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Biomedical subjects

J L Fahey

Publications and source records attributed to J L Fahey.

At least 145 records · Page 8Linked to original sources

Deficiency of interleukin-2 production and interleukin-2 receptor expression on peripheral blood leukocytes after phytohemagglutinin stimulation in pemphigus.

Peripheral blood mononuclear cells from 22 pemphigus patients with active disease and 30 normal subjects were evaluated for interleukin 2 (IL-2) production and IL-2 receptor expression following stimulation with phytohemagglutinin P (PHA-P). The IL-2 levels were lower in patients compared to corresponding controls and the production was delayed after PHA stimulation. This deficiency was most pronounced in severely affected patients. IL-2 receptor appearance also was lower after PHA stimulation in a small number of patients tested. These results indicate that some cellular immune functions are altered in pemphigus.

Acute Disease↗

Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome.

In a randomized prospective study we tested the toxicity and efficacy of recombinant alpha-2 interferon in the treatment of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. High doses (50 X 10(6) U/m2 body surface area, intravenously) or low doses (1 X 10(6) U/m2, subcutaneously) of recombinant alpha-2 interferon were administered to 20 patients for 5 days/wk, every other week, for four treatment cycles. Therapy was well tolerated subjectively and caused only mild hematologic and hepatic toxicity at both dose levels. No consistent or sustained changes were seen in immunologic variables during or after treatment. Six patients with Kaposi's sarcoma, four at high dose and two at low dose, had objective responses (complete or partial) to treatment. However, therapy did not appear to eradicate cytomegalovirus carriage or prevent opportunistic infections related to cytomegalovirus.

Acquired Immunodeficiency Syndrome↗

Multiple sclerosis.

The cause of multiple sclerosis is unknown but seems to be multifactorial. Susceptibility or resistance may be genetically determined; something in the environment interacts with the human host at the proper age to cause biochemical and structural lesions in the central nervous system. The systemic immune response and the response of the central nervous system become involved. Although multiple sclerosis cannot yet be cured, many clues are leading to an effective palliative therapy. Suppression or modulation of the immune responses may be the key to developing that treatment. If the environmental agent is one or several viruses, then antiviral regimens will be appropriate. Research must therefore continue at both basic science and clinical levels.

Adrenocorticotropic Hormone↗

Depressed interleukin 2 receptor expression in acquired immune deficiency and lymphadenopathy syndromes.

Because interleukin 2 (IL 2) production and IL 2 receptor (IL 2R) expression are essential steps in T cell proliferation, we undertook to measure these parameters, as defects in one or both seemed likely to account for the reduced proliferative response to mitogen in acquired immune deficiency syndrome (AIDS) and lymphadenopathy syndrome (LAS). Reduced proliferative responses to PHA are a well established feature of AIDS with opportunistic infection (AIDS-OI), AIDS with Kaposi's sarcoma (AIDS-KS), and LAS patient groups. IL 2R expression was significantly reduced in both AIDS groups; a similar trend was observed with the LAS group. Mean levels of IL 2 in culture supernatants for the three patient groups, however, did not significantly differ from controls. IL 2R expression was significantly correlated with proliferation and the Th:Ts ratio in the AIDS-OI and LAS groups, and a good correlation between proliferation and the Th:Ts ratio was also observed. The AIDS-KS group, in contrast, showed no significant correlations between IL 2R expression, proliferation, or Th:Ts ratio. IL 2 levels did not correlate with any of these parameters in any of the patient groups. These findings indicated that poor T cell proliferative responses to mitogen (PHA) are intrinsically related to decreased IL 2R expression in AIDS-OI and LAS. In AIDS-KS, however, a statistically significant correlational relationship between these altered immune parameters is not apparent.

Acquired Immunodeficiency Syndrome↗

Relation between sexual practices and T-cell subsets in homosexually active men.

27% of 89 young, non-ill, homosexually active men in Los Angeles had a Leu-3(OKT4)/Leu-2(OKT8) ratio less than or equal to 0 . 8. The low ratio was due to a significantly raised mean number of Leu-2 cells, whereas individuals with acquired immune deficiency syndrome had a decrease in both Leu-3 and Leu-2 cells. The term "acquired immune augmentation" may be appropriate for those with a low ratio due to raised numbers of Leu-2 cells. Those practising passive (receptive) anal intercourse had a significantly higher mean number of Leu-2 cells than did those practising only active (insertive) anal intercourse or no anal intercourse. The results of this study suggest that two distinct conditions occur in homosexually active men. Whether acquired immune augmentation is a precursor of the rarer acquired immune deficiency syndrome or is an unrelated disorder needs to be determined. In this study passive anal intercourse was associated with acquired immune augmentation.

Acquired Immunodeficiency Syndrome↗

Growth of human malignant lymphoid cell lines in serum-free medium.

Human T lymphoid cell lines (MOLT-4f, MOLT-3, HSB-2, CEM) and human B lymphoid cell lines (BJAB, RAJI, WIL-2) were grown longterm (up to 8 months) in serum-free medium. This medium consisted of Iscove's modified Dulbecco's medium (IMDM), supplemented with bovine serum albumin (BSA) and transferrin (TF). This serum-free medium containing albumin and transferrin is designated AT-IMDM. Lipids were not essential. Cell viability remained high, greater than 80%, in the serum-free medium and the cells maintained their distinctive characteristics. Interleukin-2 (IL-2) production capacity was maintained by the human T lymphoid cell lines JURKAT-77 and MO in short term culture. This simple medium composed of relatively inexpensive and readily available components should be useful for studies of lymphoid cell growth and differentiation and lymphoid cell products.

Albumins↗

Immunological studies of homosexual men with immunodeficiency and Kaposi's sarcoma.

Acquired immunodeficiency and Kaposi's sarcoma are epidemic among homosexual men in the United States. We have identified three clinically distinct disease syndromes in homosexually active men: a syndrome of severe cellular immunodeficiency including infection with Pneumocystis carinii and other opportunistic pathogens, a syndrome of chronic benign lymphadenopathy without severe opportunistic infections, and Kaposi's sarcoma. All 46 patients which we have studied with these three disease syndromes shared a common immune abnormality, that being a reduction in the circulating T-lymphocyte subpopulation bearing the Leu-3/OKT-4 antigen. The second major T-lymphocyte subpopulation, which bears the Leu-2/OKT-8 antigen, was numerically normal in all the disease syndromes, but increased as a percentage of all circulating lymphocytes. These abnormalities resulted in an inversion of the normal ratio of these two lymphocyte subpopulations. A similar, but less pronounced imbalance in circulating T-lymphocyte subpopulations was observed in a group of healthy homosexual men. The immune deficiency in these patients was most evident in the T-cell component of the immune system. Percentages of B cells, circulating immunoglobulin levels, and natural killer (NK) and antibody-dependent cell-mediated cytoxic (ADCC) functions were normal. Proliferative responses to antigen and mitogen were typically decreased in patients with the acquired immunodeficiency syndrome and some Kaposi's sarcoma patients, but not those with the prolonged lymphadenopathy syndrome or a control group of healthy homosexual men. Possible causes or factors contributing to the immunodeficiency and interrelationships among the three disease manifestations are discussed.

Acquired Immunodeficiency Syndrome↗

The acquired immunodeficiency syndrome.

Recently, a new epidemic illness, the acquired immunodeficiency syndrome, has dramatically emerged in the United States, Europe, and Haiti. The syndrome represents an unprecedented epidemic form of immunodeficiency involving prominent defects of the T-lymphocyte arm of the immune system. Pneumocystis carinii pneumonia, other opportunistic infections, and the previously rare cancer, Kaposi's sarcoma, are the most conspicuous illnesses that have this profound state of immune compromise as their underlying basis. Two years after the onset of clinical illness the case-fatality rate may exceed 90%. A steadily growing body of epidemiologic evidence indicates an infectious (probably viral) cause of the immunodeficiency although the responsible agent(s) remains obscure. Critical issues surrounding the diagnosis, screening of blood products, treatment of complicating infections and cancers, and prognosis for immunologic recovery in affected persons are unresolved. The identification of the cause of acquired immunodeficiency syndrome and the institution of effective preventive measures require the urgent attention of the medical and scientific community worldwide.

Acquired Immunodeficiency Syndrome↗

Bone marrow ablation followed by allogeneic marrow grafting during first complete remission of acute nonlymphocytic leukemia.

Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6-64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.

Bone Marrow↗

Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis.

Cyclophosphamide (CY), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-fluorouracil (5-FU) were given in single course schedules to chronic progressive multiple sclerosis (MS) patients clinically stable for 6 months. The following peripheral immune cellular parameters were measured before, during and after each drug administration: white blood count (WBC), polymorphonuclear count (PMN), lymphocyte count, percentage of T cells, T cell response to phytohaemagglutinin (PHA), percentage of B cells, percentage of cells bearing receptors for the Fc portion of immunoglobulin (% FcR cells), killer (K) cell activity defined by antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Central nervous system (CNS) immunoglobulin G (IgG) synthesis was also measured. The patients were followed carefully by both quantitative and qualitative methods for any change in their neurologic condition. Selective reduction in NK activity was observed with CY and 5-FU while no significant alteration was seen in %FcR cells and K activity. CY differed from 5-FU in reducing lymphocyte count and B cell percentage while 5-FU decreased the percentage of T cells. CCNU, but not the other drugs, reduced T cell proliferative response to PHA. In addition, CCNU, which is known to penetrate well into the nervous system, caused a modest reduction in CNS IgG synthesis, while 5-FU had an uncertain effect. Clinically the patients were unchanged or continued to progress in their disability. The results suggest an independence of the CNS immune from the systemic immune system in MS in response to many immunosuppressive drugs.

Adult↗

Suppression of natural killer cell cytotoxicity in the peripheral blood of patients receiving interferon therapy.

Lymphoblast interferon (IFN-alpha) was administered to patients with advanced stages of cancer in a phase I drug toxicity trial. IFN-alpha was given i.m. twice daily at 12-h intervals over a 7-day course of therapy in dosages ranging from 1.5 to 100 X 10(6) U/day. A total of 28 patients was studied, including 9 with breast carcinoma, 11 with other solid tumors, and 8 with lymphoid malignancies. Immune cell parameters were determined for each patient before, during, and up to 20 days after therapy. Leukopenia was evident after 1-2 days of IFN-alpha administration, became maximal after 6-7 days of therapy, and then returned to baseline values by day 13 post-therapy. Circulating natural killer (NK) cell activity was found to increase significantly by 2 h after the initial IFN injection, especially in patients receiving the higher dosages. However, most subjects demonstrated a return to baseline NK levels at 24 h despite the continued presence of elevated serum concentrations of IFN. By day 7 of therapy, NK-cell function was markedly depressed. Following cessation of IFN, NK levels rapidly returned to pretherapy baseline values. Changes in K-cell cytotoxic function (ADCC) tended to parallel those of NK-cell function. Although NK/K-cell function was affected by IFN therapy, no change in the percentage of circulating Fc receptor-bearing cells was found. This indicates that the cytotoxic cells were probably present in the circulation, but were not able to express their lytic function.

Blood Cells↗

Leukemia-derived growth factor (non-interleukin 2) produced by a human malignant T lymphoid cell line.

A growth factor was found in the supernatants of MOLT-4f, a cell line derived from acute T lymphoblastic leukemia. This factor, which we designated leukemia-derived growth factor from MOLT-4f (LDGF-M4), is different from interleukin 2. LDGF-M4 has features of a polypeptide with a molecular weight in the range of 5,000-15,000, as indicated by gel diffusion chromatography. LDGF-M4 does stimulate MOLT-4f and at least two other T cell lines that do not respond to interleukin 2. Because MOLT-4f cells produce and respond to LDGF-M4, this factor may contribute to the independence of MOLT-4f and related T leukemia cell lines.

B-Lymphocytes↗