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Biomedical subjects

J H Leech

Publications and source records attributed to J H Leech.

27 records · Page 2Linked to original sources

A comparison of knobby (K+) and knobless (K-) parasites from two strains of Plasmodium falciparum.

Erythrocytes infected with Plasmodium falciparum develop knob-like protrusions on their membranes. Knobby (K+) parasites of the FCR-3 (Gambian) strain have been shown to possess a histidine-labelled protein of apparent molecular weight 80 000 which is absent from knobless (K-) variants of the same strain. Here we report similar findings with K+ and K- parasites of another strain, the Malayan Camp strain, and also with cloned K+ and K- parasites of the FCR-3 strain. A histidine-labelled protein unique to the two K+ parasites was identified as a broad band with an apparent molecular weight of 89 000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of this protein in both K+ Malayan Camp parasites and K+ FCR-3 (Gambian) parasites and its absence from K- parasites of both strains is consistent with this protein being a major component of knobs.

Animals↗

Plasmodium falciparum malaria. An amelanotic melanoma cell line bears receptors for the knob ligand on infected erythrocytes.

Erythrocytes infected with Plasmodium falciparum trophozoites and schizonts are not seen in the peripheral circulation because they attach to venular endothelium via knoblike structures on the infected erythrocyte membrane. We have recently shown that erythrocytes containing P. falciparum trophozoites and schizonts likewise attach to cultured human venous endothelial cells via knobs. In search of a more practical target cell for large scale binding studies designed to characterize and isolate the knob ligand, we tested various normal cells and continuous cell lines for their ability to bind P. falciparum-infected erythrocytes. Of the 18 cell types tested, binding of infected erythrocytes was observed to a human amelanotic melanoma cell line and amnion epithelial cells as well as to human aortic and umbilical vein endothelial cells. 96-100% of amelanotic melanoma cells bound 17+/-4 (+/-1 SEM) infected erythrocytes per positive cell, whereas fewer endothelial cells (4-59%) and amnion epithelial cells (8-19%) were capable of binding 12+/-5 and 4+/-1 infected erythrocytes per positive cell, respectively. Further studies designed to compare the mechanism of binding to the amelanotic melanoma cell line and endothelial cells showed the following results. First, that adhesion of infected erythrocytes to these two cell types was parasite stage-specific in that only erythrocytes containing late ring forms, trophozoites, and schizonts bound. Erythrocytes containing early ring forms, which do not attach to venular endothelium in vivo, did not bind to either cell type. Second, erythrocytes infected with trophozoites and schizonts of P. vivax or a knobless strain of P. falciparum, both of which continue to circulate in vivo, did not bind to either target cell type. Third, transmission electron microscopy showed that infected erythrocytes attached to the amelanotic melanoma cells via knobs. We conclude that cultured human endothelial cells and an amelanotic melanoma cell line share common determinants on their surface and that the mechanism of binding to these two different cell types is similar. The amelanotic melanoma cell line offers a useful substitute for endothelial cells in binding studies requiring large numbers of target cells.

Amnion↗

Malignant lymphoma of peripheral T-lymphocyte origin: immunologic, pathologic, and clinical features in six patients.

In a continuing study of patients with lymphoproliferative diseases, six adult patients were encountered with a distinctive malignant lymphoma of peripheral T-lymphocyte origin. Cell suspensions from lymph nodes of these patients contained a pleomorphic, cytologically atypical population of lymphocytes, of which an average 58% marked as T cells in the E-rosette test. The average percent of surface immunoglobulin-bearing B cells in these suspensions was 6%; they were of polyclonal distribution. Lymph node biopsies revealed a malignant lymphoma with certain characteristic features of the organization of the infiltrate, the morphology of the lymphoid cells, and the nature of non-lymphoid cellular elements. The average age of the patients was 67 years; they presented with generalized lymphadenopathy, anorexia, and significant loss of weight. Four patients hd lung and/or pleural involvement by lymphoma at presentation. The immunologic, pathologic, and clinical features of these patients serve to characterize this recently recognized malignant lymphoma further.

Adult↗

Ultrastructural study of Reed-Sternberg cells. Comparison with transformed lymphocytes and histiocytes.

The ultrastructural features of Reed-Sternberg cells from 17 patients with Hodgkin's disease were compared with those of histiocytes and transformed lymphocytes in both benign and malignant conditions. Transformed lymphocytes and Reed-Sternberg cells appeared to have similar features, including large nuclei with dispersed chromatin, large nucleoli, and great numbers of cytoplasmic polyribosomes. Histiocytes contained abundant cytoplasmic lysosomal granules and microfilaments. These results are indicative of the origin of Reed-Sternberg cells from lymphocytes.

B-Lymphocytes↗

Malignant lymphomas of follicular center cell origin in man. I. Immunologic studies.

Lymphomas with histologic features indicating a follicular center cell (FCC) origin were analyzed from 26 patients of a group of 45 consecutive non-Hodgkin's lymphoma patinets whose tumors were studied for B- and T-cell characteristics. They were compared with benign, reactive lymphoid tissue from 14 patients. Cell suspensions from biopsy material, blood, or bone marrow were examined for surface Ig and for rosette formation with sheep erythrocytes (E rosettes). Of the 26 patients with FCC lymphomas, 22 had 40% or more Ig-bearing cells; all patients with FCC lymphoma tissues had 25% or less E rosette-forming cells. Cells from most FCC lymphomas of the cleaved type had surfac IgM; those from several FCC lymphomas had both IgM and IgD. Cells from lymphomas of noncleaved cell type had surface IgG or IgA. Light-chain analysis showed that cells from FCC lymphomas bore a predominant light-chain type, which indicated their monoclonal nature. Neoplastic cells from several FCC lymphomas synthesized the surface Ig which they bore. Reactive tissues usually contained fewer Ig-bearing and more E rosette-forming cells than FCC lymphomas; the Ig-bearing cells, with one exception, had a polyclonal distribution. Correlation of histologic and immunologic observations indicates that most lymphomas identified as FCC in origin by light micorscopic criteria mark as B cells with the use of immunologic techniques and that FCC lymphomas are the most common type of non-Hodgkin's lymphoma.

B-Lymphocytes↗

Malignant lymphomas of follicular center cell origin in man. II. Ultrastructural and cytochemical studies.

Tissues from malignant lymphomas with both nodular and diffuse growth patterns, thought by light microscopy to be composed of cells of follicular center cell (FCC) origin, Were examined by electron microscopy; the tumor cells were similar to lymphoid cells found in reactive follicular centers. Tumor cells from neoplasms thought to be composed of cleaved FCC often had more pronounced nuclear folding than did cleaved FCC of reactive follicles, whereas cells in tumors of noncleaved FCC type were indistinguishable from their presumed counterparts in reactive follicles. Large cell noeplasms, previously classified as "histiocytic" lymphomas were composed of cells with ultrastructural characteristics of transformed lymphocytes; they showed neither ultrastructural nor cytochemical features of mononuclear phagocytes. These findings support the concept that a major group of lymphomas arises from lymphocytes of follicular centers.

B-Lymphocytes↗

Characterization of a Cryptosporidium parvum sporozoite glycoprotein.

Polyclonal and monoclonal antibodies directed against Cryptosporidium oocysts or sporozoites were developed to identify and characterize sporozoite pellicle and apical complex antigens. A very large glycoprotein of Cryptosporidium sporozoites was identified by three monoclonal antibodies that also reacted with intracellular merozoites. The glycoprotein was also identified by polyclonal antibodies that were affinity-purified on nitrocellulose-bound recombinant proteins expressed by four lambda gtll genomic clones.

Animals↗