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Biomedical subjects

P Lake

Publications and source records attributed to P Lake.

At least 55 records · Page 3Linked to original sources
PubMed1982

Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones.

Human peripheral blood lymphocytes from an HLA-Dw1,3 individual were primed in vitro with influenza A virus (A/Texas/1-77/x-49) and subsequently cloned by limiting dilution in TCGF. Of the 96 TLCs originally obtained, nine were characterized in detail. TLCs were antigen specific, responding to influenza A virus, not to influenza B, TGAL, GAT, tetanus toxoid, or KLH, and only when antigen was presented by cells unable to form rosettes with AET-treated SRBC. Presentation of antigen by unseparated PBL often resulted in significant "back stimulation," probably via production of growth factors. The MHC requirements for the induction of TLC proliferation were analyzed. Of four representative clones analyzed, three required Dw1;DR1 compatibility for successful presentation of viral antigens by a panel of antigen-presenting cells. In contrast, one TLC showed an unusual pattern of response that could not be correlated to a particular HLA haplotype. Monoclonal anti-T cell antibody analysis of the surface phenotype of two TLCs maintained in continuous culture for 5 mo indicated that they were OKT3+, 4+, and 8-, consistent with an inducer/helper phenotype. To confirm the clonal nature of TLCs, data on the functional properties of TLC subclones are also presented.

Clone Cells↗
PubMed1982

Antigen-specific human T lymphocyte clones: viral antigen specificity of influenza virus-immune clones.

Human T lymphocyte clones (TLC) specific for type A (A/Texas/1/77) influenza virus and maintained in continuous culture with T cell growth factor, were analyzed to define the cellular specificity pattern of virus recognition. A panel of TLC were stimulated with strains of serologically characterized type A influenza subtypes. Five TLC recognized all the viral subtypes; the remaining clones recognized only subtypes that shared serologically defined determinants with the immunizing subtype. In addition, the 11 TLC were analyzed for their fine antigenic specificity by using the purified viral components hemagglutinin (HA), neuraminidase (NA), matrix protein (MP), and nucleoprotein (NP). Five TLC proliferated in response to NA, four to MP, one to HA, and one to NP. None of the clones responded to the unrelated B strain influenza virus, B/Singapore. Furthermore, the fine specificity of an MP-reactive TLC was confirmed by subcloning.

Antigens, Viral↗
PubMed1982

Viral antigens act as helper determinants for antibody responses to cell surface antigens.

Thy-1 alloantigens on murine thymus cells are weak immunogens in vivo for PFC responses in the absence of other antigenic disparities between the donor and recipient. Our previous work showed that non-H-2 alloantigens acted as helper determinants to augment anti-Thy-1 PFC responses. In this report we demonstrate that strong helper antigens are also produced by infection of donor thymus cells with viruses such as HSV-1, NDV, or vaccinia. This helper effect (as much as 30-fold) for a cellular antigen, requires linked recognition (expression of Thy-1 and virus in the same cell membrane), is T-dependent, antigen- (virus) specific, and is Thy-1-specific. The recognition of the viral helper sites is not restricted by the MHC genotype of the thymus cell donor, indicating that host reprocessing of antigen occurs. These are the first results that show that adventitious antigens may function as helper determinants for antibody responses to native membrane antigens and may be the mechanism that initiates several forms of acute post-viral autoimmune disease.

Animals↗
PubMed1982

I-J restriction of T cells that suppress in vivo antibody responses to Thy-1.

The contact-sensitizing haptens dinitrophenyl (DNP) and oxazalone (Ox) act as helper determinants for antibody responses to Thy-1 when conjugated to donor thymus cells. The helper effect is transferrable from primed to naive mice with spleen cells, producing specific augmentation of in vivo PFC responses to Thy-1. The helper cells are hapten-specific and require associative recognition of hapten and Thy-1, excluding a role for nonspecific B cell activation. The phenotype of the helper cells is Thy-1+ and Lyt-1+2-. Antigen-specific suppression could be readily generated by using an inoculum of DNP-modified syngeneic RBC. T cells from these suppressed donors (Ts) were shown to abolish the helper effects of TH in adoptive transfer experiments in vivo. These Ts were characterized as Thy-1+ and Lyt-1-2+. A requirement for MHC compatibility at the I-J subregion was necessary between the Ts and the recipient to obtain a transfer of suppression.

Animals↗
PubMed1981

Modulation of Thy-1 alloantibody responses: donor cell-associated H-2 inhibition and augmentation without recipient Ir gene control.

In this study we have found that in vivo PFC responses to Thy-1 are strongly modulated by H-2 gene products in at least 2 ways. First, a profound inhibition of primary PFC responses occurs when foreign H-2 antigens are expressed on Thy-1 incompatible donor cells. This interference effect does not reflect a requirement for H-2-restricted antigen presentation by donor cells, since it is also seen using semi-syngeneic antigenic cells that share a full H-2 haplotype with the recipient. Interference acts more profoundly on slower primary responses than on more rapid secondary responses and requires associative recognition of the H-2 and Thy-1 antigens. By contrast, strong augmentation of the anti-Thy-1 response was obtained when foreign H-2 antigens were expressed in the recipient, as shown by a poor response of an H-2k/k recipient to Thy-1.1 on AKR cells (H-2k) compared with high responses of H-2k/b recipients. A gene controlling this phenotype was mapped to the H-2IA or H-2K regions. However, subsequent experiments revealed that donor recognition of recipient H-2 antigens was required for these high responses; thus, an Ir-gene effect was excluded and an 'intimate form' of an allogeneic effect was postulated. Thus, the immune response to Thy-1 is regulated by at least 3 factors acting at the level of the donor cell, including non-H-2 helper alloantigens, H-2 interference, and H-2-associated allogeneic effects.

Animals↗
PubMed1980

Demonstration with monoclonal antibody of the glycoprotein nature of Thy-1.2 alloantigen.

Thy-1 antigen present in large amounts on the brain and thymus of mice, exists in two allelic forms, either Thy-1.1 or Thy-1.2. Previous results have shown that Thy-1.1 alloantigen is expressed on a glycoprotein of molecular weight 25 000, therefore referred to as the Thy-1 glycoprotein. However the presence of Thy-1.2 alloantigen on the purified Thy-1 glycoprotein could not be established unequivocally. The present paper demonstrates that Thy-1.2 alloantigen, identified by F7D5 monoclonal antibody, is localized on the Thy-1 glycoprotein. The limited neutralization by the glycoprotein of the reactivity of AKR anti-C3H allosera to thymocytes is explained by the fact that the antiserum contains antibodies to determinants other than Thy-1.2. The alloantisera are shown to react with viral proteins encoded for by endogenous murine leukemia virus and expressed at the surface of Friend cells and thymocytes.

Animals↗
PubMed1979

Cytotoxic and fluorescent assays for thymocyte subpopulations differing in surface thy-1 level.

A number of analytical techniques for distinguishing and separating the "high theta" "low theta" subpopulations of mouse thymocytes have been compared. A differential cytotoxic assay was compared to a quantitative immunofluorescent assay on individual cells using flow cytofluorometry and cell sorting. Conventional anti-Thy-1 antisera were compared with a monoclonal IgM anti-Thy-1. The monoclonal reagent greatly improved both types of assay, eliminated a number of artifacts and allowed either procedure to be used to give a clear distinction, based on Thy-1 level, between the two subpopulations. The distribution of Thy-1 on thymocytes is bimodal, rather than continuous. These separate "high theta" and "low theta" categories each includes a population a population of dividing cells.

Animals↗
PubMed1976

Associative control of the immune response to cell surface antigens.

The immune response to cell surface antigens is regulated by the activity of helper and suppressor cells, probably of TH and possibly of TCS types. For this to operate, recognition must take place of two or more antigenic determinants, which may be carried on the same (intramoblecular help) or different (intermolecular, intrastructural help) molecules. Regulation of this type has been shown to operate in the response to the murine allo-antigens H-2K, H-2D, Thy-1, and H-minors.

Animals↗
PubMed1976

Sudden hemorrhage in metastatic thyroid carcinoma of the brain during treatment with iodine-131.

A patient with papillary--follicular carcinoma of the thyroid, with metastases to the lungs, skeleton, and brain was treated 5 weeks after thyroidectomy with 135 mCi of 131I. Although preliminary studies with 1 mCi had not shown any iodine uptake by the brain metastasis, this lesion showed intense concentration at the time of the larger therapeutic dose. Four days later, acute hemorrhage of the tumor occurred, requiring surgical removal. Although 131I therapy would seem an unlikely cause of acute necrosis and hemorrhage in these lesions, the association of therapeutic radioiodine and hemorrhage is interesting. Since recent reports suggest that brain metastasis may be somewhat more common than previously suspected, we suggest that brain imaging be included in the workup prior to radioiodine therapy of patients with advanced metastatic disease or neurologic symptoms.

Adenocarcinoma↗
PubMed1975

Urethral adenocarcinoma (possibly originating in the glands of Littre).

Adenocarcinoma involving the bulbomenbranous urethra is a rare disease. This disease is describe in a 30-year-old man and the surgical management is detailed. The adenocarcinoma described seems to have arisen from the periurethral glands of littre. Despite the radical nature of the tumor excision, it was possible to spare the distal penis in order to achieve a more normal appearance of the external genitalia.

Adenocarcinoma↗