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Biomedical subjects

L Bruce

Publications and source records attributed to L Bruce.

At least 19 recordsLinked to original sources

Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants.

In this study we evaluated the clinical response of 12 patients with malignant melanoma and renal cell carcinoma (RCC) following administration of recombinant human interleukin-2 (rhIL-2) by continuous infusion. Serum samples taken before, during and following sequential courses of IL-2 were assayed for the presence of tumour necrosis factor alpha (TNF-alpha) IL-1 alpha, IL-6 and interferon gamma (IFN-gamma) and the presence or changes in these cytokines were examined with respect to clinical response data: our results did not show any direct correlation between the parameters measured and clinical outcome. In addition, peripheral blood mononuclear cells (PBMC) derived from 3 RCC patients were cultured in a serum-free environment and the resulting supernatants assayed for the production of these cytokines and compared to the corresponding serum levels. During one or more courses of treatment only 1 patient, who had metastatic bone disease, demonstrated detectable serum TNF-alpha; serum IL-6 levels were elevated in a proportion of all patients studied and a sustained IL-6 response occurred in a patient who had complete disease remission; IL-1 alpha was detected in the serum of 3 RCC patients; IFN-gamma could not be detected in any serum sample tested. Cytokine levels in sera and supernatants derived from 3 RCC patients were compared but no correlation was found: TNF-alpha and IL-6 were shown to be present at much higher concentrations in supernatants when compared to sera whereas the levels of IL-1 alpha were almost undetectable. This lack of correlation is probably due to the presence of "interfering" proteins in sera which either depress or enhance the ability to detect cytokines in sera using enzyme immunoassays.

Carcinoma, Renal Cell

Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2.

The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.

Aged

Abortion referrals.

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Abortion, Induced

The effects of radiotherapy on immunity in patients with localized carcinoma of the cervix uteri.

To assess the effects of radiotherapy on immune status, a wide range of assessments have been performed on patients with localized carcinoma of the cervix uteri undergoing and initially responding clinically to radical pelvic radiotherapy. Neutrophil function was essentially unchanged by treatment. Absolute neutrophil and lymphocyte counts fell after treatment and remained depressed 3 and 12 months following treatment. The proportions of T and B cells dropped with treatment but recovered to near-presentation levels during the follow-up period even though absolute counts remained depressed. In vitro tests of cellular immunity were depressed by treatment and remained so 3 and 12 months following treatment whereas skin test responses remained normal throughout the assessments. Inhibitory plasma effects were observed in phytohaemagglutinin lymphocyte transformation studies on 4 untreated patients; at follow-up these effects were not evident. A variable response in immune indices has therefore been observed in patients in remission after treatment of localized carcinoma cervix stressing the importance of assessing several aspects of immune function and implying that persistent depression of certain indices does not adversely affect the host tumor response. In two patients relapsing after apparently good initial response all aspects of immunological assessment (except serum immunoglobulin levels and neutrophil function) deteriorated.

Cell Migration Inhibition

Ferritin, a sensitizing substance in the leucocyte migration inhibition test in patients with malignant lymphoma.

The nature of the factor in Hodgkin's disease involved spleen to which many patients with malignant lymphoma react in the leucocyte migration inhibition test has been investigated. Our results suggest that ferritin from Hodgkin's disease involved spleens is antigenically different to that prepared from normal spleen. Isoelectric focusing shows the presence of more acidic 'isoferritins' in ferritin prepared from Hodgkin's disease involved spleen than in that prepared from normal spleen. Further observations using the leucocyte migration inhibition test suggest that sensitization to the abnormal ferritin, acting as an onco-fetal tumour associated substance, may be responsible for the reaction of patients with malignant lymphoma in this test.

Antigens, Neoplasm

Endoscopic evaluation of the effect of azapropazone on the gastric mucosa.

The gastro-intestinal tolerance of azapropazone, a new non-steroidal anti-inflammatory agent, was studied endoscopically in 14 volunteers with no past history of gastro-intestinal disease. This study shows that gastrointestinal tolerance to azapropazone given in a daily dose of 1200 mg for a period of 31 days is good. Istolated erosions with mild hyperemia were found in 2 subjects only. No subjective symptoms were noted during the period of the study.

Apazone

Formation of primordial yolk granules in the avia oocyte.

Electron and light microscopical investigations of early oocytes (between 1.0 mm and 5.0 mm in diameter) from the ovary of 28-30 week-old chickens, suggested the formation of primordial yolk granules from cytoplasmic vesicles. These vesicles formed an aggregation which was observed to be surrounded by membranes, giving the aggregate a multivesicular body-like appearance. At a later stage the vesicles inside the membrane disintegrated and the multivesicular bodies acquired the appearance of primordial yolk granules. The contribution of other structures to the formation of yolk granules is discussed.

Animals

Follow-up studies on the immune status of patients with Hodgkin's disease after splenectomy and treatment, in relapse and remission.

Sixty-two patients with Hodgkin's disease have been followed for one year from the start of treatment. Immunological assessments were repeated after intensive treatment, in patients relapsing and in those in remission at one year. In patients achieving remission, overall cellular immunity, after deteriorating with therapy, particularly cytotoxic chemotherapy, returned to pre-treatment levels in remission when there was little evidence of cellular immune disturbance. Serum IgG and IgM levels fell with intensive chemotherapy in splenectomized patients. IgA and IgM levels were lower (irrespective of splenectomy or therapy status) in remission than at presentation or after treatment. Relapse or non-response was usually associated with deteriorating cellular immunity. Herpes zoster/varicella and candida infections (seen in 6 patients) were preceded by, or associated with, deterioration of cellular immunity.

Adult

Sensitisation to Hodgkin's disease spleen tissue in patients with malignant lymphoma: follow-up study.

The leucocyte migration responses of patients with malignant lymphoma to an unidentified factor in Hodgkin's spleen tissue were serially studied and related to clinical progress. Initial sensitisation responses did not correlate with presenting histological or clinical status or with subsequent clinical progress. Enhancement of responses after treatment, however, was associated with good clinical progress. In patients who relapsed, sensitisation to spleen factor diminished, whereas responses were preserved at one year in those in maintained remission. Sensitisation to the splenic factor may be a useful index of response to treatment in patients with malignant lymphoma; diminishing sensitisation may indicate relapse.

Cell Migration Inhibition

Cellular immunity to Hodgkin's splenic tissue measured by leucocyte migration inhibition.

Patients with lymphoreticular malignancy were shown by a leucocyte migration inhibition technique to have cellular immunity to Hodgkin's splenic tissue. Migration was significantly inhibited in 31 out of 55 patients with Hodgkin's lymphoma and 19 out of 39 patients with other types of lymphoma. Inhibition was also shown in only three out of 29 patients with other malignancy, one out of 23 normal volunteers, and one out of 25 patients with non-malignant disease. The splenic factor that inhibits leucocyte migration, which has yet to be isolated and identified, may be a helpful diagnostic tool in patients with suspected lymphoma.

Cell Migration Inhibition

Changes in immune status in patients undergoing splenectomy for the staging of Hodgkin's disease.

The immune status of 17 patients with Hodgkin's disease was studied before and after splenectomy (undertaken in staging laparotomy) and during chemotherapy or after radiotherapy. The findings were compared with those in 19 patients not selected for splenectomy. Serum IgA and IgM levels became significantly lower after treatment in the splenectomy group. Cell-mediated immunity was depressed mainly in patients receiving quadruple cytotoxic chemotherapy. Neutrophil function was normal or enhanced and was unchanged after splenectomy and treatment despite changes in neutrophil counts. Three patients who underwent splenectomy suffered fatal septicaemia. These results suggest that humoral immunity is depressed by treatment in patients who have undergon splenectomy, and the benefits of early accurate staging must be weighed against the likelihood of infective complications.

Adult

Neutrophil function in lymphoreticular malignancy.

Neutrophil function has been assessed in 62 patients with lymphoreticular malignancy by means of the NBT test and an in vitro micro-organism killing technique. Normal or enhanced phagocytosis was found, the greatest enhancement being found in patients with disseminated disease (in the absence of infections). Candicidal capacity alone was depressed in 7 patients but 4 of these showed depressed cell-mediated immunity to Candida antigen. Splenectomy, radiotherapy and chemotherapy did not alter phagocytic function.

Antigens, Fungal