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Biomedical subjects

M J Stone

Publications and source records attributed to M J Stone.

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

Characterization of a monoclonal antibody having selective reactivity with normal and neoplastic plasma cells.

A myeloma cell-reactive monoclonal antibody (MoAb), MM4, was generated from BALB/c mice immunized with alternate injections of cells from two human multiple myeloma (MM) cell lines. Screening by the enzyme-linked immunosorbent assay (ELISA) technique showed that MM4 reacted with human MM cell lines (7 of 7 positive), as well as bone marrow aspirates from MM patients (4 of 4 cases positive). MM4 did not react with marrow aspirates from control patients (3 cases), or with peripheral blood mononuclear (PBM) cells from normal subjects, lymphocytic (12 cases) and myelogenous (8 cases) leukemia patients. In addition, MM4 was negative with polymorphonuclear leukocytes and RBCs from normal donors. By means of the immunoperoxidase technique, the MM4-reactive antigen was detected in paraffin-embedded, Zenker formalin-fixed bone marrow biopsies of MM (12 of 12 cases positive), Waldenström's macroglobulinemia (2 of 2 cases positive), asymptomatic plasma cell dyscrasia (4 of 4 cases positive), and certain lymphomas (2 of 5 cases positive). Marrow biopsies from lymphocytic (5 cases) and myelogenous (5 cases) leukemias were uniformly negative. The MM4-reactive antigen also was expressed on plasma cells generated from pokeweed mitogen (PWM)-stimulated normal PBM cultures. The pattern of reactivity of MM4 with lymphocytes of B origin was similar to that of the plasma cell MoAb PCA-1. Competitive binding studies showed, however, that these two MoAbs recognized distinct antigenic determinants. These observations suggest that MM4 may be useful for the study of human plasma cell dyscrasias.

Antibodies, Monoclonal↗
PubMed1987

Elimination of clonogenic stem cells from human multiple myeloma cell lines by a plasma cell-reactive monoclonal antibody and complement.

The monoclonal antibody (MoAb) MM4 reacts with human multiple myeloma (MM) cell lines and bone marrow from patients with plasma cell dyscrasias but not with normal peripheral blood or bone marrow cells. Treatment with MM4 and rabbit complement (C') was cytotoxic to the plasma cell-derived cell lines GM 1312, RPMI 8226, and ARH-77, as demonstrated by chromium release microcytotoxicity and trypan blue exclusion assays. The same treatment eliminated greater than 99% of clonogenic myeloma stem cell colony formation of these cell lines, with less than 20% inhibition of normal human bone marrow pleuripotent progenitor colony formation in vitro. As an experimental model to explore the efficacy of MM4 + C' in purging MM-involved bone marrow, normal marrow cells were mixed with RPMI 8226 or GM 1312 cells in the ratio of 90:10 or 50:50 (marrow:myeloma cells). Colony growth assays indicated that MM4 + C' eliminated at least 2 logs of clonogenic myeloma stem cells in both 90:10 and 50:50 preparations, while sparing the majority of normal marrow progenitors (inhibition of CFU-C:10% to 13%; BFU-E:0%). The selectivity of MM4-mediated cytotoxicity may be useful for eliminating myeloma clonogenic stem cells from bone marrow of patients with multiple myeloma.

Antibodies, Monoclonal↗
PubMed1986

Nausea and radiation-induced taste aversions in cancer patients.

The development of taste aversions was studied in 34 oncology patients undergoing radiotherapy. A target flavor was paired with irradiation on four consecutive treatment days. Self-reported nausea on treatment days reliably predicted aversion learning. The implications of this finding for the anorexia of cancer patients and the role of nausea in human taste aversion learning are discussed.

Abdominal Neoplasms↗
PubMed1986

Discrimination of human small cell and non-small cell lung tumors by a panel of monoclonal antibodies.

The immunohistochemical reactivity of biopsy specimens from different human lung tumor cell types was examined with 4 human small cell lung carcinoma (SCLC)-reactive monoclonal antibodies (MoAbs) (SCLC 1096, SCLC 2051, SCLC 3121, and SCLC 5023) generated in this laboratory, with the use of Formalin-fixed, paraffin-embedded tissue sections. Each MoAb reacted preferentially with SCLC tumors (62-97% of 29 cases tested), with low-to-moderate cross-reactivity with non-SCLC tumors (SCLC 1096, 13.7%; SCLC 2051 and SCLC 3121, 9.8% each; SCLC 5023, 41%, of 51 cases tested). None of the 4 MoAbs reacted with nonmalignant lung biopsy specimens. SCLC tumors were characterized by their collective immunoperoxidase reactivity with the MoAb panel of SCLC 2051, SCLC 3121, and SCLC 5023. Based on unequivocal positive reactions with at least 2 of the 3 MoAbs, this MoAb panel correctly identified 97% (28/29) of SCLC cases of 80 lung tumor cases tested. By contrast, only 4 of 51 (7.8%) non-SCLC cases were positive by the same criterion. These observations suggest that immunohistochemical analysis with these SCLC-reactive MoAbs could help in discriminating small cell from other human lung carcinoma cell types.

Antibodies, Monoclonal↗
PubMed1984

Characterization of two human small cell lung carcinoma-reactive monoclonal antibodies generated by a novel immunization approach.

Two human small cell lung carcinoma cell lines, NCI-H69 and NCI-H128, were used as alternating sources of immunogen to generate monoclonal antibodies to small cell lung carcinoma-associated antigens. BALB/c mice were sensitized with seven injections of live tumor cells, four with NCI-H69 cells and three with NCI-H128 cells. Somatic cell hybridization was performed by fusion of the immune murine splenocytes using syngeneic myeloma cells from the SP2/0 Ag14 cell line. Hybridoma colonies were screened against small cell lung carcinoma cells and normal lung fibroblasts with an enzyme-linked immunosorbent assay. Compared to animals immunized with only NCI-H69 or NCI-H128 cells, alternate immunization resulted in the generation of a significantly higher number of hybridomas that reacted selectively with both tumor cell lines. Monoclonal antibodies from two reactive hybrid clones generated by alternate immunization, SCLC 2051 and SCLC 5023, were uniformly negative to normal human tissues including lung, kidney, liver, spleen, breast, thyroid, brain, small intestine, and colon. While both monoclonal antibodies were nonreactive to paraffin-embedded, formalin-fixed, nonmalignant lung biopsies, the monoclonal antibody SCLC 5023 reacted with tumor cell infiltrates in biopsies from small cell lung carcinoma patients (14 of 14 cases positive), using the immunoperoxidase technique. This monoclonal reagent also reacted with other lung tumor cell types, including atypical carcinoid (5 of 5 positive), epidermoid (4 of 6 positive), undifferentiated and bronchoalveolar (3 of 4 cases each positive) carcinomas. By contrast, monoclonal antibody SCLC 2051 apparently identified an antigen expressed preferentially on small cell lung carcinoma cells (12 of 14 positive) and only rarely reacted with other lung tumor cell types (2 of 34 positive). Both monoclonal antibodies were negative to colon carcinoma, epidermoid carcinoma of the floor of the mouth, breast adenocarcinoma, and B- and T-cell leukemia and lymphoma cells, as determined by the enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoperoxidase techniques. These observations suggest that SCLC 2051 and SCLC 5023 may be of value in identifying tumor-associated antigens expressed in small cell and other lung carcinomas. In addition, the generation of antibody-producing cells towards common tumor-associated antigens may be enhanced by immunization with multiple tumor cell lines of the same histological type.

Animals↗
PubMed1983

Large cell lymphomas of the stomach: improved prognosis with complete resection of all intrinsic gastrointestinal disease.

Thirty-seven consecutive patients with large cell lymphoma involving the stomach were evaluated between 1974 and 1980. All seven stage IE patients underwent complete resection of the stomach and all patients are alive 21-41 mo after resection. Of 18 stage IIE, 11 underwent complete resection. Two resected patients without postoperative therapy died of their disease. Six patients treated with chemotherapy are alive and well, and two of three patients treated with radiotherapy remain alive without disease. Seven patients had incomplete resection or biopsy, and only one remains alive at 34 mo. Of eight stage IV patients, four had complete resection and chemotherapy without recurrence of their disease. All four patients who were not resected have died of their disease. This study strongly supports the role of early surgery in the management of gastric large cell lymphomas.

Adult↗
PubMed1983

Serum myoglobin, ionized calcium, and parathyroid function during rhabdomyolysis.

The serum ionized calcium, phosphate parathyroid hormone, and myoglobin levels were observed in a patient with idiopathic hypoparathyroidism and rhabdomyolysis. Since calcium levels best correlate inversely with serum myoglobin and lactic dehydrogenase, we suggest that these two enzymes are better markers of the activity of rhabdomyolysis than serum creatine phosphokinase or SGOT. Furthermore, a non-hormonal, nonrenal mechanism is important in the fluxes of serum calcium and phosphate in rhabdomyolysis.

Calcium↗
PubMed1982

Coexistent multiple myeloma and primary hyperparathyroidism.

A patient with multiple myeloma and hypercalcemia responded to cytotoxic chemotherapy. However, hypercalcemia persisted. Because of the absence of lytic bone lesions, the presence of a low serum phosphate level, and a family history of possible primary hyperparathyroidism, the patient was evaluated for this disorder. Serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were elevated. Exploration of the neck disclosed two enlarged parathyroid glands (1,850 mg and 210 mg), which were excised. After surgery, the patient's serum calcium levels remained normal for one year. Progressive myeloma bone disease developed that eventually resulted in recurrent hypercalcemia and death. Autopsy revealed only evidence of myeloma.

Bone Neoplasms↗
PubMed1982

Serological diagnosis of Toxoplasma gondii infections by rapid separation of serum immunoglobulins M and G with CM Bio-Gel A.

A simple and rapid method has been developed for the separation of serum immunoglobulin M (IgM) and IgG. CM Bio-Gel A chromatography was used in the technique, which resulted in an IgM-rich fraction containing 31% of the original serum IgM and less than 2% of the serum IgG. The procedure was used to detect masked IgM antibodies in patients suspected of having Toxoplasma gondii infections.

Chromatography, Ion Exchange↗
PubMed1982

Immunopathology of periodontal disease. II. Immunofluorescent studies on the localized immune response in periodontitis and juvenile periodontitis.

Local immunologic responses were studied in eleven patients with periodontitis, ten patients with juvenile periodontitis, and ten control subjects by performing immunofluorescence on gingival biopsies. F(ab')2 monospecific conjugates to human IgG, IgM, IgA, IgD, and kappa and lambda light chains were used as well as monospecific conjugates to human IgE and properdin. Biopsies from patients with juvenile periodontitis displayed a more intensified immunologic response as evidenced by increases of (I) positive cells stained with a F(ab')2 antihuman immunoglobulin conjugate; (2) IgG, IgM, and kappa and lambda containing cells; (3) extracellular fluorescence of IgG, IgM, IgA, and kappa and lambda light chains; and (4) properdin deposition. Neither IgD nor IgE conjugates reacted significantly with biopsies from the three patient groups. These findings support our previous conclusion that immunologic responses in periodontitis and juvenile periodontitis appear qualitatively similar, but that patients with juvenile periodontitis exhibit a more intense immune response.

Fluorescent Antibody Technique↗
PubMed1981

Paroxysmal nocturnal hemoglobinuria. Termination in acute myelomonocytic leukemia and reappearance after leukemic remission.

In a 71-year-old man, acute myelomonocytic leukemia developed six years after a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) had been established. The classic features of PNH disappeared with the onset of the leukemia. Chemotherapy resulted in complete leukemic remission, during which time intravascular hemolysis and a positive acidified serum (Ham's) test recurred; both findings again disappeared when the leukemia recurred. To our knowledge, this is the eighth reported case of PNH terminating in acute leukemia but is the first in which reappearance of PNH has been documented with leukemic remission. The alternating pattern of the two disorders suggests that the PNH clone survivors in the bone marrow when leukemia supervenes.

Aged↗