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Biomedical subjects

K A Foon

Publications and source records attributed to K A Foon.

At least 181 records · Page 10Linked to original sources
PubMed1981

Histiocytic lymphoma following resolution of sarcoidosis.

A 32-year-old female who developed respiratory symptoms and hilar and mediastinal lymph node enlargement had a biopsy of a mediastinal lymph node typical of sarcoidosis. The symptoms and lymphadenopathy resolved spontaneously without therapy. Eighteen months later the patient developed recurrent respiratory symptoms and a large anterior mediastinal mass, a biopsy of which showed a diffuse sclerosing histiocytic lymphoma, without evidence of sarcoidosis. The possibility of a common etiologic factor or transformation of sarcoidosis into a histiocytic lymphomas are discussed.

Adult↗
PubMed1981

Intensive chemotherapy for acute myelogenous leukemia.

A complete remission rate of 82% was obtained in a group of 68 patients with acute myelogenous leukemia treated with a high-dose induction chemotherapy (TAD) consisting of 7-day courses of 6-thioguanine, cytarabine, and daunorubicin. The patients who achieved remission received intensive consolidation chemotherapy and were randomized to receive maintenance chemotherapy with or without immunotherapy. Median remission duration was 13 months and median survival, 21 months. Neither central nervous system prophylaxis nor the addition of immunotherapy to the maintenance regimen prolonged remissions or improved survival. Age, sex, and subclassification of acute myelogenous leukemia had no effect on the remission rate or survival. These data indicate that a large proportion of patients with acute myelogenous leukemia can achieve remission with intensive induction chemotherapy. Attempts to prolong remission have been less successful.

Adolescent↗
PubMed1981

Intensive chemotherapy is the treatment of choice for elderly patients with acute myelogenous leukemia.

One-hundred and seven patients with acute myelogenous leukemia (AML) ranging in age from 15 to 82 yr who were previously untreated, received a 70 day high-dose remission induction regimen consisting of daunorubicin, cytarabine, and thioguanine (TAD). Identical complete remission rates of 65% were observed for 33 patients 60 yr of age and older and for 74 patients age 15-59 yr. Median remission duration and survival were 14 mo and 22 mo for patients 60 yr and older, and 16 mo and 22 mo for patients 15-59 yr. These differences are not significant. These data indicate that older patients respond to intensive chemotherapy in a similar manner to younger patients with this disease.

Adolescent↗
PubMed1981

Monoclonal antibodies reactive with acute myelogenous leukemia cells.

Two cytotoxic monoclonal antibodies (D5D6 and C10H5) were raised to acute myelogenous leukemia (AML) cells. One of them, D5D6, reacted with 100% of the cells from 44/50 AML patients. The second, C10H5, reacted with 100% of the cells from 13/39 AML patients. D5D6 and C10H5 were cytotoxic to 100% of the monocytes from all healthy donors tested. Apart from monocytes, these antibodies did not react with any other peripheral blood cells from normal donors or with cancerous cells either from cell culture lines or from patients with chronic myelogenous leukemia (CML), lymphoid leukemias, or solid tumors. These antibodies inhibited the growth of the myeloid-monocytic stem cell, the CFU-C, and reacted with a minor population of normal bone marrow cells by immunofluorescence. Both D5D6 and CH5 have potential utility for the differential diagnosis of acute leukemia, for the detection of early leukemic relapse, and for enrichment of human stem cells.

Animals↗
PubMed1980

Dual B and T markers in acute and chronic lymphocytic leukemia.

Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell surface membrane markers. B-cell markers included surface membrane immunoglobulin, erythrocyte-antibody complement rosette formation, and B-cell (a-like or HLA-DR) antigens detected by a B-cell antiserum. T-cell markers included spontaneous sheep red blood cell rosette formation and a cytotoxic reaction to a specific T-cell antiserum. Seven patients with CLL and two with ALL had dual B and T markers. We propose that dual B- and T-cell markers are more common in CLL and ALL patients than previously reported. With newer and more sensitive tests for identification of B and T cells, this observation may be recognized more frequently.

Absorption↗
PubMed1980

Immunologic classification of acute lymphoblastic leukemia. Implications for normal lymphoid differentiation.

Acute lymphoblastic leukemia (ALL) is a heterogeneous disease as defined by clinical characteristics and immunologic techniques. The standard cell surface markers are sheep erythrocyte receptors for T lymphocytes and surface membrane immunoglobulin for B lymphocytes. Utilizing these markers, three subtypes of ALL designated T-ALL, B-ALL and non-B, non-T or null ALL have been defined. We have studied 70 patients with ALL utilizing these standard cell surface markers. In addition, we have further subclassified these patients by testing each cell for an ALL-associated antigen, the la-like antigen, and thymocyte antigen(s) all defined by well-characterized antisera. We can define 12 subgroups of ALL by their surface antigenic characteristics. These subgroups may have relevance to the clinical expression of disease and may define identifiable stages of normal lymphocyte development.

Animals↗
PubMed1977

Analysis of the systemic corticosteroid sensitivity of patients with primary open-angle glaucoma.

Patients with primary open-angle glaucoma have an ocular and systemic sensitivity to corticosteroids. We adapted a cellular assay that used peripheral blood lymphocytes to detect this corticosteroid sensitivity in vitro in a microtiter assay. It reduced the time, cost, and amount of blood required to examine a patient. We examined ten subjects on three separate days and demonstrated that the reliability of one 50% inhibitory concentration was about 76%. We then studied 25 patients with primary open-angle glaucoma and 25 control subjects using this in vitro assay. The patients with primary open-angle glaucoma were significantly more sensitive to corticosteroids than the control subjects (P less than .001).

Administration, Topical↗
PubMed1976

Demonstration of macrophage chemotactic factors in the aqueous humor during experimental immunogenic uveitis in rabbits.

Factors in the queous humor capable of increasing the random migration and chemotaxis of monocytes were demonstrated during experimental uveitis in the rabbit. Injection of endotoxin-free human serum albumin into the vitreous produced a severe inflammation detectable after 7 days and maximal between 12 to 21 days. Aqueous humor was measured for chemotactic activity with a modified Boyden chamber, which permitted the use of volumes of less than 0.025 ml. Chematactic activity was measurable during the primary inflammation and remained elevated for a short period of time after clinical inflammation and anterior chamber cellular reaction had decreased. A severe reinduction uveitis could be initiated by the intravenous injection of human serum albumin after day 30. Chemotactic factors could be measured at high titers by 8 h after this intravenous challenge.

Animals↗
PubMed1976

Serotonin-induced production of a monocyte chemotactic factor by human peripheral blood leukocytes.

Serotonin and histamine are released during the early phase of inflammatory reactions. To determine if these vasoactive amines might play a role in the cell-mediated phase of inflammation, studies were undertaken to assess their influence on some immunologic functions of human peripheral blood leukocytes (PBL). PBL were cultured with serotonin or histamine, and assayed for a proliferative response and their cell-free supernatants were assayed for the presence of a mediator with chemotactic activity for monocytes. Neither serotonin nor histamine were directly chemotactic for monocytes. When serotonin was cultured with PBL factors chemotactic for monocytes as well as polymorphonuclear leukocytes were produced in the absence of a proliferative response. Production of the factor chemotactic for monocytes was specifically blocked by methysergide, a serotonin antagonist and nonspecifically blocked by cycloheximide which interferes with leukocyte protein synthesis. Some dearboxylated precursors of serotonin also induced the monocyte chemotactic factor. This serotonin-induced chemotactic factor was demonstrated to be a product of mononuclear cells, and the majority of chemotactic activity was physiochemically similar to the previously characterized lymphocyte-derived chemotactic factor, suggesting that this factor is a lymphocyte product. In contrast to serotonin, histamine did not stimulate the production of monocyte chemotactic factor, nor did it induce proliferation. However, when 10(-5) M histamine was added to a substimulatory concentration of serotonin (10(-5) M), chemotactic activity comparable to or greater than the peak activity of serotonin alone was measured. This synergistic effect between serotonin and histamine suggests that the combination of these two amines may contribute to the induction of monocyte exudation in inflammatory reactions.

Cell Division↗
PubMedDate not supplied

Laboratory and clinical applications of monoclonal antibodies for leukemias and non-Hodgkin's lymphomas.

Important insights into leukocyte differentiation and the cellular origins of leukemia and lymphoma have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T-cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. After using all of the aforementioned markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells, such as the anti-CD20 and anti-CD19 antibodies in combination with studies of immunoglobulin gene rearrangement, have demonstrated that virtually all cases of non-T-ALL are malignancies of B-cell origin. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-CD7, anti-CD5, and antibodies that separate T lymphocytes subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphological classification. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain utility in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American-British (FAB) classification are underway in order to document the potential prognostic utility of surface markers. Therapeutic trials using monoclonal antibodies in leukemia and lymphoma have been reported. Intravenous infusion of unlabeled antibodies is the most widely used method; transient responses have been demonstrated. Antibodies conjugated to radionuclides have been quite successful in localizing tumors of less than 1 cm in some studies. Therapy trials with antibodies conjugated to isotopes, toxins, and drugs have shown promise. Purging of autologous bone marrow with monoclonal antibodies and complement in vitro has been used in ALL and non-Hodgkin's lymphoma; preliminary data suggest that this approach may be an effective therapy and may circumvent many of the obstacles and toxicities associated with in vivo monoclonal antibody infusion.

Antibodies, Monoclonal↗
PubMedDate not supplied

A monoclonal antibody recognizing human Thy-1: distribution on human and non-human primate haematopoietic cells.

A monoclonal antibody designated 'antibody 390' (Ab 390) with anti-human Thy-1 reactivity was prepared by the hybridoma technique from the splenocytes of BALB/c mice immunized with human fetal brain. This antibody was shown to have anti-human Thy-1 reactivity because (1) it precipitated a molecule with a molecular weight of about 24,000 daltons, (2) it had a pattern of reactivity similar to that of previously described anti-human Thy-1 antibodies and (3) purified human Thy-1 antigen specifically inhibited binding of Ab 390 to a known antigen-positive cell line. It was the intent of this study to investigate the distribution of Thy-1 on normal and malignant haematopoietic cells in humans and non-human primates. We show here that Ab 390 did not react with human peripheral blood leucocytes, bone marrow cells or splenocytes by immunofluorescence but did react with subcapsular and cortical fetal thymocytes by peroxidase-antiperoxidase immunohistology. A section of fetal spleen demonstrated staining of connective tissue and blood vessels and rare reactive lymphocytes. Adult spleen contained Thy-1-positive cells surrounding the white pulp and in the marginal zone, but single-cell suspensions of splenocytes did not react with Ab 390. Ab 390 was tested against a variety of fresh human leukaemia cells and human cell lines and was shown to react with only the acute lymphoblastic leukaemia T cell lines RPMI 8402 and HPB-MLT. Non-human primate studies revealed reactivity with a number of T cell lines from New World primates (cotton-topped and red-bellied marmosets) and peripheral blood granulocytes (owl monkey). Our studies support previous findings that suggest that human Thy-1 may be a marker for early T lymphocytes in man, and its distribution on non-human primate T cell lines suggests the same for certain species of non-human primates. Not consistent with the distribution on human cells was the demonstration of Ab 390 reactivity with owl monkey granulocytes.

Animals↗
PubMedDate not supplied

Monoclonal antibody therapies for lymphomas.

Important advances in molecular biology and chelation chemistry have led to new and improved monoclonal antibody reagents. Rituximab (IDEC-C2B8) was approved by the United States Food and Drug Administration for relapsed CD20-positive lymphomas, and denileukin diftitox was approved (DAB389IL-2) for CTCL. Ibritumomab tiuxetan and iodine 131 anti-B1 have excellent activity and acceptable toxicity and likely higher responses than rituximab. These questions should be answered in phase III trials, and preliminary results from the rituximab versus ibritumomab tiuxetan trial suggest higher responses to the latter. Data on radiolabeled Lym-1, T101, LL2, and anti-Tac also look promising. The therapeutic role of immunotoxins has yet to be determined, but encouraging data with DAB389IL-2 and LMB-2 have been reported. Antibody conjugates with drugs, prodrugs, nonprotein toxins, and other agents are also under investigation. Bispecific antibodies for lymphoma may also have a future role in lymphoma therapy. It is anticipated that many of the major advances in lymphoma therapy will be antibody based.

Antibodies, Bispecific↗