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Biomedical subjects

K C Anderson

Publications and source records attributed to K C Anderson.

At least 217 records · Page 12Linked to original sources
PubMed1986

Studies of the in vitro activation and differentiation of human B lymphocytes. II. Optimization of activation by anti-immunoglobulin antibody bound to beads: analysis of the role of autocrine effects on B-cell proliferation and of T-cell help in B-cell differentiation.

We report experiments attempting to optimize the proliferative response of human B cells to rabbit anti-immunoglobulin antibody (RAHIg)-linked beads (anti-Ig beads). By choosing polyacrylamide beads of small size (3 micron) and coupling anti-Ig to them at high concentrations, beads were obtained which were both B-cell specific and more highly mitogenic than other than anti-Ig reagents and B-cell mitogens (SAC, protein A). Using these beads to activate B cells, the augmentation of the anti-Ig-induced proliferative response by added T-cell-derived growth factors was largely eliminated at high cell densities although the effect of these factors was still evident at low cell densities. However, when cultures were performed in round-bottom vessels which crowded the B cells together, the response to anti-Ig beads was independent of T-cell factors even at low B-cell densities, suggesting that normal B cells triggered by anti-Ig beads are able to maintain their own proliferation. In contrast to the proliferative response, even with the most potent anti-Ig bead preparations, no differentiation (Ig production or expression of terminal differentiation markers) was evident unless T-cell help was provided.

Antibodies, Anti-Idiotypic↗
PubMed1986

In vitro chemosensitivity of J-82 human bladder cancer cells.

While chemotherapy offers a valuable adjunct to surgery in the management of intravesical bladder cancer, an accurate in vitro predictive test for chemosensitivity has yet to be developed. Drug sensitivity of the human bladder cancer cell line J-82 was assessed using monolayer, stem cell and [3H]thymidine incorporation assays. The 72-h monolayer assay provided a rapid reflection of in vitro drug sensitivity and when combined with the labeling index the results generally paralleled those obtained with the soft agar stem cell assay without the associated large commitment of time and labor. It is suggested that 72-h monolayer assay alone or in combination with [3H]thymidine labeling index may offer valuable insight into the chemotherapeutic response of bladder tumors.

Antineoplastic Agents↗
PubMed1986

Familial Burkitt's lymphoma. Association with altered lymphocyte subsets in family members.

Two sisters in a white American family died of Burkitt's lymphoma at ages 11 and 22 years, after dramatic but transient responses to chemotherapy. Studies of peripheral blood from two healthy brothers and the mother showed an increased percentage of polyclonal B cells (13 to 28 percent; normal, less than 10 percent), and a decreased helper:suppressor T cell ratio (1.0 to 1.5; normal, 1.5 to 2.5). The mother and one brother also had a low fraction of total circulating T cells (24 to 45 percent; normal, 60 to 75 percent). An inherited disturbance of the lymphocytes in family members may have predisposed the sisters to Burkitt's lymphoma; no environmental carcinogens were identified.

Adult↗
PubMed1986

Transfusion-related sepsis after prolonged platelet storage.

The antecubital fossa venipuncture site in frequent blood donors can become scarred or "dimpled" and colonized with surface and deep bacteria that are not sterilized by standard iodophor preparation techniques. These microorganisms can be introduced into blood or platelets at the time of donation. Recent advances that permit the prolonged storage of platelets at room temperature before transfusion allow proliferation of these contaminating bacteria, particularly gram-positive microorganisms. Documented are three episodes of platelet contamination with gram-positive organisms and four cases of sepsis in recipients of these platelets, which were obtained through the "dimpled" site of a single donor and stored for at least 80 hours at 22 degrees C before transfusion. In contrast, platelets harvested from this donor's "dimpled" site and stored for not more than 50 hours were transfused to 25 patients without complication. Therefore, the extended storage of platelets at 22 degrees C prior to transfusion demands strict awareness of any possible sources of extrinsic contamination, since gram-positive bacteria can proliferate under these conditions and result in infectious complications in recipients.

Adult↗
PubMed1986

Transfusion-acquired human immunodeficiency virus infection among immunocompromised persons.

Transmission of the human immunodeficiency virus (HIV) was studied in a group of patients with cancer who received transfusion of blood components harvested from a single, asymptomatic, seropositive donor. Of ten living recipients, nine had antibodies to the virus in fresh or cryopreserved sera at a median of 384 days (range, 237 to 686) after transfusion. In three patients, an enzyme-linked immunosorbent assay was negative at the same time that Western blot and radioimmunoprecipitation techniques showed seropositivity. Cultures for HIV obtained at a median of 615 days (range, 322 to 714) after transfusion were positive in seven of nine seropositive recipients. Six seropositive recipients have developed immunologic and clinical sequelae of HIV infection at a median of 286 days (range, 56 to 745) after transfusion. The sera of the two patients without clinical sequelae neutralized HIV in an in-vitro assay, whereas the seven other seropositive patients lacked such neutralizing antibodies. Our study characterizes the clinical, serologic, virologic, and immunologic manifestations of HIV infection in immunocompromised persons.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Characterization of natural killer cells with antileukemia activity following allogeneic bone marrow transplantation.

To identify cells with potential antileukemia activity following bone marrow transplantation, we have monitored immunologic reconstitution in a patient with acute lymphocytic leukemia in second remission who received intensive chemotherapy and total body irradiation followed by infusion of allogeneic histocompatible marrow. Prior to transplantation, donor bone marrow cells were depleted of T lymphocytes by in vitro treatment with anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks following bone marrow transplantation, the predominant regenerating mononuclear cell population in peripheral blood exhibited a phenotype characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes became predominant, but NK cells persisted. Cultured peripheral blood lymphocytes obtained 12 weeks posttransplant were able to display significant cytotoxicity against leukemic blasts that had been cryopreserved at the time of relapse 5 months prior to bone marrow transplantation. To further characterize those cells with antileukemia activity, we used in vitro cloning techniques to identify four monoclonal populations, termed TC12, -48, -50, and -59, with strong antitumor activity. Cytogenetic analysis demonstrated that each clone was of donor origin. Phenotypic characterization showed that the four clones expressed NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity against genetically unrelated hematopoietic tumor cell lines such as K562, Molt-4, JM, and U937. In addition, we found that these patient clones were similar to cloned NK cells previously derived from normal individuals. Taken together, these results suggest that at least some clones with antileukemia activity following bone marrow transplantation are cells with NK-like function and phenotype. Functional analysis of these cytolytic cells in larger numbers of patients will be necessary to determine the clinical significance of this finding.

Adult↗
PubMed1986

Reduction in the plasma clearance rate of warfarin induced by cimetidine.

The interaction between the histamine H-2 receptor antagonist, cimetidine, and warfarin sodium was prospectively studied in 14 patients who were previously anticoagulated for five years. The patients received warfarin and cimetidine concomitantly for a minimum of ten days. Seven of the patients experienced increases in plasma warfarin concentrations. This correspondingly resulted in abnormal prolongation of their prothrombin times. In these patients the elevation in the steady-state warfarin concentration demonstrates that coadministration of cimetidine significantly reduces the plasma clearance rate of warfarin. The serum and urine metabolite levels of warfarin were not qualitatively different in the absence in contrast to the presence of cimetidine. It is apparent that cimetidine can act as an inhibitory influence on the catabolic degradation of warfarin.

Aged↗
PubMed1985

Mechanical properties of the rat colon: the effect of age, sex and different conditions of storage.

The mechanical properties of the rat colon were studied in old and young Sprague-Dawley rats which were also grouped by sex. Different storage media were used. Rings of colonic tissue were submitted to pulls on an Instron 1026 tensiometer. Gender did not affect the properties of the young rat colon. The rat colon has a tensile strength of around 50 g/mm2 (which places it between the dog and the cat). It increased in strength from proximal to distal, though the rectum was weaker than the colon. The pre-strain of the rat colon was 10% and it was capable of stretching to 200% of its original dimensions. The strength and ability to stretch fell with age, although it initially increased, in the first year of life. Physiological saline at 4 degrees C preserved the burst strength, percentage elongation, hysteresis and Young's modulus between 25 and 100 g stress for up to 1 week. Young's modulus between 125 and 200 g fell progressively with each day of storage. Stress relaxation rose in the first 24 h and thereafter remained constant. Salt appeared to be a good long-term storage medium. Irradiation of the colons before storage did not affect the mechanical properties.

Animals↗
PubMed1985

Mechanical properties of the colon: comparison of the features of the African and European colon in vitro.

The tensile properties of the colon have been examined using methods which gave repeatable results. They showed little change after storage in salt for up to five weeks. The burst strength remained unchanged along the length of the colon. The tensile strength fell distally, as the thickness of the colonic wall increased. The width at burst decreased distally as did the internal diameter. The visco-elastic property of stress relaxation was constant in all regions. The tensile property of the colon was well developed at birth, but fell with age as did the width at burst and the internal diameter. Stress relaxation was unaffected. Because there may be a mechanical abnormality of the colonic wall in diverticular disease and as Europeans are prone to this condition while Africans are not commonly affected, European and African colons were compared. The tensile strength in a Kampala group was greater than in an Edinburgh one, but fell significantly in both groups with age. The width at burst was greater in the Kampala group, but also declined with age. Stress-relaxation was similar in both groups. In view of the similar properties in childhood of colons from Edinburgh and Kampala, the strength of the adult African compared with European colons may derive later from environmental factors such as diet. There were, however, no differences between the colons with and without diverticular disease in European subjects over the age of 50 years.

Adolescent↗
PubMed1985

B5, a new B cell-restricted activation antigen.

The characterization of a new human B cell-restricted activation antigen (B5) is described in this report. With the use of a monoclonal antibody to B5, we show that B5 can be detected on peripheral blood or splenic B cells after 1 day of stimulation with either anti-immunoglobulin, protein A, Epstein Barr virus, or pokeweed mitogen. In contrast, B5 was not expressed on resting B, T, or myeloid cells. More important, B5 could not be detected on activated T cells or monocytes. The B5 antigen was expressed on some lymphoblastoid B cell lines and B cell neoplasms but was not expressed on leukemias or lymphomas of T or myeloid origin. The B5 antigen is distinct from previously reported B cell activation antigens by its m.w. and pattern of cellular expression. These studies suggest that B5 is a novel B cell-restricted activation antigen, which may be useful to study the events of early human B cell activation.

Animals↗
PubMed1985

Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody.

Investigation of the activation of splenic B cells by anti-immunoglobulin (Ig) antibody has enabled us to characterize the anti-Ig-responsive B cell and to analyze the phenotypic changes which accompany proliferation and differentiation. The anti-Ig antibody-responsive B cell population was characterized by the expression of high levels of the B2 antigen and represented approximately 40% of splenic B cells. Brisk mitogenesis which peaked at 3 to 4 days was induced by anti-Ig antibody. The proliferative phase was characterized phenotypically by a dramatic decline in B2 antigen expression, with most cells showing no detectable B2 by 4 days post-activation. The other hallmark of this phase was de novo expression of a group of "activation antigens." These included the B cell-restricted antigens B-LAST 1, BB1, and B5, and the T cell-associated interleukin 2 receptor and T12 antigens. Concomitantly, B1, B4, and Ia expression increased, the increase being roughly proportional to the increase in cell size. After day 4, the mitogenic response progressively diminished, while Ig synthesis increased. During this differentiation phase, cell surface antigens again displayed a distinct sequence of changes. The five activation antigens and the B1, B4, and Ia antigens began to decrease. However, two markers, T10 and PCA-1, which are found on plasmacytomas, appeared and their level of expression steadily increased. These changes and the appearance of morphologically identifiable plasma cells required the presence of T cells in this system. T cell supernatants alone induced Ig secretion but did not induce expression of PCA-1 or the appearance of cells with plasma cell morphology. The culture system developed in this study has allowed us to analyze the antigenic changes following activation by anti-Ig antibody. This sequence of changes has not only permitted the identification of antigens which, by their appearance at distinct stages may have an important role in proliferation and differentiation of B cells, but also provides us with the means of studying the function of each antigen.

Animals↗
PubMed1985

Hairy cell leukemia: a tumor of pre-plasma cells.

Monoclonal antibodies defining B-, T-, and myeloid-restricted cell surface antigens were used to characterize the lineage and state of differentiation of tumor cells isolated from 22 patients with hairy cell leukemia (HCL). These tumors were shown to be of B lineage because they strongly expressed the B cell-restricted antigens B1 and B4 and lacked T cell- and monocyte-restricted antigens. Moreover, the strong expression of the plasma cell-associated PCA-1 antigen on the majority of hairy cells suggested that these tumors correspond to later stages of B cell ontogeny. Dual fluorescence experiments further confirmed that HCL splenocytes that coexpressed B1 and PCA-1 demonstrated both the morphology and tartrate-resistant acid phosphatase positivity of hairy cells. The observation that some hairy cells either spontaneously produce immunoglobulin (Ig) or could be induced to proliferate and secrete Ig provides complementary support for the view that HCL is a pre-plasma cell tumor. However, staining of hairy cells with anti-IL2R1 monoclonal antibody, which is directed to the T cell growth factor receptor and/or with the anti-Mo1 reagent, directed to C3bi complement receptor, distinguish these cells from currently identified B cells.

Antibodies, Monoclonal↗
PubMed1985

Immunologic heterogeneity of diffuse large cell lymphoma.

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell-restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B-DLCLs.

Antibodies, Monoclonal↗
PubMed1985

Isolation and functional analysis of human B cell populations. I. Characterization of the B1+B2+ and B1+B2- subsets.

Distinct populations of human B lymphocytes can be identified by their expression and/or co-expression of the B cell-restricted antigens B1 and B2. Dual fluorochrome staining and flow cytometric cell sorting permitted the isolation of the B1+B2+ and B1+B2- cells to homogeneity. In contrast, very few B1-B2+ cells were obtainable from normal lymphoid organs. Virtually all B1+B2+ cells expressed IgM and IgD, but lacked IgG and the plasma cell antigens PCA-1 and PC-1, whereas the B1+B2- cells more frequently expressed IgG, PCA-1 and PC-1. Both populations were noncycling and were composed of similar percentages of small and large cells. The B1+B2+ cells proliferate to anti-mu or to anti-mu + PHA-LCM, but not to PHA-LCM alone. They require both T cells and PWM to produce Ig. In contrast, B1+B2-cells do not significantly proliferate to anti-mu, PHA-LCM, or anti-mu and PHA-LCM. They produce Ig in response to T cells alone without PWM. These phenotypic and functional observations provide preliminary evidence that these populations are distinct and that the B1+B2+ cell may be a "resting" B cell, whereas the B1+B2- cell appears to be more "differentiated." The present studies further suggest that they will also be helpful in characterizing B cells in some human disease states. We believe that the identification and isolation of these and similar subsets of B cells defined by differing cell surface phenotype should aid our understanding both of normal B cell differentiation and of B cell disease states.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Role of 99mTc methylene diphosphonate bone imaging in the management of lymphoma.

The role of modern techniques of 99mTc methylene diphosphonate bone imaging in the management of lymphoma patients was assessed by comparing results of 107 bone scans in 16 patients with Hodgkin's disease, and 45 patients with non-Hodgkin's lymphoma to simultaneous radiologic, clinical, and histopathologic features as well as to subsequent disease course. The sensitivity and specificity were both greater than or equal to 0.96 in both Hodgkin's disease and non-Hodgkin's lymphoma and the overall accuracy by site was 98%. The scan proved to be useful in the definition and follow-up of skeletal lymphomatous disease in both symptomatic and asymptomatic patients, and defined abnormalities which were not predicted by either serum alkaline phosphatase activity or the presence of bone marrow involvement. In no patient, however, did the bone scan result by itself alter either initial staging or estimates of extent of disease at the time of relapse. Bone scanning, therefore, cannot be recommended as a screening procedure in patients with lymphoma; rather, this test is best reserved for the definition and follow-up of skeletal metastases in patients with active, concomitant, extraosseous disease.

Bone Neoplasms↗
PubMed1984

Dizygotic twinning, cryptorchism, and seminoma in a sibship.

Cryptorchism was diagnosed in all 3 male members of 2 pairs of dizygotic twins in a sibship. Two of these brothers developed seminomas at age 31 and 33 years. Studies revealed a nephew with an atrophic testicle, but no additional instances of twinning, cryptorchism or testis cancer. Cryptorchism has been reported previously in 3 of 8 sets of twins with testis cancer, but rarely in familial testis cancer affecting other relatives. Hormonal factors may be involved in the association of twinning, cryptorchism and testis cancer in this family.

Adult↗
PubMed1984

Verapamil enhancement of chemotherapeutic efficacy in human bladder cancer cells.

The calcium influx blocker verapamil has been used to overcome drug resistance in several tumor systems. The possible in vitro enhancement of drug efficacy was assessed in bladder cancer cell line T24. Combination of thiotepa and doxorubicin hydrochloride with verapamil significantly reduced the survival and growth of T24 cells after as little as 1 hour of drug exposure. An increase in doxorubicin hydrochloride-induced inhibition of [3H]thymidine uptake resulted when verapamil was administered. However, this trend was not demonstrated when combined with thiotepa. It appears that verapamil enhances thiotepa-induced cytotoxicity while it potentiates the antimitotic nature of doxorubicin hydrochloride. The data presented is consistent with the postulate that verapamil alters active efflux of drug from malignant cells and suggests that verapamil has a role in the clinical management of bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗