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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of carrier and carrier priming on the kinetics and pattern of somatic mutation in the V chi Ox1 gene.

Priming mice with a chicken gamma globulin (CGG) carrier protein significantly accelerated the onset of somatic mutation in the V chi Ox1 gene when the mice were subsequently immunized with 2-phenyl-5-oxazolone (phOx) coupled to CGG. The first mutations were already detected 7 days after immunization, while in the true primary response, they are not apparent until day 10. It was also found that comparing the mutation pattern of V chi Ox1 genes from hybridomas derived after immunization with phOx coupled to different carriers revealed quite distinct patterns of somatic mutation. Analysis of hybridoma sequences from the primary immune response to phOx-ovalbumin showed that the codons for Ser29, Ser31 and Lys45 were hot-spots for somatic mutation. Thus, the frequency and pattern of somatic mutations in the V chi Ox1 gene depends on the available T cell help as well as on the complex structure of the immunizing antigen.

Animals↗
PubMed1995

Intestinal T cells in CD8 alpha knockout mice and T cell receptor transgenic mice.

Intraepithelial lymphocytes (IEL) refer to the T cells located at the epithelium of the intestines. Unlike the T cells in other peripheral lymphoid organs, the majority of IEL express the CD8 cell surface protein. To study the role of CD8 in the ontogeny and the function of IEL, phenotypic analysis of IEL from CD8 alpha knockout mice and normal mice was performed. The CD8 alpha gene in CD8 alpha knockout mice was disrupted by homologous recombination. These mice are defective in thymic maturation of cytotoxic T cells. In normal mice, alpha beta T cells that were CD8 alpha alpha+ or CD4+ CD8 alpha alpha+, and gamma delta T cells that were CD8 alpha alpha+, were the distinct populations found only in IEL. In CD8 alpha knockout mice, the population size of IEL remained normal, but the majority of IEL were CD4- CD8- T cells expressing alpha beta or gamma delta T cell receptors. IEL from the H-Y transgenic mice2, which express the male H-Y antigen specific T cell receptor in a normal and in a CD8 alpha-null background, were also studied. In contrast to thymic derived T cells, CD8 alpha alpha+ IEL with the autoreactive transgenic T cell receptor were not deleted, but clonally expanded in the male transgenic mice. Interestingly, no pathological symptoms were observed in the intestines of these mice. In the absence of CD8 alpha expression, the H-Y specific autoreactive IEL did not accumulate in the intestines. The results suggest that CD8 alpha alpha+ IEL are derived extra-thymically and their responses towards antigens require the CD8 accessory molecule.

Animals↗
PubMed1995

Aboriginal wellbeing and liquor licensing legislation in Western Australia.

This paper is based on the results of a project undertaken as the basis for a submission to the committee established to review the Western Australian Liquor Licensing Act 1988. It reports on key issues relating to liquor licensing, as identified by members of regional Aboriginal organisations. Among these issues are the promotion of alcohol consumption and misuse, discriminatory practices by licensees and the police and the need for greater community involvement in liquor licensing decisions. To address these issues, members of the participating organisations proposed: inclusion of a harm-minimisation objective in the Act, education and training programs for the public, licensees and the police, and industry funding for harm-minimisation programs.

Alcohol Drinking↗
PubMed1995

Evaluating government health and substance abuse programs for indigenous peoples: a comparative review.

Most health and substance abuse programs for indigenous peoples in Australia are funded by government. Over the past decade there have been calls for greater accountability in the conduct of these programs. Initial attempts focused on the development of standardised performance indicators, an approach that has been criticised on both political and methodological grounds. Recently, some government agencies have sought to identify culturally appropriate models for the evaluation of programs for indigenous peoples. In a comparative review of the evaluation of indigenous programs in Australia and Canada, conducted for the Western Australian Aboriginal Affairs Department, the authors were not able to identify any generally applicable models. However, this literature review and our own research and experience in working with Aboriginal community organisations have identified some principles that should be an essential part of any attempts to evaluate health and substance abuse programs for indigenous peoples. Underlying these principles is the realisation that evaluation is not a politically or ideologically neutral activity. Theoretical and methodological considerations of the evaluation process must take into account the very real differences between the agendas of indigenous peoples and those who seek to evaluate programs for them.

Australia↗
PubMed1995

ACE for whom? Implications for clinical practice of post-infarct trials.

OBJECTIVE: To determine how many lives would be saved if patients were routinely treated with ACE inhibitors after myocardial infarction according to the criteria of four recent major clinical trials, and to estimate the costs and benefits of these approaches. DESIGN: Retrospective survey. SETTING: The Nottingham Health District. PATIENTS: Data from 7855 patients admitted between 1989 and 1990 were combined and the selection criteria of four major clinical trials (AIRE, SAVE, GISSI-3, and ISIS-4) were applied. RESULTS: Of the patients admitted in Nottingham with confirmed myocardial infarcts 39% were eligible for AIRE and 8% for SAVE. In patients with suspected myocardial infarction as defined by the major trials, 60% would have been eligible for GISSI-3 and 63% for ISIS-4. Treating appropriate patients in accordance with these trials would have saved 20 (AIRE), 3 (SAVE), 4 (GISSI-3) and 5 (ISIS-4) lives each year in Nottingham at a drug cost of 5400 pounds, 33 pounds 791, 2730 pounds, and 4116 pounds per life per year saved respectively. CONCLUSIONS: Short-term treatment with ACE inhibition appears to be cheaper but such an approach would save fewer lives. The AIRE study is the most applicable to current clinical practice but ACE inhibitors should be offered routinely to patients satisfying the criteria of any of the four major clinical trials.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

How common is heart failure? Evidence from PACT (prescribing analysis and cost) data in Nottingham.

BACKGROUND: The aim of the study was to determine the prevalence of heart failure in Nottinghamshire by an analysis of prescriptions for loop diuretics. METHODS: An observational study was carried out in the Nottingham Health District, on the basis of Prescribing Analysis and Cost (PACT) data relating to nearly 400,000 kg of frusemide prescribed in the year 1991-1992 and general practitioner (GP) records on two groups of patients (total 903) prescribed frusemide. RESULTS: The total amount of frusemide prescribed on a daily basis in Nottinghamshire in 1,048,566 mg. The mean daily dose of frusemide per patient is 60 mg and the median dose 40 mg. There are between 13,107 and 26,214 patients taking frusemide in Nottinghamshire. Fifty-six per cent of patients prescribed loop diuretics by their GP fulfil diagnostic criteria for heart failure. CONCLUSION: The prevalence of heart failure in Nottinghamshire estimated from loop diuretic prescribing increases from 0.1 per cent in the age-group 30-39 years to 5.45 percent in patients aged over 90 years.

Adult↗
PubMed1994

Do women with acute myocardial infarction receive the same treatment as men?

OBJECTIVE: To determine whether women with acute myocardial infarction in the Nottingham health district receive the same therapeutic interventions as their male counterparts. DESIGN: Retrospective study. SETTING: University and City Hospitals, Nottingham. PATIENTS: All patients admitted with a suspected myocardial infarction during 1989 and 1990. MAIN OUTCOME MEASURES: Route and timing of admission to hospital, ward of admission, treatment, interventions in hospital, and mortality. RESULTS: Women with myocardial infarction took longer to arrive in hospital than men. They were less likely to be admitted to the coronary care unit and were therefore also less likely to receive thrombolytic treatment. They seemed to have more severe infarcts, with higher Killip classes, and had a slightly higher mortality during admission. They were less likely than men to receive secondary prophylaxis by being discharged taking beta blockers or aspirin. CONCLUSIONS: Survival chances both in hospital and after discharge in women with acute myocardial infarction are reduced because they do not have the same opportunity for therapeutic intervention as men.

Adrenergic beta-Antagonists↗
PubMed1994

Memory B cell development but not germinal center formation is impaired by in vivo blockade of CD40-CD40 ligand interaction.

To study the role of the CD40-CD40 ligand interaction in the development of memory B cells and its level of action during primary antibody responses in vivo, mice were injected with a soluble CD40 fusion protein (sCD40-gamma 1), so as to block the interaction. The effects of the treatment on the primary antibody response were reminiscent of hyper-immunoglobulin M (IgM) syndrome (HIMG1): antigen-specific IgG responses were grossly inhibited whereas the IgM response was augmented severalfold. The latter observation suggests that there is a T-dependent, CD40 ligand-independent pathway of B cell activation that leads to IgM responses and that a significant component of the IgM in HIMG1 patients is derived from T-dependent responses. The secondary response was not readily blocked by sCD40-gamma 1 treatment, indicating a relative independence of CD40 ligation of antigen-experienced B cells. The most striking finding from these studies is that the development of memory B cell populations (measured by adoptive transfer) is grossly impaired by administration of sCD40-gamma 1 during the early induction phase of the response. It is surprising that although the generation memory is diminished, there is no quantitative difference in the development of germinal centers. Whereas entry of B cells into the memory cell pathway is dependent on CD40 ligation, the clonal expansion of the potential memory precursors in germinal centers seems not to require a CD40 signal.

Animals↗
PubMed1994

Adequacy of lymphadenectomy in laparoscopic-assisted colectomy for colorectal cancer: a preliminary report.

The hypothesis that the length of bowel and amount of mesentery resected with laparoscopically assisted colectomy are comparable to traditional open techniques was tested by means of a chart review of prospectively collected data of 22 laparoscopically assisted colectomies, 35 open colectomies performed by the same surgeon, and 39 other open colectomies performed at the same institution by other community surgeons. The average length of bowel resected in the laparoscopically assisted group was 21.7 cm, for the traditionally resected group, 31.4 cm, and for the other group, 26.7 cm. No statistically significant differences existed between the three evaluable groups. Although there was a trend toward greater length of bowel resected with the open technique, there was no statistically significant difference in this study. Follow-up at a mean of 24 months after resections shows no abdominal wall recurrences or any unusual patterns of recurrence. It is concluded that laparoscopically assisted colectomy can be performed in select groups to obtain adequate surgical resection for colorectal carcinoma. Further studies to generate larger numbers of patients with longer follow-up to determine the adequacy of resection as well as the comparability of cure rate will be necessary to confirm the findings of this preliminary study.

Aged↗
PubMed1994

CD40 ligation in B cell activation, isotype switching and memory development.

Interaction of CD40 on B cells with its ligand on activated T helper cells is crucial for the generation of mature T-dependent antibody responses. Experimental observations suggest that CD40 ligation acts at several points in B cell differentiation; however, it is not clear whether the consequences of ligation are direct or indirect. While its role in B cell activation is clearly direct we discuss the several ways in which it might drive isotype switching, the influence that it has on the development of memory B cells and the possibility that certain types of T-dependent antibody response are CD40L-independent. Experiments in which the ligation of CD40 is blocked in vivo reveal that early CD40 signals are important for the development of memory B cells but this may only reflect the ability of 'memory precursors' generated by CD40 ligation to accept subsequent programming or survival signals.

Animals↗
PubMed1994

Human herpesvirus 6 (HHV-6) is a helper virus for adeno-associated virus type 2 (AAV-2) and the AAV-2 rep gene homologue in HHV-6 can mediate AAV-2 DNA replication and regulate gene expression.

We have previously described the apparent acquisition by human herpesvirus 6 (HHV-6) of the multifunctional rep gene of the helper-dependent human parvovirus adeno-associated virus type 2 (AAV-2). We report here that HHV-6 is a full helper virus for AAV-2 replication, suggesting a mechanism for transfer of the rep gene between the two viruses by recombination of replicative intermediates. The HHV-6 rep gene cloned under control of the human cytomegalovirus immediate early promoter complemented replication of a rep-deficient AAV-2 genome. In cotransfection experiments with heterologous promoters linked to the CAT reporter gene, HHV-6 rep activated the human immunodeficiency virus (HIV) long terminal repeat (LTR) in fibroblast cell lines but not in T-cells. In contrast, AAV-2 rep inhibited HIV LTR activity in both fibroblast and T-cell lines. The effect of HHV-6 and AAV-2 rep genes on the HIV LTR was independent of the NF-kappa B, Sp1, and TATA box elements. These results suggest that HHV-6 Rep is a multifunctional regulatory protein with properties related to, but distinct from, those of AAV-2 Rep.

Cell Line↗
PubMed1994

Stabilization of an anthrapyrazole antitumour agent, DuP 937, on complexation with heptakis(2,6-di-O-methyl)-beta-cyclodextrin in aqueous solution.

DuP 937, an anthrapyrazole antitumour agent that is chemically unstable in aqueous solution, was shown, by absorption spectroscopy, to form an inclusion complex with heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM beta CD) in aqueous solution. Proton nuclear magnetic resonance spectroscopy was used to determine the stoichiometry and association constant of the complex. The 1:1 stoichiometry of the complex was established by the continuous variation method by following changes in the chemical shifts of aromatic protons of DuP 937. The complex association constants determined by different techniques used in this study were in the same order of magnitude. The kinetics of degradation of DuP 937 in aqueous solution were investigated as a function of DM beta CD concentration at pH 5.5 and 60 degrees C. The results indicated about a seven-fold increase in the stability of DuP 937 in the presence of DM beta CD in aqueous solution.

Anthraquinones↗
PubMed1994

Regulation of immunological memory.

Immunological memory can be regulated during either its development or its maintenance phases. Controversy and confusion surround both methods of regulation, especially in the field of T-cell memory. Recent work has helped in improving our definition of 'a memory cell', but this has been complicated by another major point of contention: whether memory cells are maintained by antigens or other stimuli. Unequivocal advances have recently been made concerning the molecular events involved in memory B cell generation in germinal centers.

Animals↗
PubMed1994

Neuroimaging of meningeal disease.

In the past two decades, the advent of CT and MRI has made a considerable impact on the evaluation of meningeal diseases, conditions once regulated to cytological, histopathological, or postmortem analyses alone. This article reviews the imaging findings in various meningeal processes with particular attention to the anatomic definition of the meningeal layers and their relationship to the development of meningeal pathology and consequent imaging characteristics.

Central Nervous System Diseases↗
PubMed1994

An eight year experience of conservative management for aortic graft sepsis.

This paper describes the results of conservative management of 15 patients with aortic graft infection. The median time to presentation was 4 months. Six of eight grafts that were sent for culture grew organisms, of which the commonest were streptococci and coagulase negative staphylococci. Four patients did not receive intensive antibiotic treatment and all died of sepsis. Eleven patients received intensive intravenous and oral antibiotic therapy and appropriate surgical management; two of these died, one of a stroke and the other of an unknown cause. Two of the nine surviving patients had no surgery and the remainder had procedures to drain pus and unblock occluded grafts, including minimal graft excision in four patients, although two of these subsequently required total graft excision. The follow-up period for six of these nine patients is more than 4 years. For most patients with aortic graft infection aggressive antibiotic treatment supplemented by minimalist surgery is preferable to primary radical surgery.

Administration, Oral↗
PubMed1994

Methods of establishing criteria for purchasing coronary angiography in the investigation of chest pain.

BACKGROUND: Purchasers may now define how many clinical procedures they wish to buy. In the investigation of chest pain, coronary angiography provides a definitive diagnosis. In clinical practice, the use of coronary angiography varies, so purchasers may choose the sort of service they wish to buy. We reviewed the extent of variation in the investigation of patients in the Trent Region and present a system for establishing criteria for the purchase of coronary angiography. METHODS: Three studies are presented, based on patients referred to the three referral centres in the Trent Region. First, the appropriateness for investigation, defined as benefit outweighing risk, is determined by expert panel; second, an audit of patients referred for coronary angiography is presented; and third, the likelihood or probability of significant coronary disease is assessed by application of a logistic regression model. RESULTS: According to the panel criteria, 27 per cent of patients in one centre were judged inappropriate for coronary angiography, 28 per cent in the second centre and 10 per cent in the third. When referred for angiography, extent of anti-anginal medication, symptom severity, use of exercise testing, and result of and planned management after angiography varied widely among centres. The likelihood of significant coronary artery disease could be predicted in 86 per cent of patients. CONCLUSIONS: Variation in clinical practice does not make the purchasers' task easy. Based upon these studies and clinical trials of coronary artery bypass surgery and coronary angioplasty, we present potential performance indicators which may form the basis of contracts or be used as audit measures.

Coronary Angiography↗
PubMed1994

Prostatitis: a review of diagnosis and management.

Prostatitis, the most common urologic disease in men, afflicts between 25% and 50% of all adult men. It is a complex and not well understood condition, partially because of its often obscure pathogenesis. There are four prostatitis diagnostic and treatment categories: 1) acute bacterial prostatitis; 2) chronic bacterial prostatitis; 3) nonbacterial prostatitis; and 4) prostatodynia. This article reviews prostatic anatomy and pathogenesis, as well as diagnostic and treatment categories. This information can assist the primary care practitioner in the identification and management of this common and often puzzling condition.

Acute Disease↗