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Biomedical subjects

J L Fahey

Publications and source records attributed to J L Fahey.

At least 181 records · Page 10Linked to original sources

Acute effects of orally administered levamisole on random monocyte motility and chemotaxis in man.

Cellular immune functions were studied in patients with early bladder cancer 2 hours after ingestion of either levamisole or a placebo. Random monocyte motility was significantly increased (P less than 0.025) in 13 of 17 patients receiving levamisole. Monocyte chemotaxis was significantly increased (P less than 0.025) in 16 of the 17 patients. Random monocyte motility and monocyte chemotaxis did not change in either 8 patients on the placebo or in 15 normal controls. Monocytes from normal donors showed increased random motility and chemotaxis after incubation with levamisole in vitro. These results indicated that increases in peripheral blood monocyte motility followed oral administration of levamisole. Kinetic studies indicated that these effects were rapid in onset and short lived.

Administration, Oral↗

Bone-marrow transplantation in acute leukaemia.

Survival in 33 patients with resistant leukaemia treated by marrow transplantation was compared with that of 37 matched patients treated by conventional and experimental chemotherapy. All patients in the transplant group were rendered free of detectable leukaemia for periods of from 36 days to more than 2 1/2 years, while only 6 patients in the chemotherapy group achieved a haematological remission. Overall survival in both groups was poor; however, 5 patients (15%) in the transplant group remain alive and in haematological remission 1--2 1/2 years after transplantation, while no patient in the chemotherapy group survived longer than 13 months. Bone-marrow transplantation appears to offer a small but distinct possibility of long-term survival in patients with acute leukaemia resistant to conventional therapy.

Adolescent↗

Total syntheses of (+/-)-1-carbacefoxitin and -cefamandole and (+/-)-1-oxacefamandole.

The total syntheses of the (+/-)-1-carba analogues of cefoxitin (11), 7 alpha-methoxydeacetylcephalothin (5) and cefamandole (31) and the (+/-)-1-oxa analogue of cefamandole (43) are described. Their bioactivity spectra against 14 typical organisms are similar to those of their natural 1-thia counterparts, with the 1-carba compounds somewhat less active and the 1-oxa compound more active than the natural ones.

Bacteria↗

Isolation and partial characterization of plasma membranes bearing human fetal-associated antigens.

A rabbit antiserum to first-trimester human fetal tissue had greater reactivity in complement fixation and saturation binding assays with fetal tissues than with both a pool of normal adult lung, liver, and kidney and pools of the individual organs. This anti-fetal membrane reactivity was only partially inhibited by carcinoembryonic antigen. The serum still reacted strongly with human fetal and tumor cells after rendering it specific for plasma membrane components by adsorption to and elution from intact human fetal tissue culture cells. This plasma membrane-specific serum was then used to monitor the purification of the fetal membrane-associated antigens. The fetal antigens copurified with the putative plasma membrane enzymatic markers 5'-nucleotidase and Mg2+-adenosinetriphosphatase through differential and density gradient centrifugation. Insulin-binding activity only partially copurified with the antigenic activity. Little antigenic activity was found in nuclear and mitochondrial fractions. The isolation protocol gives fetal plasma membrane-associated antigens in approximately 50% yield with moderate purification. The sera and isolation procedures described should have general utility for the detection of human oncofetal antigens.

Adenosine Triphosphatases↗

Immunological responsiveness in patients with bladder cancer.

Delayed cutaneous hypersensitivity tests, especially skin tests with dinitrochlorobenzene, are impaired increasingly as the amount of tumor increases. Recall antigens are less sensitive indicators of disease. Therapy, especially radiotherapy, also depresses cell-mediated immunity. Removal of tumor, however, allows these tests to return to normal. Dinitrochlorobenzene skin testing can contribute significantly to prognostic evaluation. An important facet of the tumor-host relationship is measured, and this reflects factors that are independent of tumor staging. Combination of tumor staging and dinitrochlorobenzene-delayed hypersensitivity testing can provide a strong indication of the clinical course, especially for the year following initial treatment of invasive or metastatic transitional cell carcinoma of the bladder.

Antigens↗

Autoimmune panleukopenia.

A patient with episodic panleukopenia involving neutrophilic granulocytes, monocytes and lymphocytes had recurrent bacterial infections and a circulating cytotoxin that injured primitive myeloid cells as well as differentiated granulocytes and mononuclear cells. The cytotoxin was an immunoglobulin with activity against mouse, as well as human, myeloid stem cells. Clinical remission during cyclophosphamide therapy was associated with disappearance of the circulating leukocytotoxin. Serum from a period of active disease was cytotoxic for the patient's own lymphocytes obtained during clinical remission. Absorption of cytotoxic serum with granulocytes removed activity against both granulocytes and lymphocytes. These studies suggest an autoimmune disease in man characterized by episodic granulocytopenia, monocytopenia and lymphocytopenia due to humoral antibody against non-HLA antigens shared by several hematopoietic cell lines.

Adult↗

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↗

Critical evaluation of lymphocyte functions in urological cancer patients.

One hundred three patients with varying stages of urological cancer (bladder, prostate, kidney) were investigated with regard to the following lymphocyte functions. T-cells were assessed numerically (E rosettes), their blastogenic response to phytohemagglutinin (pHA) was determined, and their cytotoxic potential against heterologous target cells in short-term presence of PHA (e.i., PHA-dependent cellular cytotoxocity) was evaluated. Similarly, B cells were numerically assessed (EA rosettes), and their function was evaluated by antibody-dependent cellular cytotoxicity against antibody-coated deterologous target cells. The data on cancer patients, divided on the basis of extent of disease and prior radiation therapy, were compared to those of normal young and age-matched controls. Our investigations emphasize the importance of the following factors: (a) comparison of data with age-matched controls, since several lymphocyte functions appear to change with age; (b) use of multiple controls to compensate for the inherent variability found in certain tests; (c) minimized contamination by nonlymphoid cells in the purified cell preparation; and (d) the influence of certain treatment regimens (radiation, chemotherapy, etc.) on the results. Radiotherapy significantly depressed T-cell number with a depression of PHA blastogenic responses as well as PHA-dependent cellular cytotoxicity. When all of these conditions were taken into account, the urological cancer patients as a group were found to have a lower proportional value of E rosettes (T-cells) and a reduced PHA blastogenic responsiveness. Certain cancer patients displayed an elevated PHA-dependent cellular cytotoxicity as compared to age-matched controls, which may indicate the presence of activated cells in the presence of tumors. With this identification of a group of cancer patients with markedly depressed E rosette values and PHA responsiveness, it will now be possible to follow them clinically in comparison with a group of cancer patients with normal T-cell functions.

Adult↗

Secondary in vitro lymphocyte-proliferative responses to syngeneic plasma cell tumors.

Two characteristics of immune responses to weakly immunogenic plasma cell tumors were demonstrated in this study. (a) Elevated lymphoproliferative responses following in vivo inoculation of sublethal doses of plasma cell tumors were detected by a mixed lymphocyte-tumor interaction (MLTI) assay. Specificity of elevated MLTI responses correlated with resistance to in vivo tumor challenge. These responses were dependent upon the presence of thymus-derived cells. (b) Spleen and lymph node cells showed markedly different patterns of MLTI activity following plasma cell tumor immunization. Spleen cell responses were depressed for the first 30 days postimmunization, whereas lymph node cells showed augmented MLTI reactivity immediately after immunization. These observations indicated that lymphocyte populations from different lymphoid organs may show widely dissimilar responses in vitro at the same point in the in vivo development of tumor resistance.

Animals↗

Stimulation of lymphoid cells from normal and immune mice by syngeneic BALB/c plasma cell tumors.

Lymphoid cells from normal and immunized BALB/c mice could be stimulated in vitro by syngeneic PCT contrasted with an absence of response to a number of other tumors. Maximal responses of normal cells to PCT were found to occur 5 days after the initiation of the cultures at an optimal responding:stimulation cell ratio of 1:2. MLTI activity of normal cells could not be blocked or enhanced by PCT myeloma protein products indicating that MLTI reactivity was directed against non-idiotypec cell surface determinants. Lymphoid cells from immunized mice demonstrated increased MLTI responses to cells of the immunizing tumor but not to other PCT, indicating that the post-immunization MLTI responses were primarily to individual rather than shared tumor cell surface antigens. Activity of both normal and immunized spleen cells was found to involve thymus-derived lymphocytes. The persistence of residual MLTI activity after treatment with anti-theta serum and complement, however, implicated participation of non-theta antigen-bearing cells in MLTI reactivity. From these data, we conclude that lymphoid cells from un-immunized mice are capable of T cell-dependent reactivity to syngeneic PCT-associated antigens and that elevations in these reactivities after immunization may reflect specific cellular immune responses.

Animals↗

Bone marrow transplantation in man.

Bone marrow transplantation is emerging as a viable therapeutic approach to a number of diseases that are usually or uniformly fatal. We review here recent experiences in bone marrow transplantation in man at UCLA and in various other institutions throughout the world. We examine marrow transplantation in immunodeficiency diseases, acute leukemia, and aplastic anemia and consider the problems of infection in the transplant recipients. The applications of tissue typing to marrow transplantation and immunologic manipulations, which may influence engraftment and graft-versus-host disease, are also reported.

ABO Blood-Group System↗