Search PubMed⌕ Search

Biomedical subjects

A Edwards

Publications and source records attributed to A Edwards.

At least 253 records · Page 14Linked to original sources
PubMed1981

Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2.

The influence of interleukin 2(IL2) on the cytotoxic activity of lymphocytes from patients with melanoma against autologous and a variety of allogeneic melanoma cells was studied. IL2 was produced from blood lymphocytes cultured for 24 h with phytohaemagglutinin (PHA) and purified by membrane chromatography to exclude PHA. Lymphocytes from 13 patients with melanoma at various clinical stages were cultured fro 6 days with IL2 (2 U/ml) and then tested for cytotoxic activity against autologous melanoma cells, three allogeneic melanoma and three non-melanoma cells. Autologous cytotoxicity was generated by culture with IL2 alone and was not increased by culture with both IL2 and autologous tumour cells. Marked increases in cytotoxic activity were also generated against the allogeneic target cells and were maximal against the NK-insensitive Chang target cells. Similar degrees of cytotoxicity were induced by IL2 stimulation of lymphocytes from melanoma patients, patients with nonmelanoma carcinoma and normal subjects against the allogeneic target cells. Cold target inhibition studies were carried out against IL2 induced autologous cytotoxicity in five patients. In four of five studies the autologous target cells inhibited more than the allogeneic target cells. There was no significant difference between the inhibition produced by allogeneic melanoma cells and that produced by non-melanoma cells. Similarly, in studies against allogeneic target cells, there was no significant difference in the inhibition produced by allogeneic melanoma compared to non-melanoma target cells. This applied irrespective of whether effector cells were from melanoma or non-melanoma subjects. These results suggest that lymphocytes from patients with melanoma are primed against autologous antigens in vivo and that provision of a second signal, IL2, in vitro can induce cytotoxicity against the autologous tumour. The cytotoxicity generated against the allogeneic target cells did not appear to have specificity to melanoma. Several results, such as the pattern of cytotoxicity against the target cells and change in cell surface markers on the lymphocytes during culture, suggested that cytotoxicity was mediated by activated T cells rather than by nature killer cells. These findings appear to have important implications both in the understanding of tumor host relationships and for the use of IL2 in therapy.

Antigens, Neoplasm↗
PubMed1981

A double-blind controlled trial of the effect of sodium cromoglycate in preventing relapse in ulcerative colitis.

A double-blind controlled trial of the effect of sodium cromoglycate (SCG) in preventing relapse in ulcerative colitis has been completed in 100 subjects. In patients already taking sulphasalazine, SCG did not prove to be of any additional benefit. However, in patients not on any other maintenance therapy, the relapse rate was 40% for SCG as compared with 75% for placebo. A large study of the effect of SCG in patients intolerant of sulphasalazine is indicated.

Adult↗
PubMed1980

Tumour-related changes in natural killer cell activity in melanoma patients. Influence of stage of disease, tumour thickness and age of patients.

The influence of tumour growth on the natural killer (NK) activity of melanoma patients was examined by analysis of NK activity in 51Cr release assays before and at intervals after surgical removal of localized melanoma. In patients with Stage I and II melanoma, removal of the tumour was associated with changes in the level of NK activity which were not detected in patients who had surgery for skin graft after previous removal of the primary melanoma. The changes in NK activity after removal of melanoma were however different in patients with Stage I compared to Stage II melanoma. In the former, NK activity which appeared specifically directed toward melanoma cells was maximal 2-4 weeks after removal of the tumour and then decreased to normal levels. The NK activity after surgery was directly related to the thickness of the tumour. In patients with Stage II melanoma, NK activity did not increase but fell to low levels after removal of the tumour. The level of NK activity in these patients was not related to the thickness of their primary melanoma. In patients with Stage I and II melanoma the NK activity against melanoma cells showed a significant increase with age. The reason for the different sequence of changes in NK activity after removal of melanoma in the two patient groups is unknown. It is suggested however that the differences observed in patients with Stage II melanoma may reflect differences in the tumour or host response which contributed to the spread of the tumour to regional lymph nodes in these patients.

Adult↗
PubMed1980

Regulation of gene expression in primary cultures of adult rat hepatocytes on collagen gels.

The studies described in this paper demonstrate rather conclusively the efficacy of the study of the regulation of gene expression in primary cultures of adult rat hepatocytes. The utilization of these cells in completely defined medium allows one to determine the exact environmental conditions for the regulation of the expression of specific genes. In the studies described in this work, we have demonstrated that the regulation of glucokinase involved three hormones, insulin, corticosteroids, and T3. In contrast, the regulation of an enzyme involved primarily in fatty acid metabolism, ATP-citrate lyase, required only insulin and T3 for its full expression. Cyclic GMP appeared to be involved in the regulation of glucokinase, but not ATP-citrate lyase, a fact that would be extremely difficult to demonstrate clearly in vivo. The regulation of the gluconeogenic enzyme, ornithine aminotransferase, in vitro involved only a single hormone, glucagon, the inhibition of induction by corticoid steroids demonstrable in vivo being absent in cell culture. However, the repressive effect of glucose on the induction of this enzyme was quite comparable to that seen in vivo and was not mediated through cyclic AMP or insulin, based on findings in cell culture. Thus, the requirements for and the mechanisms involved in enzyme induction and repression by hormones and glucose may be much more easily studied in primary cultures of rat hepatocytes than in vivo, or even in hepatoma cell lines, where relatively few genes are expressed as compared with adult liver. In addition to the regulation of enzyme levels, the characteristics of protein secretion may be investigated in primary cultures of rat hepatocytes and compared with the biochemical and physiological parameters in the whole organism. This was exemplified by the study of the synthesis and secretion of alpha 2u-globulin that was secreted into the culture medium in both glycosylated and nonglycosylated forms but was maintained in the circulation in vivo, principally as the glycosylated form. Furthermore, the function of glycosylation in this particular instance may be deduced from a combination of the in vivo and in vitro approaches. The advantages of the use of primary hepatocyte cultures for the study of the regulation of gene expression in mammalian tissue has only recently been explored. Future investigations of the regulation of a variety of enzymes in these cultures as well as a study of the regulation of the synthesis of their messenger RNA are now possible and should provide an exciting system in which to understand at a molecular level the regulation of the expression of a number of genes.

ATP Citrate (pro-S)-Lyase↗
PubMed1980

Chronic eosinophilic pneumonia: an unusual cause of acute respiratory failure.

A 75-year-old man developed dyspnea, cough, peripheral radiographic infiltrates, eosinophilia, and severe hypoxemia requiring mechanical ventilation. An open lung biopsy revealed chronic eosinophilic pneumonia, and the patient recovered with corticosteroid therapy. Chronic eosinophilic pneumonia is a disease that should be included in the different diagnosis of treatable causes of acute respiratory failure.

Acute Disease↗
PubMed1979

Alternative postmeniscectomy regimen.

Eighty patients who had undergone routine meniscectomy were divided into two groups for postoperative management. The first 40 patients were treated by the traditional method of a compression bandage with a backsplint, followed by a 10-day stay in hospital. In the other 40 patients a compression bandage was applied, reinforced by a plaster cylinder. Weight-bearing was allowed with the aid of crutches, and patients were discharged after four days in hospital. Adequate splintage and early ambulation was more convenient and comfortable for postoperative management, and no complications ensued. Less time was needed for physiotherapy, and earlier return to work and resumption of normal activities were made easier.

Adult↗
PubMed1979

Evaluation of nocturnal penile tumescence in the differential diagnosis of sexual impotence. A quantitative study.

Nocturnal penile tumescence (NPT) was assessed in 30 impotent patients for the purpose of differential diagnosis. In 11 psychogenic cases, with several exceptions, NPT was found to be normal, with a marked discrepancy between the NPT findings and the patients' estimates of their daytime erectile capacity. In 19 organic patients, maximal NPT corresponded closely to and mirrored the patient's subjective estimate of his impaired waking performance. Statistically, the figures for frequency, degree, duration, and amount of NPT were found to be significantly and markedly greater in the psychogenic group. Statistical significance was maintained when the 11 psychogenic patients were closely age-matched with 11 of the 19 organic cases. The method is not 100% accurate; some 15% of impotent patients without organic findings have reduced NPT, several of whom were shown to be psychogenic, but others in this group may have undetected organic pathology. The NPT method is very promising, but beset by a number of methodological problems.

Adult↗
PubMed1979

Low natural-killer-cell activity in familial melanoma patients and their relatives.

Patients with melanoma who had one or more close relatives with melanoma were studied for their natural-killer-cell (NK) activity against cultured melanoma cells and Chang cells. A high proportion of the patients and their relatives were found to have low NK activity against these target cells. In most of the patients this could not be attributed to general depression of their immune function, since B- and T-cell numbers and the mitogenic response to PHA were within normal limits. The levels of NK activity of the patients and their relatives were found to be significantly correlated, suggesting that the NK activity in these families may have been genetically (or environmentally) determined. Several genetic markers were examined in the patients and their relatives for association with the disease state and NK activity. No association with HLA antigens or ABO blood groups was detected, but there was a low incidence of the Rhesus negative phenotype in the patients (the Rh phenotype had previously been associated with high NK activity). The present results indicate that NK activity has a familial association in families with a high incidence of melanoma, and raise the question whether low NK activity may be one of the predisposing factors in the development of familial melanoma.

Adult↗
PubMed1979

Relationship of natural killer-cell activity to rhesus antigens in man.

A number of previous studies have shown that the level of natural killer (NK) cell activity in humans is relatively constant for a given individual but varies widely between individuals. The factors which determine this variability are largely unknown, but genetic factors appear to be involved. In the present study it was found that Rh- normal subjects and melanoma patients had significantly higher natural cytotoxicity to target cells than Rh+ patients. This difference did not appear to be due to sensitization against Rh antigens on the target cell and may indicate that genes determining NK-cell activity are associated with those determining the expression of Rh antigens. Analysis of the survival data for Rh- and Rh+ patients did not reveal any increase in survival attributable to the higher natural cytotoxicity in Rh- patients.

Adult↗
PubMed1979

An open technique of pleural biopsy in the diagnosis of tuberculous effusions.

To assess an open technique of pleural biopsy as an aid to diagnosis in pleural disease 107 African patients with radiological evidence of pleural effusion underwent biopsy. In 87 there was radiological evidence of an effusion but not of underlying lung disease; 73 patients (84%) in this group were ultimately diagnosed as suffering from tuberculosis and of these 56 (77%) had a positive pleural biopsy. There was a heavy male predominance of tuberculous infection (male:female ratio approximately 5:1) and half of the patients were aged 21 to 30 years. In the 20 patients with radiological changes in the lung a diagnosis was established by biopsy in 13 cases. Four of these were tuberculous and a further two cases of tuberculosis were established on clinical grounds.

Biopsy↗
PubMed1978

Relationship of cell-mediated cytotoxicity against melanoma cells to prognosis in melanoma patients.

The cell-mediated cytotoxicity (CMC) of blood mononuclear cells against cultured human melanoma cells was measured in patients after surgical removal of localized melanoma, at a time when they were considered on clinical grounds to be free of melanoma. It was found that the distribution of CMC values against melanoma cells in melanoma patients was different from that in control subjects, and several sub-populations of melanoma patients were evident on the basis of these measurements. No difference in distribution of CMC values was found against non-melanoma cells, which suggested the changes were specific for melanoma. The proportion of patients with recurrence of melanoma was compared between the patient groups with low, normal or high CMC values against cultured melanoma cells after surgery. Analysis for periods extending to 2 years showed that patients with low CMC values after surgery had a significantly higher incidence of recurrence from melanoma than patients with normal or high CMC values. These results suggest there may be a sub-group of melanoma patients who have intrinsically low CMC against melanoma cells, and that this may be an important predisposing factor in the development of recurrent melanoma.

Adult↗
PubMed1978

Blocking factors against melanoma leucocyte-dependent antibody: relationship to disease activity in melanoma patients.

Previous studies have shown that many melanoma patients have cytotoxic leucocyte-dependent antibody (LDA) which is inhibited by factors in their sera. These factors were shown to be small molecular weight glycoproteins which could also be identified in the supernatants of melanoma cultures, and which were therefore most likely to be melanoma cell surface antigens. The present studies have shown that these blocking factors against melanoma LDA can be detected in patients with primary melanoma, and that the levels of this activity show an inverse correlation with the levels of LDA in the sera of melanoma patients. The appearance of melanoma LDA after surgery for localized melanoma was shown in approximately a third of the patients, and this pattern was shown to result from the disappearance of the LDA blocking activity after surgical removal of the melanoma. Assays were designed specifically to measure the melanoma LDA blocking factors by plasmapheresis. It is not yet known whether the melanoma LDA blocking activity has correlation with tumour growth in melanoma patients. The potential value of measuring this activity to assess response to therapy was shown by studies designed to remove the blocking factors by plasmapheresis. It is not yet known whether the melanoma LDA blocking activity has biological significance in regard to tumour growth, but these studies appear to indicate that measurement of these factors in the sera of melanoma patients may provide a useful in vitro monitor of tumour growth in melanoma patients.

Adult↗
PubMed1978

Rapid formation of N-nitrosamines from nitrogen oxides under neutral and alkaline conditions.

The formation of carcinogenic N-nitrosamines in neutral and alkaline aqueous solutions (pH 6-14) at 25 degrees C is reported using dissolved N2O3 and N2O4 gases. These reactions are very much faster than those with acidified nitrite: typically, 2 X 10(-3) M amine gives ca. 10-50% N-nitrosamine in a few seconds with 5-20 fold excess of nitrogen oxide. The N-nitrosamine yield in 0.1 M sodium hydroxide is independent of amine basicity from pKA 11.2-0.99, but decreases with decreasing pH of the reaction solution for the more basic amines. Significantly, N-nitrosamine yields are not lowered with diluted nitrogen oxides (1000 ppm) and moderately basic amines (eg. N-methylpiperazine) react readily at physiological pH. The mechanism by which these reactions occur is discussed, with particular reference to the existence of two reactive tautomeric forms of N2O3 and N2O4. The formation of carcinogenic N-nitrosamines from NO in ethanol at 25 degrees C is also reported. These reactions are slow in the absence of air (oxygen), I2 or metal salts. Oxygen accelerates nitrosation by converting NO via NO2 to either N2O3 or N2O4, but both I2 and metal salts are effective under anaerobic conditions, where reaction rates are virtually independent of amine basicity but depend on the nature of the added reagent. The most effective substance is I2, which gives quantitative yields of N-nitrosamine in a few minutes at 25 degrees C by forming the reactive nitrosyl iodide (NOI) reagent. Acceleration in ethanol at 25 degrees C is also observed with AgI, CuI, CuII, ZnII, FeIII and CoII salts, among others, with substantial amounts of N-nitrosamine being produced in ca. 30-300 min. Metal iodides intervene by way of the NOI reagent, as for I2, but other salts require a mechanism involving reaction between a metal-amine complex and NO, itself. The results show that carcinogenic N-nitrosamines may form under a much wider range of experimental conditions than suspected hitherto. Their relevance to human exposure is discussed, with particular reference to urban pollution and the effect of dietary antioxidants.

Amines↗