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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 289 records · Page 16Linked to original sources

Anti-gamete antibodies block transmission of human vivax malaria to mosquitoes.

Antibodies were raised in rabbits by immunizing against fresh unfixed or cryopreserved female gametes of the human malaria pathogen Plasmodium vivax. The antibodies were shown to react with the surface of gametes by the indirect immunofluorescent test. When parasite isolates from P. vivax infected individuals were fed through a membrane to Anopheles tessellatus mosquitoes in the presence of immune rabbit sera, they completely blocked the infectivity of the parasite isolates to the vector. Immunoglobulins separated from these sera also blocked infectivity to the same extent as did the immune sera indicating that antibodies were responsible for the transmission blocking effect of the sera. This study indicated that P. vivax like other malaria parasites is highly susceptible to anti gamete transmission blocking immunity.

Animals↗

Evaluation of the pendant oxygen-conserving nasal cannula during exercise.

There is much recent evidence that patients with chronic pulmonary disease who are hypoxemic benefit from continuous therapy with oxygen. These benefits include reduction in symptoms of cor pulmonale, reduction in mortality, and improvement in quality of life. Oxygen therapy is very expensive, and steady-flow delivery of oxygen is wasteful, since almost the entire benefit of the oxygen presented to the patient occurs at the very beginning of inspiration. We previously described a conserver nasal cannula (CNC) which stores oxygen during exhalation for delivery during subsequent inspirations. The CNC achieves adequate arterial oxygen saturation (SaO2) at one fourth to one half of the flow in liters of steady-flow oxygen delivery. Because some patients found the mustache configuration objectionable, a pendant nasal cannula (PNC) was designed, displacing the reservoir off of the face and onto the anterior wall of the chest. While both cannulas require some breathing by nose to function, the PNC is more esthetically acceptable. No studies with exercise have been reported using the PNC. We evaluated the PNC during treadmill exercise in ten subjects with chronic obstructive pulmonary disease and hypoxemia on exercise. We compared the PNC with steady-flow oxygen during steady level treadmill walking sufficient to cause oxygen desaturation while breathing room air at oxygen presentations of 0.5 through 3.0 L/min. At comparable workloads the SaO2 achieved by PNC required one third of the oxygen flow required by steady-flow oxygen to achieve an equivalent SaO2. These differences were statistically significant (p less than 0.01). We conclude that the PNC provides effective delivery of oxygen during exercise, as well as at rest, while minimizing oxygen flow rate and thus substantially reducing the economic burden normally associated with supplemental oxygen delivery.

Aged↗

A randomized controlled trial of low carbohydrate and low fat/high fiber diets for weight loss.

Among 135 overweight subjects, we conducted a three-month randomized controlled trial of two sets of dietary advice, each providing approximately 1,000 calories per day but differing in fiber, carbohydrate, and fat content. Information on weight and eating habits, as well as measures of lipoprotein and glucose metabolism were obtained at entry and one and three months later. We found that dieters given low carbohydrate/low fiber dietary advice tended to lose more weight than those given a higher carbohydrate/higher fiber regimen (5.0 vs 3.7 kg on average at three months). This pattern was particularly marked among women, and among participants who were under age 40 or of lower social class. There were no differences between the diet groups in the proportion complaining of hunger but, in general, members of the low carbohydrate group complained of more problems in dieting. There were only minor differences in the serum lipoprotein patterns during the diet period. In view of these results, we believe previous claims of the benefits of fiber for weight loss may have been overstated.

Adult↗

Evidence for opiate receptor involvement in the consumption of a high palatability diet in nondeprived rats.

Nondeprived adult rats were familiarized with a highly palatable diet (powdered small animal diet mixed with sweetened condensed milk and water). The palatability of food was such that it induced vigorous feeding responses, 15-20 g food consumed within the first 30 min of access. In partially-satiated male rats, the kappa receptor agonists EKC and U-50,488 (subcutaneously administered) produced large increases in food consumption in the first 30 min of access, post-injection. In experiments with naloxone and WIN 44,441-3, we found that the effects of naloxone (0.01-10 mg/kg; S.C.) were crucially dependent on the sex and dietary history of the animals. Male, obese rats were most sensitive to naloxone's anorectic effect. Lean females were completely insensitive. WIN 44,441-3 (0.01-10 mg/kg, S.C.) had no effect on food intake in any group of animals.

Animals↗

Biosynthesis of two stage-specific membrane proteins during transformation of Plasmodium gallinaceum zygotes into ookinetes.

We have studied the synthesis and expression of surface proteins in zygotes of Plasmodium gallinaceum during their transformation to mature ookinetes. The cells were biosynthetically labelled in vitro using [35S]methionine and proteins were immunoprecipitated with rabbit anti-ookinete serum or monoclonal antibodies. Early zygotes (approx. 2 h post-gametogenesis and fertilization) synthesized and expressed on their surface a protein of Mr 26 000 as observed under reducing conditions on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) (31 000 under non-reducing conditions) and continued to do so for 8-10 h; thereafter synthesis of the Mr 26 000 protein declined and little or none was synthesized in the mature ookinetes (greater than 20 h post-gametogenesis). Between 3-5 h post-gametogenesis, zygotes also began to synthesize a protein of Mr 28 000 (34 000 under non-reducing conditions). Synthesis and expression of this surface protein continued throughout development; and the Mr 28 000 protein was the predominant surface protein synthesized by the mature ookinete. Mr 26 000 and Mr 28 000 proteins have been designated earlier as PgO-1 and PgO-2 respectively (Carter and Kaushal, Mol. Biochem. Parasitol. (1984) 13, 235-241). Neither protein was synthesized in the gametocytes prior to gametogenesis. Both proteins could be labelled with [3H]glucosamine or [3H]mannose. When zygotes were incubated with [3H]palmitic acid both PgO-1 and PgO-2 bound fatty acids in covalent linkage. The two proteins do not otherwise appear to be structurally related. They were differentially immunoprecipitated by different monoclonal antibodies and gave rise to distinct patterns of peptides following digestion with proteases such as Staphylococcus aureus V-8, trypsin and chymotrypsin.

Animals↗

Effects of transmission-blocking monoclonal antibodies on different isolates of Plasmodium falciparum.

The strain diversity in Plasmodium falciparum has been studied with respect to gamete surface antigens which are the targets of transmission-blocking antibodies. Of 12 isolates tested, 11 were positive by immunofluorescence with the three monoclonal antibodies studied. The exception was a Liberian isolate, two clones of which were found to react with only one of the three monoclonal antibodies. Antibodies IIC5-B10 and IA3-B8, which previously have been shown to act synergistically to block infectivity of 7G8, a Brazilian clone of P. falciparum, acted in an exactly similar way with another Brazilian isolate, It.D12, and an isolate from Thailand. In the presence of complement either IA3-B8 or a third antibody, IID2-A10, strongly suppressed infectivity of It.D12 as well as 7G8, but neither isolate was strongly suppressed by IIC5-B10. IA3-B8 and IID2-A10 did not react by immunofluorescence or immunoprecipitation with gametes of L.E5; IIC5-B10 reacted positively with L.E5 gametes in these tests. In the absence of complement, the combination of IA3-B8 and IIC5-B10 did not suppress infectivity of L.E5 to mosquitoes. In contrast to its effect on gametocytes of other isolates, IIC5-B10 in the presence of complement strongly suppressed infectivity of L.E5 to mosquitoes. These results imply that IA3-B8 and IIC5-B10 react with two structurally distinct epitopes on the surface of gametes of P. falciparum and that the properties of both epitopes on gametes of L.E5 differ from those on gametes of the other isolates tested.

Animals↗

Two apparently nonrepeated epitopes on gametes of Plasmodium falciparum are targets of transmission-blocking antibodies.

One-site and two-site immunoradiometric assays have been developed against an antigen on gametocytes of Plasmodium falciparum, using monoclonal antibodies (Mabs) which block transmission of the parasites to mosquitoes. Three such Mabs have been studied, each of which immunoprecipitates a complex of three gamete surface proteins of apparent Mr 260,000, 59,000, and 53,000 from Triton X-100 extracts of the parasites. The assays showed that the Mabs recognized one or the other of two distinct, nonrepeated epitopes on the target antigen(s). In the one-site assay certain combinations of two Mabs interacted at appropriate concentrations to enhance binding of the Mabs to the antigen. The same combinations of Mabs synergize to suppress infectivity of gametocytes to mosquitoes.

Animals↗

Low-concentration oxygen therapy via a demand oxygen delivery system.

Recent heightened concern about the costs of medical care has stimulated research and development in devices and schemes for saving costs while retaining quality of care. Consistent with that concern is the fact that standard steady-flow oxygen delivery is so wasteful. Almost its entire benefit occurs at the very beginning of inspiration. We compared the efficacy of nasal oxygen delivery via a new demand oxygen delivery system (DODS) with the standard steady-flow (SF) method. The DODS incorporates a valve and sensor interposed between the oxygen reservoir and the patient, which meters oxygen to the patient only during early inspiration. Twelve COPD subjects with hypoxemia at rest received oxygen at flow settings of 1 to 4 L/min via SF and at various breath interval settings via the DODS method, calculated to match the above spectrum of the SF. We measured oxygen delivery using an ear oximeter. The results indicate that significantly less oxygen was required to provide equivalent saturations using the DODS compared with the SF method (p less than .001). The mean comparative savings in oxygen is better than seven to one favoring the DODS over the SF method. Further study is warranted, since the widespread use of such a device could result in substantial cost saving while increasing the range of portable oxygen delivery.

Aged↗

Spatial contrast sensitivity in patients with multiple sclerosis.

Contrast sensitivity tests a basic visual function which is not examined by conventional visual acuity testing or visual evoked responses. It is frequently abnormal in patients with multiple sclerosis. The lack of relationship between VERs and SCSF implies that contrast sensitivity measures aspects of the visual system not examined by the conventional electrophysiological technique, probably visual function situated beyond the anterior visual pathway. It is therefore a useful complementary diagnostic test for patients with multiple sclerosis. Both VER and spatial contrast sensitivity separately detect a high proportion of patients with multiple sclerosis. When used in combination, the two techniques give a yield which approaches 100%. Contrast sensitivity testing as used here is cumbersome and time-consuming. Use of fewer spatial frequencies and/or adaptation of VER techniques for estimation of a contrast threshold may be more applicable for clinical use.

Adult↗

Target antigens in malaria transmission blocking immunity.

Malaria transmission blocking immunity has been found to operate against two distinct phases of development of malaria parasites in the mosquito midgut: (i) against the extracellular gametes and newly fertilized zygotes shortly after ingestion by a mosquito of parasitized blood and (ii) against the zygotes during their subsequent development into ookinetes. Immunity is antibody-mediated and stage-specific. A set of three proteins, synthesized in the gametocytes, expressed on the surface of the gametes and newly fertilized zygotes and subsequently shed during later transformation of the zygotes, has been identified as the target antigens of anti-gamete fertilization blocking antibodies. A single protein, synthesized and expressed on the zygote surface during its development to ookinetes, has been identified as the target of antibodies which block the development of the fertilized parasites in the mosquito. Immunization of human populations against gamete or zygote antigens, while not directly protecting an immunized individual from inflection, would reduce the transfer of malaria within the population. Such immunity, in addition to reducing the overall rate of malaria transmission, would, if combined with a vaccine against the asexual (disease-causing) stages, reduce the chance of selection of parasites that are resistant to the asexual vaccine by preventing their entry into the mosquito population.

Animals↗

Determination of immunoglobulin class by pattern of absorption to protein A-sepharose coupled with immunoglobulin class specific antibodies.

The pattern of absorption of the different major immunoglobulin classes by protein A and protein A coupled with antibody to human IgA or IgM has been evaluated as a simple means of identifying the class of a particular immunoglobulin in small volumes of human serum. Rabbit anti-IgA or anti-IgM coupled with protein A-Sepharose gel effectively removed IgA or IgM respectively from human serum in addition to the subclasses of IgG removed by protein A alone. The manner in which an immunoglobulin-related property is removed from human serum by protein A and its conjugates with specific antibodies can thus serve as an index of the class of that particular immunoglobulin.

Absorption↗