Search PubMed⌕ Search

Biomedical subjects

I Royston

Publications and source records attributed to I Royston.

At least 37 records · Page 2Linked to original sources
PubMed1991

Expression of shared idiotypes in chronic lymphocytic leukemia and small lymphocytic lymphoma.

The expression of shared idiotypes (Slds) has been studied on malignant CD5+B cells from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) using a panel of 37 murine monoclonal antibodies previously demonstrated to be reactive with Slds derived from follicular B-cell lymphomas. Thirteen anti-Slds identified tumor cells from 31 of 105 (30%) CLL patients and 4 of 6 SLL patients. In comparison, the same panel of anti-Slds is reactive with 33% of follicular and diffuse B-cell lymphomas. Ten of these anti-Slds reacted with CLL cases at similar frequencies to that of the B-cell lymphomas. Two anti-Slds, which are known to react with autoantibodies, were significantly more prevalent in CLL than in B-cell lymphomas. These data confirm the presence of Slds in CLL and provide further evidence of an association between CLL and autoimmunity. The identification of a panel of antibodies reactive with a significant number of CLL and SLL patients will facilitate the application of anti-idiotype antibody therapy in these diseases.

Adult↗
PubMed1991

The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B.

Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR.

Adolescent↗
PubMed1990

Radioimmunotherapy of human B-cell lymphoma with 90Y-conjugated antiidiotype monoclonal antibody.

We report the first case of 90Y-conjugated monoclonal antibody (MoAb) administration for human radioimmunotherapy. Ten mCi 90Y-labeled antiidiotype (anti-Id) MoAb were administered to a patient with B-cell lymphoma whose tumor successfully imaged with 111In-labeled anti-Id MoAb. No significant toxicities were observed. More than 2 g of unlabeled anti-Id MoAb were administered while clearing the circulating IgM idiotype prior to administration of the 90Y-MoAb. Transient partial regression of disease was observed. Serial fine needle aspirations of a malignant lymph node documented in vivo anti-Id penetration into a site that did not image by radioimmunoscintigraphy. The radiosensitivity of B-cell lymphoma, the tumor specificity of anti-Id, the antitumor activity of anti-Id alone, and the safe administration of 10 mCi 90Y-labeled anti-Id MoAb in this report suggest further investigation of this radioimmunoconjugate for therapy of B-cell lymphoma is warranted.

Adult↗
PubMed1989

Shared idiotypes expressed by human B-cell lymphomas.

Each B-cell lymphoma expresses a surface immunoglobulin that contains unique antigenic determinants (idiotypes). We have produced 199 murine monoclonal antibodies reactive with the idiotypes isolated from 67 patients with follicular small-cleaved-cell lymphoma. These antiidiotype antibodies were analyzed for their ability to react with lymphoma cells from patients other than the one against which each antibody was made. Twenty of the 199 antiidiotype antibodies were reactive with lymphoma cells from more than one patient. Depending on the antibody, the frequency of idiotype sharing ranged from 0.6 to 6.2 percent of B-cell lymphoma tumors evaluated. Tumors could be grouped into distinct families on the basis of their reactivity with these antibodies. In the aggregate, the 20 antibodies reacted with a total of 49 of 150 B-cell lymphomas (33 percent), including 30 of 110 follicular small-cleaved-cell lymphomas (27 percent). Many of these shared idiotypes were expressed by more than one histopathological subtype of lymphoma. We conclude that a panel of antibodies reactive with shared idiotypes can be produced for patients with B-cell lymphoma, obviating the need to produce an antiidiotype antibody for each patient.

Antibodies, Anti-Idiotypic↗
PubMed1988

Unique subset of thymic epithelial cells defined by the expression of a novel neuroendocrine antigen.

Murine monoclonal antibodies (MoAbs) were produced against a rat medullary thyroid carcinoma to identify neuroendocrine differentiation antigens. One of these antibodies (1D4) identified a novel 62- to 69-kDa antigen expressed by subsets of immune system epithelial and neuroendocrine cells. This antigen is expressed by distinct subsets of thymic epithelial and splenic reticular cells and is shared by discrete subsets of anterior pituitary and thyroid neuroendocrine cells. In the thymus, 1D4 expression identified a unique subset of stellate-shaped Ia+ medullary epithelial cells which did not react with thymosin alpha-1 antisera nor with the MoAb A2B5 specific for a GQ ganglioside expressed by thymic hormone-producing cells. The availability of the 1D4 MoAb should facilitate further characterization of 1D4+ immune system epithelial cells and may advance our understanding of neuroendocrine-immune system interactions.

Animals↗
PubMed1988

Morphologic and cytochemical characterization of adult lymphoid leukemias which express myeloid antigen.

Cancer and Leukemia Group B demonstrated that adults with acute lymphoid leukemia (ALL) possessing blast cells with myeloid antigens (My+ALL), as identified by monoclonal antibodies against CD13 and CD33, have a worse prognosis than those lacking myeloid antigens (My-ALL). Consequently, we further studied this group of adults with ALL to determine if these immunological groups could be distinguished by morphological and cytochemical criteria. Bone marrow films were classified according to French-American-British Co-operative Group Criteria, assessed for myelodysplasia, and examined for blasts with azurophilic granules. More cases of My+ALL had L2 morphology than did My-ALL (68% vs. 49%, p = 0.04), and more cases of My+ALL were positive for acid alpha-naphthyl acetate esterase (61% vs. 31%, p = 0.03). The presence of myelodysplastic changes was not significantly different in My+ALL (13%) as compared to My-ALL (5%), but more cases of My+ALL had unusual blasts (monocytoid features and cytoplasmic buds) than did My-ALL (19% vs. 0%, p less than 0.01). In addition, more cases of My+ALL had greater than 5% of the blasts with azurophilic granules (42% vs. 13%, p = 0.01). In the My+ALL group the presence of azurophilic granules was associated with a longer median survival (13.5 months vs. 1.5 months, p less than 0.01). We conclude that My+ALL can be suspected when cases possess L2 morphology, unusual blasts, positive staining for acid alpha-naphthyl acetate esterase, and greater than 5% azurophilic granules. In addition, the poor risk group (My+ALL) can be further subdivided into better and poorer risk subgroups based on the presence of azurophilic granules.

Adolescent↗
PubMed1988

Immunophenotyping in the diagnosis and classification of acute lymphoblastic leukemia.

The identification of ALL immunophenotypes with distinctive clinical features and prognostic significance indicates the importance of these studies in the evaluation of ALL patients for both clinical and research purposes. For differential diagnosis, the expression of pan-B-cell or pan-T-cell lymphoid antigens and the absence of myeloid/monocyte antigens represent the most useful markers for distinguishing ALL from AML. However, the increasing appreciation of large numbers of patients with clinically significant mixed lymphoid-myeloid phenotypes suggests that rigid classification of acute leukemias into exclusive lymphoid and myeloid categories may be somewhat artificial. In adult ALL, patients with My+ phenotypes (B+sIg-T-My+ and B-sIg-T-My+) have a lower incidence of complete remission and shorter survival times than do patients with My- marker profiles. Preliminary studies in childhood ALL also suggest a correlation between myeloid antigen expression and poor prognostic factors. In addition, children with sIg+ "B-cell," cIg+ "pre-B-cell," and T-cell ALL phenotypes have shorter disease-free survival times than do patients with more common "early pre-B" (B+cIg-sIg-T-) marker profiles. Application of immunologic markers in concert with cytogenetic and gene rearrangement studies has led to the identification of novel subgroups of leukemia with distinct clinical characteristics. Future studies incorporating a multiparameter diagnostic approach including immunophenotyping, gene rearrangement studies, and karyotypic analyses should further our understanding of the heterogeneity of acute leukemias, guide the development of new therapeutic strategies, and provide for more clinically relevant classification of these disorders.

Antibodies, Monoclonal↗
PubMed1987

Establishment of a human B-cell tumor in athymic mice.

Human B-cell tumors have been established in athymic, BALB/c mice using the EBV-positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors developed at the site of injection and reached approximately 300 mm2 (product of cross-sectional diameters) after 21 days; no metastases were found. Histological analysis showed that tumors consisted solely of lymphoid cells. Immunofluorescence assays demonstrated that while 85% of the tumor cells retained reactivity with the monoclonal B-cell antibody BA-1, 96% retained reactivity with antibody BA-2 and 43% with BA-3. A similar reactivity profile was observed with cultured Namalwa cells. Tumors were passaged serially 10 times without significant change in BA-1, BA-2, or BA-3 reactivity. Indirect immunofluorescence demonstrated that antibody BA-2 reached tumor cells within 2 h following i.p. injection; antigen modulation was not observed. These results demonstrate the suitability of this B-cell model for testing the in vivo efficacy and stability of anti-B-cell immunoconjugates.

Animals↗
PubMed1987

Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia.

To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-My+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell-receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P less than 0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. greater than 26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated.

Adult↗
PubMed1987

Monoclonal antibodies to purified ricin A-chain: production and properties.

Ricin A-chain was purified from native ricin using lactosyl-Sepharose. It was non-toxic to whole cells at a concentration of 1 microM yet nearly as effective as an equimolar concentration of ricin in blocking in vitro protein synthesis. Hybridomas secreting monoclonal antibodies to ricin A-chain were produced using the murine myeloma cell line NS-1. These anti-ricin A-chain antibodies cross-reacted with whole ricin but exhibited little cross-reactivity with purified ricin B-chain. Antibodies 2F2 and 2F5 both immunoprecipitated ricin A-chain. Both antibodies also precipitated ricin B-chain, as did the irrelevant control antibodies MOPC-21 and MPC-11. Pre-incubation of B-chain with 0.1 M galactose eliminated greater than 90% of precipitation by 2F2, MOPC-21 and MPC-11 but effected minimally precipitation by 2F5. Enzyme-linked immunosorbent assays using antibodies 2F2 and 2F5 to detect ricin A-chain in murine or human serum were linear between 40 and 800 ng ricin A-chain per ml. Anti-ricin A-chain antibodies 2F2 and 2F5 produced some inhibition of in vitro A-chain catalytic activity. Specific monoclonal antibodies to A-chain hemitoxin will be useful for characterization of functional hemitoxin domains, in in vitro assays for the stability of A-chain immunotoxins, and in characterizing the cellular internalization and processing of conjugates containing ricin or ricin A-chain.

Animals↗
PubMed1987

Genetically stable human hybridomas secreting tumor-reactive human monoclonal IgM.

Human lymphocytes obtained from regional draining lymph nodes of patients with cancers of the cervix, kidney, prostate, and vulva were immortalized by polyethylene glycol-mediated somatic cell hybridization with either human UC 729-6 or murine P3-NS-1-Ag4-1. Four reactive human IgM-secreting hybridomas, termed CLNH5, MHG7, VLN1H12, and WLNA67 were isolated and characterized. Hybrids obtained by fusions with UC 729-6 have remained tetraploid for over 18 months, have doubling times from 25-35 hours, and have continuously secreted approximately 0.5-5.0 micrograms IgM/10(6) cells/ml per day. MHG7, a mouse-human hybrid, required subcloning every 4-6 months to maintain human IgM secretion. Binding of these human monoclonal antibodies (MoAbs) against a panel of cell lines was assessed by an enzyme-linked immunoassay (EIA). CLNH5 reacted with carcinomas of the cervix, lung, and vulva. MHG7 reacted with carcinomas of the prostate, stomach, and vulva. VLN1H12 reacted with carcinomas of the cervix, lung, prostate, stomach, and vulva. WLNA6 reacted strongly with a carcinoma of the lung. All four human MoAbs failed to react by EIA with hematopoietic cells or normal fibroblast cell lines. The data suggest that regional draining lymph nodes of cancer patients have been primed to produce antibodies against antigens associated with tumor cells and that UC 729-6 served as a genetically suitable vector for the capture and immortalization of these Ig-secreting B lymphocytes.

Antibodies, Monoclonal↗
PubMed1987

Epidermal growth factor receptor expression in human lung carcinomas defined by a monoclonal antibody.

Acetone-fixed frozen tissue sections from 56 cases of human lung carcinoma were tested for reactivity by an indirect immunoperoxidase technique with a monoclonal antibody (MAb 528) specific for the external domain of the epidermal growth factor receptor (EGFR). MAb 528 reacted with all epidermoid (22/22) and large-cell (4/4) lung carcinomas evaluated. The antibody was also positive with a subset of lung adenocarcinomas (13/21) and did not react with small-cell lung cancers (SCLCs) (0/9). MAb 528 also stained normal bronchial epithelium identified within the tumor sections of 5 cases. Thus EGFR was expressed by all epidermoid and large-cell lung carcinomas examined, a subset of lung adenocarcinomas, and normal bronchial epithelium. EGFR expression was not identified in any of the SCLCs tested. These data imply that immunohistochemical detection of EGFR expression may find future application in distinguishing epidermoid, large-cell, and some adenocarcinomas of the lung from SCLCs.

Adenocarcinoma↗
PubMed1987

Phase II trial of thymosin fraction 5 and thymosin alpha 1.

Previous Phase I trials have established the safety of administering thymosin fraction 5 and thymosin alpha 1 to patients with advanced cancer. These same trials also suggested potential immune-enhancing doses of these agents. In this study, 12 patients with colon cancer were treated with thrice weekly thymosin fraction 5 at a dose of 120 mg/m2, and 10 patients with non-small-cell lung cancer received thymosin alpha 1 at 1.2 mg/m2 thrice weekly. Five patients with hypernephroma also received one or both agents by a thrice weekly schedule. There were no tumor responses observed in any of these patients, and immune enhancement was neither obtained nor sustained. We conclude that at these doses and schedules, these hormones have very limited, if any, antitumor properties and that they are incapable of producing immune augmentation as defined by the assays used in this study.

Drug Evaluation↗
PubMed1986

Elevated serum chromogranin A concentrations in small-cell lung carcinoma.

Serum chromogranin A concentrations measured by radioimmunoassay in patients with small-cell lung carcinoma were compared with values from healthy adults and patients with non-small-cell lung carcinoma or chronic obstructive pulmonary disease. The mean (+/- SE) level was significantly higher (p less than or equal to 0.02) in patients with small-cell lung carcinoma (815 +/- 290 ng/mL, n = 46) than in normal controls (123 +/- 6 ng/mL, n = 20) or patients with chronic obstructive pulmonary disease (169 +/- 18 ng/mL, n = 39), lung adenocarcinoma (180 +/- 22, ng/mL, n = 62), large-cell lung carcinoma (183 +/- 23 ng/mL, n = 18), or lung epidermoid carcinoma (203 +/- 37 ng/mL, n = 78). The mean concentration in extensive-stage small-cell lung carcinoma (1155 +/- 449 ng/mL, n = 29) was significantly greater (p = 0.026) than in limited disease (234 +/- 56 ng/mL, n = 17). Elevated serum chromogranin A values were seen in 53% of patients with limited and 72% with extensive disease. Four patients originally classified as having non-small-cell lung carcinomas with raised chromogranin A levels were subsequently found to have mixed small-cell and non-small-cell tumors. Serum chromogranin A concentrations may be a useful marker of small-cell lung carcinoma disease activity.

Adult↗
PubMed1985

Applications and limitations of peripheral blood lymphocyte immunoglobulin light chain analysis in the evaluation of non-Hodgkin's lymphoma.

Surface immunoglobulin (sIg) light chain analysis of peripheral blood lymphocytes (PBL) from 63 patients with non-Hodgkin's lymphoma (NHL) was performed to determine the ratio of kappa-bearing lymphocytes to lambda-bearing lymphocytes (kappa/lambda ratio). In 43% an abnormal kappa/lambda ratio was detected, implying the presence of a malignant clone in the peripheral blood (clonal excess). In 67% of cases with an abnormal kappa/lambda ratio, the absolute lymphocyte count was within normal limits and 20% did not have morphologic bone marrow involvement. Light chain analysis of bone marrow aspirates was performed in three of four patients with a circulating clone and normal bone marrow morphology. All three patients had abnormal bone marrow aspirate kappa/lambda ratios. The presence of a circulating clone was associated with morphologic bone marrow involvement (P less than 0.05). Nine patients with documented B-cell NHL were followed with repeated examinations. The presence of a circulating clone persisted in two patients refractory to therapy and in two patients otherwise believed to be in remission. Conversion to an abnormal kappa/lambda ratio occurred in two patients coincident with the development of new bone marrow involvement and in a third patient prior to the onset of frank leukemia. In three instances, the PBL light chain analyses remained within normal limits in patients with stable lymphadenopathy. The kappa/lambda ratio returned to normal in one patient responding to treatment with a partial remission, and remained within normal limits despite progression of lymphadenopathy in one patient, and local disease recurrence in another patient. These findings suggest that the detection of a circulating clone by sIg light chain analysis may be useful as a noninvasive approach to identify disseminated disease activity unsuspected on the basis of morphologic evaluations, but may not reflect the presence, progression, or recurrence of localized tissue lesions.

B-Lymphocytes↗
PubMed1985

The use of monoclonal antibodies and flow cytometry to detect peripheral blood and bone marrow involvement of a diffuse, poorly differentiated lymphoma.

Using monoclonal antibodies and flow cytometry, we were able to characterize the phenotype of a diffuse, poorly differentiated lymphoma and to isolate subpopulations of cells from the blood and bone marrow that expressed the malignant phenotype even though the patient exhibited no absolute lymphocytosis. Because the circulating clone reacted with the anti-T cell monoclonal antibody T101, we initiated serotherapy with T101 as part of a phase I study. A 10 mg infusion of T101 resulted in the rapid clearance of normal T cells from circulation, but the clone showed evidence of modulation and was not cleared. Twenty-four hours following infusion, all cell populations had returned to pre-treatment levels. Our study suggests that, by using monoclonal antibodies and flow cytometry, blood and bone marrow involvement of a lymphoma can be demonstrated in patients without absolute lymphocytosis, a finding which may influence the staging and treatment of the disease.

Antibodies, Monoclonal↗