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Biomedical subjects

R C Reed

Publications and source records attributed to R C Reed.

At least 19 recordsLinked to original sources
PubMed1997

Rapid onset of malaria-induced mortality by immunizations with lipo-peptides: an experimental model to study deleterious immune responses and immunopathology in malaria.

We have recently shown that circumsporozoite (CS) protein-based cytotoxic T-cell epitope of Plasmodium berghei coupled to monoplamitic and tripalmitic acid was able to induce cytotoxic T-cell responses. In the present study, we investigated whether lipopeptide derivatized CS protein B and T helper epitopes in different combinations will be able to induce protective immune responses against sporozoite challenge. Several P. berghei CS peptides with monopalmitic fatty acid tails were prepared, suspended in an oil-in-water emulsion, and used to immunize and boost female A/J mice. The mice were challenged iv. with viable sporozoites of P. berghei (ANKA) two weeks after the last immunization. While immunization with some of these vaccine formulations induced protective immune responses, others shifted the typical bimodal pattern of P. berghei sporozoite induced death toward a rapid onset of death in a peptide specific manner. Therefore, demonstration that immunization with formulations of malarial peptides can cause enhanced malaria-related death provides an experimental model to delineate characteristics of deleterious immune responses.

Amino Acid Sequence↗
PubMed1997

Multiple antigen constructs (MACs): induction of sterile immunity against sporozoite stage of rodent malaria parasites, Plasmodium berghei and Plasmodium yoelii.

We prepared multiple antigen constructs (MACs) using circumsporozoite (CS) protein-based B-epitopes from Plasmodium berghei, (PPPPNPND)2 and Plasmodium yoelii, (QGPGAP)3QG, along with a P. berghei T-helper epitope KQIRDSITEEWS. Mice were immunized with individual MACs in oil-in-water or water-in-oil vehicles containing block copolymer (P1005) and detoxified RaLPS (RaLPS) as well as other adjuvants. Sporozoite challenge results demonstrated that MACs in adjuvant could induce antibodies capable of active and passive protection. Water-in-oil vaccines induced the highest level of protection in mice immunized with either P. berghei or P. yoelii MACs. In a study aimed at co-eliciting immunity against P. berghei and P. yoelii, three immunizations with MACs induced protective antibodies against P. berghei but not P. yoelii parasite challenge. Therefore, it can be concluded that individually MACs are capable of inducing strong and protective immune responses to either species of rodent malaria, and that protection can be passively transferred. When MAC formulations were used together as a combined vaccine, P. berghei MACs induced a strong protective antibody response while P. yoelii MACs induced a weaker nonprotective response.

Animals↗
PubMed1997

Induction of protective antibodies in Saimiri monkeys by immunization with a multiple antigen construct (MAC) containing the Plasmodium vivax circumsporozoite protein repeat region and a universal T helper epitope of tetanus toxin.

Previous attempts in inducing protective immunity against Plasmodium vivax in human volunteers and nonhuman primates with recombinant circumsporozoite (CS) proteins have been unsuccessful, largely due to the failure of generating antibodies against the protective B epitope AGDR in the CS protein repeat region. We report here an immunization study in Saimiri monkeys with a multiple antigen construct (MAC) containing the P. vivax CS protein repeat region and a T helper epitope of tetanus toxin formulated in different adjuvants. Monkeys immunized three times with MAC in copolymer P1005, copolymer P1005 plus RaLPS, or MF-75 had titers of antibodies against CS repeat, sporozoites and the protective B epitope AGDR significantly higher than those immunized with MAC in alum or PBS (P < 0.05). Antibody levels in animals that received P1005 were maintained at high level for 7 months after the last immunization. Upon challenge with 10000 sporozoites 2 weeks after the last immunization, 75% (three of four) of monkeys from the alum group, 50% (three of six) of monkeys from the P1005 plus RaLPS group, 40% (two of five) of monkeys from the P1005 group, 33% (two of six) of monkeys from the MF-75 group, and 17% (one of six) of monkeys from the MAC alone group were fully protected. When immunized animals were challenged again with 30000 sporozoites 22 weeks after the last immunization. 40% (two of five) monkeys from the P1005 group were fully protected. The remaining (three) in this group developed low parasitemia (< 2000 parasites mm-3 of blood) after significantly longer prepatent period (P < 0.05). In addition, 17% (one of six) of monkeys each from the P1005 plus RaLPS and MF-75 groups were also fully protected. Protected animals had higher levels of prechallenge anti-AGDR antibody titers than unprotected (1933 vs 281 for the first challenge, P > 0.05; 21527 vs 196 for the rechallenge, P < 0.05). Anti-AGDR antibody titers were positively correlated with the prepatent period of infected animals (r = 0.42 for the first challenge, P > 0.05; r = 0.60 for the rechallenge, P < 0.05) and negatively correlated with the peak parasitemia (r = -0.39 for the first challenge, P < 0.05; r = 0.50 for the rechallenge, P < 0.05). The results suggested that when combined with the use of potent adjuvants and T helper epitopes, MAC subunit vaccines may potentially offer protection against malaria infection.

Amino Acid Sequence↗
PubMed1997

Protective immunity induced in squirrel monkeys with a multiple antigen construct against the circumsporozoite protein of Plasmodium vivax.

Saimiri boliviensis monkeys were immunized with a multiple antigen construct [(PvCS)2]2(P2)2 directed against the circumsporozoite protein of Plasmodium vivax or a combination of the multiple antigen construct with nonionic copolymer P1005, with P1005 and lipopolysaccharide, with muramyl tripeptide Mf-75, or with alum. Following intravenous challenge with 10,000 sporozoites of the Salvador I strain of P. vivax, 11 of the 26 monkeys were protected against patent parasitemia. Ten additional animals were partially protected. Following rechallenge of the 26 monkeys with 30,000 sporozoites of the homologous strain of parasite, four monkeys were totally protected and nine animals were partially protected.

Adjuvants, Immunologic↗
PubMed1996

Re-investigation of the circumsporozoite protein-based induction of sterile immunity against Plasmodium berghei infection.

Although the circumsporozoite protein (CSP) of the malaria parasite is the most immunologically characterized protein, the goal of using this protein in an effective vaccine has not yet been realized. Monoclonal antibody against the repetitive immunodominant B-epitope of the CSP can protect mice from malaria, but vaccines that induce antibody against this epitope do not consistently induce protection. Toward developing a rationale for a CSP-based effective vaccine, we have re-investigated the ability of anti-CSP repeat antibodies, as induced by different CSP vaccine formulations with several adjuvants, to confer sterile immunity against sporozoite challenge. Using Plasmodium berghei rodent malaria model and several CSP subunit vaccine constructs, we found that a formulation consisting of the P. berghei CSP repetitive epitope, (DPPPPNPN)2 (CS), conjugated to BSA by carbodiimide, formulated in a block copolymer and detoxified lipopolysaccharide (RaLPS) adjuvant, was particularly promising. Mice were immunized and boosted with vaccines that contain varying malarial peptide-carrier ratios of 6:1 (CS6-BSA), 55:1 (CS55-BSA) and 170:1 (CS170-BSA). Following immunization, the animals were challenged with live sporozoites. Two types of effects were observed in vaccinated mice. First, sterile immunity was induced in 100%, 50% and 29% of mice that were immunized with the CS170-BSA, CS55-BSA, and CS6-BSA vaccine conjugates, respectively. The second effect of immunization was observed with the CS170-BSA conjugate vaccine primed mice; a boost in IFA titers followed sporozoite challenge. In addition, we observed that IgG1 isotype titer against the surface of the sporozoite, as measured by IFA, and antibody avidity parallel sterile immunity. These findings reiterate the potential of the CSP as a malaria vaccine candidate antigen, and suggest that the induction of sterile immune responses depends on inducing antibody of the appropriate isotype, avidity and specificity.

Animals↗
PubMed1994

Collaborative research-academic appointments: the myth and the reality.

The following article is written from the experience of its authors with a collaborative research-academic appointment. Many advantages and disadvantages were found. The disadvantages included the division of time, responsibilities, loyalties, and energy required by two work settings rather than one. When the challenges are met, however, the rewards are many for the institution, its professional staff, its patients, and the researcher. The joint research appointment brings to the institution, clinicians, students of the researcher, and to the researcher a broadening of the professional practice and experience. Opportunities develop that would have been impossible in other situations. The quality of the teaching may improve and the quality of patient care is enhanced. The profession is advanced. The authors conclude that the additional time and effort necessary to maintain a collaborative research appointment are more than compensated.

Faculty, Nursing↗
PubMed1990

The interactive model of psychotherapy.

The authors of this article present a new model of psychotherapy, the interactive model. The model is based on the assumptions that individual functioning is based not only on the cognitive, affective, and psychomotor (behavioral) domains but also on the interaction among these domains. This therapy model directs the clinician toward assessment and intervention of these interactions.

Adult↗
PubMed1989

Chaining nursing diagnosis: the use of etiological sequencing in the development of a plan of care.

There has been an explosion of information on nursing diagnosis. A recent computer search of the literature revealed a total of 595 publications on nursing diagnosis. Only 6 of these manuscripts were released between the years 1971 and 1974 inclusively; 11 between 1975 and 1979, 178 manuscripts appeared between 1979 and 1985, while 400 were published from 1985 and 1989. In addition, a search of the Nursing and Allied Health Data Base revealed 1,068 articles published from 1982 to 1989. These data clearly emphasize the increased interest in this important topic. Consequently, a plethora of information has been made available to the educator, the clinician, the researcher, and the student. However, through over 15 years of experience with nursing diagnosis, this author has found the issue of cause and effect (etiology and problem) to be an ongoing problem.

Humans↗
PubMed1988

Single high dose-large field irradiation for palliation of advanced malignancies.

Single high dose-large field irradiation (SHD-LFI) has been used for palliation of symptoms secondary to widely disseminated malignancy. Fifty patients with various malignancies were treated with this technique in a private free-standing radiation therapy center between May 1982 and December 1984. Sixty-four treatments were delivered to the 50 patients. Thirty-two treatments were delivered to upper half-body fields, 15 to midbody, and 17 to thoracic fields. The most frequently used dose was 6 Gy which was used for 55 treatments. Thirty-nine patients had favorable response to treatment. All 22 patients with performance status (PS) 1-2 improved following treatment and 17 of 28 PS 3-4 improved. Only mild hematologic and gastrointestinal toxicity was seen. One case of possible radiation pneumonitis developed. It is concluded that SHD-LFI is a valuable palliative technique for general clinical use.

Adult↗
PubMed1986

Circadian variation in steady-state trough theophylline concentrations.

The temporal variation in trough (i.e., predose) theophylline concentrations at steady state was examined. In general, adult subjects dosed with solid theophylline formulations have morning trough theophylline concentrations 10-16% greater than corresponding evening troughs; this morning-to-evening drop is statistically significant. Large-percentage diurnal changes (greater than +/- 20% and even greater than or equal to +/- 40%) in trough-to-trough serum theophylline concentrations are not uncommon in adults. However, the change in absolute trough theophylline concentrations is pronounced in only some individuals. Repetitive studies in four of five individuals tested generally demonstrated within-individual reproducibility in the direction (but not magnitude) of the temporal variation in trough theophylline concentration. This finding further substantiates the morning-to-evening change in trough theophylline concentration as a real phenomenon and not merely the result of random variability. It is believed that the temporal variability in trough concentration observed after peroral theophylline administration requires monitoring theophylline dosage needs by obtaining blood samples at the same time each day.

Adult↗
PubMed1984

Lack of influence of an intensive antacid regimen on theophylline bioavailability.

We examined the influence of a large-volume, therapeutic antacid regimen, administered for three full days, on the steady-state bioavailability of a conventional-release and sustained-release theophylline product, Aminophyllin and Theodur, respectively. Nine stable asthmatics voluntarily completed a four-phase investigation requiring a total stay of 12 days in the Clinical Research Unit. The treatments consisted of administration of the formulations mentioned with and without antacids to each patient in a randomized sequence. Four patients participated in an additional phase where antacids were administered q2h around the clock for three days. After coadministration of theophylline plus antacids for two days, theophylline therapy was discontinued while numerous blood samples were obtained over 22 hr and analyzed for theophylline content via radioimmunoassay. Antacids had no predictable, consistent influence on theophylline absorption rate as determined by the absorption rate constant, the time to maximal theophylline concentration, or the lag time for theophylline absorption. Antacids had no detectable influence on theophylline elimination half-life and had no consistent, statistically significant effect on the extent of theophylline bioavailability, according to measurements of maximal concentration, AUC measured over the appropriate steady-state dosing interval, or elimination-rate adjusted AUC. The substantial intraindividual changes for all parameters of theophylline bioavailability that occurred for control and treatment phases likely represent spontaneous, random between-day variability in theophylline disposition independent of antacid administration, as evidenced by the comparability of the percent coefficient of variation for parameters of bioavailability across all phases. Our data demonstrate that therapeutic antacid administration has no effect on steady-state theophylline bioavailability and does not alter the intrinsic variability in theophylline absorption. Based on the results of our data, it is unlikely that a clinically significant (greater than 20%) decrease in theophylline absorption would occur in any patient treated intensively with antacids concurrently.

Adult↗
PubMed1984

Modification of the theophylline radioimmunoassay.

The routine utilization of a commercially available radioimmunoassay (RIA) for theophylline (GammaDab), although reliable, is currently prohibited by the high cost of the reagents. In an effort to reduce these costs we have diluted the [125I]theophylline tracer and theophylline antiserum reagents by one-half, contrary to the manufacturer's recommendations. We have demonstrated that an excellent correlation exists (r = 0.968) between our modified RIA method and a conventional high-performance liquid chromatographic technique, despite reagent dilution. Accordingly, our reagent costs have been reduced by half. We conclude that the GammaDab kit reagents can be diluted twofold and still provide an accurate determination of serum theophylline. We must also emphasize that any further alteration(s) of this theophylline RIA procedure would require a thorough evaluation before its routine use could be substantiated.

Chromatography, High Pressure Liquid↗
PubMed1979

Comparison of five information services as sources for bioavailability data.

The usefulness of five drug information services in obtaining bioavailability data from journal literature is compared. The deHAEN Drugs in Use system, the Iowa Drug Information Service (IDIS), Index Medicus, MEDLINE and International Pharmaceutical Abstracts (IPA), each for a 10-year period, were searched for citations on bioavailability studies on the oral dosage forms of acetaminophen, lithium carbonate, phenytoin, nitrofurantoin and theophylline. Both quantity of references indexed and quality of data were considered. No significant difference was found in the mean value scores for the five services. Index Medicus provided 79 citations but required 7.7 hours of search time. MEDLINE yielded 62 citations but required only 1.1 hours to search. IPA, IDIS and deHaen had lower numbers of citations and intermediate search times. IPA, deHaen and Index Medicus all cited unique articles, with 11%, 7% and 3%, respectively. Index Medicus had the lowest percent of articles duplicated by two or more services (49%). The most comprehensive serch with the fewest duplicate citations would be obtained from searching deHaen's Drugs in Use, IPA and Index Medicus.

Biological Availability↗
PubMed1976

Complement activation in vivo in cancer patients receiving C. parvum immunotherapy.

Serum complement levels were assayed in 26 patients with disseminated cancer, who received immunotherapy with infusion of C. parvum. Complement activation, indicated by the consumption of C3 or C4 or both, was found in 46% of the patients. Serum samples showed direct correlation between decreased C3 and conversion of C3 proactivator, whereas such conversion did not occur when C4 alone was decreased. It is concluded that the bypass (properdin) pathway was activated in patients in whom C3 consumption was detected, while the classical (C1) pathway was activated in the patients with C4 consumption unaccompanied by C3 decrease. Direct correlation was observed between delayed cutaneous hypersensitivity reactions to recall antigens and the incidence of C. parvum-associated complement activation.

Complement C3↗
PubMed1975

Adjuvant immunotherapy and chemoimmunotherapy in colorectal cancer of the Dukes' C classification. Preliminary clinical results.

Fifty-eight patients with Dukes' C classification of carcinoma of the large bowel were placed on adjuvant immuno- or chemoimmunotherapy with Bacillus calmette guerin (BCG) or combination of 5-fluorouracil (5-FU) plus BCG following primary and definitive surgery, and were followed for up to 21 months. Of twenty-six patients receiving BCG alone by scarification, five have relapsed with 75% of freedom from disease estimated at 15.1 months compared with 10.1 months in a group of carefully selected historical controls who had surgery alone (p = 0.12). The survival of all patients receiving BCG alone has not reached the 75 percentile yet, and the difference from controls is currently estimated at the 18% level. The combination of 5-FU plus BCG (studied in 32 patients) may be superior to BCG alone at this time, in that it appears to more effectively protect against tumor recurrence (75 percentile not yet reached compared to control, (p = 0.08). The survival of patients on 5-FU plus BCG also appears to be improved (p = 0.09). No patients have expired compared to a 75 percentile survival of 16.6 months in the control. Serial determination of plasma CEA was crucial in the clinical follow-up of these patients. Frequent CEA detetminations have led to early detection of clinical relapse. In the elevation of CEA suggests tumor recurrence with a high degree of probability in patients with past history of cancer of the large bowel.

BCG Vaccine↗