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Biomedical subjects

C A Maxwell

Publications and source records attributed to C A Maxwell.

50 records · Page 3Linked to original sources

Transport and Partitioning of CO(2) Fixed by Root Nodules of Ureide and Amide Producing Legumes.

Nodulated and denodulated roots of adzuki bean (Vigna angularis), soybean (Glycine max), and alfalfa (Medicago sativa) were exposed to (14)CO(2) to investigate the contribution of nodule CO(2) fixation to assimilation and transport of fixed nitrogen. The distribution of radioactivity in xylem sap and partitioning of carbon fixed by nodules to the whole plant were measured. Radioactivity in the xylem sap of nodulated soybean and adzuki bean was located primarily (70 to 87%) in the acid fraction while the basic (amino acid) fraction contained 10 to 22%. In contrast, radioactivity in the xylem sap of nodulated alfalfa was primarily in amino acids with about 20% in organic acids. Total ureide concentration was 8.1, 4.7, and 0.0 micromoles per milliliter xylem sap for soybean, adzuki bean, and alfalfa, respectively. While the major nitrogen transport products in soybeans and adzuki beans are ureides, this class of metabolites contained less than 20% of the total radioactivity. When nodules of plants were removed, radioactivity in xylem sap decreased by 90% or more. Pulse-chase experiments indicated that CO(2) fixed by nodules was rapidly transported to shoots and incorporated into acid stable constituents. The data are consistent with a role for nodule CO(2) fixation providing carbon for the assimilation and transport of fixed nitrogen in amide-based legumes. In contrast, CO(2) fixation by nodules of ureide transporting legumes appears to contribute little to assimilation and transport of fixed nitrogen.

Journal Article↗

Seasonal changes in the sensitivity of ovine pineal beta-adrenoceptors to steroids.

Immunoneutralization of endogenous gonadal steroids has recently been shown to modify pineal beta-adrenoceptor function in intact Merino ewes. In the current study, interactions between gonadal steroids and these receptors have been further investigated. beta-Adrenoceptor density and binding affinity both showed time-related changes in ewes; the significance of these changes requires further study. Two observations, firstly modification of beta-adrenoceptor function by androstenedione and 17 beta-estradiol in ovariectomized, but not in intact ewes, and secondly that steroid-mediated effects on receptor density and binding affinity in the pineal of ovariectomized Merino ewes could be demonstrated during anestrus, but not during the breeding season for intact ewes, indicate that gonadal steroids may regulate pineal beta-adrenoceptor variables in Merino ewes. It is suggested that gonadal steroids may regulate ovine pineal function in ewes, and that the seasonal differences in sensitivity of luteinizing hormone release to steroid feedback may be mediated in part via effects on the pineal gland.

Androstenedione↗

Response of pineal beta-adrenoceptors in different breeds of sheep to immunization against selected steroids.

Active immunization of Merino and Wiltshire Horn X Merino cross-bred sheep against a range of gonadal steroids has revealed that pineal beta-adrenoceptors in both breeds are sensitive to hormonal modification by androgens, but only in the less seasonal, non-shedding Merino do these receptors appear to be sensitive to regulation by estrogens. Neither breed showed sensitivity of its pineal beta-adrenoceptors to active immunization against the pineal hormone melatonin under either normal or reversed photoperiod treatment. These results (a) suggest that pineal related seasonal differences between the breeds (i.e. wool shedding and/or reproductive function) may reside in differential sensitivity of the pineal gland to regulation by specific circulating steroid hormones, and (b) indicate an absence of end-product regulation of beta-adrenoceptor-mediated pineal melatonin biosynthesis in both seasonally shedding and non-shedding sheep.

Androgens↗

Sheep pineal beta-adrenoceptor function--interaction with gamma-aminobutyric acid.

To clarify the role and site of action of gamma-aminobutyric acid (GABA) in ovine pineal glands, we have investigated the effects of aminooxyacetic acid (AOAA), an inhibitor of GABA transaminase, on endogenous GABA content and beta-adrenoceptor mediated pineal function in Merino sheep. A significant elevation of endogenous GABA levels was noted in the glands, but no effect was observed on radioligand binding in vitro to pineal beta-adrenoceptors following in vivo administration of AOAA. Incubation of washed pineal membranes with GABA or AOAA had no effect on ligand binding to beta-adrenoceptors. Incubation of Merino pineal slices with GABA inhibited isoprenaline-stimulated but not basal serotonin N-acetyltransferase (NAT) activity. Incubation of whole pineal homogenates with GABA was without effect on either isoprenaline-stimulated or basal adenyl cyclase activity. Thus, Merino pineal glands resemble bovine pineals in that beta-adrenoceptor mediated melatonin biosynthesis in both species may be regulated in part by GABA. Our results indicate that GABA may exert its effect on Merino pineal NAT activity at a locus distal to the site of action of adenyl cyclase; however, the detailed mechanism and physiological role of this regulation remain to be elucidated.

Acetyltransferases↗

Alfalfa root nodule carbon dioxide fixation : I. Association with nitrogen fixation and incorporation into amino acids.

In vivo CO(2) fixation activity and in vitro phosphoenolpyruvate carboxylase activity were demonstrated in effective and ineffective nodules of alfalfa (Medicago sativa L.) and in the nodules of four other legume species. Phosphoenolpyruvate carboxylase activity was greatly reduced in nodules from both host and bacterially conditioned ineffective alfalfa nodules as compared to effective alfalfa nodules.Forage harvest and nitrate application reduced both in vivo and in vitro CO(2) fixation activity. By day 11, forage harvest resulted in a 42% decline in in vitro nodule phosphoenolpyruvate carboxylase activity while treatment with either 40 or 80 kilograms nitrogen per hectare reduced activity by 65%. In vitro specific activity of phosphoenolpyruvate carboxylase and glutamate synthase were positively correlated with each other and both were positively correlated with acetylene reduction activity.The distribution of radioactivity in the nodules of control plants (unharvested, 0 kilograms nitrogen per hectare) averaged 73% into the organic acid and 27% into the amino acid fraction. In nodules from harvested plants treated with nitrate, near equal distribution of radioactivity was observed in the organic acid (52%) and amino acid (48%) fractions by day 8. Recovery to control distribution occurred only in those nodules whose in vitro phosphoenolpyruvate carboxylase activity recovered.The results demonstrate that CO(2) fixation is correlated with nitrogen fixation in alfalfa nodules. The maximum rate of CO(2) fixation for attached and detached alfalfa nodules at low CO(2) concentrations (0.13-0.38% CO(2)) were 18.3 and 4.9 nanomoles per hour per milligram dry weight, respectively. Nodule CO(2) fixation was estimated to provide 25% of the carbon required for assimilation of symbiotically fixed nitrogen in alfalfa.

Journal Article↗

Modification of sheep pineal beta-adrenoceptors by some gonadal steroids but not by melatonin.

The effects of active immunization against a range of gonadal steroids on pineal beta-adrenoceptors were studied in cycling Merino ewes. In selected cases, the effects of exogenous steroids were also investigated. Immunization against progesterone had no detectable effect on pineal beta-adrenoceptor density or ligand binding affinity. Immunization against estrone or 17 beta-estradiol significantly increased binding affinity and decreased beta-receptor density. Testosterone immunization in ewes caused similar effects but to a lesser degree. In contrast, immunization against androstenedione resulted in a decreased affinity and an increase in receptor density in ewes. In subsequent experiments, some parameters of pineal function in intact cycling and ovariectomized ewes were compared; a significant decrease in beta-receptor density and an increase in binding affinity were noted in the ovariectomized animals. Androstenedione-releasing implants decreased beta-receptor density and increased beta-receptor affinity in pineals from intact ewes, but these implants had no effect on pineal parameters in ovariectomized ewes. Immunization of ewes against 17 beta-estradiol had no significant effects on basal or isoprenaline-stimulated N-acetyltransferase or adenyl cyclase activities. Immunization of ewes against melatonin, or in vitro incubation of pineal glands with the hormone had no effects on the pineal parameters studied. It is concluded that estrogens affect the pinealocyte beta-receptors in ewes, while specific androgens may act indirectly on these receptors to modify their interaction with estrogens.

Androstenedione↗

Effects of steroids on beta-adrenergic binding sites in sheep pineal glands.

As an initial step in investigations of putative differences between central nervous system light-sensitive mechanisms in seasonally shedding and non-shedding breeds of sheep, some beta-adrenoceptor characteristics of Merino sheep pineal glands were determined, using [3H]dihydroalprenolol as the labelled ligand. Overall, a dissociation constant of 17.2 +/- 2.6 nmoles/l and a daytime beta-receptor density of 1.6 +/- 0.3 pmoles/mg were determined at 37 degrees. The binding sites exhibited stereospecificity, saturability and apparent homogeneity. 17 beta-Estradiol and progesterone implants that provided hormone concentrations in the physiological range had no significant effect on pineal beta-receptors in male sheep castrated shortly after birth. Dexamethasone injections, on the other hand, in doses sufficient to loosen the attachment of wool fibres to the skin, resulted in decreased pineal beta-receptor density and increased receptor affinity for dihydroalprenolol. This effect was apparently not mediated by altered plasma catecholamine concentrations, since the glucocorticoid treatment did not affect jugular venous noradrenaline, adrenaline or dopamine levels. The possible involvement of glucocorticoids in the regulation of wool growth could thus have a central neuronal component, medicated via action on pineal beta-adrenoceptors in sheep; however, the existence of the putative gonadal steroid feedback on beta-adrenoceptor-mediated pineal function remains to be demonstrated in this species.

Animals↗

Control of Bancroftian filariasis by integrating therapy with vector control using polystyrene beads in wet pit latrines.

In the town of Makunduchi, Zanzibar, wet pit latrines provided breeding places for Culex quinquefasciatus and there were few other mosquito breeding places available. The adult mosquito population in bedrooms was monitored for a year and found to consist almost entirely of Cx quinquefasciatus of which 2.45% carried infective larvae of Wuchereria bancrofti. It was estimated that each person received about 24,993 bites per year, of which 612 were potentially infective. After a year of baseline data collection, polystyrene beads were expanded in boiling water and applied to form floating layers on all infested pits. Subsequently the adult mosquito population declined remarkably so that the estimated number of bites per person per year was only about 439. To retain control, surveillance for newly wet pits continued to be necessary. Initially the microfilarial rate in the human population was 49.5%, with many cases of filarial disease. The microfilarial rate was reduced to 10.3% by mass treatment with diethylcarbamazine, with no sign of resurgence a year after treatment. The infective rate among mosquitoes was reduced to 0.41% and the combined effect of the vector and microfilarial control was to reduce the number of infective bites per person per year by 99.7%.

Adolescent↗

Insecticide-impregnated bed nets reduce malaria transmission in rural Zanzibar.

There has been concern that impregnated bed nets are an insufficiently powerful method to control malaria in areas with very high perennial transmission, as in the humid lowland parts of tropical Africa. We carried out a 'cross-over' trial among children under 5 years of age in 2 villages in rural Zanzibar. In 1989, one village was supplied with newly permethrin-impregnated bed nets whereas the other served as unprotected control. In 1992, when those nets had lost their insecticidal activity and were badly torn, the village which had previously been the control was given newly impregnated bed nets. Each time, reinfection with Plasmodium falciparum was measured after initially clearing the parasites by administering a therapeutic dose of sulfadoxine/pyrimethamine. The introduction of bed nets led to a 74-78% reduction in the weekly rate of reinfection with malaria parasites, in all age groups. The nets apparently also affected perceived clinical symptoms, haemoglobin levels, and the mosquito sporozoite rate.

Animals↗

A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.

Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.

Antimalarials↗

Comparison of bednets impregnated with different pyrethroids for their impact on mosquitoes and on re-infection with malaria after clearance of pre-existing infections with chlorproguanil-dapsone.

Comparisons of bednets treated either with alphacypermethrin or lambdacyhalothrin showed similar effectiveness by various entomological criteria. Lambdacyhalothrin was associated with significantly more reports of nasal irritation than alphacypermethrin. The 2 net treatments were equally effective in reducing incidence of new malaria infections and the treated nets were much more effective than untreated nets. These measurements were made after clearing existing infections with chlorproguanil-dapsone. This drug combination was more than 99% effective in clearing infections 1 week after treatment and a study of children taken to an altitude with no malaria transmission showed that there were very few recrudescences.

Antimalarials↗

Identification of a seasonal elevation in daytime melatonin levels associated with the rut in fallow bucks (Dama dama): the effect of day length and exogenous melatonin.

The timing of the seasonal reduction in voluntary food intake and hormonal changes associated with the rut were investigated in mature fallow bucks subjected to artificial long-day exposure with and without superimposed melatonin-releasing implants. Circulating testosterone profiles and the period of inappetence, signalling the onset of the period of reproductive activity in untreated bucks under natural photoperiod, were phase-advanced in both treatment groups. In the long-day treated group, these profiles were phase-advanced by 1 week, while in the long-day + melatonin group, the phase advance was 6 weeks compared to the controls. Circulating daytime melatonin, elevated in all three groups, corresponds with seasonal changes in circulating testosterone levels associated with the rut. Prolactin profiles followed ambient photoperiod, being high during natural or artificial long days and low during natural short days. Exogenous melatonin administered during long-day exposure initiated a rapid and reversible decrease in circulating prolactin levels. The elevation in plasma melatonin could not be separated temporally from the seasonal testosterone peak by exposure to long days or to exogenous melatonin. However, this daytime melatonin profile was abolished by the ablation of circulating testosterone following immunization against luteinizing hormone releasing hormone (LHRH). The presence of this endogenous melatonin during daylight was observed only during the rut, as measured in two radioimmunoassays and confirmed by mass spectrometry. It is likely that both testosterone and melatonin influence the onset of the seasonal rut in fallow bucks.

Animals↗

Insecticide treated nets: impact on vector populations and relevance of initial intensity of transmission and pyrethroid resistance.

Insecticide treated bednets locate a deposit of a quick-acting insecticide of low human toxicity between a sleeper and host-seeking mosquitoes. Thus a chemical barrier is added to the often incomplete physical barrier provided by the net. Treated nets may be considered as mosquito traps baited by the odour of the sleeper. Trials in Assam, Tanzania and elsewhere have shown that when a whole community is provided with treated nets, so many mosquitoes of anthropophilic species are killed by contact with the nets that the density and/or sporozoite rate of the vector population is reduced. In order to gain this "mass" or community effect, in addition to widespread personal protection, and thus to achieve the full potential of the treated net method, a high per cent coverage of the community is needed. This suggests that organised free provision of treated nets, comparable to a house spraying programme, is likely to be more cost-effective than trying to market nets and insecticide to very poor rural people. In areas with high malaria transmission, where acquisition of immunity to malaria is very important, it has been argued that vector control (without vector eradication) could, in the long run, make the situation worse by preventing the normal build-up of immunity. However, our data from Tanzania do not support this idea--3-4 years after provision of nets (which are re-treated annually) young children are still showing clear health benefits; older children are not "paying" for this by showing worse impact of malaria. There is less malaria morbidity in a highland area where malaria transmission is about 15x less intense than in a nearby lowland area. The per cent impact of treated nets malaria morbidity in both area was very similar. At present only pyrethroids are used for net treatment which suggested that emergence of pyrethroid resistance would have a disastrous effect. However, in West Africa, where there is now a high frequency of the kdr resistance gene in Anopheles gambiae, it is reported that treated nets continue to have a powerful impact on vector populations. In Tanzania, pyrethroid resistance has not been detected in malaria vectors, but it has emerged in bedbugs after seven years use of treated nets.

Animals↗