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Biomedical subjects

C O'Toole

Publications and source records attributed to C O'Toole.

At least 37 records · Page 2Linked to original sources

Ultrastructure, karyology and immunology of a cell line originated from a human transitional-cell carcinoma.

A cell line (J82) was derived from a poorly differentiated, invasive, transitional-cell carcinoma, Stage T3. The cells have been propagated in vitro for 5 years and showed 100% aneuploidy and a mixed epithelial-fibroblastic morphology. The majority of cells contained 2Y chromosomes and several distinctive markers. Peripheral-blood lymphocytes from the donor of the J82 cells were tested sequentially for cytotoxicity toward autologous and allogeneic tumour cells. Autologous cytotoxicity was detected against J82 cells in early in vitro passage. Allogeneic lymphocytes from some patients with transitional-cell carcinoma were also cytotoxic to J82 cells in primary culture. However, selective cytotoxicity by lymphoid cells from bladder-carcinoma patients was not detected against J82 cells in long-term tissue culture.

Carcinoma, Transitional Cell↗

Effect of a low protein diet on in vitro protein synthesis in thymus, spleen, and bone marrow in young adult rats.

Young adult rats (body weight 90 g) were given a low protein (3% casein) diet for 6 days. Under these conditions, thymus and spleen organ wet weights and DNA content decreased as compared with control rats given a high protein (20% casein) diet. The in vitro incorporation of amino acids into protein was followed using leucine as the radioactive precursor. Ribosomes of tissues from the dietary rats were incubated together with soluble enzymes from liver of rats fed a stock diet, and cofactors. Ribosomal capacity for leucine incorporation into protein diminished in thymus by 33% per mg ribosomal RNA, 77% per total ribosomal RNA, and 43% per mg DNA. In spleen the corresponding reductions were 29%, 81%, and 31%; in bone marrow the decrease was 29% per mg ribosomal RNA, 56% per total ribosomal RNA, and 19% per mg DNA. A reduction in physiological activity is thus evident in these tissues soon after protein restriction.

Amino Acids↗

Anti-squamous tumor antibodies in patients with squamous cell carcinoma.

Patients with advanced squamous cell carcinomas were shown to have serum antibodies directed towards cultured squamous tumor cells as shown by quantitative membrane immunofluorescence. The sera of these same patients did not react with a variety of other cultured tumor cells. Serum obtained from normals or from patients with other forms of cancer (transitional cell carcinoma, adenocarcinoma, and melanoma) did not give positive reactions. When the sera of squamous carcinoma patients were chromatographed on Sephadex G-150, tumor-reactive antibodies were recovered solely in the 19 S fraction, suggesting immunoglobulin M as the immunoglobulin isotype involved. Identification of the squamous tumor cell-reactive immunoglobulin as ijmunoglobulin M was confirmed by quantitative immunofluorescence with the use of class monospecific antisera to human immunoglobulins.

Adult↗

A 51chromium isotope release assay for detecting cytotoxicity to human bladder carcinoma.

A 51chromium isotope release assay is described for measuring in vitro cytotoxicity reactions against allogenetic target cells. Lymphoid cells from some patients with localized transitional cell carcinoma (TCC) were shown to selectively lyse targets derived from two long-term cell lines of TCC. The effector cells in this reaction did not form E rosettes. Cytotoxicity was successfully recovered after cryopreservation.

Carcinoma, Transitional Cell↗

Cryopreservation of immunological memory and other lymphoid cell functions.

The following components of the immune response by mouse spleen cells were retained after cryopreservation at --110 degrees C: direct and indirect plaque formation, avidity of antibody secreted by plaque forming cells, and induction of primary or secondary adoptive transfer responses. Human peripheral blood lymphocytes retained the capacity to mediate antibody-dependent cytotoxicity and cell mediated immunity to tumor in vitro.

Animals↗

Lymphocyte response to transitional cell carcinoma: peripheral cytotoxicity and local tumor infiltration.

The cytotoxicity of peripheral lymphocytes from patients with transitional cell carcinoma was evaluated and the results were compared to the degree of local lymphocytic infiltration in the bed of the primary tumor. Although a clear correlation was not established local lymphocytic infiltration was associated more commonly with tumor-related peripheral lymphocyte cytotoxicity.

Carcinoma, Transitional Cell↗

A cell line from an anaplastic transitional cell carcinoma of human urinary bladder.

A cell line, TCCSUP, derived from an undifferentiated, Grade IV transitional cell carcinoma is described. The karyotype showed an abnormal distribution of chromosomes, with no obvious modal number. Distinct marker chromosomes were observed in both early and late in vitro passages. These cells have been subcultured over 50 times during a 20-month period. TCCSUP differs in certain morphological and immunological features from other cell lines from transitional cell carcinomas.

Carcinoma, Transitional Cell↗

Human lymph node lymphocytes fail to effect lysis of antibody-coated target cells.

Human lymphocytes prepared from peripheral blood, lymph nodes, spleen and thymus were titrated for ability to mediate lysis of human target cells coated with rabbit anti target antibody. Lymphocytes from blood and spleen produced efficient lysis of targets in the presence of antibody. Lymph node cells and thymocytes were essentially non-reactive in this system. Lymph node preparations from non-cancer patients contained approximately 25% of non-T cells with receptors for Fc,C3 and/or Ig. Regional lymph nodes from patients with primary tumours contained 37-50% non-T cells by the same criteria. Failure of lymph node lymphocytes to effect lysis of antibody-coated targets did not therefore correlate with content of Fc or C3 bearing cells per se. The effector cell in antibody-dependent cytotoxicity in other systems has been shown to carry Fc and C3 receptors, but not surface Ig. This cell type appears to be absent or non-functional in human lymph nodes.

Antigen-Antibody Reactions↗

A cell line (SCABER) derived from squamous cell carcinoma of the human urinary bladder.

An established cell line derived from a documented squamous cell carcinoma of human urinary bladder is described. The cultured cells retained the characteristic morphology of the tumor of origin for 40 in vitro passages. Numerous desmosomes were found between cultured cells. Chromosome analysis showed hypotetraploidy with no obvious modal number, while distinctive marker chromosomes and a male karyotype were present.

Adenoviridae↗

Immunotherapy and human tumor immunology.

Present knowledge about the immune response to tumors in man is briefly reviewed, and the effects of cancer on immune-system functions are noted. The concepts that human tumors elicit cell-mediated immune responses to tumor antigens are re-examined and modified; for example, cell-mediated immunity may be detectable only at certain stages of tumor growth. Introduction of more sensitive methods for detecting antibodies is providing additional evidence for humoral immune responses to tumor-associated antigens. The present proliminary approaches to immunotherapy, particularly the use of adjuvants such as BCG and Corynebacterium parvum, are assessed, and initial pharmacoimmunologic findings with these agents are reported. The field of tumor immunology is in a dynamic state of development, with input from many areas of immunology and oncology. Carefully controlled clinical trials of these therapeutic regimens will be required to establish the value and indications for the use of such procedures.

BCG Vaccine↗

Cellular immunity to transitional cell carcinoma of the urinary bladder. III. Effects of hydrostatic pressure therapy.

The effects of hydrostatic pressure therapy on in vitro cellular cytotoxicity responses have been studied in 19 patients with transitional cell carcinoma of the bladder (TCC). Cytotoxicity was quantitated against allogeneic targets in a microplate assay or by 51chromium isotope release. Two types of reactivity were detected, the most common being a differential cytotoxicity for targets derived from TCC, in either short-term or long-term tissue culture. This reaction is operationally termed "tumor-specific". Less frequently, a general cytotoxicity for targets of diverse histogenic origins was observed. For the present, this is termed "non-specific". Nine patients were tested before pressure therapy and of these only two gave a specific reaction and one a non-specific reaction, while six were non-reactive. Eighteen patients were tested at varying intervals after treatment and of these 11 gave a specific reaction and one a non-specific effect, while six were non-reactive. Three individuals who were non-reactive prior to therapy had a specific reaction post therapy. Two who reacted specifically before therapy became non-reactive post therapy. The results of serial in vitro testing for cytotoxicity are presented with individual case histories, tumor staging and grading and the clinical outcome of hydrostatic pressure therapy.

Adult↗

The influence of tumour burden and therapy on cellular cytotoxicity responses in patients with ocular and skin melanoma.

Using a microassay for cellular immunity, tumour specific cytotoxicity was detected in 2/5 cases of ocular melanoma and 1/3 cases of primary cutaneous melanoma before treatment. Reactivity was measured against allogeneic skin melanoma target cells in short or long term in vitro culture. Lymphoid cells from patients with disseminated cutaneous melanoma were either non-reactive (4/8 cases) or gave a nonspecific cytotoxicity on target cells of diverse histogenic origins. Among tumour-free patients tested after surgery, 0/2 patients with ocular tumour were non-reactive 3-4 months post surgery. After sugical excision of cutaneous melanoma 2/2 patients gave tumour specific reactions during the first month after surgery. After longer time intervals, from 5 months to 3 years, only 1/8 patients were reactive. Preoperative radiotherapy in a total skin dose of 10,000 rad produ-ed a transient tumour specific reaction 24 h after therapy in a single case. Following local tumour excision in patients given preoperative irradiation, 2 cases which had previously demonstrated tumour specific CMI lost reactivity. Among 14 tumour-free individuals tested only after preoperative radiotherapy and surgery, at intervals from 5 day to 13 years, a single case gave tumour specific CMI. Palliative irradiation in doses 4000-4960 rad to the inguinal or axillary lymph nodes was found to induce a generalized lymphopenia within 48 h after treatment. Lymphoid cell preparations from patients with localized melanoma contained significantly increased numbers of immature cells (lymphoblasts and myeloblasts) and myeloid precursor elements. Those prepared from patients with disseminated disease had in addition elevated levels of eosinophils but reduced numbers of recoverable lymphocytes.

Aged↗

Lymphoid cells mediating tumor-specific cytotoxicity to carcinoma of the urinary bladder. Separation of the effector population using a surface marker.

Peripheral lymphocytes from patients with urinary bladder carcinoma and controls have been separated on the basis of rosette formation with sheep erythrocytes. The fractions were tested for tumor-specific cytotoxicity. The E rosette-forming cells of purity 90% respond well in PHA-induced cytotoxicity but are totally inactive in the tumor assay. The non-E rosette-forming cells (purity 91%) give enhanced activity in the tumor-specific cytotoxicity as well as in antibody-mediated target cell lysis in a model system. These data support the notion that the effector cells in cell-mediated immunity to carcinoma of the urinary bladder are members of the nonthymus-derived population of peripheral lymphocytes.

B-Lymphocytes↗