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Biomedical subjects

J L Fahey

Publications and source records attributed to J L Fahey.

At least 163 records · Page 9Linked to original sources
PubMed1982

Regeneration of T cell subpopulations after bone marrow transplantation: cytomegalovirus infection and lymphoid subset imbalance.

Immune reconstitution was studied serially by using T lymphocyte cell surface differentiation antigens in 37 individuals receiving bone marrow transplants. Antigen expression was assessed by immunofluorescence analysis using monoclonal antibodies to T lymphocytes including Leu-3, which defines a T lymphocyte subpopulation in healthy individuals with T helper or inducer activity (L3+), and Leu-2, which defines a T lymphocyte subpopulation in healthy individuals with T helper or inducer activity (L3+), and Leu-2, which defines a T lymphocyte subpopulation with suppressor or cytotoxic activity (L2+). These studies demonstrated that the L2+ subpopulation regenerated more rapidly after transplant than did the L3+ subpopulation. Imbalances between these two T lymphocyte subpopulations, indicated by a decreased L3/L2 ratio, persisted for periods up to 12 mo post-transplant. Expression of a cell surface antigen associated with immature lymphocytes (OKT-10), and of HLA-DR (Ia-like) antigens was markedly increased during the post-transplant period. HLA-DR antigen expression did not appear related to immune activation in that increased reactivity was not detected with a monoclonal antibody (anti-TAC) specific for activated T cells. These observations in bone marrow transplant recipients and other disorders characterized by lymphoid restoration or immaturity indicate that inversion of the normal L3/L2 ratio and increased expression of OKT-10 and HLA-DR antigens may be features of a regenerating immune system. Furthermore, serial observation of individual patients indicated that infection with cytomegalovirus was associated with a progressive decrease in the L3/L2 ratio.

Antibodies, Monoclonal↗
PubMed1982

Reversal of acute ("malignant") myelosclerosis by allogeneic bone marrow transplantation.

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor.

Acute Disease↗
PubMed1982

Immunologic classification of lymphocytic leukemias based on monoclonal antibody-defined cell surface antigens.

A panel of monoclonal antibodies reactive with normal lymphocyte subsets was used to classify cases of lymphocytic leukemia on the basis of cell surface antigen expression. The antibodies employed were commercially available and included a common framework HLA-DR antibody, two pan-T antibodies (Leu-1 and OKT-3), and antibodies defining cytotoxic/suppressor (Leu-2 and OKT-8) and helper/inducer (Leu-3 and OKT-4) subpopulations of normal T lymphocytes. Cases of ALL could be subgrouped into non-T non-B, pre-T and T-ALL on the basis of reactivity with HLA-DR, Leu-1, and OKT-3 antibodies. Leukemic cells from patients with T-cell CLL could be divided into Leu-2/OKT-8 reactive and Leu-3/OKT-4 reactive subpopulations, as well as a subgroup in which the majority of cells were unreactive with either of these antibodies. With the exception of one individual, all Sézary cell leukemias expressed a phenotypic pattern similar to that of the Leu-3 subgroup of T-CLL. Malignancies of B-cell lineage (B-CLL, prolymphocytic leukemia, and lymphosarcoma) that were examined were reactive with both the HLA-DR and Leu-1 antibodies. On the contrary, normal B lymphocytes and lymphoid cell lines of B-cell origin did not express surface antigens recognized by the Leu-1 antibody.

Antibodies, Monoclonal↗
PubMed1982

Serum-free medium for the in vitro growth of normal and malignant urinary bladder epithelial cells.

A serum-free medium, DH-S1, is described which is valuable for the establishment of primary cultures of normal and malignant transitional epithelium (transitional cell carcinoma of the bladder). Growth of epithelial cells in DH-S1 is facilitated but that of fibroblasts is suppressed. Another established human transitional cell carcinoma cell line, 647V, has grown continually in DH-S1 for over 36 passages. Morphological and antigenic studies comparing 647V cells growing in serum-containing and serum-free medium reveal differences which are pronounced at low cell density but which almost disappear at higher densities. A new human transitional cell carcinoma cell line, LA-B1, is described whose initial growth was supported by this serum-free medium.

Animals↗
PubMed1981

Altered cellular immune functions in patients with Down's syndrome.

Cell-associated immunocompetence was evaluated in 42 patients with Down's syndrome (DS) and compared with that of institutionalized patient control and normal control groups. B lymphocytes, as both percent of total lymphoid cells and absolute number, were markedly reduced in patients with DS. T-lymphocyte proliferative response to phytohemagglutinin mitogen also was significantly decreased. This altered response of the lymphocyte population was evident in both the presence and absence of accessory helper monocytes. Increased Fc receptor (FcR) cell activity, as measured by antibody-dependent cellular cytotoxicity was seen in both the patients with DS and the control patients. This probably resulted from common environmental factors such as exposure to infectious factors such as exposure to infectious agents. No change was found in the WBC counts, percentages of lymphocytes and monocytes, percentages of t cells and FcR cells, or in the natural killer cell activity.

Adult↗
PubMed1981

Depression of the generation of cell-mediated cytotoxicity by macrophage-like suppressor cells in bladder carcinoma patients.

Depressed T-lymphocyte function as assessed by delayed-type hypersensitivity reactions and in vitro proliferative response to mitogens is a characteristic finding in many types of solid tumors, including bladder carcinoma. Peripheral blood leukocytes from 16 patients with transitional cell carcinoma of the bladder were compared with age-matched, control subjects. Both the unfractionated leukocytes containing 10 to 30% monocytes and the lymphocyte-enriched preparations, obtained by monocyte depletion with iron filing ingestion, were analyzed. Mixed leukocyte culture-induced cytotoxicity was depressed in the patient group; the amount of depression was directly correlated to the extent of the disease. In patients who underwent surgical removal of tumor, the mixed leukocyte culture-induced cytotoxicity appeared normal. This mixed leukocyte culture-generated cytotoxic response was a more sensitive indicator of tumor effect than was the induced proliferative response. Removal of phagocytic or adherent monocytes from the responding cell population caused a significant increase in the generated cytotoxicity, especially in those patients with invasive disease. These suppressive effects could be partially reconstituted by quantitative addition of the separated monocytes back to the responding lymphocyte culture. The depressed lymphocyte-mediated cytotoxicity present in these bladder cancer patients was due, in a major part, to a circulating macrophage-like cell with active suppressor function.

Carcinoma, Transitional Cell↗
PubMed1980

Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia.

Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia.

Acute Disease↗
PubMed1980

Comparison of immune derangements in patients with different malignancies.

Immune function was evaluated in 109 patients with carcinoma of the breast, bladder, head and neck, and lung. Patients with head and neck cancer showed the most profound derangements of immune function; patients with lung cancer showed no detectable abnormalities. Non-irradiated patients with disseminated head and neck cancer had significantly depressed lymphocyte counts (mean 1357/mm3, P less than .05), E-rosette forming cells (mean 770/mm3, P less than .05), and response to phytohemagglutinin (P less than .05) as compared to controls. This immunodeficiency was detected in patients with localized as well as advanced disease. Although significant differences were noted between patients with head and neck cancer and the other tumors, these differences were minimized by radiation therapy. All irradiated patients showed comparable degrees of immune dysfunction. Absolute Fc-receptor cells were depressed in all irradiated patients and in non-irradiated patients with disseminated breast cancer.

Adult↗
PubMed1979

Immunologic evaluation of patients with advanced head and neck cancer receiving weekly chemoimmunotherapy.

Patients with advanced head and neck cancer have significant reduction in their circulating lymphocyte mass which is reflected in decreased numbers of T cells, Fc receptor cells, and in derangements of T lymphocyte functions, i.e., decreased responsiveness to several dilutions of phytohemagglutinin and lack of development of delayed hypersensitivity to 2,4-dinitrochlorobenzene (70% of patients were DNCB (-)). A population of phagocytic cells capable of decreasing lymphocyte responsiveness to mitogens were demonstrated. Removal of these cells resulted in an increment in lymphocyte responsiveness. Immunological impairment seemed to correlate with patients' ability to become sensitized to DNCB. Those patients who were DNCB (+) had less derangement in their immunological parameters. Weekly administration of Corynebacterium parvum in conjunction with chemotherapy did not have a discernible effect on patient's immune reactivity.

Adult↗
PubMed1979

Idiotype anti-idiotype complexes in cerebrospinal fluids of multiple sclerosis patients.

The involvement of idiotype-anti-idiotype complexes in multiple sclerosis was approached by ultracentrifuge studies. Specimens of the immunoglobulin G fraction obtained from the cerebrospinal fluids of multiple sclerosis patients which contained distinct oligoclonal bands, were subjected to analytical ultracentrifugation. None of these samples revealed the presence of any detectable amount of oligomeric immunoglobulin G, namely dimer or trimer. By comparison with control mixtures containing known amounts of dimeric immunoglobulin, it was evaluated that the cerebrospinal fluid samples contain less than 5% dimer. These findings indicate that the spinal fluids of multiple sclerosis patients do not contain idiotype-anti-idiotype complexes to an extent that would account for the oligoclonal immunoglobulin bands as representing complementary idiotypes and anti-idiotypes.

Antibodies, Anti-Idiotypic↗
PubMed1978

Continuous intravenous deferoxamine infusion. Treatment of secondary hemochromatosis in adults.

Adult patients with chronic iron overload were given oral ascorbic acid and continuous intravenous infusions of deferoxamine mesylate. The dosage of deferoxamine mesylate was altered every 48 hours from 1 g/sq m/24 hr to 2 or 4 g/sq m/24 hr. The average iron mobilization was 55.6 mg per day at the 1 g/sq m/24 hr dosage level, 78.6 mg every 24 hours at the 2 g/sq m/24 hr dosage level, and 90.1 mg every 24 hours at the 4 g/sq m/24 hr dosage level. Iron mobilization was undiminished when successive 14-day courses of deferoxamine separated by six-week intervals were administered.

Administration, Oral↗
PubMed1978

Phase I studies of C. parvum given intravenously: effects of dexamethasone on its biologic and toxic properties.

Three biologic effects were clearly associated with C. parvum infusions: a) granulocytosis with lymphomonocytopenia, b) increase in responsiveness to phytohemmagglutinin and c) increase of specific antibodies to C. parvum antigens. Addition of dexamethasone moderately altered the kinetics of leukocyte changes without affecting other properties. Side effects after intravenous administration of C. parvum (2.5 mg/m2) consisted primarily of chills and fever which lasted for periods of 6-24 hours. Side effects occurred in 77% of the infusions. Addition of dexamethasone (4 mg IVP) reduced significantly the frequency (only 22% of patients) and intensity (fever 102 F and chills for only 30-60 minutes) of side effects. Clearly, dexamethasone of the dosage employed did not abrogate C. parvum effects while reducing significantly its toxic properties.

Adult↗