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Biomedical subjects

A F LoBuglio

Publications and source records attributed to A F LoBuglio.

At least 91 records · Page 5Linked to original sources
PubMed1987

Radioimmunoscintigraphic detection of occult gestational choriocarcinoma.

Localized recurrent gestational choriocarcinoma, evidenced by a rising level of the beta-subunit of human chorionic gonadotropin, can be difficult to localize for surgical resection. We describe a patient with a rising level of the beta-subunit of human chorionic gonadotropin after extensive therapy for choriocarcinoma in which gamma scanning of the distribution of an intravenously administered iodine 131-labeled monoclonal antibody preparation (5F9.3) allowed localization of a focus of recurrent choriocarcinoma in the lung. Other imaging methods showed this only as a focus of stable scarring. The antibody scan guided surgical resection of this tumor focus, which on gamma counting had a tenfold excess of antibody activity compared with that of the normal lung. This approach may be useful in detecting occult foci of gestational choriocarcinoma for surgical resection in patients with rising levels of the beta-subunit of human chorionic gonadotropin and is under further evaluation.

Adult↗
PubMed1987

Development and characterization of a monoclonal antibody to human embryonal carcinoma.

A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with 131I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21. This antibody thus has selective reactivity with the surface of tumor cells from embryonal carcinoma (testicle) and choriocarcinoma both in vitro and in vivo.

Animals↗
PubMed1987

Ultrastructural analysis of human natural killer cell activation.

In this study we describe characteristic ultrastructural changes of CD3- large granular lymphocytes (LGL), ie, natural killer (NK) cells, following stimulation with recombinant (r) interleukin 2 (IL 2) or r-gamma interferon (r-gamma IFN) and after interaction with K562 target cells (TC) or Sepharose-bound anti-Fc gamma receptor (FcR) monoclonal antibody (MoAb). When compared to resting cells the cytolytic activity of r-IL 2- and r-gamma IFN-stimulated cells against K562 TC was enhanced. The r-IL 2-stimulated LGL were larger and consistently displayed the shape and cytoskeletal rearrangement characteristic of activated cells. The Golgi apparatus was expanded, and the number of electron-dense granules and vesicles was increased. The ultrastructural changes in r-gamma IFN-stimulated LGL were markedly different from those observed following r-IL 2 activation. Cells did not exhibit changes in size, shape, cytoskeletal organization, or in the structure of the Golgi apparatus. However, r-gamma IFN-stimulated cells exhibited distinctive changes in the structure and content of electron-dense granules with deaggregation of the matrix and parallel tubular arrays (PTAs). Within organelles apparently derived from the electron-dense granules, vesicular and tubular structures were noted that may be the morphological equivalent of cytotoxic factors produced by cytolytic effector cells. These ultrastructural observations indicate that r-IL 2 and r-gamma IFN enhance the lytic ability of NK cells by acting on distinct cell machineries. The cytolytic ability was decreased when LGL were pretreated with K562 TC or immobilized anti-FcR antibody. In both experimental conditions cells displayed ultrastructural features indicating activation as well as loss of cytoplasmic granules and other Golgi-derived organelles. Stimulation of r-gamma IFN- or r-IL 2-activated LGL with K562 TC or Sepharose-bound anti-FcR antibody decreased their cytolytic ability, with cells depleted of granules at the ultrastructural level. Intracytoplasmic fusion of granules and a massive release of the granule content were found in r-IL 2-stimulated cells, reminiscent of the mechanism of basophil degranulation. These observations suggest that multiple activation signals involving distinct surface membrane molecules induce release of cytolytic factors by both resting and activated NK cells.

Cell Line↗
PubMed1987

Platelet surface-bound IgG in patients with immune and nonimmune thrombocytopenia.

We quantitated the amount of platelet surface-bound IgG using an 125I monoclonal anti-IgG assay in 149 patients with thrombocytopenia and 260 normal donors. The normal subjects had 122 +/- 5 molecules of IgG/platelet (mean +/- SE). Fifty-five patients with nonimmune thrombocytopenia had 338 +/- 37 molecules of IgG/platelet, whereas 67 patients with immune thrombocytopenia studied at the time of their initial evaluation had 4,120 +/- 494 molecules of IgG/platelet. An analysis of the distribution of values in these two groups indicated that 90% of the patients with immune thrombocytopenia had greater than 800 molecules of IgG/platelet, whereas only 7% of patients with nonimmune thrombocytopenia exceeded this amount. The immune thrombocytopenia patients included 39 idiopathic, 14 secondary, and 14 drug-induced disorders, and they did not significantly differ in their distribution of values for platelet IgG. The nonimmune thrombocytopenic patients included 12 cases with a platelet destructive mechanism; their platelet-bound IgG was similar to that of the other nonimmune patients. Twenty-seven patients with treatment resistant immune thrombocytopenia were also studied they had 2,100 +/- 670 molecules of IgG/platelet. Their values were significantly greater than those of the nonimmune thrombocytopenic patients and not significantly different from those of immune thrombocytopenic group. Their distribution of values was much broader, however, with 33% of patients having less than 800 molecules of IgG/platelet, suggesting possible alternate mechanisms in their thrombocytopenia. Thus, patients with immune thrombocytopenia have a high frequency of elevated IgG on the platelet surface which reflects the pathophysiology of this disorder. Quantitation of platelet-bound IgG provides a useful laboratory tool in the differential between immune and nonimmune thrombocytopenia.

Antibodies, Monoclonal↗
PubMed1986

In vitro effects of gammaglobulin (IgG) on human monocyte Fc receptor function. I. Effect on monocyte membrane-associated IgG and Fc receptor-dependent binding of antibody-coated platelets.

Intravenous immunoglobulin (IV IgG) has been reported to be clinically beneficial for the treatment of immune thrombocytopenic purpura (ITP). The mechanism of effect still remains unknown. We examined the in vitro effects of two commercially available IV IgG preparations. Exposure of normal monocytes to IgG in vitro produced a significant increase in monocyte-bound IgG. Prior treatment of the commercial IgG preparations by filtration through a 0.2-micron Millipore filter or ultracentrifugation caused a dramatic decrease in IgG bound to the monocyte surface, indicating that IgG aggregates were responsible for this effect. Exposure of monocytes to IgG levels as high as 150 mg (Sandoglobulin) and 400 mg (Gamimune) did not result in a statistically significant inhibition of monocyte-platelet interaction as examined by a morphologic rosetting assay. Thus, despite the ability of IV IgG preparations to cause substantial increments in monocyte surface IgG, impairment of Fc receptor-mediated monocyte binding of antibody-coated platelets was not observed.

Blood Platelets↗
PubMed1986

Radioimmunoassay of free beta-subunit of human chorionic gonadotropin as a prognostic test for persistent trophoblastic disease in molar pregnancy.

A new radioimmunoassay system was established with a monoclonal antibody (1E5) that distinguishes the free beta-subunit of human chorionic gonadotropin in the presence of intact human chorionic gonadotropin, showing only 0.23% cross-reactivity with the intact human chorionic gonadotropin molecule and virtually no cross-reactivity with other glycoprotein hormones or their beta-subunits. Serum samples, taken at initial diagnosis from nine patients with hydatidiform mole and spontaneous remission and 12 patients with subsequent progression to persistent trophoblastic disease, were assayed for free and total levels of the beta-subunit of human chorionic gonadotropin. The assay results were expressed as a ratio of nanograms of free beta-subunit per 1000 mIU of total beta-subunit. Eight of nine patients with mole and spontaneous remission had a ratio value less than 4 whereas 10 of 12 patients with subsequent persistent disease had a ratio value greater than 4. Statistical analysis with chi 2 showed a highly significant correlation of high ratios with eventual progressive disease (p = 0.0009). This study suggests that excessive production of the free beta-subunit of human chorionic gonadotropin may identify patients with a high likelihood of developing persistent trophoblastic disease.

Chorionic Gonadotropin↗
PubMed1986

Measurement of platelet surface-bound IgG by a monoclonal 125I-anti-IgG assay.

We have described the use of a monoclonal 125I-labeled anti-IgG (125I-MA) to assay IgG antibody displayed on the surface of platelets from normal and immune thrombocytopenic patients and reported levels of IgG 10-100-fold lower than previous studies. This report describes the immunologic characteristics of the 125I-MA and the assay for surface IgG. The 125I-MA has a high binding affinity for surface-displayed IgG (2.22 X 10(9) M-1), reacts equally well with all four subclasses of IgG and not at all with IgM or IgA. In our assay, the binding of 125I-MA was found to be greater than or equal to 99% specific for IgG (no nonspecific association of 125I-MA with platelets) and the binding ratio of 125I-MA to IgG displayed on the cell surface was 0.91 (close to unity). Finally, platelet lysates were found to contain large amounts of IgG protein (39,597 +/- 27,418 molecules/platelet) as compared to surface-displayed IgG (124 +/- 86 molecules/platelet). This assay has excellent characteristics for quantitation of IgG on platelets and the discrepancy with other techniques may, in part, be due to intentional or inadvertent lysis of platelets during assay conditions.

Antibodies, Anti-Idiotypic↗
PubMed1985

Etretinate therapy for psoriasis. Reduction of antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes.

We monitored the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from 14 patients with psoriasis before and during etretinate therapy. Neutrophils obtained from the patients with psoriasis at pretherapy demonstrated significantly greater cytotoxic activity than control cells. After four weeks of etretinate therapy, the cytotoxicity of neutrophils from the psoriatic patients decreased significantly and was no longer significantly different from the control value (at a 1:1 effector-to-target ratio). The decline in neutrophil cytotoxicity preceded significant clearing of our patients' psoriasis. The reduction in the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from patients with psoriasis occurs early during therapy and may represent one of the mechanisms of action of etretinate.

Adult↗
PubMed1984

Dose-response and dose-survival advantage for high versus low-dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer. A Southwest Oncology Group study.

One-hundred fourteen patients with advanced testicular cancer were randomized to treatment consisting of either high-dose (120 mg/m2, monthly) or low-dose (15 mg/m2, daily X 5 monthly) cisplatin, both combined with vinblastine and bleomycin. There were 60 (53%) complete remissions and 42 partial remissions for an overall response rate of 90%. An additional 11 patients, 4 with carcinoma and 7 with mature teratoma, following surgical cytoreduction, were rendered free of disease. There was a significantly higher complete response rate for high dose induction chemotherapy, 63%, when compared with low dose, 43% (P = 0.03). A survival advantage was also observed for patients receiving high-dose therapy (P = 0.009). For the subgroup of patients with maximal disease and embryonal +/- teratoma +/- seminoma histology there was a clear advantage in favor of high-dose over low-dose therapy both in complete response rate and survival (P = 0.03). There have been only four relapses, all occurring within 1 year of study entry. While there has been a higher frequency of leukopenia, renal, neuromuscular, and mucosal toxicity with high-dose therapy, thus far no irreversible toxicity leading to functional impairment has been seen. The authors have demonstrated a clear-cut relationship for dose of therapy, not only with response and survival, but with the increased potential for cure as well.

Adolescent↗
PubMed1984

Human monocyte interaction with antibody-coated platelets. I. General characteristics.

The interaction of human monocytes with antibody-coated and normal platelets was studied using an assay system that employed rate zonal centrifugation to separate monocyte-associated (bound) platelets from free platelets. At a monocyte:platelet ratio of 1:10, monocytes bound 21.2 +/- 6.6% of antibody-coated platelets and less than 2.2 +/- 1.3% of control platelets. Monocyte binding of antibody-coated platelets was rapid and inhibited by monomeric IgG and staphylococcal protein A. Specific binding was positively related to the number of monocytes present and the amount of IgG displayed on the platelet surface. Transmission and scanning electron micrographs illustrate the membrane binding of antibody-coated platelets to monocytes and suggest that phagocytosis of platelet targets occurs as well. Thus, these observations indicate that monocytes can participate in Fc-receptor binding of anti-PlA1-sensitized platelets. This novel assay may be useful in the analysis of monocyte-macrophage Fc-receptor interaction with platelets sensitized with IgG from both iso- and autoimmune disorders as well as in the characterization of treatment modalities which may alter monocyte Fc-receptor recognition and binding.

Antibodies↗
PubMed1984

Randomized trial of radiotherapy versus radiotherapy plus metronidazole for the treatment metastatic cancer to brain. A Southwest Oncology Group study.

One hundred sixteen eligible patients with metastatic cancer to the brain were randomized to receive either radiotherapy 3000 rad/10 fractions (treatment 1) or the same radiotherapy plus metronidazole 6 gm/m2 (treatment 2). One hundred eleven patients were either fully or partially evaluable. The response rates (CR + PR) and survival showed no significant differences between treatments. Treatment 1: CR + PR 24%, median survival 14 weeks, Treatment 2: CR + PR 27%, median survival 12 weeks. There were no differences observed in response rates based on primary tumor site, neurologic performance status, or extent of metastatic disease. Metronidazole therapy was associated with substantial nausea and vomiting but no neurotoxicity was observed. Oral metronidazole given every other day during radiation therapy provided no clinical benefit for patients with brain metastases compared to radiotherapy alone.

Age Factors↗
PubMed1984

Quantification of platelet-bound IgG by 125I-Staphylococcal protein A in immune thrombocytopenic purpura and other thrombocytopenic disorders.

In this report we describe the use of an 125I-Staphylococcal protein A (SPA) assay to measure platelet-bound IgG in the evaluation of 62 thrombocytopenic patients. Platelets from 150 normal subjects were found to bind 146 +/- 112 molecules of SPA per platelet (mean +/- 2 SD). Nineteen of 20 patients with untreated immune thrombocytopenia had platelet IgG values above this range, with 15 of 20 having values above 1,000 molecules of SPA per platelet. Patients with immune thrombocytopenic purpura by clinical criteria, but who had failed conventional therapy (corticosteroids or splenectomy), had a wide range of platelet IgG levels: 4 of 20 had normal values, 6 of 20 had minimally elevated levels in the range seen with nonimmune thrombocytopenia, and 10 of 20 had much higher values. Fifteen patients with thrombocytopenia of apparent nonimmune origin and 7 others with chronic stable thrombocytopenia of unknown etiology were found to have platelet IgG levels within or only slightly above the normal range. Because of its simplicity, accuracy, and clinical correlation, the 125I-SPA assay provides an important new approach for studying platelet IgG in thrombocytopenic states. The data obtained with this technique are similar to those found in immune hemolytic anemia and suggest that the platelet-bound IgG so measured has pathophysiologic relevance in immune thrombocytopenic purpura.

Adult↗
PubMed1984

Colchicine therapy for refractory idiopathic thrombocytopenic purpura.

Fourteen patients with idiopathic thrombocytopenic purpura (ITP) refractory to splenectomy and corticosteroids (prednisone, 1 to 2 mg/kg of body weight per day) received at least 1.2 mg of oral colchicine daily for a minimum of two weeks. Three patients had complete responses and one had a partial response (response rate, 29%). Responses were evident within two weeks of commencing therapy. Only the patient with a partial response was receiving concomitant therapy, a stable dose of prednisone. Responsiveness to colchicine did not seem to correlate with responsiveness to vincristine sulfate. Side effects of colchicine therapy were mild and complications did not occur. A possible mechanism of action for colchicine in ITP is decreased clearance of opsonized platelets secondary to inhibition of microtubule-dependent events in macrophages. Colchicine is useful in the treatment of ITP resistant to standard treatment.

Administration, Oral↗
PubMed1983

Immune thrombocytopenic purpura. Use of a 125I-labeled antihuman IgG monoclonal antibody to quantify platelet-bound IgG.

We used a radiolabeled monoclonal antibody to the Fc portion of human IgG to measure platelet-bound IgG in 54 thrombocytopenic patients and in 48 normal controls. The control group had a mean (+/- 1 S.D.) of 169 +/- 79 IgG molecules bound per platelet--10 to 100 times lower than values generally reported with other assay techniques. Sixteen of 17 patients with untreated thrombocytopenic purpura considered to be of immune origin had values ranging from 790 to 13,095--levels well above those found in normal subjects and in patients with "nonimmune" thrombocytopenia (246 +/- 156). In a second group, consisting of 11 patients with "immune" thrombocytopenic purpura who did not respond to conventional therapy (corticosteroids or splenectomy), the values were quite divergent: two patients had levels in the normal range, three had levels in the range of subjects with nonimmune thrombocytopenia, and six had much higher levels. Measurement of platelet-bound IgG with this monoclonal-antibody technique can help differentiate between immune and nonimmune thrombocytopenias. Low platelet counts in patients who have immune thrombocytopenia according to clinical criteria but are resistant to therapy may be related to factors other than IgG antibody.

Adult↗
PubMed1983

Phase II evaluation of MGBG in non-small cell carcinoma of the lung. A Southwest Oncology Group study.

One hundred and eight patients with non-small cell lung cancer were treated in a Phase II trial with MGBG at a dose of 600 mg/m2 i.v. weekly. Partial responses were noted in 3/43 patients with adenocarcinoma and 1/40 with squamous cell carcinoma. No responses were noted in 24 patients with large cell carcinoma. Overall, the drug was reasonably well-tolerated. At this dosage and schedule, MGBG has no substantial antitumor activity for patients with non-small cell lung cancer.

Drug Evaluation↗