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Biomedical subjects

D Crowther

Publications and source records attributed to D Crowther.

At least 181 records · Page 10Linked to original sources
PubMed1982

Bone marrow involvement in adult soft tissue sarcomas.

Bone marrow biopsy was performed as part of the initial assessment in 74 patients with soft tissue sarcoma. Infiltration of the marrow by tumour was present in four cases, all from the group of 56 patients who had other evidence of metastatic disease, giving an overall incidence of 7%. The histological subtypes were pleomorphic rhabdomyosarcoma, angiosarcoma, synovial sarcoma and myxoid liposarcoma, of which the first three were high-grade tumours. Although it was not possible to determine whether response to chemotherapy was influenced by marrow involvement, haematological toxicity seemed excessive.

Adolescent↗
PubMed1982

Studies of lectin binding to normal and neoplastic lymphoid tissues. I. Normal nodes and Hodgkin's disease.

Lectins are proteins which have the ability to interact specifically with carbohydrate residues of glycoproteins and other glycoconjugates. The staining patterns of 10 fluorescein conjugated lectins (F-Con A, F-LCA, F-RCA, F-WGA, F-PHA, F-PWM, F-LTA, F-SBA, F-PNA, F-DB) and a protease inhibitor (F-LA) have been studied in histological sections of 11 normal or reactive lymph nodes and 6 nodes and one skin biopsy involved by Hodgkin's disease. On the basis of the patterns of lectin binding, and current knowledge of their saccharide specificities, we found that within germinal centres there is an orderly carbohydrate rich extracellular matrix which contains a higher concentration of GlcNAc and terminal Gal residues than the surface membranes of component cells. This suggests active secretion rather than simple membrane shedding, and it is possible that this pericellular domain plays a part in the regulation of the proliferative response, or controls migration of lymphocytes in and out of the germinal centre. Lectin binding in Reed-Sternberg cells suggests that the huge nucleoli contain glycoconjugates of diverse structure, which may be linked with their failure to undergo cytokinesis.

Fluoresceins↗
PubMed1982

Studies of lectin binding to normal and neoplastic lymph nodes. II. Non-Hodgkin's lymphoma.

Fluorescein conjugated lectins have been used as histochemical stains in lymph node sections from 22 patients with non-Hodgkin's Lymphoma. Variations in the distribution and structure of glycoprotein sequences between the different types of lymphoma, and also normal nodes, have been detected. The lectin-binding patterns of neoplastic lymphocytes of small cell lymphomas, both follicular and diffuse, suggested a predominance of sialylated glycopeptides, as in normal small lymphocytes of the mantle zone of germinal centres. In contrast, the staining patterns of large cell follicular and diffuse lymphomas showed a greater diversity of carbohydrate structure, with enhanced cytoplasmic staining and increased numbers of incomplete oligosaccharide sequences. Heterogeneity of staining, together with reduced sialic acid expression at all cellular sites was a common feature of lymphoblastic lymphomas and seemed to be linked with a poor prognosis. The extracellular matrix of small cell follicular lymphomas showed altered saccharide content, but retained some degree of organization. The large cell follicular lymphomas were characterized by a prominent disorderly matrix, with staining characteristics which suggested shedding of surface membrane from component cells. The loss or disordered production of the normal extracellular matrix may reflect a breakdown of control mechanisms within neoplastic follicles.

Fluoresceins↗
PubMed1982

Lectin-binding characteristics of human natural killer cells.

Human natural killer (NK) cells separated initially by density centrifugation of lymphocytes (E+) forming rosettes with sheep red blood cells (SRBC), were further fractionated on gradients of bovine serum albumin (BSA). Low density fractions contained effector cells which displayed high cytotoxicity against the NK-sensitive erythroleukaemic cell line, K562. These low density cells, which expressed receptors for Fc and the monoclonal antibody OKMI, showed enhanced cytotoxicity when treated with lymphoblastoid interferon (IFN-alpha). They also showed an increased response to phytomitogen in comparison with unseparated cells or those recovered from high density fractions. Two lymphocyte subsets one of high and one of low lectin binding capacity were identified in the E+ populations by their reactivity with Lens culinaris agglutinin (LCA). High LCA binding was observed only in low density fractions and was associated with a marked enrichment of NK activity. This property was used to separate the NK active population in E+ cells by fluorescence-activated cell sorting (FACS). These data add a new dimension to the cell surface properties of human NK cells and suggest the presence of LCA-reactive glycoproteins which are either enriched in, or uniquely associated with, cells of the NK subset. The experiments indicate that lectins can serve as useful probes of lymphocyte function and provide the basis for effective cell sorting.

Adult↗
PubMed1981

Effects of Corynebacterium parvum on cellular immunity of cancer patients, assayed sequentially over 63 days.

The immunologic effects of Corynebacterium parvum (2 mg/M2) infused at three-week intervals were determined by 19 sequential assays in each of nine patients with metastatic malignancy. Peripheral blood immunologic profiles were followed for 63 days. No statistical significant changes (P greater than 0.05) occurred in total white cell, lymphocyte, or monocyte counts. Subpopulation assays demonstrated significant increases in E rosetting cells but not in sIg-bearing cells; there was a corresponding significant decrease in null-cell proportions. Killer cell lymphocytotoxicity was measured by 51Cr release from Chang target cells. Significant increases were observed one week after immunization and were maintained on subsequent immunizations. NK- and K-cell cytotoxicity were particularly augmented; T-cell cytotoxicity expressed as lytic units/ml was significantly increased on fewer assay occasions. Killer cell function has a possible in vivo antitumor role and methods of boosting and maintaining the activity deserve consideration. A three-week immunization schedule with C. parvum is supported by the current work and is the basis of a randomized adjuvant immunotherapy study of patients with malignant melanoma.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Malignant melanoma in children and adolescents.

Thirty-one children and adolescents with malignant melanoma were treated at the Christie Hospital and Holt Radium Institute between 1945 and 1977. Locations of primary lesions included head-neck 14, trunk nine, and extremity eight. Twenty-five patients had clinically localized tumor at diagnosis, four had regional disease, and two had generalized tumor. Surgery was the primary modality of therapy. Fifteen patients survive without active disease from two years to more than 18 years, and 16 patients died of disease.

Adolescent↗
PubMed1981

The involvement of ferredoxin-NADP+ reductase in cyclic electron transport in chloroplasts.

The sites of action, in spinach thylakoid, of known inhibitors of electron transport at the reducing end of photosystem I have been more accurately located by parallel investigation of effects on three partial reactions: photo-reduction (from water) of added NADP+, photoreduction of added cytochrome c, and dark reduction of cyto-chrome c by added NADPH. Comparison with inhibitory effects on cyclic electron flow (registered by the slow phase of the electrochromic response during repetitive flash excitation) permitted assessment of the role of ferredoxin and ferredoxin-NADP+ reductase (ferredoxin: NADP+ oxidoreductase, EC 1.18.1.3) in the cyclic electron transport pathway around photosystem I. Disulfodisalicylidenepropane-1,1-diamine inhibited all the above partial reactions except the ferredoxin-dependent photoreduction of cytochrome C. thereby indicating its interference with the reductase or the complexation between reductase and ferredoxin. Studies with purified ferredoxin-NADP+ reductase established it as the sensitive component. Cyclic flow is also sensitive to the above inhibitor and thus presumably involves the reductase. Supporting evidence for this came from studies of inhibition by substituted maleimides, which are inhibitors of electron transfer through the isolated reductase; these also inhibited the slow phase of the electrochromic response and all partial reactions except the photoreduction of cytochrome c. In contrast, an antiserum against the reductase affected only reactions involving NADP. The conclusion is drawn that the pathway of cyclic electron transport includes both ferredoxin and ferredoxin-NADP+ reductase, but not the NADP-binding site on the reductase.

Chloroplasts↗
PubMed1981

Lack of prognostic value of the thymidine-labelling index in adult acute leukaemia.

A study has been made of the thymidine labelling index (TLI) of marrow blast cells in 201 adults with untreated acute leukaemia. There was no significant difference between the TLI in 172 patients with acute myeloblastic leukaemia and 29 patients with acute lymphoblastic leukaemia. The TLI did not correlate with the age, sex, peripheral-blood or marrow blast-cell count, or the platelet count at presentation. In neither acute myeloblastic leukaemia nor acute lymphoblastic leukaemia was there any correlation between the TLI and the response to the initial therapy, the duration of the first complete remission or survival.

Adolescent↗
PubMed1981

The migratory properties of indium-111 oxine labelled lymphocytes in patients with chronic lymphocytic leukaemia.

These studies describe the application of a new method for following the migration of autologous lymphocytes in normal subjects and patients with chronic lymphocytic leukaemia (CLL). There is evidence that Indium 111 oxine is a reliable radioactive cell label for in vivo studies of lymphocyte traffic in man. In normal subjects, where 60-70% of the lymphocytes labelled are T cells, the results are different from those of previous workers. The lymphocytes leave the blood initially but later return to it. It is believed that this is due to the reappearance of cells which at first entered the spleen. It is suggested that the difference between these data and those of Hersey (1971) is due to the failure of lymphocytes in the latter studies to return to the blood after primary migration. In CLL no such reappearance in the blood is seen and the lymphocytes do not leave the spleen in significant numbers over 48 h. This suggests that CLL B cells either do not recirculate through spleen or that their transit time is greater than 48 h. Bone marrow localization in CLL patients is greater than in the normal subjects, suggesting that either a larger proportion of the neoplastic B lymphocytes enter this compartment or their transit time through it is longer than the transit time of a normal T cell predominant population. Localization in normal-sized lymph nodes in patients with CLL is less than that in the lymph nodes of normal subjects. This may possibly be explained by the greater propensity of T lymphocytes to enter lymph nodes than B lymphocytes, or by the altered migratory properties of CLL B lymphocytes as compared with normal B cells.

Adult↗