-1, i.p.) significantly increased food consumption in rats for up to 4 h after dosing, but unlike idazoxan (10 mg kg-1, i.p.) did not increase water consumption. RS-45041-190 is therefore a selective, high-affinity ligand at I2 imidazoline receptors and its hyperphagic effect may suggest a role for I2 imidazoline receptors in the modulation of appetite.However, in the absence of a selective agonist it is unclear whether this ligand is an agonist or an antagonist at I2 receptors.

Adrenergic alpha-Antagonists↗