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Biomedical subjects

R Ireland

Publications and source records attributed to R Ireland.

At least 19 recordsLinked to original sources
PubMed2005

Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta1-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention. METHODS: We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula. RESULTS: Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit). CONCLUSIONS/INTERPRETATION: Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta1-blockade may help prevent sudden death, if we can identify those at high risk.

Adrenergic beta-Antagonists↗
PubMed2001

A preliminary communication on whether general dental practitioners have a role in identifying dental patients with mental health problems.

OBJECTIVE: To examine whether general dental practitioners regard themselves as having a role in identifying dental patients with mental health problems. METHOD: Telephone interviews were conducted with, and postal questionnaires were sent to, a random sample (n = 94) of general dental practitioners on Health Authority lists within the Mersey Region. A total of 84 general dental practitioners responded, resulting in an 89% response rate. RESULTS: The majority of general dental practitioners had encountered patients with mental health problems (78% of interviewees, 56% of questionnaire responders). However, nearly half of the interviewees (46%) do not refer patients with mental health problems. When referrals to dental specialists were made, they tended to be regarding a physical manifestation rather than a psychological one. The majority of interviewees and questionnaire responders (55% and 82% respectively) expressed a 'positive' response to the development of a referral role. Nevertheless, there were some reservations concerning the practicalities of its development and implementation. CONCLUSION: The majority of general dental practitioners consider a role in identifying patients with possible mental health problems. This role might include, being able to identify patients with undiagnosed mental health problems, and being aware of dental conditions which may be caused by mental health problems. To achieve this, inter-professional co-operation between general dental practitioners and other health professionals requires development.

Attitude of Health Personnel↗
PubMed2001

Online orthodontic advice: a protocol for a pilot teledentistry system.

A prototype teledentistry service was established that incorporated a PC-based expert system designed to assist in orthodontic cases. It guided the general dental practitioner (GDP) through the assessment of a patient's malocclusion and helped ensure that all relevant clinical observations were made and details recorded. The resulting data file, containing radiographic images and clinical data, was then transferred via the Internet to a dental specialist. The specialist's recommendations were returned by the same route or, where appropriate, a realtime videoconference was conducted. During an eight-month trial, six GDPs referred 158 cases through the teledentistry system; another 24 cases were referred directly to a local consultant. The protocol used during the trial worked satisfactorily. The GDPs found that it was straightforward and covered all aspects of the cases they submitted.

Child↗
PubMed1999

Hormonal activation of phosphorylase in cockroach fat body trophocytes: A correlation with trans-membrane calcium flux.

This study is an investigation of the temporal relationship between transmembrane Ca(2+) fluxes, and glycogen phosphorylase activation in dispersed trophocytes from the fat body of the cockroach, Periplaneta americana. Phosphorylase is maximally activated within 5 min after treating the trophocytes with either of the hypertrehalosemic hormones, Pea-HTH-I and Pea-HTH-II. Activation caused by Pea-HTH-II is sustained for a longer period than that produced by Pea-HTH-I. Chelation of extracellular Ca(2+) with EGTA blocks the activation of phosphorylase by HTH. Similarly, chelation of intracellular Ca(2+) with Quin 2 greatly diminishes the phosphorylase activating effect of both HTHs. The data support the view that an increase in the intracellular Ca(2+ )concentration is required for the activation of phosphorylase and that extracellular Ca(2+) is an essential, although not necessarily sole, source of Ca(2+) for this purpose. Using (45)Ca(2+) to trace the movement of Ca(2+) following a challenge with either Pea-HTH-I or -II, it was shown that (45)Ca(2+)influx nearly doubled during the first 30 s. At this time, the trophocytes begin to expel Ca(2+) at a rate higher than that of untreated cells and this state persists for approximately 4 min. The Ca(2+) fluxes are consistent with its postulated role in the activation of phosphorylase. Arch.

Aminoquinolines↗
PubMed1998

A survey examining the attitudes of general dental practitioners toward change in undergraduate dental education.

AIM: To determine the attitudes of general dental practitioners toward aspects of change in undergraduate dental education. DESIGN: Descriptive postal survey using a cross-sectional random sample of general dental practitioners administered in 1997. SUBJECTS: 689 general dental practitioners practising in five regions of England with close proximity to a dental school selected by a one in two stratified random sample. RESULTS: Response rate: 70%. The questionnaire was both valid and reliable with an internal consistency reliability coefficient of 0.84. Responses identified strong support for preparing dental students for the wider role of the dentist and an emphasis toward self-directed learning. Other themes emerging from the investigation included support for learning to work as part of a dental team and for students to have experience of general dental practice early on in the undergraduate course. CONCLUSIONS: These responses have implications for curriculum design, syllabus, teaching methods, resources and staff development for dental schools in the UK.

Attitude of Health Personnel↗
PubMed1998

The use of intravenous intermediate dose melphalan and dexamethasone as induction treatment in the management of de novo multiple myeloma.

The variable absorption of melphalan from the gastrointestinal tract results in response rates between 40 and 60%. High dose melphalan increases response rates but at the cost of increased morbidity and mortality. We have investigated intravenous intermediate dose melphalan and dexamethasone in the treatment of patients presenting with de novo multiple myeloma with the object of reducing toxicity while preserving an improved response rate compared to oral melphalan and prednisolone. The results show that this treatment can be delivered safely on an outpatient basis in patients up to the age of 78 yr; 82% of patients achieved an objective response and 30% a complete haematological and clinical remission. Median overall survival for the whole group is 37 months.

Administration, Oral↗
PubMed1997

Vaccine-specific antibody responses induced by HIV-1 envelope subunit vaccines.

The first generation of candidate vaccines to prevent HIV infection consisted of recombinant envelope proteins (Env, gp120, and gp160) derived from a single laboratory strain of HIV, designated IIIB/LAV, but produced with different expression systems. In this study we examined the fine specificity of the human Ab response to each vaccine and compared them to the responses of laboratory workers infected with the same strain of HIV. The best responders from each vaccine protocol were studied and compared. Detailed comparisons of the fine specificity of the Ab response were possible because all immunologic assays were performed using homologous recombinant proteins, peptides, and virus stocks. Although the total amounts of anti-Env Ab were comparable, the groups exhibited significant differences in epitope specificity, avidity, and functional capacity of the Ab response. The data demonstrate that the form of the immunogen (e.g., live virus or recombinant protein) is important in determining the quality of the Ab response. Conclusions are also drawn regarding characteristics of the anti-HIV-neutralizing Ab response. These studies represent one of the most detailed analyses of the human Ab response to any Ag and have implications for the development of vaccines for HIV as well as for other microbial pathogens.

AIDS Vaccines↗
PubMed1995

Protective efficacy of nonneutralizing monoclonal antibodies in acute infection with murine leukemia virus.

We have used an experimental retrovirus infection to study the roles played by different antibodies in resistance to both infection and disease. A molecularly cloned chimeric murine leukemia virus was used to induce acute lethal neurological disease in neonatal mice. A panel of monoclonal antibodies directed against the Gag and Env proteins was tested for protective efficacy. In vitro neutralization assays demonstrated that anti-Env antibodies gave different degrees of neutralization, while no anti-Gag neutralized the virus. In vivo experimental endpoints were onset of clinical signs and premoribund condition. As expected, different anti-Env antibodies demonstrated different degrees of protection which correlated with their neutralizing abilities. Surprisingly, anti-Gag antibodies directed against both p15 (MA protein) and p30 (CA protein) were also protective, significantly delaying the onset of disease. No protection was seen with either of two control antibodies. The protection with anti-Gag was dose related and time dependent and was also produced with Fab fragments. Treatment with anti-Gag did not prevent viremia but resulted in a slight slowing in viremia kinetics and decreased levels of virus in the central nervous systems of mice protected from disease. These data indicate that nonneutralizing antiretroviral antibodies can influence the outcome of retroviral disease. The data also suggest a functional role for cell surface expression of Gag proteins on murine leukemia virus-infected cells.

Animals↗
PubMed1995

Leadership issues: health care in the year 2004.

The intent of this article is to develop a plausible scenario for health care in the year 2004. We hope to engage the reader in a process that will help discern the exogenous forces that are currently impacting the way that health care organizations do business. By identifying these forces, we can track their development and learn to adapt and change proactively as may be necessary. We also discuss the current and projected trends that are shaping health care delivery. Our theme is that the future of health care is continually being reinvented and that the potential for dealing effectively with the dramatic change that the future is bringing already exists in most health care organizations. The future is only waiting to be reinvented.

Delivery of Health Care↗
PubMed1994

The preparation of trophocytes from disaggregated fat body of the cockroach (Periplaneta americana).

A method has been developed for disaggregating the fat body of the adult American cockroach, Periplaneta americana, using collagenase. The yield of cells is sensitive to the osmolarity of the dispersing medium and to the age of the cockroaches from which the fat bodies are taken. Trophocytes uncontaminated with other cells were obtained by taking advantage of the low density of these cells which causes them to float to the top of the dispersion medium. In contrast, the mycetocytes and urocytes being denser than the medium sink to the bottom. The trophocytes retain the ability to respond to the synthetic hyperglycaemic hormones, CCI and CCII, as shown by the activation of phosphorylase and the stimulation of trehalose efflux. The trophocytes incorporated leucine into protein secreted by the cells in a time dependent manner.

Aging↗
PubMed1993

The organisation and expression of the genes encoding the mitochondrial glycine decarboxylase complex and serine hydroxymethyltransferase in pea (Pisum sativum).

Restriction fragment length polymorphisms have been used to determine the chromosomal location of the genes encoding the glycine decarboxylase complex (GDC) and serine hydroxymethyltransferase (SHMT) of pea leaf mitochondria. The genes encoding the H subunit of GDC and the genes encoding SHMT both show linkage to the classical group I marker i. In addition, the genes for the P protein of GDC show linkage to the classic group I marker a. The genes for the L and T proteins of GDC are linked to one another and are probably situated on the satellite of chromosome 7. The mRNAs encoding the five polypeptides that make up GDC and SHMT are strongly induced when dark-grown etiolated pea seedlings are placed in the light. Similarly, when mature plants are placed in the dark for 48 h, the levels of both GDC protein and SHMT mRNAs decline dramatically and then are induced strongly when these plants are returned to the light. During both treatments a similar pattern of mRNA induction is observed, with the mRNA encoding the P protein of GDC being the most rapidly induced and the mRNA for the H protein the slowest. Whereas during the greening of etiolated seedlings the polypeptides of GDC and SHMT show patterns of accumulation similar to those of the corresponding mRNAs, very little change in the level of the polypeptides is seen when mature plants are placed in the dark and then re-exposed to the light.

Amino Acid Oxidoreductases↗
PubMed1992

Identification and localization of multiple forms of serine hydroxymethyltransferase in pea (Pisum sativum) and characterization of a cDNA encoding a mitochondrial isoform.

Serine hydroxymethyltransferase (SHMT) has been purified from the mitochondria of green pea leaves. Activity can be fractionated into two distinct peaks by ion exchange chromatography. While these two forms of the enzyme are immunologically indistinguishable, immunoinhibition experiments show the presence of a distinct non-mitochondrial third form of the enzyme to also be present in green pea leaves. While this mitochondrial form of SHMT is abundant in leaves it is absent from roots, although the two tissues have comparable SHMT activity. An antibody raised to purified mitochondrial SHMT was used to screen a cDNA expression library. The sequence of one of the isolated positive clones contained an open reading frame, which encoded a sequence that matched the amino acid sequence determined from the N terminus of the mature protein. The open reading frame encodes a mature protein of 487 amino acids with a M(r) of 54,000, together with a 27-31 amino acid serine-rich leader sequence, presumably required for mitochondrial targeting. The cDNA hybridizes to a small multigene family of 2-3 genes, which appear to be expressed predominantly in leaves. Comparison of the deduced amino acid sequence with the amino acid sequences of the rabbit mitochondrial and cytoplasmic SHMT, show that pea mitochondrial SHMT is equally similar to both of these enzymes. In addition, the rabbit sequences are more like one another than they are to the pea sequence, suggesting an interesting evolutionary relationship for these proteins.

Amino Acid Sequence↗
PubMed1992

Purification and primary amino acid sequence of the L subunit of glycine decarboxylase. Evidence for a single lipoamide dehydrogenase in plant mitochondria.

In order to purify the lipoamide dehydrogenase associated with the glycine decarboxylase complex of pea leaf mitochondria, the activity of free lipoamide dehydrogenase has been separated from those of the pyruvate and 2-oxoglutarate dehydrogenase complexes under conditions in which the glycine decarboxylase dissociates into its component subunits. This free lipoamide dehydrogenase which is normally associated with the glycine decarboxylase complex has been further purified and the N-terminal amino acid sequence determined. Positive cDNA clones isolated from both a pea leaf and embryo lambda gt11 expression library using an antibody raised against the purified lipoamide dehydrogenase proved to be the product of a single gene. The amino acid sequence deduced from the open reading frame included a sequence matching that determined directly from the N terminus of the mature protein. The deduced amino acid sequence shows good homology to the sequence of lipoamide dehydrogenase associated with the pyruvate dehydrogenase complex from Escherichia coli, yeast, and humans. The corresponding mRNA is strongly light-induced both in etiolated pea seedlings and in the leaves of mature plants following a period of darkness. The evidence suggests that the mitochondrial enzyme complexes: pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and glycine decarboxylase all use the same lipoamide dehydrogenase subunit.

Amino Acid Oxidoreductases↗
PubMed1992

Cloning and characterization of the P subunit of glycine decarboxylase from pea (Pisum sativum).

A pea leaf cDNA library constructed in lambda gt11 was screened with an antibody raised to the P subunit of glycine decarboxylase. One of the positive clones isolated was sequenced and shown to contain an open reading frame, which encoded the entire P subunit polypeptide. Aligning the deduced amino acid sequence with the amino acid sequence determined directly from the NH2 terminus of the mature P subunit shows the presence of a putative 86 amino acid leader sequence, presumably required for import into the mitochondria, and gives a Mr of the mature protein of 105,000. Comparison of this deduced amino acid sequence with the sequence of a pyridoxal phosphate-containing peptide isolated from the P subunit of chicken liver glycine decarboxylase shows remarkable conservation. The P subunit, however, shows little sequence homology with other published amino acid decarboxylases. Expression of the P subunit mRNA shows a pattern very similar to that of the corresponding polypeptide: it is strongly light induced and is expressed at a much higher level in leaves than in other tissues. Southern blot analysis suggests that the P subunit is encoded by a small multigene family.

Amino Acid Oxidoreductases↗
PubMed1992

Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus in southern Chinese.

OBJECTIVE: To investigate the predisposing role of major histocompatibility complex (MHC) genes to systemic lupus erythematosus (SLE) in a Chinese population. METHODS: Polymorphism in the HLA-DRB, DQB, complement component C4, and 21-hydroxylase genes was analyzed by restriction fragment length polymorphism analysis and oligonucleotide probing of in vitro-amplified DNA from 88 Chinese patients with SLE and 69 matched control subjects. RESULTS: HLA-DRw15 and DQw1 were significantly more frequent in patients (corrected P less than 0.006, relative risk 5.2), but none of the 9 sequence variants of DQw1 were increased. The C4A gene deletion usually associated with SLE in Caucasoid and black patients was absent from all Chinese subjects, but possession of other C4 deletions and of DRw15 conferred the greatest risk (relative risk = 8.3). CONCLUSION: Different MHC haplotypes predispose to lupus in Chinese than in other ethnic groups. Our data suggest that the susceptibility lies at, or telomeric to, the DR locus, and that DRw15 and C4 deletions may act synergistically in conferring disease susceptibility.

China↗
PubMed1992

Fetal and maternal erythropoietin levels in normal pregnancy.

In a cross-sectional study of 120 pregnancies undergoing cordocentesis for prenatal diagnosis (n = 90) or elective caesarean section (n = 30), the umbilical cord and maternal venous plasma erythropoietin (Epo) concentrations were measured. Fetal Epo levels increased from a mean of 4 mU/ml at 16 weeks to 13 mU/ml at 40 weeks' gestation. There were no significant associations between fetal plasma Epo concentration and fetal blood gases, haemoglobin concentration, oxygen content or erythroblast count. The maternal plasma Epo concentration (mean = 14 mU/ml, range 1-77 mU/ml) did not change with gestation but was significantly higher than levels in non-pregnant females (mean = 6.6 mU/ml, range 1-25 mU/ml).

Erythroblasts↗
PubMed1991

Interleukin-5, interleukin-3, and granulocyte-macrophage colony-stimulating factor cross-compete for binding to cell surface receptors on human eosinophils.

Human interleukin (IL)-5 receptors were characterized by means of binding studies using bioactive 125I-labeled IL-5. Of purified primary myeloid cells, eosinophils and basophils but not neutrophils or monocytes expressed surface receptors for IL-5. Binding studies showed that eosinophils expressed a single class of high affinity receptors (Ka = 1.2 x 10(10) M-1) with the number of receptors being small (less than 1000 receptors/cell) and varying between individuals. Among several cell lines examined only HL-60 cells showed detectable IL-5 receptors which were small in numbers (200 receptors/cell) and also bound 125I-IL-5 with high affinity. The binding of IL-5 was rapid at 37 degrees C while requiring several hours to reach equilibrium at 4 degrees C. Specificity studies revealed that the two other human eosinophilopoietic cytokines IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited the binding of 125I-IL-5 to eosinophils. No competition was observed by other eosinophil activating or nonactivating cytokines. The inhibition of 125I-IL-5 binding by IL-3 and GM-CSF was partial up to a concentration of competitor of 10(-7) M with GM-CSF consistently being the stronger competitor. Converse experiments using IL-5 as a competitor revealed that this cytokine inhibited the binding of 125I-IL-3 and of 125I-GM-CSF in some but not all the individuals tested, perhaps reflecting eosinophil heterogeneity in vivo. Cross-linking experiments on HL-60 cells demonstrated two IL-5-containing complexes of Mr 150,000 and Mr 80,000 both of which were inhibited by GM-CSF. The competition between IL-5, IL-3, and GM-CSF on the surface of mature eosinophils may represent a unifying mechanism that may help explain the common biological effects of these three eosinophilopoietic cytokines on eosinophil function. This unique pattern of competition may also be beneficial to the host by preventing excessive eosinophil stimulation.

Binding, Competitive↗