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Biomedical subjects

J L Fahey

Publications and source records attributed to J L Fahey.

At least 127 records · Page 7Linked to original sources
PubMed1986

Leukemia derived growth factors produced by human malignant T-lymphoid cell lines.

An autocrine (noninterleukin 2) growth factor, which we term leukemia derived growth factor (LDGF), has previously been found in the culture supernatant of the human malignant T-lymphoid cell line MOLT-4f. We now show that two other human malignant T-lymphoid cell lines, CCRF-CEM and CCRF-HSB-2 also produce such a factor. All three factors, i.e., the LDGF from MOLT-4f, CCRF-CEM, and CCRF-HSB-2 are similar to each other both in biological activity and in physicochemical characteristics. In addition to their autocrine activity, these LDGFs stimulate the growth of other malignant T-lymphoid cell lines, but they do not stimulate B-lymphoblastoid or myeloid cell lines. The results therefore suggest that these LDGFs are T-cell specific.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Prognostically significant classification of immune changes in AIDS with Kaposi's sarcoma.

Sixteen immunological parameters were assessed quantitatively for their value in providing an immunologically-based and prognostically significant classification of the immune alteration in 97 patients with AIDS and Kaposi's sarcoma (AIDS-KS). The dimensions of reductions in the T4 (T helper-inducer cells) subpopulation of lymphoid cells in the T4-T8 ratio were found to correlate most closely with prognosis. Most other immunological changes did not relate to clinical course. T4 lymphocyte levels greater than 300/microL and a T4-T8 ratio greater than 0.5 indicated a relatively good prognosis, eg, 85% to 95% survival at 12 months. T4 levels less than 100/microL and/or a T4-T8 ratio less than 0.2 had a very poor prognosis, eg, less than 25% survival at 12 months. Intermediate T4 levels and T4-T8 ratios had intermediate prognosis. These immunological findings were found to have independent prognostic value for survival when compared with disease classifications based on tumor stage (I through IV) or on clinical status A (without) or B (with fever, night sweats, or weight loss). Reduced proliferative capacity, increased OKT10 antigen expression, elevated levels of serum IgA, and immune complexes also correlated with prognosis. Elevated levels of serum IgG, cellular HLA-DR expression, and skin test anergy occurred frequently in AIDS-KS but did not have prognostic significance. Variations in level of total lymphocyte, T8 (T suppressor/cytotoxic) cell, gamma FcR receptor-positive cell number, NK activity, or level of serum IgM were less common in AIDS-KS and did not correlate with prognosis.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Defective monocyte function in acquired immune deficiency syndrome (AIDS): evidence from a monocyte-dependent T-cell proliferative system.

T-cell proliferative responses to the mitogenic monoclonal antibody anti-Leu 4 were assessed in healthy controls, lymphadenopathy syndrome (LAS) patients, and acquired immune deficiency syndrome (AIDS) patients. While 19% of the control group showed low anti-Leu 4 responses (less than 12,000 cpm), 60% of the LAS patients, 71% of the AIDS-opportunistic infection patients, and 50% of the AIDS-Kaposi's sarcoma patients showed low responses. T-cell responsiveness in healthy low responders was greatly enhanced by the addition of monocytes from an anti-Leu 4 high responder (responder monocytes). We therefore sought to determine if the low-responder state in LAS and AIDS patients was also mediated by monocytes and, thus, correctable by the addition of responder monocytes. In the LAS low-responder group, the level of enhancement by healthy responder monocytes was similar to that observed for the healthy low-responder group. In the AIDS low-responder group, however, the level of enhancement was significantly lower than that observed in the healthy low-responder and LAS low-responder groups. These findings suggest that impaired proliferation to anti-Leu 4 in LAS patients may be due to a monocyte defect similar to the monocyte defect responsible for low anti-Leu 4 responses in healthy controls. AIDS patients, however, show additional defects in anti-Leu 4-induced proliferation that are not fully corrected by the addition of responder monocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Monoclonal antibodies against transitional cell carcinoma for detection of malignant urothelial cells in bladder washing.

The diagnosis of transitional cell carcinoma by cytological examination of exfoliated urinary cells is important in the early detection and followup of patients with this disease. Proper interpretation requires a skilled pathologist. Accuracy also is influenced by collection methods and nonmalignant pathological conditions of the bladder. An immunocytochemical technique using monoclonal antibodies G4 and E7 successfully identified tumor-associated antigens on the surface of transitional carcinoma cells obtained by bladder washings. The method, which uses immunoperoxidase staining, was compared to conventional Papanicolaou staining of bladder washings from 75 patients with and without transitional cell carcinoma. Patients were divided into 4 groups: group 1 (nontumor control)--15 patients with no pathological condition of the bladder or nonmalignant urological diseases, group 2 (nontransitional cell carcinoma)--19 patients with other urological malignancies, group 3-18 patients with active transitional cell carcinoma and group 4-23 patients with a history of transitional cell carcinoma but no evidence of tumor at the time of the washing. The incidence of positive staining in these groups was 0, 5, 78 and 0 per cent, respectively. The diagnostic value of immunoperoxidase staining was similar to that of Papanicolaou staining in the control group and in patients with high grade transitional cell carcinoma, and provided specific morphological criteria not possible by conventional cytology studies. Interpretation of immunoperoxidase staining was difficult in washings with a large number of inflammatory cells if endogenous peroxidase activity was not blocked properly. The application of the immunoperoxidase staining method for diagnosis of low grade tumor is under further investigation.

Antibodies, Monoclonal↗
PubMed1985

Reduced ecto-5'-nucleotidase activity and enhanced OKT10 and HLA-DR expression on CD8 (T suppressor/cytotoxic) lymphocytes in the acquired immune deficiency syndrome: evidence of CD8 cell immaturity.

Markedly reduced ecto-5'-nucleotidase activity was found in peripheral blood lymphocytes from 27 out of 30 homosexual men with the acquired immune deficiency syndrome (AIDS) in association with Kaposi's sarcoma (AIDS-KS; 2.67 +/- 1.70 U/10(6) cells; n = 13), opportunistic infections (AIDS-OI; 9.29 +/- 7.32; n = 7), or the AIDS-related complex (ARC; 9.82 +/- 6.12; n = 10). These values were significantly different from healthy controls (22.70 +/- 4.58; p less than 0.001). In AIDS-KS patients, both T cells and non-T cells exhibited significantly reduced ecto-5'-NT activity (p less than 0.001). AIDS-KS CD8 cells contained 20% of the mean ecto-5'-NT activity (7.04 +/- 3.53) displayed by control CD8 cells (34.07 +/- 4.86; p less than 0.001). No significant difference in enzyme level was observed between control and AIDS-KS CD4 cells (11.93 +/- 4.98 vs 7.98 +/- 3.28, respectively). In AIDS patients, lymphocyte ecto-5'-NT activity was inversely related (r = -0.518; p less than 0.01) to the absolute number of OKT10+ cells, but no correlation was found with the number of HLA-DR+ cells (r =-0.224). Two-color analysis of lymphocytes from AIDS-KS patients revealed that 75 +/- 12% of circulating CD8 cells expressed the OKT10 antigen, whereas only 10 +/- 6% of control CD8 cells did. HLA-DR antigens, which are not normally found on circulating resting T cells, were expressed in AIDS-KS CD8 cells, although to a lesser extent than OKT10. These data demonstrate that most AIDS CD8 cells differ from control CD8 cells. Although it has been suggested that these cells are activated cytotoxic or suppressor cells, the data presented here support the hypothesis they are immature. Reduced T cell ecto-5'-NT activity and enhanced expression of OKT10 and HLA-DR antigens on circulating CD8 cells, in conjunction with lack of transferrin receptor-(OKT9) and IL 2 receptor-(Tac) bearing lymphocytes, sustain this latter hypothesis. The correlation of the numerical reduction of CD4 cells with the reduced levels of ecto-5'-NT (r = 0.606; p less than 0.01) suggests that the abnormal maturation of CD8 cells seen in AIDS might be a consequence of the CD4 deficiency characteristic of this syndrome.

5'-Nucleotidase↗
PubMed1984

The relation of cytomegalovirus and Epstein-Barr virus antibodies to T-cell subsets in homosexually active men.

Eighty-nine homosexual men participated in a study of sexual practices, T-cell subsets, and antibody titers to cytomegalovirus (CMV) and Epstein-Barr virus (EBV). The prevalence of antibody to CMV was 96% and to EBV, 94%. Titers to CMV were higher in those practicing receptive anal intercourse. The CMV antibody titers were positively correlated with the T-helper/suppressor ratio, number of partners and venereal disease episodes, number of T-suppressor cells, and EBV titers. Twelve percent of the participants had a low ratio only, 18% T-suppressor augmentation, and 3% T-helper deficiency. The CMV titer and prevalence of receptive anal intercourse were higher in those with a low ratio only, T-suppressor augmentation, and T-helper deficiency. These results suggest that CMV infection is acquired through receptive anal intercourse and is associated with an increase in T-suppressor cells and, in some persons, a decrease in T-helper cells.

Adult↗
PubMed1984

Nontransmission of T-cell subset abnormalities from hemophiliacs to their spouses.

Hemophiliacs who are exposed to pooled clotting factor concentrate constitute one group at increased risk for development of acquired immune deficiency syndrome. To determine the prevalence of cellular immune aberrations in asymptomatic hemophiliacs, we studied a group of 65 adult hemophiliacs for T-cell subset abnormalities. Sixty-five percent of concentrate recipients had an abnormal T-helper to T-suppressor cell ratio, 40% had a depressed absolute T-helper cell level, and 29% had an elevated absolute T-suppressor cell count. To determine whether horizontal transmission of T-cell subset abnormalities from hemophiliacs to their female sexual partners occurred, we studied 41 spouses. We found no correlation between paired husband and wife values for T-cell ratio or any other immune parameter studied. There were no significant differences found between wives of hemophiliacs with reversed T-cell ratios and wives of hemophiliacs with T-cell ratios of 1.0 or greater, with respect to immunologic tests. We conclude that there is no evidence to date for heterosexual or household-contact transmission of T-cell subset abnormalities from hemophiliacs to their spouses in our study population.

Adolescent↗
PubMed1984

Outcome of bone marrow transplantation in patients with extramedullary involvement of acute leukemia.

Infiltration of extrahemopoietic tissue with leukemic cells was evaluated as a prognostic indicator in 18 patients with acute leukemia undergoing bone marrow transplantation. When compared to 107 patients who did not have extramedullary leukemia at any time prior to marrow grafting, the patients with leukemic invasion into organs outside the hemopoietic system had a significant increase of leukemic recurrence and a significant decrease in survival after marrow transplantation. Extramedullary leukemia may be a negative prognostic indicator for bone marrow transplantation candidates.

Acute Disease↗
PubMed1984

HLA studies in acquired immune deficiency syndrome patients with Kaposi's sarcoma.

To investigate the possible contribution of genetic susceptibility to Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS-KS), 21 patients were typed for HLA-A, B, C, and DR antigens. Significantly increased frequencies of HLA-Aw23, and HLA-Bw49 antigens were observed in the Caucasian AIDS-KS group. In this same group, the frequencies of HLA-DR5 and HLA-Bw44 antigens were increased at the P less than 0.1 level. Increased frequencies of HLA-A29 and HLA-Cw4 antigens and a decreased frequency of HLA-B8 antigen were also noted, but with P greater than 0.1, in the Caucasian AIDS-KS group.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Azathioprine suppression of natural killer activity and antibody-dependent cellular cytotoxicity in renal transplant recipients.

The relative effects of azathioprine (AZA) and prednisone (PRED) on natural killer (NK) activity and the antibody-dependent cellular cytotoxicity (ADCC) of K (killer) cells and the number of FcR and other lymphoid cells were examined in renal transplant recipients. In addition to both long-term (greater than 6 months) and short-term (less than 6 months) transplant recipients receiving conventional AZA-PRED therapy, an important group of long-term recipients receiving PRED but not AZA was studied for the first time. Both NK activity and ADCC are profoundly reduced in the long-term AZA-PRED group but are normal in the long-term PRED-alone (no-AZA) group. The short-term AZA-PRED group exhibits NK and ADCC levels significantly lower than normal but not as low as those of the long-term AZA-PRED group. Patient groups with low NK and ADCC also have low circulating Fc receptor-bearing (FcR) cells. A single patient in the long-term AZA-PRED group was removed from AZA therapy, and approximately 3 months was required for the patient's suppressed NK and ADCC to return to normal. These findings indicate that AZA rather than PRED is the major drug important in suppressing ADCC and NK activity in renal transplant recipients. Several months are required for combination AZA-PRED therapy to reduce these cytotoxic activities. Similarly, several months are required for suppressed ADCC and NK activity to return to normal upon discontinuation of AZA.

Adolescent↗
PubMed1984

Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders.

Quantitative measurements of the immune cell subgroups, T helper (Leu 3+/OKT4+) cells and T suppressor/cytotoxic (Leu 2+/OKT8+) cells, were made in patients having acquired immune deficiency syndrome (AIDS) with Kaposi's sarcoma and in patients with AIDS and opportunistic infection, as well as in three other relevant populations. These included patients with lymphadenopathy syndrome, e.g., homosexually active males with lymphadenopathy who sought medical care for additional symptoms, and healthy male homosexuals, as well as a control population. Decrease in the number of T helper cells is characteristic of AIDS with Kaposi's sarcoma or opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population is rare in AIDS with Kaposi's sarcoma but is more frequent in AIDS with opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population, however, may occur in a variety of circumstances, including cytomegalovirus and other viral infections, in healthy, homosexually active males, and in otherwise healthy hemophiliac subjects receiving factor VIII treatment. Reduced T helper:T suppressor/cytotoxic cell ratio can be caused by either decrease in the number of T helper cells or augmentation of the T suppressor/cytotoxic cell population. Lowered T helper:T suppressor/cytotoxic cell ratio does not, by itself, help to distinguish between AIDS and other causes of reduced ratios. Quantitative measurements are needed to define the T subset changes. AIDS is characterized by decrease in the number of T helper cells and reduced T helper:T suppressor/cytotoxic cell ratio. The T helper (Leu 3+) and T suppressor/cytotoxic (Leu 2+) cell subpopulations can change independently. Identification of decrease in the number of T helper cells as an alteration that occurs independently of numerical change in other lymphoid subpopulations, such as T suppressor/cytotoxic cells and B cells, and the close association of the decrease in the number of T helper cells with AIDS are consistent with a distinct pathogenesis (and cause) for AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Murine hybridoma antibodies against human transitional carcinoma-associated antigens.

Spleen cells from mice immunized with the human urinary bladder transitional cell carcinoma cell line 647V have been fused with a syngeneic myeloma cell line to produce hybridomas. Screening of supernatants from 40 hybridomas which reacted with the immunizing cell line identified antibodies recognizing a variety of common, shared and tumor-associated antigens as well as newborn calf serum dependent antigens. Three hybridoma antibodies, 9A7 , 2E1 and 2A6 , recognize antigens found on all the human transitional cell carcinoma cell lines and tissue preparations tested, but the antigens were not found on normal human tissue (including urothelium), thus demonstrating the capability of the antibodies to distinguish normal from malignant bladder transitional epithelium. These antibodies, however, otherwise differ in their patterns of reactivity, with 1 recognizing an antigen which is also expressed on highly anaplastic malignant non-transitional cell carcinoma cell lines and tumors, while the other 2 demonstrate reactivities which are far more restricted to transitional cell carcinoma.

Animals↗
PubMed1984

Growth stimulating activity produced by human bladder cancer cells.

Growth promoting properties have been identified in the conditioned serum-free medium from cultures of the human transitional cell carcinoma cell line 647V. This activity appears to reside in a molecule of more than 5000 MW. The factor responsible for 647V growth is distinguished from epidermal growth factor, since it fails to inhibit the specific binding of epidermal growth factor by 647V cells, and 647V cells are not stimulated to grow by epidermal growth factor. It also does not appear to be an insulin-like growth factor-like molecule since it fails to competitively bind with human insulin-like growth factor-carrier protein.

Binding, Competitive↗
PubMed1984

The use of three baseline values in intervention studies: application to evaluation of immune modulation therapies.

In studying the effects of a treatment intervention on immunological parameters, we have found that three baseline values are a practical number to obtain on each patient. Three baseline values 1) increase the chances of detecting a statistically significant effect of the intervention, 2) provide an assessment of the daily variability of the assay and patients, and 3) enable the identification of individual patients who demonstrate significant changes associated with the intervention.

Drug Evaluation↗