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Biomedical subjects

K Sikora

Publications and source records attributed to K Sikora.

At least 163 records · Page 9Linked to original sources

Detection of lymphocytes in malignant gliomas by monoclonal antibodies.

Lymphocytes are not present in normal brain but are known to infiltrate malignant gliomas. The reasons for this infiltration and the signals involved are not understood. The lymphocyte content of 15 malignant gliomas removed at time of surgery was studied, using monoclonal antibodies to T and B cell surface antigens and immunofluorescence. An average of 41% of infiltrating cells possessed surface Ig, with 21% bearing the common T cell marker. There was no evidence of oligoclonal restriction of light chain types.

Adolescent↗

Human hybridomas from malignant gliomas.

Intratumoral lymphocytes from 12 patients undergoing craniotomy for malignant glioma were fused with a specially derived human myeloma line LICR-LON-HMy2. 71 stable hybridomas were obtained from 5 of the 12 patients. Such hybridomas had a DNA content equal to the sum of that present in lymphocytes and the parent myeloma. The hybridoma supernatants contained human monoclonal immunoglobulins. Glioma-binding activity was detected in 7 out of the 71 supernatants. These results suggest that malignant gliomas contain a population of B lymphocytes which may be involved in host defence against the tumour.

Adolescent↗

Monoclonal antibodies in oncology.

Molecular biology has made tremendous strides over the last five years. The new biology allows us to prepare monoclonal antibodies to defined antigens; to detect, isolate and clone specific genes; and to insert these genes into defined sites in different cells giving new functions to old organisms. These revolutionary developments have been followed closely by researchers, businessmen, politicians and philosophers, as well as by those involved in the clinical care of patients. Although our understanding of human molecular biology is increasing rapidly, it is the development of monoclonal antibodies that has the most immediate application in the clinic. There have been several reports of their use in the diagnosis, localisation and treatment of human malignant disease. This review describes developments that are likely to have direct relevance to patient care in the near future.

Animals↗

Human monoclonal antibodies to lung-cancer antigens.

Lymphocytes obtained from hilar and bronchial lymph nodes from 23 patients undergoing radical surgery for carcinoma of the bronchus were fused with established rat or mouse myeloma lines. 62% of the resultant hybrids were found to be secreting human Ig detected by a sensitive staphylococcal Protein A-coupled SRBC assay. Immunoglobulins synthesized by such hybrids were internally labelled with 3H-lysine and their antibody activity against a variety of membrane preparations determined. Nine monoclonal antibodies were found which bound to molecules on lung-cancer membranes and not on normal lung membranes from the same patient.

Aged↗

Pituicyte fine structure in the developing neural lobe of the rat.

The fine structure of pituicytes was investigated between 15 days of fetal life and 120 days postnatum. Prior to the penetration of neurosecretory axons into the neural lobe a uniform population of undifferentiated pituicytes is presented. Coincidental with the first appearance of neurosecretory axons in the neural lobe at 16 1/2 days of fetal life is the beginning differentiation of those pituicytes into two varieties, an active and an inactive one. The active variety predominates and has all of the morphologic characteristics of an active secretory cell, especially during axonal growth in the neural lobe; between 16 1/2 days and birth most of the undifferentiated pituicytes have differentiated into active pituicytes. The inactive variety is rarely encountered before birth; the classification as an inactive cell is based on the lack of organelles involved in secretion. After adult conditions are reached between 25 and 30 days postnatum, the active pituicytes continue to prevail in the neural lobe, although they are less active than in the developmental period as judged by morphologic criteria. The inactive pituicytes increase in number with increasing age. In addition to the pituicytes two other cells are described, microglial cells and a cell whose exact nature remains to be determined.

Aging↗

The heterogenization of tumour cells with tuberculin. I. The coupling of tuberculin to cell surfaces using con-A as ligand.

The introduction of an antigenic determinant strongly recognized by T cells on to a cell enhances the immune response to weak cellular antigens. Tuberculin (PPD) is a particularly suitable antigenic determinant for this purpose since it behaves in many ways as a 'T-cell hapten'. It has been found that direct chemical coupling of PPD to cell surfaces damages their antigenicity, but that this can be circumvented by coupling PPD to the lectin Concanavalin A and using this as the ligand for binding PPD to the cell. Techniques for preparing Con-A/PPD using little glutaraldehyde or SPDP as cross-linking agents are described.

Animals↗

The heterogenization of tumour cells with tuberculin. II. Studies of the antigenicity of tuberculin-heterogenized murine tumour cells in syngeneic BCG positive and BCG negative mice.

The possibility of enhancing the antigenicity of tumour cells by chemically attaching purified protein derivative (PPD) of tubercle bacillus as an immunogenic carrier determinant into the tumour cell surface has been explored in these studies. It was observed that multiple immunizations with PPD-coupled tumour cells did potentiate a marked anti-rumour response even to tumours that were very weakly antigenic. Moreover, such immunizations could be used to retard the growth of tumours in previously unimmunized animals. An attempt has been made to elucidate the important factors involved when PPD heterogenized tumour cells are used for immunization.

Animals↗

Follow-up observations on the effect of human leukocyte interferon in non-Hodgkin's lymphoma.

Follow-up data for 11 patients with non-Hodgkin's lymphoma treated with partially purified human leukocyte interferon is presented. The interferon preparation used was 0.1% pure and treatment consisted of 5 x 10(6) U given intramuscularly twice daily for 60 injections. One complete, three partial, and three minimal responses were observed in five of seven evaluable patients with nodular non-Hodgkin's lymphoma. Duration of response appears to be from 6 to 12 mo. One patient achieved a second partial response on retreatment with interferon in spite of having received chemotherapy in the interval between interferon treatments. No responses were seen in three patients with rapidly progressive diffuse histiocytic lymphoma. Dose-limiting toxicity is leukopenia, which necessitated modification or cessation of treatment in three patients. Nonhematologic toxicities consisted of fever, malaise, arthralgia, and loss of appetite. In conclusion, interferon has activity against non-Hodgkin's lymphoma, and prior treatment with chemotherapy does not preclude a response to interferon.

Adult↗

Inhibition of lymphoma hybrids by human interferon.

A set of stable mouse-human hybrids was constructed from the neoplastic lymphocytes from a patient with nodular lymphoma and from another with chronic lymphocytic leukaemia. Both patients had shown a clinical response to human leucocyte interferon. The same interferon preparation inhibited the growth rate of 14 out of 17 established hybrid cell lines. This system provides evidence of a direct growth inhibitory effect of interferon on neoplastic B lymphocytes. Such a system could be used to predict the sensitivity of a patient's tumour before therapy.

Aged↗