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C Diggs

Publications and source records attributed to C Diggs.

15 recordsLinked to original sources
PubMed2000

Synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined HLA genotypes.

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.

Adult↗
PubMed2000

Immunogenicity and efficacy in aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1.

The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP1(19)) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP1(19) constructs elicited high levels of antibodies to MSP1(19) but only one construct, the 19-kDa fragment expressed as a secreted fusion protein from Saccharomyces cerevisiae (yP30P2MSP1(19)), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP1(19) in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.

Adjuvants, Immunologic↗
PubMed2000

Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys.

A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Palo Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, 1 of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge.

Adjuvants, Immunologic↗
PubMed1999

Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid.

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.

Adolescent↗
PubMed1998

High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction: results of a phase II study of the Eastern Cooperative Oncology Group.

BACKGROUND: To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS: Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS: During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n=14; Ivor Lewis, n=16; other, n=3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months; P <0.05). CONCLUSION: High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.

Adenocarcinoma↗
PubMed1981

Inhibitory effects of immune monkey serum on synchronized Plasmodium falciparum cultures.

We studied the effects of heat-inactivated immune monkey serum on the growth of a partially synchronized culture of Plasmodium falciparum. By light microscopy, parasites within erythrocytes were morphologically indistinguishable from those cultured in normal serum. Immune serum reduced by 90% the number of erythrocytes containing newly invaded rings. Clusters of extracellular merozoites, usually around clumps of malarial pigment, were seen frequently in cultures grown with immune serum but rarely in cultures with normal serum. Electron microscopy confirmed the normal development of intraerythrocytic parasites. In immune serum cultures, electron-dense precipitates were found on the surface of schizonts, merozoites, and the excrescences on the plasma membrane of schizont-infected erythrocytes. Merozoites in immune serum culture appeared to aggregate by adherence between adjacent surface coats. These findings support the hypothesis that immune serum agglutinates merozoites and thereby inhibits their invasion into uninfected erythrocytes.

Animals↗
PubMed1979

Combined modality treatment of Hodgkin's disease confined to lymph nodes. Results eight years later.

Eighty-seven patients with newly diagnosed Hodgkin's disease, pathologic stages IA, IIA, IIB and IIIA, were assigned at random to receive either extended field radiotherapy alone or that therapy followed by six cycles of MOPP (nitrogen mustard, Oncovin, procarbazine, prednisone) chemotherapy. Patients were entered into the study from January 1970 to January 1974. Patients were followed for a median of 69 + months from the end of all treatments. Patients whose disease was less than stage IIIA had a 31 per cent relapse rate with radiotherapy alone compared to a 6 per cent relapse rate with combined modality treatment (P = 0.04). No deaths from Hodgkin's disease have occurred in patients who received combined modality therapy, whereas 24 per cent of the patients who received radiotherapy alone have died with active disease. However, three patients with stage IIIA disease who were treated with both modalities have died from other causes (myocardial infarction, adenocarcinoma of lung, acute leukemia). Combined modality therapy of patients with early Hodgkin's disease may be superior to radiotherapy alone, especially for certain subgroups of patients discussed in detail.

Adolescent↗
PubMed1978

Antibody-dependent cytotoxicity against Trypanosoma rhodesiense mediated through an alternative complement pathway.

A quantitative in vitro method was used to examine the role of classical and alternative pathways of complement activation in cytotoxicity against African trypanosomes by immune serum. This assay is based on the estimation of the extent of antibody-mediated cytotoxicity by measurement of inhibition of incorporation of [(3)H]leucine as an indicator of trypanosome metabolic integrity. To determine which pathway(s) is activated during cytotoxic events, complements sufficient in all components (C4S) and deficient in C4 (C4D) were used. Immune inhibition of [(3)H]leucine uptake by trypanosomes was observed in the presence of both complement sources. Treatment of C4S or C4D serum with cobra venom factor or disodium ethylenediaminetetraacetic acid abolished antibody-mediated cytotoxicity as well as immune hemolysis, thus suggesting the requirement for late-acting complement components. Ethyleneglycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid had no effect on inhibition of leucine incorporation, whereas immune hemolysis was inhibited, suggesting that cytotoxicity did not require C1 activation, a Ca(2+)-dependent event. The dependence of the cytotoxic process on Mg(2+) and not Ca(2+) ions and the fact that C4D guinea pig serum is fully active in trypanosome cytotoxicity indicate that an alternative pathway of complement activation is sufficient for activity.

Animals↗
PubMed1976

Immune serum-mediated cytotoxicity against Trypanosoma rhodesiense.

The metabolic integrity of Trypanosoma rhodesiense can be assessed in vitro by the extent of incorporation of radiolabeled leucine into trichloroacetic acid precipitable material or into material retained after filtration on a glass fiber filter. Incorporation is an approximately linear function of time, and the rate of incorporation is linearly dependent on cell concentration in the presence of normal rat serum. Incorporation is completely prevented if the organisms are reacted wiith fresh serum from animals immunized with gamma-irradiated parasites; the degree of inhibition is a function of the dose of immune serum used. This serum-mediated cytotoxic activity is abrogated by heating the serum, but can be fully restored by addition of fresh rat or guinea pig serum to the heated immune serum. The serum activity arises promptly after one to four immunizing doses of irradiated parasites, falls to lower levels by 1 month, but persists for at least 2(1/2) months, and is unaffected by challenge with viable trypanosomes.

Animals↗
PubMed1975

Protein synthesis in vitro by cryopreserved Plasmodium falciparum.

Plasmodium falciparum-parasitized erythrocytes obtained from infected owl monkeys (Aotus trivirgatus) and stored in the frozen state retain both the capacity to incorporate 14C isoleucine into protein and to infect animals. The cryopreservation method involves the use of glycerol and the reconstitution of isotonicity after thawing. Animals have been infected from material held for up to 273 days and protein synthesis has been demonstrated in vitro for up to 180 days after freezing. The specificity of protein synthesis as an activity of the parasites was shown by the inactivity of control uninfected erythrocytes stored by the same method. Additional evidence for the specificity of the reaction was obtained from inhibition studies with chloroquine; a 7 X 10(-5) M concentration of the drug resulted in 50% inhibition of the initial rate of protein synthesis.

Animals↗
PubMedDate not supplied

Our experiences with breeding of nine-banded armadillos (Dasypus novemcinctus) in captivity.

The nine-banded armadillo is considered the best animal model in the study of leprosy. Armadillos have never been successfully bred in the laboratory and therefore animals required for the experiments are captured from the wild and are likely to carry many diseases including leprosy. An attempt was made to breed them in captivity. Our attempt to house them in various combinations in their natural environment in the farmlands of Louisiana was successful. Although a significant increase in conception and delivery was recorded, consistent breeding of the animals was not obtained.

Animal Husbandry↗