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Biomedical subjects

I Campbell

Publications and source records attributed to I Campbell.

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

Adenoviral transfer of xenogeneic MHC class I gene results in loss of tumorigenicity and inhibition of tumor growth.

The immune system confers protection against a variety of pathogens and contributes to the destruction of neoplastic cells. Foreign major histocompatibility complex (MHC) protein serves as a potent stimulus to the immune system. In this report, a mouse H-2Kb gene was introduced into two poorly immunogenic tumor cell lines, a mouse colonic carcinoma cell line, MCA-26 (H-2Kd), and a rat mammalian carcinoma cell line, LN-4, in an effort to stimulate tumor rejection. Our results showed that the expression of xenogeneic MHC class I antigen completely abolished the LN-4 tumorigenicity in rats, whereas the expression of allogeneic MHC class I antigen only partially reduced the MCA-26 tumorigenicity in mice. Rats with tumor regression of LN-4/H-2Kb developed a T helper type 1-dominant response, whereas rats with LN-4 tumor growth developed a T helper type 2-dominant response. The immunized rats that experienced LN-4/H-2Kb tumor regression further developed protective immunity against a subsequent challenge of LN-4 cells. This protective immunity was mediated by the LN-4 tumor-specific cellular immune response against both the transduced and the parental LN-4 cells. Recombinant adenoviral vectors are highly efficient at in vitro and in vivo gene delivery. The LN4 cells transfected with the recombinant adenovirus AdV-H-2Kb in vitro expressed the cell surface H-2Kb molecule by fluorescence-activated cell sorter analysis. Adenovirus-mediated H-2Kb gene transfer in vivo can further significantly inhibit pre-established LN-4 tumors. Those rats with complete tumor regression further developed protective immunity against the subsequent challenge of a parental LN-4 tumor. Therefore, our study indicates that the adenovirus-mediated transfer of xenogeneic MHC class I gene may be an effective alternative to the current protocol of cancer gene therapy in which the allogeneic MHC class I gene is used.

Adenoviridae↗
PubMed2000

Adenovirus-mediated p16INK4 gene transfer significantly suppresses human breast cancer growth.

The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancers. However, the efficiency of the p16INK4 gene with regard to growth inhibition of human breast cancer has not been studied extensively. To examine its tumor-suppressive function and its potential in breast cancer gene therapy, the wild-type p16INK4 gene was expressed in an adenovirus-mediated gene delivery system and introduced into breast cancer cell lines that do not express p16INK4 protein. Expression of the introduced p16INK4 blocked tumor cell entry into the S phase of the cell cycle, induced tumor cell apoptosis, and inhibited tumor cell proliferation both in vitro and in vivo. These results strongly suggest that p16INK4 is a tumor suppressor gene and suggest that it has potential utility in breast cancer gene therapy.

Adenoviridae↗
PubMed2000

The utility of polysporin ointment in the eradication of methicillin-resistant Staphylococcus aureus colonization: a pilot study.

We evaluated the efficacy of an ointment containing bacitracin, polymyxin B, and gramicidin for the eradication of colonization by methicillin-resistant Staphylococcus aureus in 11 medical patients, 10 (91%) of whom had previously failed a 1-week course of topical mupirocin. Mupirocin resistance was documented in 5 (45%) of 11 patients. Successful decolonization was achieved in 9 (82%) of 11 patients (based on 2 months of follow-up).

Aged↗
PubMed2000

The effect of the general practice registrar year on perceived skills in palliative care in the West Midlands.

OBJECTIVES: To ascertain the effect of 12 months spent as a GP registrar on perceived skills in palliative care. DESIGN: A previously validated questionnaire for use with medical undergraduates is modified and used to survey perceived skills in five aspects of providing palliative care in five different scenarios at two points during the 12-month period of general practice vocational training where no specific teaching intervention is conducted. SETTING: The West Midlands. PARTICIPANTS: 210 GP registrars. RESULTS: Perceived skill ratings were seen to significantly increase during the 12-month period, but anxiety in caring for the dying did not significantly decrease. Ratings of skills were lowest when caring for a child dying with leukaemia or a young adult dying with AIDS. In addition, other important variables which had a statistically significant influence were gender and age, but interestingly not the number of previous senior house officer (SHO) posts undertaken or whether the respondent had had formal teaching on the subject in the past. CONCLUSION: It might therefore be postulated that training as a GP registrar has an important impact on the development of perceived skills in palliative care.

Adult↗
PubMed1999

Effect of oral rotavirus/iscom vaccines on immune responses in gnotobiotic lambs.

A comparison of the effect on the immune responses in gnotobiotic lambs was made between an iscom vaccine prepared from recombinant rotavirus VP6 protein, an inactivated rotavirus/iscom-matrix vaccine and a vaccine comprising inactivated rotavirus alone. All three vaccines induced immunological priming and some degree of protection was observed after a single oral dose. However, different immune responses were induced in response to a virulent infection. The group vaccinated with the rotavirus/iscom-matrix vaccine showed a Th2-like response characterised by rotavirus-specific antibodies and a down-regulation of IFNgamma in jejunal Peyer's patches. Both Th1-like and Th2-like immune responses were induced in the group receiving the VP6 vaccine as seen by significantly increased expressions of IFNgamma and IL-6 in the jejunal Peyer's patch together with an increased percentage of CD8+ T cells in the intestine and rotavirus-specific antibodies at mucosal surfaces. Iscom vaccines given orally have the ability to induce both Th1-like and Th2-like immune responses in a ruminant model.

Administration, Oral↗
PubMed1999

beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours.

The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH(2)-regulatory domain of beta-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the beta-catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here beta-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the beta-catenin gene. All mutations were missense changes within the GSK3beta consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of beta-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.

Biological Transport↗
PubMed1999

Report of the IDECG Working Group on the modulating effect of stressors on the upper and lower limits of lipid and carbohydrate intake. International Dietary Energy Consultative Group.

The recommended caloric intake should be increased by 2870kJ (670Kcal)/d in the exclusively breast-feeding woman. Of this increase, 10% should be ingested as protein, up to 50% as lipid and no less than 40% as carbohydrate. If weight loss is desired lipid intake can be reduced but carbohydrate intake should be maintained. Of the total energy increment 3% should be supplied by essential fatty acids (linoleic and alpha-linolenic acids) and 0.5% by n-3 fatty acids. The issue of dietary supplementation with long-chain polyunsaturated fatty acids remains for future research.

Dietary Carbohydrates↗
PubMed1999

Lack of efficacy of oral bacitracin plus doxycycline for the eradication of stool colonization with vancomycin-resistant Enterococcus faecium.

In a prospective observational cohort study designed to assess the role of oral bacitracin solution plus doxycycline in the eradication of intestinal carriage of vancomycin-resistant Enterococcus faecium (VREF) in patients on a renal ward, rectal swab specimens were obtained from 15 treated and 24 control patients. Cultures of the rectal swabs were negative for 15 (100%) of the antibiotic-treated vs. eight (33.3%) of the untreated patients (P < .001) on day 14. However, follow-up for a mean of 127 and 130 days revealed 9 of 15 (60%) and 15 of 24 (62.5%) in the treated and untreated cohorts (P = .86), respectively, carried VREF intermittently or persistently. Quantitative VREF stool cultures in the treated cohort revealed an initial 3.1-log10/g decrease, but there was an increase to pretreatment levels at 2-4 and 5-7 weeks post-treatment (7.8 and 7.4 log10/g). Oral bacitracin and doxycycline were not efficacious in reducing the carriage of VREF beyond the 2-week interval during which they were given.

Administration, Oral↗
PubMed1999

Use of single-frequency bioimpedance at 50 kHz to estimate total body water in patients with multiple organ failure and fluid overload.

OBJECTIVE: To investigate the relationship between single-frequency bioimpedance at 50 kHz (both total body impedance and segmental impedance) and total body water, measured using tritiated water in the presence of the severe fluid retention seen in multiple organ failure. DESIGN: Prospective, controlled study. SETTING: General intensive care unit. SUBJECTS: Twenty patients with multiple organ failure and 30 normal volunteers, of whom a subgroup of ten had total body water measured. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total body water and total and segmental bioimpedance values at 50 kHz were measured using tritiated water and a Holtain body composition analyzer in 20 patients with multiple organ failure and in ten normal volunteers. An additional 20 normal volunteers also had segmental and total body impedance measured. There was no difference in the linear regression lines constructed for the patients and the volunteers, but the SEM in the patients (7.6 L) was four times that seen in the normal subjects (1.9 L). In a further seven patients, the impedance technique overestimated the change in total body water, deduced from acute changes in weight, by between 0% and 46% (median, 12%). In the patients, who were supine, the knee-ankle segment contributed significantly more to total body impedance than it did in the normal volunteers (42.5% vs. 34.4%; p < .001), who were upright and mobile immediately before the measurement. CONCLUSIONS: Although single-frequency bioimpedance does give an indication of total body water and change in total body water, it is neither precise nor accurate enough to be the sole guide to fluid therapy. The proportion of total impedance contributed by the knee-ankle segment, which contains relatively little water, was significantly greater in the patients than in the controls, probably reflecting better drainage of fluid from the lower limb in the supine position.

Adult↗
PubMed1998

Strain specific variation in IFN-gamma inducible lymphocyte adhesion to rat brain endothelial cells.

We have examined the interferon-gamma (IFN-gamma) induced increase in lymphocyte adhesion to rat brain endothelial cells (BEC) in the experimental allergic encephalomyelitis (EAE) susceptible LEW and resistant PVG strain. A significant increase in adhesion of mitogen activated lymphocytes could be demonstrated by stimulating LEW BEC with 50 U/ml IFN-gamma for 24 h. In contrast the same treatment failed to induce a significant increase in lymphocyte adhesion in the PVG strain. Flow cytometric analysis of lymphocyte integrin expression indicated a marked increase in the number of cells expressing both LFA-1 and VLA-4 following mitogen activation and was similar between the LEW and PVG strain. Depletion of LFA-1 and VLA-4 positive lymphocytes resulted in an equivalent inhibition of adhesion to BBB-EnC indicating that the adherent population was comprised predominantly of the VLA-4 + /LFA-1 + phenotype. We conclude that this strain variation in the IFN-gamma activation of BEC may be related to the disease phenotypes of these strains.

Analysis of Variance↗
PubMed1998

Characterisation of the primary local and systemic immune response in gnotobiotic lambs against rotavirus infection.

This study characterised the primary immune response in gnotobiotic lambs after infection with a lamb rotavirus (RV). Lambs were infected and killed over a 7 week period together with controls. RV-ELISA and neutralising antibodies were determined in serum, nasal secretions, and intestinal scrapings. RV-antibody secreting cells (ASC) were enumerated in blood. Lymphocyte proliferations were determined in blood and gut-associated lymphoid tissues and cytokine expression was analysed in jejunal Peyer's patches (JPPs) and mesenteric lymph nodes (MLNs). Infected lambs cleared the virus by 8-9 days after infection without showing any clinical signs. The first indication of a specific immune response to RV was an increased expression of IL-4 mRNA in the JPPs in the infected group compared to the control group 3 days after infection. Rotavirus-specific IgA ASC in blood and IgA antibodies in serum and nasal secretions were detected from 7 days after infection followed at 10 days after infection by RV-specific IgG ASC and antibodies. Rotavirus-specific IgA antibodies were not detected in intestinal scrapings in the first 10 days after infection, but were detected by 52 days after infection. No RV-specific neutralising antibodies were seen in the intestine during the course of the experiment.

Animals↗
PubMed1998

Sources of error in bioimpedance spectroscopy.

Two different makes of bioimpedance spectrometer (UniQuest-SEAC SFB-3 and Xitron 4000B) were used for a series of measurements on volunteers and patients in intensive care. Although each machine was accurate over the frequency range 5 to 500 kHz when bench tested on model resistor-capacitor circuits, significant differences in their recorded impedance parameters appeared when used in vivo, especially on intensive care patients. A series of laboratory tests was performed on each machine simulating the situation in vivo to identify possible reasons for these differences. Whilst stray capacitance in the environment was identified as the major contributor to variability in high-frequency performance, interaction between electrode impedance and lead positioning was also a factor. The observed phase shift with frequency or time delay (Td) used in the Xitron modeling software appears to be the result of a time constant caused by stray capacitance and so is unlikely to have any biological meaning. Significant differences in the in vivo numerical values produced by bioimpedance spectrometers may be attributed to instrument design, data processing and, in particular, the clinical environment.

Adult↗
PubMed1998

Management of tuberculosis in Wales: 1986-92.

OBJECTIVES: To describe the epidemiology of childhood tuberculosis in Wales and to assess the standard of management of patients with tuberculosis. DESIGN: Retrospective study of data retrieved from case notes and review of radiographs of all identified patients. SUBJECTS: Forty eight cases of tuberculosis and 10 of tuberculosis chemoprophylaxis in children under 15 years of age, in Wales, between January 1986 and December 1992. MAIN OUTCOME MEASURES: Management of childhood tuberculosis in Wales compared with the published recommendations of the Joint Tuberculosis Committee of the British Thoracic Society. RESULTS: Documentation was poor in most of the 48 cases of tuberculosis and only 31 (65%) were formally notified. One third of patients were asymptomatic and were detected by contact tracing; only eight (17%) were culture positive. Only 20% of patients from ethnic minorities had previously been immunised with BCG. Management and chemotherapy varied widely. Few patients were managed jointly by paediatricians and chest doctors. Only 10% completed treatment with a recommended chemotherapy regimen. In 37% of patients treatment was inadequate, and in the remainder either the choice of drugs or the duration of treatment was inappropriate. No patient died, nor had any relapsed by June 1995. CONCLUSIONS: Very few cases of childhood tuberculosis were managed according to the recommendations of the British Thoracic Society.

Adolescent↗