Does gene expression play any role in the mechanism of the antiaging effect of dietary restriction?
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Aging↗
Biomedical subjects
A Richardson
Publications and source records attributed to A Richardson.
Guanine nucleotide-binding protein-coupled and -uncoupled states of opioid receptors and their relevance to the determination of subtypes.
Opioid receptors are currently classified as mu, delta, and kappa types, but various subtypes have also been proposed. We have investigated whether subtypes exist by using [3H]bremazocine. [3H]Bremazocine binds to twice as many naloxone-sensitive sites as other nonselective opioid agonists, as shown in four membrane types that have very different ratios of mu, delta, and kappa receptor types. [3H]Bremazocine binding is completely inhibited by an excess (in unlabeled form) of other opioid ligands, with Hill coefficients of 0.8-0.95. These paradoxes can be explained if there are high- and low-affinity states of the mu, delta, and kappa receptors and bremazocine binds with similar affinities to both states. We propose that these states are the guanine nucleotide-binding protein (G-protein)-coupled form and the uncoupled form of each receptor. As evidence for this proposal, the [3H]bremazocine binding suffered little or no loss with G-protein-uncoupling treatments, whereas binding of other opioid agonists was fully sensitive. We conclude that [3H]bremazocine offers a tool for the measurement of the total pools of coupled and uncoupled opioid receptors and that much of the previous characterization of opioid receptor subtypes reflects, instead, a significant pool of G-protein-uncoupled opioid receptors.
Analgesics↗
Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic lymphocytic leukemia.
B cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have few and apparently random mutations. However, in this study, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03% in B-CLLs whereas the somatic mutation levels are much lower in CD5+ and CD5- cord B cells, adult peripheral blood B cells, and Epstein-Barr virus-transformed CD5+ B cell lines (0.45, 0.93, and 1.92%, respectively). Complementary determining region 1 (CDR1) mutation in CLLs is particularly prevalent, and interchanges in CDRs often lead to acquisition of charge. Analysis of somatic mutations and mutations to charged residues demonstrated that the mutations in CLLs are highly selected.
Adult↗
Prolonged exposure to inositol 1,4,5-trisphosphate does not cause intrinsic desensitization of the intracellular Ca(2+)-mobilizing receptor.
The rapid release of Ca2+ from intracellular stores stimulated with inositol 1,4,5-trisphosphate (InsP3) has required superfusion or stopped-flow techniques to resolve the kinetics of Ca2+ mobilization and made it difficult to determine whether the InsP3 receptor desensitizes during prolonged stimulation. Here we have overloaded the intracellular Ca2+ stores of permeabilized rat hepatocytes by incubating them with ATP and 45Ca2+ in the presence of pyrophosphate, which precipitates Ca2+ within the lumen of the stores. Subsequent ATP removal initiated slow 45Ca2+ efflux that followed zero-order kinetics, allowing us to examine the effects of InsP3 over a prolonged time course. InsP3 produced a concentration-dependent increase in the 45Ca2+ efflux rate that was sustained for several min. The rate rapidly returned to the unstimulated level after the addition of decavanadate, a competitive antagonist of InsP3 at its receptor. Prior incubation with a submaximal concentration of InsP3 (1 microM) did not affect the subsequent enhanced rate of 45Ca2+ efflux stimulated by a higher, but still submaximal, concentration of InsP3 (3 microM). We conclude that prolonged exposure to InsP3 does not desensitize the InsP3 receptor and that intrinsic receptor desensitization cannot provide an explanation for the quantal responses to InsP3 observed in several cell types.
Animals↗
Protection by opioid ligands against modification of the opioid receptor by a carbodiimide.
Opioid receptors in membranes prepared from guinea-pig cerebellum were modified irreversibly by treatment with a water soluble carbodiimide, 1-ethyl,3-(3-dimethylaminoethyl)carbodiimide (EDAC). This decreased the number of [3H]bremazocine binding sites (Bmax reduced from 140 to 100 fmol/mg by 1 mM EDAC) without changing their affinity. When the EDAC concentration used was sufficient (500 mM) to inactivate almost all of the opioid receptors, the modification was partly prevented by inclusion of high concentrations (100 microM) of opioid agonists ([D-Ala2, MePhe4, Glyol5]-enkephalin, [D-Ala2, D-Leu5]-enkephalin,(+)-trans-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzo(b)thiophene-4-acetamide hydrochloride), although they exhibited equal efficacy irrespective of their mu, delta or kappa type selectivity. However, almost all of the opioid binding sites were protected when a guanine nucleotide analogue (GppNHP, 100 microM) was also included with the agonists during carbodiimide treatment.
Animals↗
Public opinion and purchasing.
OBJECTIVES: To explore the use of a questionnaire to obtain representative public opinions on health services. To examine residents' priorities, knowledge, and views on the public's role in decision making. DESIGN: Self administered postal questionnaire. POPULATION: Random sample of 1500 residents in Bath District Health Authority, drawn from electoral registers. MAIN OUTCOME MEASURES: Levels of agreement or disagreement with statements provided and degree of importance given to services and aspects of services. RESULTS: 70 questionnaires were returned unopened. Completed questionnaires were returned by 704 (49.2%) of the 1430 remaining residents. Kidney dialysis was thought very important by 559 (87%) respondents and family planning by only 58 (9%). Public priorities did not seem to reflect value for money. Clear information about treatment was rated as very important by 530 (76%) and comfortable waiting areas by 70 (10%). 372 (53%) of respondents said that they would definitely travel to a hospital outside the district to reduce their wait for surgery. Knowledge of the services provided by the authority and the money available to it was poor. 446 (65%) respondents wanted greater public involvement in decision making. CONCLUSIONS: A postal questionnaire can provide useful information about public priorities and perceptions about the services provided. More information about health services and their costs and benefits should be given to the public to assist greater public participation in decision making.
Community Participation↗
Chronic pancreatitis beginning in childhood and adolescence.
We identified 10 patients with symptoms beginning before the age of 20 years in a group of 69 patients with proven chronic pancreatitis. Six of the 10 patients were women. There was a family history of pancreatitis in three patients and alcohol exposure in seven patients. Three patients were dependent on narcotics at the time of presentation. Six of the 10 patients had pancreatic duct dilatation to 10 mm or more in diameter during observation. These six patients underwent pancreaticojejunostomy, with clinical improvement in five patients. The median time of follow-up was 19 years from presentation. No patient developed diabetes and one developed malabsorption. Only three patients were free of pain, but four other patients had only mild episodes that rarely required hospital admission. One patient died of metastatic abdominal carcinoma of unknown origin 51 years after developing familial pancreatitis. Chronic pancreatitis beginning at a young age is sufficiently common to merit special awareness. It is compatible with prolonged survival, and pancreaticojejunostomy may help if the pancreatic duct reaches sufficient size. The disease does not seem to burn out with time.
Adolescent↗
Studies exploring self-care for the person coping with cancer treatment: a review.
Individuals living with an illness such as cancer and receiving chemotherapy must often meet a new set of demands, that are not amongst their usual repertoire of skills and knowledge. Little is known about how patients manage the illness of cancer and in particular what self-care actions they develop and perform to cope with the side-effects of treatment. This paper outlines Orem's theory of self-care and describes its utilization in the design of a number of research studies in the cancer patient population. In particular, work which has explored the role of self-care in relationship to the control of chemotherapy induced nausea and vomiting is reviewed. The role of manipulating food and fluid intake, exercise and sleep and diversionary activities are explored; self-care is considered a vital part of the battle against combating nausea and vomiting induced by chemotherapy and further studies are urged.
Adaptation, Psychological↗
Purification of the inositol1,4,5-trisphosphate receptor by heparin affinity chromatography using decavandate.
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Animals↗
A prospective, randomized, blind comparison of three biopsy techniques in the management of patients after renal transplantation.
Although conventional histology (CH) of needle core biopsies has been accepted as the gold standard for diagnosis of renal allograft rejection, this assumption has never been tested. Fine-needle aspiration cytology (FNAC) and monoclonal antibody (panleukocyte) staining of needle core biopsies (MABS) have been suggested to be superior to CH. A total of 50 patients received a cadaveric renal transplant followed by immunosuppression with triple therapy. Biopsies were taken routinely at days 7,14,21,28, and 90, with additional biopsies taken between these times if rejection was suspected (total biopsy sessions = 219). Specimens were taken for CH, FNAC, and MABS at each biopsy session, but only the result of one technique (previously randomly allocated) was communicated back to the clinical team, using a standardized grading system. Subsequently the presence or absence of rejection was determined by retrospective analysis of the clinical and biochemical course by 4 clinicians, without reference to the biopsy result. Graft survival was not significantly different in the three groups. The sensitivities for CH, FNAC, and MABS were 75%, 59%, and 77%, respectively, while the specificities were 87%, 96%, and 80%, respectively. Inadequate samples for analysis occurred frequently with the MABS technique--and, to a lesser extent, with CH--and both techniques tended to overdiagnose rejection. FNAC most often gave an answer but did miss clinically important rejection episodes. Needle-core biopsy processed for CH remains the most reliable biopsy technique for the diagnosis of rejection of renal allografts. FNAC is a useful technique for monitoring grafts with stable function or nonfunction. MABS does provide information equivalent to CH, but, in this study, had a high incidence of inadequate samples.
Antibodies, Monoclonal↗
Hepatic focal nodular hyperplasia: a benign incidentaloma or a marker of serious hepatic disease?
Amongst 17 patients with hepatic focal nodular hyperplasia (FNH) encountered at Westmead Hospital between 1981 and 1990, FNH was found in association with hepatocellular carcinoma (HCC) in three (3/17), one male and two females, one of whom also had peliosis and an hepatic adenoma. FNH was also found in association with other conditions which may affect hepatic function, structure or circulation, including chronic obstructive airways disease (2), congestive cardiomyopathy (1), chronic active hepatitis (1), granulomatous hepatitis (1), coeliac artery stenosis (1) and metastatic malignant melanoma (1). This report, derived from our experience with FNH over 10 years draws attention to a possible link between FNH, hepatic malignancy and conditions which may disturb the hepatic circulation. We suggest that patients with FNH should be investigated thoroughly and an aggressive management policy should be adopted.
Adult↗
Serum IgG and IgM levels in new and regular long-term plasmapheresis donors.
This Australian study monitored the effects of monthly plasmapheresis on donor serum IgG and IgM levels in 127 new and 124 established plasma donors who donated 1014 units over a five-month period. Of the 251 donors, 3% had reduced total serum protein (TSP) levels, 7% had low IgG levels and 12% had low IgM levels prior to donation on at least one occasion over the study period. Statistical analysis showed that the TSP, IgG and IgM levels of new donors who had donated plasma on less than 10 occasions were no more likely to fall below normal than those of old donors. However, new and old donors whose IgG or IgM levels fell below normal at any time during the study had significantly lower levels of the relevant parameter on entry to the study. Followed longitudinally, IgG and IgM levels in old and new donors tended to fall, although levels fluctuated throughout the study. Statistical analysis failed to show any correlation between TSP levels and IgG or IgM levels. These parameters did not correlate significantly with the number of previous plasmaphereses, donor weight, volume collected or history of infection. This study highlighted the need for regular, specific quantitation of IgG and IgM levels as well as TSP in regular plasmapheresis donors. The frequency of testing is yet to be determined, in view of the high materials and labour costs of such a programme.
Adolescent↗
Self-help groups: their impact and potential.
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Forecasting↗
Prevalence of heart failure in three general practices in north west London.
There is little recent information on the prevalence of heart failure in the United Kingdom. Assuming that patients with heart failure would be taking diuretic drugs all such patients were identified in three general practices in north west London. The practice records of these patients were examined to determine which patients had heart failure. Of the 30,204 patients served by the practices, 117 had heart failure, a prevalence of 3.9 per 1000 patients. The mean age of these patients was 74 years. The prevalence of heart failure among patients under 65 years of age was 0.6 per 1000 patients rising to 27.7 per 1000 among those aged 65 years and over. The aetiology of heart failure was considered to be coronary heart disease for 32% of patients, valve disease for 19%, hypertension for 6%, cor pulmonale for 4% and congenital heart disease for 2%. The aetiology for the remaining 37% of patients was unknown. Most patients were referred to hospital and only 20% had been treated solely by the general practitioner. An electrocardiogram and chest radiograph had been obtained for over 80% of patients but only 28% had an echocardiogram. Heart failure occurs primarily in elderly patients, and coronary heart disease is the dominant aetiological factor.
Aged↗
Late developing odontome in the lower premolar area--the enigmatic variations.
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Adolescent↗
A ten-point plan for meeting carers' needs.
The needs of people requiring extra care--people who are elderly, chronically ill or disabled--are now gaining long overdue recognition. Yet the somewhat different needs of those who look after them at home--known as "carers"--remain largely ignored. Two years ago, representatives of a group of organizations in Britain joined together to commission a project to redress this balance. They were concerned both to set out the range of carers' needs and to issue guidance on the kinds of services necessary to meet them. These documents, prepared following extensive consultation with people working in the field, have now been published (Richardson et al, 1989). This short article provides a brief overview of the issues.
Caregivers↗