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Biomedical subjects

J Lesley

Publications and source records attributed to J Lesley.

52 records · Page 3Linked to original sources
PubMed1985

Antibodies against the transferrin receptor block the induction of cytotoxic T lymphocytes. A new method for antigen-specific negative selection in vitro.

The induction of cytotoxic T lymphocytes (CTL) specific for alloantigen in a primary mixed lymphocyte culture (MLC) was used as a model system to study the potential usefulness of monoclonal antibodies directed against the murine transferrin receptor in eliminating antigen-activated T cells. Two monoclonal antibodies were used which are able to block the transferrin-mediated uptake of iron by growing cells. One of these antibodies is cytotoxic in the presence of complement (C). Treatment of MLC cells from control, uninhibited cultures with the cytotoxic anti-transferrin receptor antibody plus C completely knocked out all CTL effector activity showing that all of the effector cells expressed the receptor. However, surviving cells from such antibody-plus C-treated populations were not depleted of precursors since they were able to mount a strong CTL response to the original alloantigen upon restimulation. Blocking antibody against the transferrin receptor, in the absence of C, when present during the course of a primary MLC, completely inhibited the generation of effector CTL. Conditions were optimized such that antibody present during the course of the MLC could completely and specifically eliminate all antigen-activated T cells including precursors as assessed by secondary restimulation with the original, plus third-party antigens, in the absence of blocking antibody. This method for producing specifically unreactive T cell populations appears to be superior to previously described techniques.

Animals↗
PubMed1985

The Pgp-1 antigen is expressed on early fetal thymocytes.

The Pgp-1 glycoprotein is expressed on the bone marrow prothymocyte and on a class of intrathymic progenitor cells in the adult animal. Only 5% of adult thymocytes are strongly Pgp-1+. When fetal thymocytes of day 13-14 of gestation are examined by flow cytometric analysis, 80-90% of thymocytes are Pgp-1+, while the bulk of thymocytes are Thy-1-. By day 15-16, the percentage of Pgp-1+ cells begins to fall while nearly all cells become Thy-1+. Two-color immunofluorescence indicates that many Pgp-1+ cells are Thy-1+. The percentage of Pgp-1+ cells continues to fall over the next several days, reaching adult levels by day 19. These observations are consistent with the interpretation that at least some classes of thymocyte progenitors are Pgp-1+.

Animals↗
PubMed1984

Expression of transferrin receptor on murine hematopoietic progenitors.

We have used a monoclonal antibody against the murine transferrin receptor to study the expression of the transferrin receptor on the hematopoietic progenitor cells (BFU-E, CFU-E, and CFU-C) present in mouse bone marrow. Elutriation and cell-sorting data are consistent with the hypothesis that most CFU-E are transferrin receptor positive while most BFU-E express much less transferrin receptor. CFU-C comprise both transferrin-receptor-positive and -negative cells.

Animals↗
PubMed1984

Effect of an anti-murine transferrin receptor-ricin A conjugate on bone marrow stem and progenitor cells treated in vitro.

A monoclonal antibody with specificity for murine transferrin receptor was conjugated with the toxic A subunit of ricin. The dose range, specificity, and kinetics of inhibition of protein synthesis of the conjugate were determined on the murine T-lymphoma cell line, BW5147. When toxin was present throughout the period of culture, in vitro myeloid (CFUc) and erythroid (CFUe and BFUe) bone marrow colonies were inhibited by doses of conjugate comparable to those that inhibit protein synthesis in murine cell lines (IC50 of 5 X 10(-11)M). Bone marrow exposed briefly (30 min to 6 h) to anti-transferrin receptor antibody-ricin A conjugate was assayed for myeloid (CFUc) and erythroid (CFUe and BFUe) progenitors in vitro and for in vivo spleen colony formation (CFUs). Only CFUe were depleted by this pulse exposure, consistent with the higher frequency of proliferating cells and transferrin receptor expression in the CFUe population relative to other progenitors.

Animals↗
PubMed1983

Monoclonal antibodies to murine leukemia virus gp 70 recognize the same T lymphoma cell surface molecules as anti-immunoglobulin.

Chicken antisera to mouse immunoglobulin (anti-Ig) detect molecules on T lymphocytes of mice consisting of "heavy chains" similar in size to IgM mu chains and "light chains" similar in size to lambda or kappa chains. Because these T cell-derived proteins react with anti-Ig and are composed of Ig-like heavy and light chains, these molecules have been viewed as candidates for "IgT," the putative T lymphocyte receptor for antigen. We have demonstrated, by immunoprecipitation and two-dimensional gel analysis, that the lymphoma surface molecule precipitated by chicken anti-Ig is identical to the viral 70,000 dalton glycoprotein (gp 70) expressed by that lymphoma and is unassociated with any "light chain" or equivalent. For each of the three lymphomas analyzed, the gp 70 two-dimensional gel pattern was individually distinctive, and, in each case, the molecules precipitated by anti-Ig exhibited the same pattern as the gp 70. The viral gp 70 does have cross-reacting determinants with mouse IgM as seen by the chicken antiserum. We have substantiated these results by demonstrating that monoclonal antibodies to viral gp 70 precipitate the same molecules as chicken anti-Ig. These findings demonstrate that these T lymphoma cell surface molecules do not represent the T cell immunoglobulin receptor for antigen unless gp 70 itself is an antigen receptor.

Animals↗
PubMed1982

Murine cell surface transferrin receptor: studies with an anti-receptor monoclonal antibody.

A rat monoclonal antibody against the murine transferrin receptor has been identified. The receptor is a 95,000 molecular weight species that exists in the cell membrane as a disulphide-bonded dimer. Whereas 29 of 29 murine hematopoietic tumor cell lines express detectable numbers of transferrin receptors, less than 1% of adult thymocytes or spleen cells and only 5% of bone marrow cells are positive. However, fetal liver and neonatal spleen contain substantial numbers of transferrin receptor-positive cells. Induction of Friend cells in vitro with dimethyl-sulphoxide leads to an overall increase in the expression of transferrin receptors on the cell surface. The anti-transferrin receptor antibody we have obtained partially blocks iron uptake from 59Fe-transferrin by a variety of murine cell lines and inhibits the growth of a murine myeloma cell line in vitro.

Animals↗
PubMed1982

Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues.

A murine leukocyte surface glycoprotein (Mr = 95 000) has been defined by means of xenogeneic monoclonal antibodies. In normal hematopoietic tissues, the glycoprotein is found in highest amounts in the bone marrow. Flow cytometric analysis shows that essentially all bone-marrow cells express the glycoprotein and that it is a major component of a subpopulation of cells containing predominantly granulocytic precursors. In contrast, only about 5 percent of thymocytes express sufficient glycoprotein to be detected by flow cytometric analysis, although under stringent conditions up to 20 percent of thymocytes are susceptible to complement-mediated cytotoxicity using a monoclonal antibody against the glycoprotein. Functional assays showed that both prothymocytes and colony forming unit-spleen express the glycoprotein which is broadly distributed on murine hematopoietic tumor cell lines. However, although some Thy-1+ (T) cell lymphomas express large amounts of the glycoprotein, others do not express detectable quantities of the molecule. The glycoprotein is not restricted to hematopoietic cells and can be detected on lung, kidney, brain, and liver as well as cultured fibroblasts. Monoclonal antibodies against the glycoprotein cross-react with an antigen present on human cells. As described in the accompanying paper, the glycoprotein exists in two antithetical allelic forms and we show that it is identical to a polymorphic surface molecule independently characterized by Colombatti and co-workers.

Animals↗
PubMed1982

Genetic characterization of a polymorphic murine cell-surface glycoprotein.

As described in the preceding paper, monoclonal antibodies have been raised by immunization of rats with mouse hematopoietic cells which detect a major cell-surface glycoprotein (Mr = 95 000) of mouse bone-marrow cells of the granulocytic series. While most of the monoclonal antibodies detect this molecule one bone-marrow and spleen cells of all mouse strains, two antibodies recognize alternative allelic forms of the molecule. One alloantigen is expressed in all the remaining inbred strains examined. The alloantigens are codominantly expressed on the cells of F1 mice. Backcrosses of DBA/2 and C57BL/6 with F1 mice (B6D2F1) confirmed that a single genetic locus is involved in the expression of the two antigenic forms and demonstrated linkage to Ly-m11 which has previously been mapped to mouse chromosome 2. These genetic mapping experiments and the biochemical properties of the glycoprotein suggested that it might be identical to a glycoprotein first identified on murine fibroblasts by Hughes and August and designated Pgp-1. This has been firmly established by exchange of monoclonal antibody reagents and sequential immunoprecipitations.

Animals↗
PubMed1970

Antigen receptor molecules: inhibition by antiserum against kappa light chains.

Rabbit antiserum against mouse kappa chains, the predominant class of light chains found in mouse immunoglobulins, inhibits the immune response in vitro of mouse spleen cells to erythrocyte antigens. The inhibition becomes irreversible if the mouse spleen cells are treated briefly with both antiserum to kappa chains and complement.

Animals↗
PubMedDate not supplied

Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor beta-chain gene.

The development of T cells within the thymus is not well understood. It is known that thymocytes are derived from a progenitor cell in the bone marrow, the prothymocyte, and that cells in the subcapsular area of the thymus can give rise to progeny in both the cortex and the medulla. However, it is not clear whether all medullary thymocytes are necessarily derived from cortical cells. In particular, it has been difficult to distinguish intrathymic progenitor cells. Recently, however, Lesley et al. have defined a thymocyte subpopulation which can be isolated by treatment of the thymus with cytotoxic anti-Thy-1 antibodies and that seems to be enriched for thymocyte progenitors as measured first by its ability to repopulate transiently the thymus of an irradiated host, and second, by its high content of cells bearing Pgp-1 (refs 10, 11), a cell-surface glycoprotein of relative molecular mass 95,000 that is present on most or all prothymocytes of the bone marrow and on fetal thymocytes, but on only a few per cent of cells in the adult thymus. We show here that the gene encoding the beta-chain of the T-cell receptor for antigen, which is rearranged during T-cell ontogeny, is predominantly in the germline configuration in these cells.

Animals↗
PubMedDate not supplied

A survey of diabetes services in hospitals in Papua New Guinea.

AIM: To determine the number and distribution of diabetic persons in Papua New Guinea (PNG), and to document available services. METHODS: Survey of the 19 hospitals thought to be the most significant centres for care of diabetes. RESULTS: 16 hospitals were successfully surveyed. Type 1 diabetes is very rare, with 18 known cases in the country (6 less than 15 years old). Known type 2 cases totalled around 4600 with almost all cases in coastal centres, particularly Port Moresby, East New Britain and Manus. There were very few cases in the highlands. Insulin is generally available, along with oral hypoglycaemic drugs. Testing for complications is very limited, and glycosylated haemoglobin (HbA1c) testing is available in only one centre. Only 3 trained diabetes educators are available in the country, with 1 dietitian and no specialist endocrinologists. CONCLUSIONS: The vast majority of persons with type 2 diabetes in PNG are undiagnosed and are not receiving treatment: based on the lower of two country prevalence estimates, less than 3% of the diabetic persons in the country are seen at health facilities. Services are limited, with only a handful of health professionals specially trained in diabetes. Expansion of services and awareness and prevention programs are urgently needed.

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

Type 1 diabetes mellitus in children in Papua New Guinea.

Anecdotal and published information suggest a low incidence and prevalence of type 1 diabetes in Papua New Guinea (PNG). Incidence and prevalence were followed prospectively from July 1996, using the PNG Paediatric Surveillance Unit (PSU). No children were receiving insulin in Papua New Guinea at the start of the period. Over the next 4.5 years, 8 cases were reported--an annual incidence of 0.08/100,000 children aged < 15 years and a prevalence of 0.28/100,000 aged < 15 years. These figures are as low as any reported elsewhere. Three cases were from the small expatriate population. All cases in Melanesian children posed significant management problems, with two children dying during the study period.

Child↗