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Biomedical subjects

I Cunningham

Publications and source records attributed to I Cunningham.

At least 73 records · Page 4Linked to original sources

Antigenic analysis by immunofluorescence of in vitro-produced metacyclics of Trypanosoma brucei and their infections in mice.

The antigenic types in populations of Metacyclic trypanosomes of Trypanosoma brucei isolated from Glossina morsitans head-salivary gland trypanosome cultures and bloodstream forms in the early parasitemias produced from whole culture supernatant fluids containing metacyclic forms, were analyzed by the indirect fluorescent antibody test using clone-specific antisera. Metacyclic trypanosomes in cultures initiated with cloned bloodstream forms with heterogeneous with respect to their variable antigenic type (VAT). Trypanosomes comprising early parasitemias in immunosuppressed mice infected with metacyclics produced in cultures also had a range of VATs. Three of the VATs detected in the early parasitemias in mice have also been identified by other investigators in tsetse fly-transmitted populations of the same stock.

Animals↗

The separation and structure of infective trypanosomes from cultures of Trypanosomas brucei grown in association with tsetse fly salivary glands.

Infective trypanosomes developed when Trypanosoma brucei was cultivated at 28 C in a liquid medium containing tsetse fly head-salivary gland explants. They were separated from the noninfective culture forms using DEAE-cellulose column chromatography. It was demonstrated by light and electron microscopy that the separated organisms were morphologically similar to metacyclic stages found in a tsetse fly and that they had a characteristic surface coat. Single metacyclic trypanosomes isolated from the cultures gave rise to infections in mice.

Animals↗

Antigenic analysis by agglutination of Trypanosoma brucei brucei parasitemias initiated in mice with in vitro-produced metacyclics.

Trypanosomes from 14 first-peak parasitemias initiated in mice by injection of in vitro-produced metacyclics were stabilated. Strains derived from these stabilates were analyzed for their antigenic composition by cross-agglutination with immune sera produced in rabbits against 12 of the stabilates. The antigenic composition of the 14 stabilates was compared also with two first-peak parasitemias from mice inoculated with fly-derived metacyclics, the variant-specific antigen of the strain used to initiate the cultures that ultimately became infective, and the antigenic variant that was used to infect the flies. One variant-specific, presumably basic, antigen was found, either as the predominant (nine parasitemias) or as a minor (seven parasitemias) antigen, in all first peak-parasitemia strain initiated with culture- or fly-derived metacyclics; it was absent, however, from the strains (not first-peak parasitemias) used to start the cultures or to infect the flies. Only one of the first-peak parasitemias appeared to have the basic antigen alone. The remaining parasitemia populations seemed to have from about two to six antigens, some of which were common to culture- and fly-derived infections. There was very little, if any, antigenic relationship between the foregoing populations and the strains employed for initiation of cultures or for infection of flies. It is evident from the results that much antigenic similarity exists between the culture- and tsetse fly-derived first-peak parasitemias.

Adsorption↗

Infectivity of Trypanosoma brucei cultivated at 28 C with tsetse fly salivary glands.

When transformed procyclic noninfective trypanosomes of several unrelated stocks of Trypanosoma brucei were cultivated in T-30 Falcon flasks at 28 C in a liquid medium containing head-salivary gland explants of Glossina morsitans morsitans some of the organisms developed into forms infective for mice. Infective trypanosomes were detected 7 to 14 days after the cultures were prepared and they persisted for varying periods of up to 88 days when the cultures were terminated. A few of the salivary glands became invaded with parasites about the time infective organisms appeared in the cultures. Using T. brucei TREU 929, it was shown that trypanosomes grown with between 2m and 50 explants were capable of producing infections consistently for prolonged periods. On the other hand, trypanosomes cultivated with 25 or fewer explants rarely infected mice. Infectivity titrations on trypanosome suspensions from cultures of stocks TREU 1275 and TREU 929 revealed that the maximum number of infective organisms was present 26 to 50 days after initiation of the cultures. Control cultures of trypanosomes grown in medium alone were generally not infective but 2 of the 6 stocks gave rise to a few sporadic infections. A few epimastigote-like and metacyclic-like trypanosomes were seen in stained preparations of infective inocula.

Animals↗

Results of treatment of Ph'+ chronic myelogenous leukemia with an intensive treatment regimen (L-5 protocol).

Thirty-seven patients with Philadelphia-chromosone-positive (Ph'+) chronic myelogenous leukemia who were untreated or minimally pretreated were entered on the L-5 protocol. This protocol consisted of sequential treatment with splenic irradiation, splenectomy, arabinosylcytosine and 6-thioguanine, and L-asparaginase. Maintenance therapy was hydroxyurea or a multiple-drug regimen. The median survival of the 37 patients is 50 mo. Twelve patients showed a temporary reduction in the percentage of Ph'+ marrow metaphases to less than one-third of the initial values and in 7 of these patients none were found. The duration of the Ph'+ chromosome reduction ranged from 1 to 43 mo. The median survival of the responders has not yet been reached. It is concluded that whereas overall survival is not appreciably extended, patients who have a reduction in Ph'+ cells in the marrow may survive longer than the average; also, the reduction occurs most frequently in patients who have relatively small spleens at diagnosis. The reduction is difficult to maintain, and it may be reinduced in some patients with intensive chemotherapy.

Adolescent↗

The L-5 protocol: intensive treatment for patients with chronic myeloid leukemia.

An aggressive treatment program combining splenic irradiation, splenectomy and intensive cytotoxic combination chemotherapy was used in 37 patients with Ph1 chromosome positive chronic myelogenous leukemia. Cytogenetic Ph1 chromosome determination on marrow cells revealed a significant but transient decrease in the Ph1 positive cell population in 12/37 (32%) cases. Survival duration appears longer in patients who show a reduction in the Ph1 positive population. Blastic transformation occurred in 18/37 (49%) cases, not different from our historical control.

Adolescent↗

Analysis of the antigenic composition of Trypanosoma brucei brucei bloodstream and culture forms by the quantitative direct fluorescent antibody methods.

The quantitative direct fluorescent antibody (QDFA) methods were employed for the antigenic analysis of bloodstream forms and culture procyclics of 2 variants, TRUM (Trypanosome Research University of of Massachusetts) 106 and TRUM 107, of Trypanosoma brucei brucei. Intact and trypsinized trypanosomes were studied. It was demonstrated that: (A) The specific variant antigens are localized in the surface coat of bloodstream trypomastigotes. (B) In addition to the common antigens shared by bloodstream forms and culture procyclics, there are also certain antigens unique to these latter stages. (C) Still another group of antigens, not found in the culture procyclics, appears to be shared by the bloodstream forms, irrespective of their variant-specific antigens. These antigens may be present in part in the coat or on the cell membrane and in part within the cytoplasm. (D) Irrespective of the bloodstream-form variant from which they are derived, the procyclics are antigenically the same. The QDFA results are analyzed statistically and discussed in the light of the available literature.

Animals↗

Infectivity reacquisition by Trypanosoma brucei brucei cultivated with tsetse salivary glands.

Reacquisition of infectivity four mice was observed in cultures of Trypanosoma brucei brucei grown in the presence of tests fly salivary gland explants in a medium based on the amino acid composition of Glossina hemolymph and containing fetal bovine serum. High infection rates were obtained in mice inoculated with about 1.5 X 10(8) organisms. Infectivity reacquisition was correlated with invasion of the salivary glands by the parasites. Few small trypanosomes with subterminal kinetoplasts (metacyclic-like forms) were found in the infective inoculums. The parasitemias in mice consisted of pleomorphic cultivable trypanosomes. Cultures initiated by these organisms and then placed with the head-salivary gland preparations became infective for mice.

Animals↗

Acute lymphoblastic leukemia in adults and children. Differences in response with similar therapeutic regimens.

Twenty-three adult patients (ages greater than 15 years) and 75 children with acute lymphoblastic leukemia were treated with similar intensive, sequential cytotoxic protocols (L-2). The adult patients have lower remission rate (78%) than the children (98%). The duration of remission and the length of survival are also shorter in adults. The incidence of central nervous system (CNS) relapse in adults (27.7%) is higher than in children (7.1%) suggesting that prolonged prophylactic intrathecal methotrexate as given to the children is more effective than the schedule used for adults where intrathecal methotrexate was given only in the first 2 months of therapy. The low incidence of CNS involvement in children on the L-2 protocol compares favorably with other series reported using a combination of cranial irradiation and intrathecal methotrexate. In both adults and children there seemed to be a higher incidence of CNS involvement in patients with initial white blood cell counts greater than 25,000 cells/mm3.

Adolescent↗