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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 73 records · Page 4Linked to original sources

Chemical and physiological characterization of fluo-4 Ca(2+)-indicator dyes.

We have developed fluo-4, a new fluorescent dye for quantifying cellular Ca2+ concentrations in the 100 nM to 1 microM range. Fluo-4 is similar in structure and spectral properties to the widely used fluorescent Ca(2+)-indicator dye, fluo-3, but it has certain advantages over fluo-3. Due to its greater absorption near 488 nm, fluo-4 offers substantially brighter fluorescence emission when used with excitation by argon-ion laser or other sources in conjunction with the standard fluorescein filter set. In vitro, fluo-4 exhibited high fluorescence emission, a high rate of cell permeation, and a large dynamic range for reporting [Ca2+] around a Kd(Ca2+) of 345 nM. We have also developed several Ca(2+)-indicators related to fluo-4 having lower affinities for Ca2+ that are useful in cellular studies requiring quantification of higher [Ca2+]. In a variety of physiological studies of live cells, fluo-4 labeled cells more brightly than did fluo-3, when challenged with procedures designed to elevate calcium levels. Fluo-4 is well suited for photometric and imaging applications that make use of confocal laser scanning microscopy, flow cytometry, or spectrofluorometry, or in fluorometric high-throughput microplate screening assays. Because of its higher fluorescence emission intensity, fluo-4 can be used at lower intracellular concentrations, making its use a less invasive practice.

3T3 Cells↗

Comparison of the SF-36 health survey questionnaire with the Nottingham Health Profile in long-term survivors of a myocardial infarction.

BACKGROUND: Health-related quality of life, an important outcome measure in health interventions, can readily be assessed by questionnaire. Two widely evaluated examples are the Short Form 36 (SF-36) and Nottingham Health Profile (NHP) questionnaires, but as yet the discriminatory power of these tools has not been compared in a large population of patients with coronary heart disease. METHODS: All 4-year survivors of a myocardial infarction, identified from the Nottingham heart attack register, were sent the SF-36, NHP and additionally the Rose angina and dyspnoea questionnaires. Mean scores on the SF-36 and NHP were compared with age- and sex-adjusted norms in patients under and over 65 years. Sensitivity of the respective tools was assessed in distinguishing patients with differing degrees of cardiovascular symptomatology. RESULTS: In patients under 65 years the SF-36 and NHP differed to the same extent from normative data--scores were lower in the comparable domains physical functioning/mobility, bodily pain/pain and energy/vitality, but not in mental health/emotional reaction scores. In social functioning/social isolation results were disparate--SF-36 scores were lower and the NHP similar to normative data. In patients over 65 years mean scores in all five domains were not significantly different from normative data for either tool. The SF-36 was more sensitive than the NHP at detecting the impact of breathlessness, particularly in patients with mild symptoms. Similarly, the SF-36, but not the NHP, could distinguish the effect of differing degrees of angina severity and frequency on social functioning. CONCLUSION: At least in myocardial infarction survivors, the SF-36 appears a more sensitive tool and may have benefits for assessing health-related quality of life in this patient group.

Activities of Daily Living↗

Tryptophan hydroxylase polymorphisms in suicide victims.

Both environmental and genetic factors appear to contribute to the risk for suicide. The serotonergic system has been implicated in depression, impulsivity and suicidality. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Suicide has been associated with polymorphisms in intron 7 of the TPH gene. These alleles were studied in samples from 47 deceased Caucasian males as part of the Utah Youth Suicide Study. A 918 base pair fragment spanning the region of interest was amplified. The A218C polymorphism was visualized by restriction fragment length polymorphism (RFLP) and the A779C was sequenced. Neither A218C nor A779C appeared to be associated with suicide in this population. These results did not change when the sample was stratified by age (10-21 years, 22-31 years) or when violent suicides were selected. The complexity of the phenotype of suicide may reflect multiple biological and social etiologic factors, and poses a worthy challenge for genetic studies.

Adolescent↗

Regional variation in alcohol consumption in the Northern Territory.

OBJECTIVE: To identify any regional variation in per capita consumption of alcohol and the types of beverages consumed in the NT; and to estimate the relative contributions to consumption by Aboriginal and non-Aboriginal people. METHOD: Per capita consumption estimates were based on wholesale purchases of alcohol by license and Census population data. Mean levels and the percentages of each beverage type consumed were compared between regions and through time. Estimates of per capita levels of consumption between Aboriginal and non-Aboriginal segments of the population were based on reports of the proportion of frequent and occasional drinkers in each group and the ratio of consumption among Aboriginal and non-Aboriginal drinkers. RESULTS: Mean quarterly per capita consumption was higher in both the Lower Top End (4.22 litres) and the Central NT (4.04 litres), and less in the Barkly (3.44 litres) than in the Top End (3.55 litres). Over the four-year period, consumption in the Top End rose 6.4%, but dropped 22.5% in the Barkly. In the Lower Top End and the Central NT a larger percentage of alcohol was consumed as cask wine than in the Top End. Before licensing restrictions were introduced, this was also the case in the Barkly. In the NT, per capita consumption among Aboriginal people is approximately 1.97 times, and among non-Aboriginal people about 1.43 times, the national average. CONCLUSIONS: Alcohol consumption in the NT is greater than in Australia as a whole and there is significant regional variation. The problem is not simply an Aboriginal problem, and a broad range of strategies--including a component to address regional variation--is required to reduce it.

Adolescent↗

Beating the grog: an evaluation of the Tennant Creek liquor licensing restrictions.

OBJECTIVE: To review the effectiveness of, and community attitudes towards, increased restrictions on the availability of alcohol in Tennant Creek. METHOD: Estimates of quarterly per capita consumption of pure alcohol by persons aged > or = 15 years, admissions data from the local hospital, women's refuge and sobering up shelter, and police data on detentions in custody and common offences were compared for the 12 months prior and 24 months subsequent to the introduction of the restrictions. A random sample survey of residents aged > or = 18 years was conducted to ascertain attitudes towards the restrictions. RESULTS: Over the two years following the introduction of the restrictions, there was a reduction of 19.4% in annual per capita consumption of pure alcohol. This was accompanied by declines in: hospital admissions for acute alcohol-related diagnostic related groups; and persons taken into police custody and the proportions of offences reported on Thursdays. A majority of survey respondents was in favour of retaining or strengthening the existing restrictions. CONCLUSIONS: The restrictions were effective in reducing alcohol consumption and acute related harm and had the support of the majority of people in Tennant Creek. On the basis of this evidence, the NT Liquor Commission made a decision to retain them. Restrictions do not provide a simple answer to the problems associated with excessive alcohol consumption. However, they can be an effective part of a broad public health strategy to deal with such problems.

Adolescent↗

Circadian variation in witnessed out of hospital cardiac arrest.

OBJECTIVES: To examine the effect on circadian variation of out of hospital cardiac arrest according to the underlying aetiology and presenting rhythm of arrest, and to explore strategies that might help to improve survival outcome using circadian variation. DESIGN: Population based retrospective study. SETTING: County of Nottinghamshire with a total population of 993 914 and an area of 2183 km(2). SUBJECTS: Between 1 January 1991 and 3 December 1994, all witnessed cardiac arrests attended by the Nottinghamshire Ambulance Service, of which 1196 patients had a cardiac cause for their arrest (ICD, 9th revision, codes 390-414 and 420-429) and 339 had a non-cardiac cause. RESULTS: The circadian variation of the cardiac cases was not significantly different from that of non-cardiac cases (p = 0.587), even when adjusted for age, sex, or presenting rhythm of arrest. For cardiac cases, the circadian variation of those who presented with ventricular fibrillation was significantly different from those presenting with a rhythm other than ventricular fibrillation (p = 0.005), but was similar to the circadian variation of bystander cardiopulmonary resuscitation (p = 0.306) and survivors (p = 0.542). Ambulance response time was also found to have a circadian variation. CONCLUSIONS: There is a common circadian variation of out of hospital cardiac arrest, irrespective of underlying aetiology, where the presenting rhythm is other than ventricular fibrillation. This is different from the circadian variation of cases of cardiac aetiology presenting with ventricular fibrillation. The circadian variation of ventricular fibrillation, and consequently survival, may be affected by the availability of bystander cardiopulmonary resuscitation and the speed of ambulance response.

Aged↗

Chest pain, enzymes and hypothyroidism.

Hypothyroidism is a common disorder and when presenting with classical symptoms and signs is easy to recognise. However, hypothyroidism may present in a manner suggestive of an acute myocardial infarction with an elevated creatine kinase and electrocardiographic abnormalities. We report a case of severe hypothyroidism presenting as a cardiac event whose symptoms and signs dispersed following treatment with thyroxine.

Chest Pain↗

Evaluation of an electric bed frame and pressure-reducing mattresses.

Pressure ulcers remain a challenge to all healthcare professionals. With the trend towards caring for ill patients in the community there is a need to ensure that equipment used to prevent pressure ulcers in these patients is effective. It is not always appropriate to simply use equipment designed for hospital. This article describes the evaluation of an electric bed frame and three mattresses specifically designed for patients in the community, in either their own homes or nursing home/residential care. The location of this research can reduce the number of participants recruited. In order to compensate for this, three different methods of evaluation were employed - clinical, laboratory and anecdotal - which have produced results relevant to both purchasers and users of the system tested.

Aged↗

Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development.

B cells convert what are normally conditions for Th1 differentiation into an environment suitable for Th2 development. This capacity is dependent on CD40 as B cells from CD40-/- mice do not elicit Th2 differentiation. To elucidate the basis of this effect, we surveyed cytokine RNA made by naive B cells after activation with anti-Ig and anti-CD40. Resting B cells make TGF-beta message only, however, 4 days after activation, RNA encoding IL-6, IL-10, and TNF-alpha was found. The expression of these messages was accelerated by 2 days in the presence of IL-12. The relevance of these observations to T cell differentiation was investigated: addition of OVA peptide to splenic cells from DO.11.10 transgenic mice causes most T cells to make IFN-gamma. Coactivation of B cells in these cultures reduces the number of IFN-gamma-producing T cells and increases the number synthesizing IL-4. Abs to IL-6 and IL-10 block the IL-4 enhancement. Dissection of the component APC demonstrated that interaction of B cells with IL-12-producing dendritic cells is crucial for B cell-mediated IL-4 enhancement: Thus, B cells preactivated in the presence of dendritic cells from IL-12-/- mice show little IL-4-inducing activity when used to activate T cells. This immune regulation is initiated by IL-12 and therefore represents a feedback loop to temper its own dominant effect (IFN-gamma induction).

Adjuvants, Immunologic↗

Neurochemical organization of inferior pulvinar complex in squirrel monkeys and macaques revealed by acetylcholinesterase histochemistry, calbindin and Cat-301 immunostaining, and Wisteria floribunda agglutinin binding.

To investigate whether the inferior pulvinar complex has a common organization in different primates, the chemoarchitecture of the visual thalamus was re-examined in squirrel monkeys (Saimiri sciureus) and macaques (Macaca mulatta). The inferior pulvinar (PI) complex consisted of multiple subdivisions and encompassed the classic PI, and adjacent ventral parts of the lateral and medial pulvinar (PL and PM, respectively). In keeping with nomenclature suggested previously for macaques, the PI subdivisions were termed the posterior, medial, central, lateral, and lateral-shell (PI(P), PI(M), PI(C), PI(L), and PI(L-S)). In both species, PI(P) was intense for calbindin, light for acetylcholinesterase (AChE), and very light for Wisteria floribunda agglutinin (WFA) histochemistry. The PI(M) was calbindin poor, AChE rich, and moderate for WFA. The PI(C) was calbindin intense, lighter for AChE, and exhibited little WFA binding. PI(L) and PI(L-S) contained populations of large calbindin or WFA cells that were more numerous in PI(L-S). Although staining with the monoclonal antibody Cat-301 differed between macaques and squirrel monkeys, the same subdivisions were displayed. Moderately dense, patchy Cat-301 stain was found in PI(M) of macaques, whereas in squirrel monkeys PI(M) was light. Connections of the rostral dorsolateral (DLr) and middle temporal (MT) areas of visual cortex in squirrel monkeys were compared with PI subdivisions revealed by the newer histochemical methods in the same cases. The major connections of DLr were with PI(C) and of MT were with PI(M).

Acetylcholinesterase↗

The place of general practitioners in the management of out-of-hospital cardiopulmonary resuscitation.

BACKGROUND: The involvement of general practitioners in community based resuscitation of out-of-hospital cardiac arrest has been found to be effective in improving survival rates. The aim of the study was to assess the potential for including general practitioners in Nottinghamshire in the resuscitation of out-of-hospital cardiac arrest victims by first determining whether they had the skill, experience and equipment to provide cardio-pulmonary resuscitation in the community; and second to ascertain what proportion of them would be prepared to establish a 'rapid response' scheme for patients requiring resuscitation. METHODS: A postal questionnaire survey, between March and April 1997, of all 738 general practitioners in Nottinghamshire who serve, in total, a population of 1 million. RESULTS: A total of 592 general practitioners (80%) responded to our survey. The majority worked in a predominantly urban environment and carried out their own out-of-hours on-call duties. Of them 93% had previous experience in cardiopulmonary resuscitation (median of 3 years), while 72.1% had experience of advanced life support, including use of a defibrillator but not recently (median of 8 years). General practitioners in rural practices were more likely to be trained in advanced life support (ALS), had more recent experience in cardiopulmonary resuscitation (including defibrillation) and were more willing to be involved in any proposed local resuscitation scheme. Only 9% of general practitioners carried a defibrillator when on-call and only 13% had access to a defibrillator within their practice premises. Of the general practitioners surveyed 349 (59%) reported a willingness to participate in a 'rapid response cardiac arrest' scheme and general practitioners who had no formal advanced life support training were as willing to become involved in such a scheme as those who were trained in ALS. CONCLUSIONS: General practitioners may have an important role to play in improving the survival outcome of out-of-hospital cardiac arrest as many are ALS trained and have recent experience in resuscitation. However, few have access to a defibrillator and many do not have recent experience of defibrillation. Any proposed local resuscitation scheme would be particularly applicable to rural general practitioners as many have recent training in ALS, recent experience in advanced life support and most of all, are more willing to participate in such a scheme.

Attitude of Health Personnel↗

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.

Animals↗