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Biomedical subjects

A Mills

Publications and source records attributed to A Mills.

At least 91 records · Page 5Linked to original sources
PubMed1993

Characterization of a novel exon within the D3 receptor gene giving rise to an mRNA isoform expressed in rat brain.

A novel D3 receptor cDNA containing an insertion of 84 bp has been isolated from a series of alternatively spliced D3 receptor cDNAs by polymerase chain reaction on RNA isolated from rat basal forebrain. Sequence analysis of both subcloned cDNAs and genomic DNA clones, has identified a 84 bp insertion resulting in a 28 amino acid insertion in the first extracellular loop. A comparison of the cDNA sequence of the novel D3 cDNA and the isolated genomic sequence indicates that the novel insertion corresponds to a new exon and arises via an alternative splicing event. The mRNA for the novel insertion could be detected by PCR in several areas of the brain co-localized with the wild type form of the D3 receptor. Moreover, genomic Southern blot analyses suggest that the D3-receptor exon giving rise to this novel D3 mRNA variant might exist in other species.

Alternative Splicing↗
PubMed1993

Expression and characterization of human D4 dopamine receptors in baculovirus-infected insect cells.

The human D4 dopamine receptor has been genetically engineered for expression in insect cells using the baculovirus system. A D4 cDNA gene fusion construct [(1991) Nature 350, 610-614] was synthetically modified to remove two introns from the coding region, and expressed in S. frugiperda (Sf9) cells as a fusion with a short sequence from the polyhedrin protein. Binding assays with [3H]spiperone indicated high levels of D4 receptor binding 90 h after infection and a pharmacological profile identical to that reported for D4 receptors expressed in COS-7 cells using the cDNA gene hybrid. We also show that the agonist binding affinity of D4 receptors expressed in Sf9 cells can be shifted by GTP-gamma-S, indicating coupling to G-proteins.

Animals↗
PubMed1993

Modelling the carbohydrate recognition domain of human E-selectin.

The three-dimensional structure of the carbohydrate recognition domain of the human E-selectin endothelial-leucocyte adhesion molecule (ELAM-1) was modelled on the basis of the recently determined X-ray crystallographic structure of the homologous domain found in the rat mannose-binding protein. The EGF-like module, which is contiguous to the E-selectin lectin domain, and which is also involved in binding the tetrasaccharide ligand, was modelled on the recently determined NMR structure of the EGF-like module of human factor IX. The rule-based homology modelling procedures developed at Birkbeck and encoded in the program COMPOSER were used. The model of the two domains combined is discussed in terms of cation and ligand binding.

Amino Acid Sequence↗
PubMed1993

Is malaria control a priority? Evidence from Nepal.

The research reported here assessed the value of malaria control through a cost-effectiveness study of the vertically-organized malaria control programme in Nepal. It presents a methodological framework for analysing cost-effectiveness which includes resource-saving consequences as well as health consequences. The methods used to collect data on control costs, cases and deaths prevented, treatment costs averted and production gains are described and the assumptions required by the analysis are made explicit. A variety of cost-effectiveness ratios are calculated, sensitivity analysis applied and the policy implications of the results considered. The results from Nepal are compared to estimates for parasitic disease and other health programmes in other countries: it is concluded that the Nepalese programme appears no less cost-effective than many other health interventions. It can also be justified by reference to the population groups benefiting from malaria control.

Absenteeism↗
PubMed1993

Signal transduction mechanisms of recombinant bovine neurokinin-2 receptor stably expressed in baby hamster kidney cells.

The bovine neurokinin-2 (NK-2) receptor gene was stably transfected into Baby hamster kidney (BHK-21) fibroblasts and one recombinant clone expressing 17,700 high-affinity [125I]neurokinin A (NKA) binding sites/cell characterized further. [125I]NKA binding was displaced by unlabeled NKA with an IC50 of 8.26 +/- 2 nM (n = 5) and with the rank order of potency NKA > neurokinin B (NKB) > Substance P (SP) confirming pharmacological characteristics of an NK-2 receptor subtype. Stimulation with NKA resulted in a rapid and dose-dependent increase in inositol 1,4,5-trisphosphate (IP3) levels (EC50 = 32 +/- 10 nM; n = 7) which was paralleled by a transient biphasic rise in intracellular free calcium concentration [Ca2+]i (EC50 = 35 +/- 20 nM; n = 3). In addition to phosphoinositide (PI) hydrolysis and Ca2+ mobilization, NKA was found to stimulate both cyclic AMP formation (EC50 = 1.02 +/- 0.26 microM; n = 7) and [3H]arachidonic acid mobilization (EC50 = 0.65 +/- 0.45 microM; n = 4). Interestingly, cyclic AMP levels also rose after addition of an exogenous arachidonic acid metabolite, prostaglandin E2 (PGE2) (EC50 = 11.5 +/- 2 microM). Similar observations of NKA-induced IP3 production, Ca2+ mobilization, arachidonic acid liberation, and cAMP formation have been made previously following expression of the bovine NK-2 receptor in Chinese hamster ovary (CHO) epithelial cells. The present results suggest that activation of NK-2 receptors leads to characteristic and reproducible intracellular second messenger responses in a subclass of cell types which includes fibroblasts and epithelial cells irrespective of their genetic and phenotypic background.

Animals↗
PubMed1993

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 8. Cost-effectiveness of bed net impregnation alone or combined with chemoprophylaxis in preventing mortality and morbidity from malaria in Gambian children.

In The Gambia, insecticide impregnation of bed nets, used alone or combined with Maloprim, reduced morbidity and mortality from malaria amongst children between one and 4 years of age. Taking expenditure of both time and money by public authorities and village volunteers into account, the costs and cost-effectiveness of each intervention were estimated. Bed net impregnation alone and the combined strategy cost US $5.65 and US $7.49 per child-year protected respectively (1990 figures). Insecticide (and drugs) accounted for more than 80% of the costs of each intervention strategy. They were both highly cost-effective. Estimated costs per death and per clinical episode of malaria averted were US $188 and US $28 for bed net impregnation and $257 and $19 for impregnation combined with chemoprophylaxis. Estimated costs per healthy year of life saved, discounted at 3%, were US $7.90 and US $10.84.

Antimalarials↗
PubMed1993

Community financing of health care in Africa: an evaluation of the Bamako initiative.

The Bamako Initiative, a controversial attempt to strengthen Primary Health Care using community financing and community participation and management was launched at a meeting of African Ministers of Health in 1987. This evaluation focuses particularly on the community financing aspects of the Initiative. Previous experiences of community financing highlight particular lessons for the development of the Initiative and issues likely to be encountered in implementation attempts. Four country case studies of the Initiative at its early stages of implementation (in June, July and August 1991) were conducted in Burundi, Guinea, Kenya, and Nigeria. Similar activities in Uganda were also studied. These were short studies of one month each and utilised methods of rapid evaluation. The studies aimed to direct implementers quickly to issues requiring attention rather than to reach overall conclusions regarding the success of the Initiative which would be premature at this stage. Price structures used by the Initiative need to consider the access of marginalised groups more than is the case at present. In addition, there is a need to ensure against over-prescription and commercialisation and to ensure that incentives for utilising most appropriate levels of care are maintained. The evidence suggests that most people do find amounts of money to pay for health services which are large in relation to their income. This is probably a tribute to extensive community support mechanisms. Nevertheless, it highlights the plight of those who fall through this safety net for whom even charges for very basic care may be prohibitive. On the other hand, it appears that in most cases, the Initiative's activities provide a service which is cheaper when all costs to the household are taken into account, than was available before. The quality of services included in the Initiative's activities in the five countries was highly variable. Success in raising substantial revenues has also been mixed. In some countries however, substantial funds have been generated and used to achieve real improvements in health services. Overall, the experiences of the five countries appear to have been highly dependent on a number of 'environmental' characteristics: a tradition or not of 'free' services; the adequacy of current resource availability and that immediately preceding the introduction of the Initiative; the existing stage and nature of decentralisation within the country; and the competition the Initiative's activities face with alternatives.

Burundi↗
PubMed1993

Pressure events surrounding oesophageal acid reflux episodes and acid clearance in ambulant healthy volunteers.

Previous studies of the mechanisms that precipitate acid reflux episodes and acid clearance have used unphysiological, short term hospital based data. A new 24 hour pH and motility recording system combined with computerised data analysis have been used to study naturally occurring acid reflux episodes in healthy ambulant volunteers. A variety of events that produced recognisable transdiaphragmatic pressure patterns were associated with acid reflux episodes (particularly belching). Peristaltic waves were the predominant contractions leading to oesophageal acid clearance and were the commonest contraction type during reflux episodes. Peristaltic wave parameters (amplitude, velocity, frequency, and percentage proportion) varied during different periods of the 24 hour recording. This study has produced new information about 24 hour oesophageal function and naturally occurring acid reflux which will provide a basis for comparison with patients with gastro-oesophageal reflux disease.

Adolescent↗
PubMed1993

The costs of HIV prevention strategies in developing countries.

Since many evaluations of HIV (human immunodeficiency virus) prevention programmes do not include data on costs, a preliminary analysis of the costs and outputs of a sample of HIV prevention projects was attempted. Case studies, representing six broad HIV prevention strategies in developing countries with differing levels of per capita gross domestic product, were sought on the basis of availability of data and potential generalizability. The six prevention strategies studied were mass media campaigns, peer education programmes, sexually transmitted disease treatment, condom social marketing, safe blood provision, and needle exchange/bleach provision programmes. Financial cost data were abstracted from published studies or were obtained directly from project coordinators. Although estimates of cost-effectiveness were not made, calculations of the relative cost per common process measure of output were compared. Condom distribution costs ranged from US$ 0.02 to 0.70 per condom distributed, and costs of strategies involving personal educational input ranged from US$ 0.15 to 12.59 per contact.

Blood Transfusion↗
PubMed1993

The household costs of malaria in Nepal.

This paper presents the results of a survey of the costs of malaria falling on households in 6 Nepali districts. Information is presented on the age and sex distribution of cases, use made of sources of treatment other than those offered by malaria control agencies, expenditure on these treatment sources, and days of work and school lost. It is found that adults are more likely than children to be affected by malaria; that 47-77% of patients consult alternative sources of treatment, sometimes spending quite large sums; and that 6-14 days of work and 4-14 days of school were lost on average, the precise figure varying considerably by district and strongly influenced by species of parasite and delay before obtaining treatment from malaria control agencies. The question of the value of lost time is deliberately not addressed, since this requires detailed information on how the household responds to the illness of one of its members.

Absenteeism↗
PubMed1992

Newly observed binding mode in pancreatic ribonuclease.

Dinucleotides containing guanine, when soaked into crystals of bovine pancreatic ribonuclease, have been found to bind in an unexpected manner, quite unlike interpretations of earlier X-ray diffraction studies. This finding has prompted a reexamination of three mononucleotide-RNase complexes from this laboratory resulting in a re-interpretation of the complex that involved a guanine mononucleotide.

Binding Sites↗
PubMed1992

Ambulatory measurement of oesophageal function: clinical use of a new pH and motility recording system.

Conventional oesophageal manometric studies are open to criticism in that they take place on fasted immobile subjects in the artificial setting of a motility laboratory. A new 24-h pH and motility recording system combined with computerized data analysis was used to study patients with gastro-oesophageal reflux disease and oesophageal motor abnormalities under ambulant conditions. Acid reflux episodes were found to be precipitated by a variety of events with recognizable pressure patterns. Acid clearance abnormalities were demonstrated in patients with erosive oesophagitis but were confined to those with abnormal oesophageal motor function. Improved diagnostic accuracy was demonstrated in the recognition of oesophageal motor disorders.

Circadian Rhythm↗
PubMed1992

Functional characterization of neurokinin-1 receptors on human U373MG astrocytoma cells.

The neurokinin-1 (NK-1, substance P) receptor belongs to the class of seven transmembrane domain (7-TM) receptors that interact with cellular effector systems via guanine nucleotide binding regulatory proteins (G-proteins). In this study, coupling mechanisms of functional NK-1 receptors endogenously expressed in a human astrocytoma cell line (U373MG) were analyzed. Stimulation with substance P (SP) resulted in 1) a rapid increase in inositol 1,4,5-trisphosphate (IP3) synthesis; 2) a rise in cytosolic free calcium concentration ([Ca2+]i); 3) induction of immediate early gene transcription as monitored by c-fos and c-jun expression; and 4) a significant increase in de novo DNA synthesis. Thus, the functional responses induced by stimulation of NK-1 receptors on U373MG strongly correlate with those observed after treatment of primary astrocytes with SP and make U373MG cells a useful in vitro model system for the analysis of NK-1 receptor function on astrocytes in vivo.

Astrocytoma↗
PubMed1992

Electric organ morphology of Sternopygus macrurus, a wave-type, weakly electric fish with a sexually dimorphic EOD.

In several species of electric fish with a sex difference in their pulse-type electric organ discharge (EOD), the action potential-generating cells of the electric organ (electrocytes) of males are larger and more invaginated compared to females. Androgen treatment of females and juveniles produces a longer-duration EOD pulse that mimics the mature male EOD, with a concurrent increase in electrocyte size and/or membrane infolding. In Sternopygus macrurus, which generates a wave-type EOD, androgen also increases EOD pulse duration. To investigate possible morphological correlates of hormone-dependent changes in EOD in Sternopygus, we examined electric organs from both fish collected in the field, and untreated and androgen-treated specimens in the laboratory. The electrocytes are cigar shaped, with prominent papillae on the posterior, innervated end. Electrocytes of field-caught specimens were significantly larger in all parameters than were electrocytes of specimens maintained in the laboratory. EOD pulse duration and frequency were highly correlated, and were significantly different between the sexes in sexually mature fish. Nevertheless, no sex difference in electrocyte morphology was observed, nor did any parameters of electrocyte morphology correlate with EOD pulse duration or frequency. Further, whereas androgen treatment significantly lowered EOD frequency and broadened EOD pulse duration, there was no difference in electrocyte morphology between hormone-treated and control groups. Thus, in contrast to results from studies on both mormyrid and gymnotiform pulse fish, electrocyte morphology is not correlated with EOD waveform characteristics in the gymnotiform wave-type fish Sternopygus. The data, therefore, suggest that sex differences in EOD are dependent on changes in active electrical properties of electrocyte membranes.

Analysis of Variance↗