PubMed Health⌕ Search

Biomedical subjects

A F Lobuglio

Publications and source records attributed to A F Lobuglio.

12 recordsLinked to original sources
PubMed1993

In vivo treatment with a monoclonal chimeric anti-CD4 antibody results in prolonged depletion of circulating CD4+ cells in chimpanzees.

Chimeric M-T412 (cM-T412), an anti-CD4 antibody, was tolerated in chimpanzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, or 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chimpanzees showed a prolonged CD4-cell depression. Weak chimpanzee antibody responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction immediately after receiving its seventh dose. Following supportive treatment, the animal recovered and remained asymptomatic during the non-treatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermittent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh dose. Chimeric M-T412 also induced an anti-cM-T412 response in some of the other animals. The level of this response was lower than the anti-mouse responses observed in animals treated with murine anti-CD4. Moreover, the anti-cM-T412 response was mainly directed to idiotypic determinants. The decrease in CD4+ cells observed for all chimeric M-T412-treated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is, however, much longer than observed for other CD4-specific MoAbs described. No selective loss of either memory or naive CD4+ cells was observed after either the single, 7-day or twice-weekly treatments. The CD4+ cell depression was reversible, although individual variation in time to recovery was observed. Therefore, cM-T412 could be a good candidate for clinical use in autoimmune conditions.

Animals↗
PubMed1987

Immune thrombocytopenia: effects of maternal gamma globulin infusion on maternal and fetal serum, platelet, and monocyte IgG.

A 24-year-old woman with lupus-like serologic abnormalities had immune thrombocytopenia that resolved after splenectomy, but increased quantities of platelet surface IgG persisted. Three years later, during the 36th week of her first pregnancy, gamma globulin (400 mg/kg daily for 5 days) was administered intravenously to decrease the risk and/or severity of immune thrombocytopenia in her infant. The infusion produced marked but transient elevations of maternal concentrations of serum IgG and quantities of monocyte surface IgG, but no significant changes in Fc receptor-mediated rosetting of peripheral blood monocytes with antibody-sensitized platelets occurred. Modest increases in quantities of platelets and plasma platelet-specific IgG were demonstrated. The infant, delivered by cesarean section 2 days after the end of the infusion, had a normal platelet count; cord blood had a normal concentration of serum IgG, but an elevated quantity of platelet surface IgG (by comparison with values for normal adults). Infant values of plasma platelet-specific IgG, monocyte surface IgG, and monocyte/platelet rosettes also were within the range of normal for adults. Anticytomegalovirus antibody was present in large amounts in the gamma globulin infused, first appeared in maternal serum after therapy, and was detected in cord serum. The significance of these observations to the management of immune neonatal thrombocytopenia is discussed.

Adult↗
PubMed1986

Phase I clinical trial of CO17-1A monoclonal antibody.

Twenty patients with metastatic gastrointestinal cancer received one or more weekly infusions of 400 mg CO17-1A monoclonal antibody. The most common side effect was mild gastrointestinal symptoms in 9/20 patients. Two of five patients receiving three weekly infusions had reversible anaphylactic reactions at the time of their third infusion. The pharmacokinetics of the antibody were similar at the first, second or third infusion. Human antibody to 17-1A occurred in 17/20 patients with 11/20 having antibody detectable by 8 days following initial infusion. Thus, one or two infusions (weekly) of large doses of 17-1A were well tolerated but allergic responses limit ability to administer therapy by 15 days post-initial infusion.

Animals↗
PubMed1984

Immunoperoxidase staining of early human melanoma colonies with monoclonal antibodies. A new method for in vitro antigenic-morphologic correlation.

The ability to evaluate antigenic expression within the clonogenic fraction of a tumor population has heretofore been limited by the need to grow large numbers of cells derived from clonogenic cells prior to immunoassay. This preliminary report describes the authors' initial experience with a simplified, efficient technique for analyzing antigenic expression among and within early colonies from a human solid tumor. Avidin-biotin immunoperoxidase staining of human melanoma colonies grown in semisolid medium yielded excellent cell retention, morphologic preservation, and antigenic localization. This method appears promising for antigenic-morphologic correlations among clonogenic tumor cells and may be useful for further studies of human tumor heterogeneity and differentiation.

Animals↗
PubMed1982

Combination chemotherapy of refractory lymphoma with cis-dichlorodiamineplatinum, vinblastine, and bleomycin.

Therapy of advanced lymphomas after failure of chemotherapy with cytoxan and adriamycin containing combinations remains poor. We have treated 17 patients with refractory lymphomas of various histologies with an intensive regimen of cisplatin, vinblastine and bleomycin. These were three complete clinical responses (6, 10+, 8 months, respectively) and five partial responses (2.5, 3, 4, 7, 18 months, respectively) for a total of 8/17 responders. Four of the eight responders had bone or bone marrow involvement. In addition, three patients had dramatic shrinkage of measureable lesions, but the duration (less than 1 month) was too short to allow classification as a response. Toxicity included severe myelosuppression requiring that patients be hospitalized to the majority of cases, mild to moderate rise in serum creatinine levels in 41% of patients and one case of fatal pulmonary fibrosis. This regimen may be useful in patients with refractory or relapsing lymphoma; alternatively, it may be useful as part of an initial treatment protocol utilizing non-cross-resistant regimens for the management of patients with poor prognosis lymphomas.

Adult↗
PubMed1980

Correlation of prognostic factors and blood lymphocyte subtypes in non-Hodgkin's lymphoma.

The total lymphocyte, T, B, and null cell content of peripheral blood from 32 healthy individuals and 30 patients with non-Hodgkin's lymphoma was determined. The patients had a significant reduction of B cells (complement receptor and membrane immunoglobulin positive cells) and a significant reduction in T cells. Correlation of patients' characteristics with lymphocyte abnormalities demonstrated several findings. Patients with advanced disease (III and IV) had significantly lower total lymphocyte and T cells than patients with localized disease (I and II) or normal controls. Patients with hypogammaglobulinemia had lower total lymphocyte and T cells than patients with normal gamma globulin status or normal controls. Patients with diffuse histology and B symptoms had lower total lymphocyte and T cells than normal controls. Discriminant analysis of lymphocyte populations categorized patients by disease extent and gamma globulin status with 70 and 68% accuracy, respectively.

Agammaglobulinemia↗
PubMed1979

Re-examination of the EA rosette assay (Ripley) for Fc receptor leucocytes.

Numerous investigations has utilized rosette formation with Ripley antibody-coated human erythrocytes (EA) to identify or deplete Fc receptor-bearing K lymphocytes in whole mononuclear cell preparations. This study examines the interaction between Ripley EA and purified preparations of human lymphocytes, monocytes and neutrophils and demonstrates that this technique is not specific for K lymphocytes. Indeed, 100% of blood monocytes rosette these EA target cells. Moreover, data from both rosetting studies and antibody-dependent cytotoxicity (ADCC) reactions suggest that the avidity of Ripley EA is actually greater for monocytes than for lymphocytes. In contrast to previous reports, 100% human neutrophils were found to possess Fc receptors, as determined by their ability to rosette Ripley EA. Thus, the extent of rosetting and ADCC by all three Fc receptor-bearing leucocytes depends significantly on the degree of antibody sensitization with neutrophils requiring the greatest, and monocytes the least, amount of target-bound antibody for Fc receptor-mediated interaction.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Human monocyte cytotoxicity to tumor cells. I. Antibody-dependent cytotoxicity.

Recent investigations examining mononuclear cell antibody-dependent cell-mediated cytotoxicity against tumor cell lines suggest that K lymphocytes and not monocytes are active in this cytotoxic reaction. We have found, however, that in an allogeneic assay system, human monocyte monolayers as well as lymphocytes mediate substantial lysis of 51Cr-labeled antibody-coated CEM lymphoblast tumor cells. This cytotoxicity is temperature-dependent and rapid, with most 51Cr release occurring in the first 4 hr of co-incubation. Interaction between target cell-bound antibody and the monocyte Fc receptor is necessary as demonstrated by the marked fall in antibody-dependent cell-mediated cytotoxicity (ADCC) produced by staphylococcal protein A, high concentrations of nonspecific immunoglobulin, and dilution of the target cell antiserum. Morphologic and functional characteristics of the monocyte-monolayer preparations establish their relative purity (greater than 95%) and indicate that monocytes and not contaminating lymphocytes are responsible for tumor cell lysis. Furthermore, preincubation of monocyte and lymphocyte preparations with latex particles or low concentrations of immunoglobulin distinguished monocyte from lymphocyte ADCC. Thus, normal human monocytes have the capacity to carry out antibody-dependent cytotoxicity against nucleated malignant target cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Human monocyte glucose metabolism in lymphoma.

Glycolysis (GU), hexose monophosphate shunt (HMPS) activity, and Krebs cycle activity were determined in monocytes from 32 normal subjects and 22 untreated patients with lymphoma. All of these parameters of glucose metabolism were significantly elevated in the lymphoma patients as a group when compared to normal subjects, suggesting monocyte activation by lymphoma. When the results were evaluated on the basis of sex and age, significant enhancement of glucose metabolism by lymphoma was evident in the 13 male patients compared to 18 normal men but not in monocytes from nine women with lymphoma compared to 14 normal subjects. Male patients over and under 40 years of age had significantly enhanced HMPS activity compared to normal subjects (p less than 0.05 and p less than 0.01, respectively), and GU was significantly increased in patients over 40 years (p less than 0.01). In contrast, no significant differences were noted in any of the values of women with lymphoma compared to normal subjects matched according to menstrual status. This discrepancy is apparently due to the high values for HMPS noted in healthy women, especially menstruating women. Although lymphoma may activate monocyte glucose metabolism, this effect can be masked by the normally high values seen in healthy women. The sex of the subject must be considered in evaluating human monocyte function and metabolism.

Blood Glucose↗