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Biomedical subjects

K C Anderson

Publications and source records attributed to K C Anderson.

At least 235 records · Page 13Linked to original sources
PubMed1984

B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation.

The expression of B cell associated and restricted antigens on tumor cells isolated from 138 patients with non-T cell acute lymphoblastic leukemia (non-T cell ALL) was investigated by flow cytometric analysis by means of a panel of monoclonal antibodies. Tumor cells from these patients could be assigned to one of four subgroups: human leukocyte antigen-DR-related Ia-like antigens (Ia) alone (4%, stage I); IaB4 (14%, stage II); IaB4CALLA (33%, stage III); and IaB4CALLAB1 (49%, stage IV). The expression of B cell-restricted antigens (B4 and B1) and rearrangements of Ig heavy chain genes provided strong evidence for the B cell lineage of stages II, III, and IV tumors. The lineage of the Ia alone group is still unknown. The B4 antigen was expressed on approximately 95% of all non-T cell ALLs tested, and given its absence on T cell and myeloid tumors, it appears to be an exceptional marker to define cells of B lineage. The demonstration that Ia alone, IaB4, IaB4CALLA, and IaB4CALLAB1 positive cells can be readily identified by dual fluorescence analysis in normal fetal and adult bone marrow provided critical support for the view that these leukemic pre-B cell phenotypes were representative of the stages of normal pre-B cell differentiation. It was interesting that the IaB4+ cell was more frequently identified in fetal bone marrow than in adult marrow, whereas the predominant cell found in adult marrow expressed the IaB4CALLAB1 phenotype. These data suggest that the leukemogenic event may be random, since the predominant pre-B cell leukemic phenotype appears to correspond to the normal pre-B cell phenotype present in these hematopoietic organs. Our observations provide an additional distinction between adult and childhood ALL, since these studies show that most non-T cell ALLs seen in children less than 2 yr old are of stage II phenotype, whereas the majority of non-T ALLs in adults are of stage IV phenotype. Finally, it should be noted that the present study suggests that the analysis of leukemic B cell phenotypes and their normal counterparts can provide a mechanism for the investigation and orderly definition of stages of pre-B cell differentiation in man.

Adult↗
PubMed1984

Combination chemotherapy for advanced non-Hodgkin's lymphomas other than diffuse histiocytic or undifferentiated histologies.

A combination chemotherapy program using methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD), which resulted in a high complete response rate and prolonged disease-free survival in lymphomas of the unfavorable diffuse histiocytic and diffuse undifferentiated histopathologic subgroups, was administered to 44 patients with advanced favorable and intermediate-prognosis non-Hodgkin's lymphomas, including nodular lymphoma of the poorly differentiated lymphocytic, mixed, and histiocytic subtypes, and diffuse lymphoma of the poorly differentiated lymphocytic or mixed histologic subtypes. High-dose methotrexate (3 g/m2) was given on Day 14 between cycles of bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone, administered every 3 weeks for ten cycles. Leucovorin factor (10 mg/m2) was given iv 24 hours after the methotrexate infusion was completed, and was continued at 10 mg/m2 by mouth every 6 hours for 72 hours. Therapy was well-tolerated, with predictable myelosuppression in the majority of patients. The complete response rate was 57% (25 of 44 patients), including ten of 18 (56%) patients with nodular and 15 of 26 (58%) patients with diffuse lymphomas. Median overall follow-up among living patients is 65 months, 58 months for patients with nodular and 69 months for patients with diffuse histologic subgroups. Overall survival at 5 years was 64% for patients who achieved complete response, 32% for partial responders, and 0% for those patients who did not respond. Disease-free survival of complete responders was 43% at 5 years, with only one disease-related death noted after 36 months. The nodular and diffuse patient subgroups had similar overall and disease-free survivals. Although initial bone marrow involvement was documented in nine of 18 (50%) nodular patients and in 13 of 26 (50%) diffuse patients, CNS relapse occurred in only one complete and two partial responders. The prolonged disease-free survival observed after M-BACOD therapy demonstrates that durable responses can be achieved with intensive chemotherapy.

Adolescent↗
PubMed1984

A monoclonal antibody with reactivity restricted to normal and neoplastic plasma cells.

A monoclonal antibody that defines a new and distinct plasma cell antigen, termed PC-1, was developed against human plasmacytoma cells. This antigen is strongly expressed on normal plasma cells isolated from bone marrow and on abnormal plasma cells isolated from myelomas, plasma cell leukemias, and plasmacytomas. The antigen is not detected on normal T or B lymphocytes, granulocytes, or monocytes, and with the exception of plasma cells, is absent on malignancies of B, T, or myeloid origin. Utilizing pokeweed mitogen to induce human B lymphocyte differentiation in vitro, PC-1 is expressed when B cell determinants are lost and the plasmacytoid morphology, intracytoplasmic immunoglobulin-staining, and surface PCA-1- and T10-staining characteristic of plasma cells appear. This antigen is useful for the study of the terminal stages of normal B cell differentiation to plasma cells, and may offer insight into the heterogeneity of the plasma cell dyscrasias.

Animals↗
PubMed1984

Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation.

A series of monoclonal antibodies that define B cell restricted and associated antigens was utilized in an attempt to characterize tumors of B lineage and to relate these tumors to B cell differentiative stages. Antigens that were previously shown to be B cell restricted on normal B lymphocytes were similarly expressed only on B cell malignancies. In contrast, antigens that were B cell associated were also found on tumors of other lineages. Moreover, on the basis of cell surface phenotypes, tumors of B cell origin were divided into three major subgroups, which corresponded to the level of differentiation of the malignant tumor cell: pre-B cell stage (non-T acute lymphoblastic leukemia and chronic myelocytic leukemia in lymphoid blast crisis); the mid-B cell stage (chronic lymphocytic leukemia, poorly differentiated lymphomas); and secretory B cell stage (large cell lymphomas and plasma cell tumors). A hypothetical model is derived that relates the malignant B cell to its normal cellular counterpart on the basis of cell surface expression of this panel of B cell-restricted and B cell-associated antigens.

Antibodies, Monoclonal↗
PubMed1983

Isolation and characterization of human B lymphocyte enriched populations. I. Purification of B cells by immune rosette depletion.

In the present study we describe a technique for the preparation of a highly purified B cell population from peripheral blood mononuclear cells (PBMC) by immune rosette depletion of non-B cells utilizing monoclonal antibodies directed at T cells, monocytes and null cells. The non-rosetted population contains greater than 90% B cells after a single rosetting step. The technique is simple, rapid and reproducible and results in minimal cell loss. In contrast, the E rosette negative (E-) fraction contains approximately 20% B cells whereas the surface immunoglobulin positive (sIg+ population obtained by Sephadex-anti-F(ab')2 column chromatography is comprised of approximately 60-80% B cells.

Antibodies, Monoclonal↗
PubMed1983

High-dose gallium imaging in lymphoma.

The role of gallium-67 imaging in the management of patients with lymphoma, traditionally assessed using low tracer doses and the rectilinear scanner, was assessed when using larger doses (7 to 10 mCi) and a triple-peak Anger camera. Gallium scan results in 51 patients with non-Hodgkin's lymphoma and 21 patients with Hodgkin's disease were compared with simultaneous radiologic, clinical, and histopathologic reports. Subsequent disease course was also evaluated in light of radionuclide findings. Sensitivity and specificity of the scans were 0.90 or greater for both non-Hodgkin's lymphoma and Hodgkin's disease, and overall accuracy by site was 96 percent. Although there are insufficient numbers of pretreatment scans to allow any conclusions, our data suggest that newer approaches to gallium scanning in treated patients are (1) highly specific in all lymphomas and most sensitive in high-grade non-Hodgkin's lymphoma and Hodgkin's disease; (2) valuable in assessing the mediastinum in both non-Hodgkin's lymphoma and Hodgkin's disease; and (3) helpful adjuncts to computed tomographic scanning and ultrasonography in assessing abdominal node disease.

Gallium Radioisotopes↗
PubMed1983

Antigens on human plasma cells identified by monoclonal antibodies.

Two monoclonal antibodies that define distinct plasma cell-associated antigens, termed PCA-1 and PCA-2, were developed against human plasma cell leukemia cells. These antigens are strongly expressed on human myelomas, plasma cell leukemia, and plasmacytoma tumor cells, but are not detected on other lymphoid malignancies of B, T, null, or myeloid origin. PCA-1 and PCA-2 are not expressed on either normal T or B lymphocytes, but are weakly expressed on granulocytes and monocytes. When pokeweed mitogen is used to induce human B lymphocyte differentiation, PCA-1 is expressed when other B cell determinants are lost and plasmacytoid morphology, intracytoplasmic immunoglobulins, and surface T10 staining characteristic of plasma cells appear. In contrast, PCA-2 cannot be induced and may therefore appear later in the B cell differentiation scheme. These antigens may be of utility for the study and regulation of normal and abnormal plasma cell growth, traffic, and tissue distribution and may aid in understanding heterogeneity within plasma cell dyscrasias.

Animals↗
PubMed1983

B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes.

The characterization of a new B cell-specific antigen (B4) is described in this report. With the use of a monoclonal antibody to B4, it was shown that B4 is present on B cells isolated from peripheral blood and lymphoid organs, on cell lines derived from normal and malignant B cells, and on tumor cells isolated from patients with B cell-derived neoplasms. B4, in contrast, was not detected on normal, activated, or malignant cells of T or myeloid origin. The B4 antigen is distinct from known B cell antigens, including sIg, Ia, B1, B2, Fc, and C3. Examination of mitogen-stimulated B lymphocytes suggests that the B4 antigen initially increases with B cell activation and then is lost at the terminal stage of B cell differentiation. Moreover, the observation that B4 is expressed on almost all early B cell tumors suggests that it may precede B1, CALLA, cytoplasmic mu, and B2 in early B cell ontogeny.

Animals↗
PubMed1983

Predictive values of the in vivo diffusion chamber for cyclophosphamide treatment of L1210 murine leukemia.

In vivo culture of tumor cells using the Millipore diffusion chamber implanted i.p. into female C57BL X DBA/2 F1 (hereafter called BD2F1) mice provides a means for direct examination of drug effect on tumor cells. The effect of various doses and schedules of i.p. cyclophosphamide (CY) on murine L1210 leukemia cell count in the chambers was compared to survival of leukemia-bearing animals treated similarly. Tumor cell viability was assessed by transfer of chamber contents to recipient animals who were then observed for survival. Unless perturbed by CY, L1210 cells grew in log phase within chambers to 10(8) cells/cu mm. The effect of CY on chamber cell count was dose related, quantifiable, reproducible, and predictive of survival of leukemia-bearing animals treated similarly. Single doses proved to be more effective than were equally divided doses in decreasing chamber cell number and prolonged leukemic animal survival. Reinjection of L1210 cells rescued from chambers after hosts had been treated with CY revealed that many could not produce tumors. Results suggest that this technique provides reproducible information on drug effects and may be a valuable tool for designing clinically useful dose schedules.

Animals↗
PubMed1983

Phase I trial of mitoxantrone by 24-hour continuous infusion.

Mitoxantrone (DAD) is a new agent which intercalates into DNA. Preclinical studies have demonstrated activity equal to or greater than that of doxorubicin in all tumor systems tested. In this phase I clinical trial, the schedule of drug administration consisted of a 24-hour continuous iv infusion repeated at 21-day intervals. Twenty-nine patients received a total of 66 courses over a dose range of 4-15 mg/m2. The dose-limiting toxic effect was leukopenia, with a wbc count nadir on Day 12 and resolution prior to Day 21. Other toxic effects were thrombocytopenia, mild phlebitis, and blue discoloration of veins. Objective tumor responses were seen in a patient with adenocarcinoma of the breast and in another patient with clear cell carcinoma of the vagina. An additional six patients with acute leukemia were treated at a dose of 12 mg/m2; a decrease in peripheral blast count was observed in four of these six patients. The toxicity of DAD by 24-hour iv infusion was similar to that previously reported for iv bolus administration. We recommend phase II evaluation of DAD at a dose of 12 mg/m2 by single iv injection at 21-day intervals. Patients with acute leukemia should be evaluated at higher dose levels.

Adolescent↗
PubMed1982

Percutaneous central venous catheterization performed by medical house officers: a prospective study.

We prospectively determined the complications of percutaneous central venous catheterizations performed by medical house officers in 302 patients. We also analyzed the factors affecting the success and complication rates of such invasive procedures. The central vein was successfully catheterized in 363 (77%) of 470 attempts. The internal jugular and subclavian vein approaches were significantly more successful (86%) than the external jugular vein approach (61%, P less than 0.001 by chi 2). The success rate improved significantly when catheterization was attempted under elective circumstances (P less than 0.003) and also after the vein was initially located with a small-gauge needle (P less than 0.001). Our results suggest that efforts should be abandoned after the third unsuccessful pass with a large-gauge needle in the same site. Complications of catheter insertion included bleeding (ten patients), hematoma (15 patients), inadvertent arterial punctures (14 patients), iatrogenic pleural effusions (four patients), and pneumothoraces (eight patients). No complications appeared to have a major adverse effect on a patient's clinical course. The inexperienced operator (fewer than 25 prior catheterizations) has a success rate equal to that of the more experienced operator (more than 25 prior catheterizations), but he may be more likely to produce a complication. Medical house officers can perform percutaneous central venous catheterizations with a high rate of success and a low risk to the patient.

Arteries↗
PubMed1982

Induction of human B cell antigens in non-T cell acute lymphoblastic leukemia.

Leukemic cells from 70% of patients with Ia+CALLA+ non-T cell acute lymphoblastic leukemia (ALL) express an antigen (B1) found on all normal B lymphocytes. In this study, ALL cells that do not express the B1 antigen were studied in an attempt to further elucidate the cellular lineage of these tumors. Non-T cell ALL lines and tumor cells isolated from patients with non-T cell ALL that are Ia + CALLA + B1- were studied in vitro with a variety of agents known to promote cellular differentiation. Phorbol diester (TPA) or phytohemagglutinin conditioned leukocyte culture media were capable of inducing the expression of B1 on all four non-T cell ALL lines tested. In contrast, B1 could not be induced under the identical conditions on a promyelocytic leukemia line or a T cell lymphoblastic leukemia line. With the induction of B1 on non-T cell ALL lines, cytoplasmic mu-heavy chain (c mu) became undetectable, whereas the expression of CALLA and Ia were unchanged. The expression of B1 was accompanied by a decrease of cellular proliferation and DNA synthesis, but not significant morphologic changes were noted. In addition, no other B or T cell antigens were detected. The cellular origin of non-T cell ALL was further investigated using tumor cells isolated from leukemic patients. Tumor cells from eight patients with Ia + CALLA + B1-c mu- ALL could be induced in vitro with TPA to express both B1 and c mu. In contrast, cells from five patients with Ia + CALLA-B1-c mu- non-T cell ALL could not be induced with TPA to express CALLA, B1 or c mu. These studies suggest that the non-T cell ALL are heterogeneous and represent a spectrum of early B cell differentiation including the pre- pre-B cell (Ia + CALLA + B1-c mu-), the intermediate pre-B cell (Ia + CALLA +B1 + c mu-), and finally the "true" pre-B cell (Ia + CALLA + B1 + c mu+). The cellular origin of the remaining Ia + CALLA-B1-c mu- form of non-T cell ALL (20%) is still unknown.

Antigens↗
PubMed1981

Diagnosis and treatment of anticoagulant-related adrenal hemorrhage.

Anticoagulant-related adrenal hemorrhage, as a cause of adrenal insufficiency, is rarely suspected and diagnosed during life. We report three patients in whom prompt diagnosis allowed successful treatment with replacement doses of corticosteroids. In all three patients, a hypotensive episode preceded the signs and symptoms of acute adrenal insufficiency. The symptoms and signs of adrenal hemorrhage were nonspecific and variable, making clinical diagnosis difficult. In none of our patients was the prothrombin time, partial thromboplastin time, or Lee White clotting time prolonged beyond the therapeutic range, and in none were excessive doses of anticoagulant therapy employed. Characteristic serum chemistry abnormalities, serum ACTH stimulation tests, and daily urinary collections for free cortisol, 17-OH ketosteroids, and 17-ketosteroids confirmed the clinical suspicion of primary adrenal insufficiency in all cases. Diagnosis was aided in one patient by abdominal computerized axial tomographic scan. In all patients, response to replacement doses of corticosteroids was prompt and gratifying, underlining the importance of suspecting this complication of anticoagulant therapy and instituting prompt lifesaving therapy. Adrenal hemorrhage is a complication of anticoagulant therapy that has been diagnosed during life in only 11 reported cases. We describe three patients in whom early diagnosis allowed prompt medical therapy and favorable outcome. The clinical presentation, diagnostic laboratory features, and therapeutic modalities are reviewed. Prolongation of prothrombin time, high levels of stress, and hypotension predispose to this complication in a patient maintained on anticoagulant therapy.

Adrenal Gland Diseases↗
PubMed1981

Acute myelocytic leukemia in two brothers with polyposis coli and carcinoma of the colon.

Two brothers developed multiple adenomatous polyps of the colon and colonic adenocarcinoma, the classic features of familial polyposis coli. Both also developed acute myelocytic leukemia. This constellation of neoplasms is distinct from other genetic syndromes that feature polyposis coli. The parents of the brothers are first cousins, suggesting autosomal recessive inheritance of these multiple neoplasms. Autosomal dominant of X-linked transmission is also possible and should be evaluated in other affected families.

Adenocarcinoma↗