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Biomedical subjects

R Tierney

Publications and source records attributed to R Tierney.

15 recordsLinked to original sources
PubMed2006

Botulinum type A toxin neutralisation by specific IgG and its fragments: a comparison of mouse systemic toxicity and local flaccid paralysis assays.

In this study, we have compared two in vivo assay methods to measure the type A botulinum toxin neutralising activity of specific immunoglobulin G (IgG) and its fragments (F(ab')(2), Fab', Fab) purified from pentavalent botulinum antisera raised in goats. Each assay method was repeated on three separate occasions in mice and relative potencies calculated with respect to a type A equine reference antitoxin. The conventional assay, which measures the number of mice surviving typically after 72 or 96 h following the intraperitoneal administration of a mixture of toxin and antitoxin, gave the following order of potency IgG>F(ab')(2)>Fab'>Fab (6.8>4.7>3.5>2.6 IU/mg). Differences in potency are likely to be due to differences in the pharmacokinetics of the antitoxins, which are related to their molecular weight. The alternative local flaccid paralysis assay, where toxin and antitoxin are injected subcutaneously into the left inguinocrural region, gave results with a narrower range of activities: IgG>Fab'>F(ab')(2)>Fab (6.0>5.9>5.5>4.6 IU/mg). Comparison of the two assay methods showed no significant differences for IgG, F(ab')(2) or Fab', although the Fab fragment was significantly more potent in the non-lethal assay probably because of the reduced influence of antitoxin pharmacokinetics in this localised assay. These findings show that a local flaccid paralysis assay provides a less time consuming and more humane alternative to the lethal assay for the potency testing of botulinum IgG and F(ab')(2) antitoxins.

Animals↗
PubMed2002

Calibration of replacement international standard and European pharmacopoeia biological reference preparation for tetanus toxoid, adsorbed.

Here we report the characterisation of a preparation of tetanus toxoid, adsorbed, and its calibration by 27 laboratories in 19 countries in a joint international collaborative study co-sponsored by World Health Organization (WHO) Expert Committee of Biological Standardization (ECBS) and the European Biological Standardisation Programme of European Directorate for the Quality of Medicines (EDQM), Council of Europe. Calibration was in terms of the Second International Standard (I.S.) for Tetanus Toxoid, Adsorbed, by the established WHO/European Pharmacopoeia (Ph Eur) challenge methods. The replacement standard preparation was found to have a unitage of 469 IU/ampoule on the basis of its calibration in guinea-pigs and 496 IU/ampoule on the basis of its calibration in mice. Assessment, both within the collaborative study and as part of candidate characterisation, indicated satisfactory stability of the candidate preparation. This study also provided some information on the effect of mouse strain on potency testing of tetanus vaccines. A limited assessment of the impact of the replacement standard on testing of current production batches of vaccines was also carried out by four manufacturers. This study did not directly address the serological approaches to potency testing. However, one laboratory offered data from mouse serology assay, which gave comparable estimates to in vivo mouse bioassay. Based on the results of this study and with the agreement of participants, the candidate standard was established as the Third International Standard for Tetanus Toxoid, Adsorbed (coded 98/552) by the WHO Expert Committee of Biological Standardization (ECBS) in November 2000. The same preparation was also established as the second Ph Eur Biological Reference Preparation (Ph Eur BRP, batch no. 2) by the Steering Committee of the Biological Standardisation Programme of the EDQM and approved by the European Pharmacopoeia Commission.

Animals↗
PubMed2001

Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat.

Early life environmental manipulations have been shown to affect hippocampal-dependent learning, hippocampal volume and cerebral lateralization. In this study, we investigated the effects of neonatal stimulation on hippocampal volumetric asymmetry. Long-Evans hooded rats were exposed to a novel non-home environment 3 min daily for the first 3 weeks of life. Histological measures of the left and right hippocampus were made at 8 months of age. We found that neonatal novelty exposure resulted in a long-lasting change in hippocampal volumetric asymmetry. Specifically, this brief and transient early life stimulation increased the right hippocampal volumetric dominance at mid-adulthood.

Animals↗
PubMed2000

The Epstein-Barr virus promoter initiating B-cell transformation is activated by RFX proteins and the B-cell-specific activator protein BSAP/Pax5.

Epstein-Barr virus (EBV)-induced B-cell growth transformation, a central feature of the virus' strategy for colonizing the human B-cell system, requires full virus latent gene expression and is initiated by transcription from the viral promoter Wp. Interestingly, when EBV accesses other cell types, this growth-transforming program is not activated. The present work focuses on a region of Wp which in reporter assays confers B-cell-specific activity. Bandshift studies indicate that this region contains three factor binding sites, termed sites B, C, and D, in addition to a previously characterized CREB site. Here we show that site C binds members of the ubiquitously expressed RFX family of proteins, notably RFX1, RFX3, and the associated factor MIBP1, whereas sites B and D both bind the B-cell-specific activator protein BSAP/Pax5. In reporter assays with mutant Wp constructs, the loss of factor binding to any one of these sites severely impaired promoter activity in B cells, while the wild-type promoter could be activated in non-B cells by ectopic BSAP expression. We suggest that Wp regulation by BSAP helps to ensure the B-cell specificity of EBV's growth-transforming function.

B-Lymphocytes↗
PubMed1998

Patient satisfaction with daycase laparoscopy.

A prospective audit was performed on all patients preselected for daycase surgery over a 3-month period. The aim of the study was to evaluate patient acceptability and satisfaction with laparoscopy performed as a daycase procedure. Patients completed standard questionnaires before operation and at 4 weeks after surgery. Questions included satisfaction with daycase surgery, subjective pain experience, time taken to resume normal activities, adequacy of analgesia and necessity to call general practioners. Analysis of results revealed that 69% of patients were satisfied with day surgery laparoscopy. However there were highly significant differences (P less than 0.001) between resumption of normal activity, pain experienced and length of stay between patients satisfied and dissatisfied with daycase surgery. This study suggests that guidelines for daycase procedures may be overambitious as 31% of patients already pre-selected, were dissatisfied with daycase surgery.

Journal Article↗
PubMed1996

Cardiac Na+ pump current-voltage relationships at various transmembrane gradients of the pumped cations.

Thermodynamic considerations predict changes of the Na+ pump current (Ip)-voltage (V) relationship of animal cells upon variations of the electrochemical gradients against which cations must be pumped. Experimental data in support of the predictions are sparse. Therefore, the effect on the Ip-V relationship of various electrochemical gradients for pumped Na+ and Cs+ was studied at constant deltaGATP (approximately -39kJ/mol in cardioballs from sheep Purkinje fibres. Control of the subsarcolemmal ionic concentrations during whole-cell recording was ensured by activation of Ip below its half maximal activity or by measuring the initial Ip following reactivation of the Na+/K+ pump. With gradients close to physiological conditions Ip was outward over the entire voltage range and the Ip-V relationship showed a maximum near zero potential. Steepening the ionic gradients diminished the Ip amplitude and outward pump current was no longer detectable between -65 mV and -110 mV. Flattened ionic gradients increased the Ip amplitude and shifted apparently the reversal potential Erev to more negative values. These changes are in line with theoretical considerations. The measured Ip-V relationships were fitted by curves computed on the basis of a simplified Post-Albers scheme of Na+/Cs+ pumping. The increased Ip amplitude at flat ionic gradients was due to a decrease of [Cs+]o for half maximal Ip activation. The maximal Ip amplitude remained unaffected

Animals↗
PubMed1996

Human papillomavirus infection and risk of progression of epithelial abnormalities of the cervix.

The polymerase chain reaction has been used to determine the presence of human papillomavirus (HPV) 16 and HPV 18 DNA sequences in archival histological material removed from a cohort of untreated women with cervical epithelial abnormalities. The detection of HPV 16 or HPV 18 DNA sequences in the initial biopsy specimen was associated with a significantly increased risk of subsequent disease progression.

Cervix Uteri↗
PubMed1995

Effects of variations in flow on aortic valve area in aortic stenosis based on in vivo planimetry of aortic valve area by multiplane transesophageal echocardiography.

This study provides evidence that acute changes in stroke volume and cardiac output do not result in significant alterations in the anatomic AVA measured with multiplane TEE in patients with AS of moderate or severe degree. Thus, TEE could be useful in the assessment of severity of AS in both low- and high-output states.

Adult↗
PubMed1995

Non-Hodgkin's lymphoma, coeliac disease, and Epstein-Barr virus: a study of 13 cases of enteropathy-associated T- and B-cell lymphoma.

A group of 166 patients with coeliac disease was followed for a period of up to 25 years. During this time, 17 patients developed intestinal tumours that were diagnosed as lymphoma, of which 15 cases were available for review. Eleven of the lymphomas were of T-cell type (enteropathy-associated T-cell lymphoma, EATL) and two were of B-cell type. Two cases were reclassified as undifferentiated carcinoma. The interval between the diagnosis of enteropathy and the onset of lymphoma varied from less than 2 months in four patients to more than 5 years in seven. Seven of the T-cell and both B-cell lymphomas were investigated for the presence of Epstein-Barr virus (EBV) by in situ hybridization (ISH) using probes against Epstein-Barr virus-encoded RNAs (EBERs) and by immunohistochemistry with EBV-specific monoclonal antibodies. All EATL cases were negative, suggesting that EBV is not an important factor in these cases. In one of the B-cell cases, EBV was detectable by ISH and immunohistochemistry in most tumour cells in the mesenteric lymph nodes, but not in any of the tumour cells in the primary ileal tumour, indicating that in this case EBV infection was a late event in the neoplastic process. These results show that lymphoma may develop any time after the onset of coeliac disease and that in our cases of EATL, EBV was not an important factor. In some cases of EBV-related neoplasia, virus infection may be a late event.

Adult↗
PubMed1994

Latent Epstein-Barr virus infection in cottontop tamarins. A possible model for Epstein-Barr virus infection in humans.

The association of Epstein-Barr virus (EBV) with a growing number of human malignancies underlines the importance of efforts aimed at preventing the infection with this potential carcinogen and of establishing animal models for human virus-associated tumors. Cottontop tamarins have been used in EBV vaccine studies because virus infection regularly induces lymphomas similar to those seen in human immunocompromised individuals. In recent years, several vaccines based on the gp340/220 envelope protein of EBV have been developed and shown to prevent the development of EBV-associated lymphomas in this model. Using in situ hybridization and immunohistology, we have characterized EBV infection in one nonimmunized and three immunized animals after challenge with a standard tumorigenic dose of EBV. In the nonimmunized animal, EBV-infected lymphoid cells were detected in numerous tissues showing no obvious lymphoma infiltration. Surprisingly, variable numbers of virus-carrying cells were also found in all three immunized animals that were protected against the development of virus-associated lymphoma. This observation demonstrates that vaccination does not induce sterilizing immunity against EBV infection in this model. Double labeling suggested a B cell phenotype of the majority of these cells. EBV infection of nonlymphoid cells was not observed. Analysis of viral gene expression in immunized animals suggested a restricted form of virus latency different from that seen in EBV-driven lymphomas in nonimmunized cottontop tamarins. These results raise the possibility that immunized cottontop tamarins protected against the development of EBV-driven lymphoma or animals exposed to a sublymphomagenic dose of virus may serve as a model for EBV infection in humans.

Animals↗
PubMed1988

Lack of peptide YY immunoreactivity in adenomatous colonic polyps: evidence in favor of an adenoma-carcinoma sequence.

The aim of endoscopic polypectomy is to prevent colorectal cancer, as it is assumed that most, if not all, large bowel cancers are derived from adenomatous polyps. While it is now recognized that colonic endocrine cells, like other mucosal epithelial cells, have an endodermal origin, they are relatively sparse components of large bowel tumors. Peptide YY (PYY) is the most abundant endocrine regulatory peptide localized to the distal bowel. Endocrine cells, like the other cells of the mucosal epithelia, are derived from a common stem cell in the base of the crypts. The presence of endocrine peptides may thus be viewed as a marker for cellular differentiation in the gut. PYY was therefore measured in colonic carcinomas and adenomatous polyps, as its absence would be evidence in favor of genetic alterations in epithelial stem cell maturation. PYY concentrations in extracts of surgically removed colonic carcinomas (n = 22) from all regions were very low compared with those of adjacent normal bowel. Similarly, PYY concentrations in extracts of polyps (n = 39) obtained during endoscopic polypectomy were also very low when compared with those of adjacent normal mucosa. These varied between 1 and 11% of the normal epithelial content, depending upon the region. Low PYY levels appeared to reflect the malignant potential of these lesions: highest in tubular polyps, lower in villous polyps, and lowest in carcinomas. The very low concentrations of PYY in adenomatous polyps, like those of colonic cancer, are consistent with epithelial dysplasia and the incomplete formation of mucosal endocrine cells. These findings support the hypothesis of an adenoma to carcinoma sequence in colonic cancer.

Adenoma↗
PubMedDate not supplied

An issue of conflicting rights: nursing student charged with drug trafficking.

One semester before graduation, a nursing student was charged with a class A felony for drug trafficking. The nurse administrator recommended to university administration that the student be suspended from all clinical activity until charges were resolved. Initially, a summary action was issued by university administration to support this recommendation. A summary disciplinary action allows for temporary suspension of a student charged with misconduct when the student's presence threatens harm to the student or any other person. However, after legal review, the summary action was rescinded based on the complexity of conflicting interests and rights that required consideration and protection. The law provides some guidance but lacks the specificity to move an issue like this from equivocal to unequivocal in a short time frame. Consequently, the student was allowed to complete the program. Shortly after commencement, the graduate was convicted. In retrospect, it was found that ample case law exists allowing for a more aggressive defense of a summary action then had been taken. As pointed out in Krasnow v. Virginia Polytechnic Institute (1976), standards of student conduct established by a university may prohibit action that interferes with the mission or functions of the institution, and these standards may go beyond standards established by criminal law and may require greater ethical or moral behavior. Being prepared for situations such as the one presented here requires that schools have in place clearly defined policies and procedures that assure due process, allow for disciplinary action, reduce time and energy required to resolve conflicts, and assure consistent and fair outcomes.

Civil Rights↗