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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 271 records · Page 15Linked to original sources

Exercise conditioning in the rehabilitation of patients with chronic obstructive pulmonary disease.

Fifty-nine patients with severe chronic obstructive pulmonary disease (COPD) performed pulmonary function and exercise tests before and after participation in a 12-day pulmonary rehabilitation inpatient program. Postdischarge follow-ups were performed at three months. Training consisted of twice daily aerobic exercise of 30 to 40 minutes' duration. Intensity of training was determined after exercise testing and approached the maximal limits of ventilation. In general, the program failed to demonstrate significant changes in pulmonary function. Exceptions were mid-expiratory flow rate (FEF25-75) (p less than .02) and peak flow rate (p less than .05). Evaluation of exercise capacity via maximal exercise testing yielded significant increases in caloric expenditure (p less than .001), peak exercise oxygen consumption (p less than .001), and work output (p less than .0001). Peak exercise ventilation increased significantly (p less than .005) due to an increase in tidal volume (p less than .002). Work efficiency improved with training, but the change was not statistically significant. Resting oxygen consumption and carbon dioxide production were decreased (p less than .05); tidal volume was increased (p less than .005). However, the significant increase noted in tidal volume did not alter minute ventilation. In general, the changes noted at 12 days were maintained at three months postdischarge. These data support the hypothesis that a short-term, in-hospital program of general exercise conditioning can improve work output, gas exchange, and mechanical efficiency without significantly affecting spirometric indices. These changes may translate into improved performance of activities of daily living and a sense of general well-being.

Efficiency↗

The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies.

Immunization with extracellular sexual stages of the malaria parasites can induce the production of antibodies which block the development of the parasites in the midgut of a mosquito after a blood meal. We have generated a number of monoclonal antibodies against gametes and zygotes of the human malaria Plasmodium falciparum. Two monoclonal antibodies (mAb) reacting with a 230-kDa gamete surface protein (mAb 1B3 and 2B4 both isotype IgG2a) were found to block transmission of P. falciparum to mosquitoes. Blocking was complement dependent and this was verified in vitro by the rapid lysis of newly formed gametes and zygotes in the presence of the mAb and active complement. Both mAb reacted by immunofluorescence with the surface of gametes and zygotes from isolates of P. falciparum from various geographical areas. Each mAb immunoprecipitated a 230-kDa protein from 125I-labeled surface proteins of newly formed gametes and zygotes and immunoblotted a protein doublet of about molecular mass 260 and 230 kDa from gametocytes and gametes of P. falciparum. Only the 230-kDa protein is expressed on the surface of newly formed macrogametes and zygotes. The 230-kDa gamete surface protein forms a molecular complex with two proteins of 48 and 45 kDa. The 48- and 45-kDa gamete surface proteins have previously been shown to be targets of mAb which block infectivity of P. falciparum to mosquitoes. The present study now demonstrates that antibodies against the 230-kDa gamete surface protein block transmission of P. falciparum to mosquitoes. The 230-kDa gamete protein is thus a potential candidate for a gamete vaccine.

Animals↗

Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain.

Concentrations of total cholesterol and cholesterol in the various lipoprotein fractions were measured in vegans, vegetarians, fish eaters (who did not eat meat), and meat eaters. Total and low density lipoprotein cholesterol concentrations were higher in meat eaters than vegans, with vegetarians and fish eaters having intermediate and similar values. High density lipoprotein cholesterol concentration was highest in the fish eaters but did not differ among the other groups. There were striking trends with age in total and low density lipoprotein cholesterol concentrations, which differed between men and women: women showed a steady increase in concentration with age, whereas concentrations in men did not increase appreciably after the age of 40, which may partly explain sex differences in the prevalence of coronary heart disease. The differences in total cholesterol concentration suggest that the incidence of coronary heart disease may be 24% lower in lifelong British vegetarians and 57% lower in lifelong vegans than in meat eaters.

Adult↗

Genetic analysis of the human malaria parasite Plasmodium falciparum.

Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. The parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. A cross was made between two clones of Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. Parasites showing recombination between the parent clone markers were detected at a high frequency. Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization. Since patients are frequently infected with mixtures of genetically distinct parasites, mosquito transmission is likely to provide the principal mechanisms for generating parasites with novel genotypes.

Adenosine Deaminase↗

A histidine-rich protein gene marks a linkage group favored strongly in a genetic cross of Plasmodium falciparum.

Two histidine-rich protein genes in Plasmodium falciparum are related by an ancestral duplication and interchromosomal transposition. We have followed the inheritance of these genes in a cross between two clones of P. falciparum. Examination of progeny shows that one gene, encoding the protein HRP-II, behaves as expected and may be inherited from either parent. The other gene, encoding HRP-III, has been found to derive from one parent in all progeny examined. We conclude the linkage group marked by HRP-III is favored strongly in the cross. This linkage group spans a region at one end of chromosome 13. Growth studies suggest the favored inheritance is explained by rapid expansion of progeny possessing the HRP-III marker relative to slower growth of progeny without it.

Chromosome Mapping↗

Effect of dietary cholesterol on plasma cholesterol concentration in subjects following reduced fat, high fibre diet.

One hundred and sixty eight subjects participated in a randomised crossover study to determine whether halving or doubling the present dietary cholesterol intake from eggs had any influence on blood cholesterol concentration in people following current dietary recommendations. During the first eight weeks all participants were advised to follow a reduced fat diet (26% total energy for hyperlipidaemic patients, 35% total energy for normolipidaemic volunteers) with an increased ratio of polyunsaturated to saturated fatty acids. This background diet was continued throughout the 16 week experimental period, during which participants ate either two or seven eggs a week. A small but significant increase in total cholesterol was seen after four weeks in the group eating seven eggs a week compared with that in the group eating two eggs a week, but this was no longer apparent after eight weeks. Previous studies suggesting that dietary cholesterol has a greater effect on the serum cholesterol concentration either have been carried out against a background of a higher fat intake or have contrasted extreme cholesterol intakes. A further reduction in dietary cholesterol seems to be unnecessary in those people who have already reduced their intake of saturated fat and increased the ratio of polyunsaturated to saturated fatty acids and fibre rich carbohydrate.

Cholesterol↗

Human T clones reactive to the sexual stages of Plasmodium falciparum malaria. High frequency of gamete-reactive T cells in peripheral blood from nonexposed donors.

Malarial gametocytes, which are taken up by mosquitoes during a blood meal, develop in the gut of the mosquito into gametes. Gametes and gametocytes contain the target antigens of transmission-blocking immunity. Here, we show that the peripheral blood of nonexposed donors contains Plasmodium falciparum gamete-reactive T cells at frequencies ranging from 1/300 to 1/4000. Studies on long-term clones demonstrated that these cells often recognized antigens shared between gametes and asexual stage parasites or even between heterologous gametes, although it has been possible to derive a P. falciparum gamete-specific T clone. The T clones examined were T3+, T4+, T8-, and either HLA-DR- or HLA-DQ-restricted. They responded to gametes by both proliferation and the secretion of gamma-interferon. The gamete-specific clone and other asexual cross-reactive clones examined could be stimulated in vitro by a preparation of mature gametocytes within RBC, but not by RBC alone, suggesting that gametocytes are immunogenic or can become immunogenic for T cells in vivo. The significance of these observations to mosquito transmission of malaria and development and application of a gamete vaccine are discussed.

Adult↗

Response time in monkeys with unilateral neglect.

Four monkeys were trained to open a door with either the right or left hand in response to a tactile stimulus to either leg. After unilateral frontal arcuate ablation inducing unilateral neglect, the response time on this task increased most when the monkey responded with the hand contralateral to the lesion, but also increased when the monkey used the hand ipsilateral to the lesion. The side of stimulation had no effect on response time. Control (anterior superior temporal) lesions did not cause neglect and only affected response time slightly in one monkey (using the limb contralateral to the lesion). We conclude that response time is increased in animals with unilateral neglect and that the increase results from a defect in intention to act (motor neglect) rather than from sensory neglect.

Animals↗

Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans.

Immunity to malarial infections in human populations is known to affect the development of the asexual blood stages of the parasites in the human host and to be capable of conferring significant protection against morbidity and mortality due to the disease. In this study we show that during acute infection with Plasmodium vivax malaria, one of the two main malarial pathogens of humans, most individuals also develop immunity that suppresses the infectivity of the sexual stages of the parasite to mosquitoes. The immunity is antibody mediated and is directed against the parasites in the mosquito midgut shortly after ingestion of blood by a mosquito. This immunity could be expected to have significant effects on the natural transmission of P. vivax malaria.

Animals↗

Demand oxygen delivery during exercise.

Nine hypoxemic patients with COLD, whose hypoxemia is aggravated by minimal exercise, volunteered for this study. Each subject underwent two treadmill exercise trials at two oxygen delivery settings, each on the DODS and SF delivery systems for a total of four exercise trials. We measured SaO2 via ear oximetry and recorded oxygen usage per minute. We compared the oxygen usage required for the two techniques to achieve an SaO2 of 90 percent. The results indicate that the mean oxygen requirement using the DODS to achieve an SaO2 of 90 percent was 211.4 ml/min as compared to SF delivery which required 1,610.9 ml/min. This implies an oxygen savings advantage of the DODS over SF of 7:1. The fact that the DODS oxygen savings extends to exercise conditions lends support to its use in portable oxygen therapy. Widespread use of this and other oxygen savings techniques could result in significant cost savings while maintaining the desired benefits of supplemental oxygen administration.

Aged↗

Predicting maximal exercise ventilation in patients with chronic obstructive pulmonary disease.

Shortness of breath is a chief complaint of many individuals with cardiopulmonary diseases. Exercise testing is often used to help differentiate cardiac from pulmonary involvement. In assessing pulmonary dysfunction during exercise it is essential to know the point at which ventilatory limitation will occur. Numerous authors have presented regression equations based on the FEV1 for predicting either MVV or VEmax. Resting pulmonary function studies were obtained from 53 patients with COPD. Symptom-limited maximal exercise testing was completed on a cycle ergometer using increments of 10 watts/min. Each regression equation for predicting MVV or VEmax was then applied to the data set. Results showed that the FEV1 correlated with the measured VEmax (r = .81) as did PEF (r = .81), MVV (r = .78), IC (r = .78), DCO (r = .68), VA (r = .67), VE (r = .65) and FVC (r = .64). Single post-bronchodilator FEV1 measurements ranged from 0.56 to 1.64 L (mean 1.0 L) while VEmax ranged from 16 to 78 L/min (mean 37.69 L/min). The equation VEmax = 37.5 X FEV1 was the most robust equation found in the literature for predicting VEmax in this sample. This equation was not statistically different from the line of identity when predicted VEmax was plotted against the measured VEmax. The intercept was 0.91 with a slope of 0.98. In addition, this equation had a smaller mean square error in predicting VEmax than those of the other equations investigated.

Adult↗

Complement effects of the infectivity of Plasmodium gallinaceum to Aedes aegypti mosquitoes. II. Changes in sensitivity to complement-like factors during zygote development.

During transformation into ookinetes, the zygotes of Plasmodium gallinaceum are initially resistant to lysis by heat-labile and EDTA-sensitive factors in the serum of their natural host, the chicken. Between 6 and 8 hr postgametogenesis, zygotes cultured in vitro lose their resistance to these factors. Loss of resistance to these factors in vitro is reflected by loss of infectivity of the zygotes to Aedes aegypti mosquitoes in the presence of native chicken serum. These factors are probably components of the alternative pathway of complement (APC) of chicken serum. Gametocytes of P. gallinaceum in chicken blood are able to infect A. aegypti mosquitoes apparently due to inactivation of the APC in a blood meal within 3-4 hr after ingestion, i.e., several hours before the zygotes lose their resistance to chicken APC. In addition to the heat-labile factors (APC) in chicken serum, the zygotes are transiently sensitive to other factor(s) in the mosquito blood meal. These factor(s) are not destroyed by prior heating of the chicken serum given in a blood meal and therefore cannot be complement components. The antiparasitic effects of the factors are neutralized by addition of EDTA to the blood meal and could be due to an EDTA-sensitive metalloprotease present in the mosquito midgut.

Aedes↗

Research toward malaria vaccines.

Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

Antigens, Protozoan↗

Complement effects on the infectivity of Plasmodium gallinaceum to Aedes aegypti mosquitoes. I. Resistance of zygotes to the alternative pathway of complement.

Gametocytes are the intraerythrocytic stages of malaria parasites that infect mosquitoes. When gametocytes of the chicken malaria parasite Plasmodium gallinaceum are ingested by a mosquito they become extracellular in the mosquito midgut, form gametes, and fertilize within 10 to 15 min after the insect has taken a blood meal. Gametocytes of P. gallinaceum were infectious when fed to Aedes aegypti mosquitoes in blood meals containing native serum from chickens or from the non-host species, man or sheep. Gametocytes stimulated to undergo gametogenesis and to fertilize in vitro were also infectious when fed to mosquitoes in native chicken serum. However, native serum from most non-host species, including sheep and man, suppressed the infectivity of newly fertilized zygotes to mosquitoes and lysed the zygotes in vitro. These effects were shown to be due to the activity of the alternative pathway of complement (APC) in the serum of the non-host species. After mild trypsin treatment, the zygotes of P. gallinaceum no longer infected mosquitoes in the presence of native chicken serum, although in heat-inactivated chicken serum their infectivity was normal. We conclude that trypsin-sensitive components on the zygotes surface protect them from destruction by the APC of their native host. The ability of gametocytes of P. gallinaceum to infect mosquitoes in the presence of native human serum is probably due to proteases that inactivate the APC of human serum before the gametes and zygotes emerge as extracellular parasites in the blood meal.

Aedes↗

Options in the management of perforations of the esophagus.

A study of 90 cases of esophageal perforation in the antibiotic era emphasizes individualized treatment and options of therapy based on a fundamental understanding of modifying pathophysiologic factors. If the patient is seen during the first 24 hours, surgical repair and irrigating tube drainage continue to be the treatment of choice in the thoracic and abdominal regions, with certain exceptions. The exceptions include small perforations proved by a thin media esophagram or esophagoscopy without pleural involvement or constitutional symptoms. Such patients may be treated nonoperatively, with gastric drainage, antibiotics, and parenteral alimentation. However, for large perforations with extensive contamination of the mediastinum and pleura, an esophageal exclusion operation may be life saving. In the cervical region, irrigating tube drainage may be just as effectual as repair and drainage. In patients seen after 24 hours, size of the perforation and the amount of mediastinopleural infection, rather than the time that has elapsed, dictate optimal treatment.

Anti-Bacterial Agents↗