Search PubMed⌕ Search

Biomedical subjects

A J Green

Publications and source records attributed to A J Green.

At least 19 recordsLinked to original sources
PubMed1992

Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies.

Anti-neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminol-amplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti-double stranded DNA positive sera (P < 0.01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminescence system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f-Met-Leu-Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan-activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1990

Accurate quantification of 131I distribution by gamma camera imaging.

The development of targeted therapy requires that the concentration of the therapeutic agent can be estimated in target and normal tissues. Single photon emission tomography (SPET), with and without scatter correction, and planar imaging using 131I have been compared to develop a method for investigation of targeted therapy. Compton scatter was investigated using line spread functions in air and water, these data were used to set a second peak, adjacent to the photopeak, for scatter correction. The system was calibrated with an eliptical phantom containing sources in background activity of various intensities. Scatter corrected reconstructions gave accurate estimates of activity in the sources regardless of background activity. For planar scanning and SPET without scatter correction there was an overestimate of activity in the source of 290% and 40% respectively. The validity of this method was confirmed in patients by comparing activity in the cardiac ventricles measured by SPET with scatter correction with that in a simultaneous blood sample. A coefficient of correlation of 0.955 was achieved with 25 data points. SPET with scatter correction was compared with planar imaging in measuring activity in the liver and spleen of patients receiving 75 mCi 131I-antibody to CEA intravenously. Planar imaging gave significantly higher values than SPET for the spleen (t = 5.4, P less than 0.001 by the paired t-test) but no significant difference for the liver. SPET with scatter correction forms a basis for an improved technique of quantifying the targeting efficiency.

Humans↗
PubMed1989

The effect of second antibody clearance on the distribution and dosimetry of radiolabelled anti-CEA antibody in a human colonic tumor xenograft model.

Radioimmunotherapy in humans is limited by toxicity to normal tissues, caused by circulating radio-antibody. Second antibody directed against the first (anti-tumor) antibody accelerates clearance of first antibody from normal tissues, and may thus improve the therapeutic ratio. The effect of second antibody both on anti-tumor antibody distribution and on tumor and normal tissue radiation doses, has been investigated in nude mice bearing colonic tumor xenografts. Second antibody, given either 6 or 24 hr after the first, rapidly cleared circulating activity and reduced the calculated radiation dose to all tissues except the spleen, where it rose by 11 and 43% respectively. The dose received by the blood fell by 87% and 71%, while that to the tumor was reduced by 81% and 58%, after 6 or 24 hr second antibody. Administration of second antibody therefore improved the tumor to blood ratios. Tumor identification by gamma camera was greatly facilitated by the use of second antibody, and required no background subtraction. Results obtained from this system demonstrate the utility of second antibody in protecting normal tissues from prolonged circulating radioactivity during radioimmunotherapy.

Adenocarcinoma, Mucinous↗
PubMed1989

Comparison of sympathetic skin response with quantitative sudomotor axon reflex test in diabetic neuropathy.

The sympathetic skin response (SSR), the quantitative sudomotor axon reflex test (Q-SART), and cardiac beat-to-beat variability with respiration as measured by the expiratory/inspiratory ratio (E/I ratio) were studied in 39 patients with diabetic neuropathy of whom 33 also had one or more symptoms of autonomic involvement. In the lower extremities 87% of the patients with an absent SSR had an abnormal Q-SART (P less than 0.001), and 81% of patients with the SSR present had a normal Q-SART (P less than 0.02). The E/I ratio was abnormal in all but one of 23 patients with an absent SSR in the foot, and a normal E/I ratio was present only in those patients (n = 7) with the SSR present in hand and foot, and in an eighth patient who had SSR absent in the foot and present in the hand. A similar correlation was found between the E/I ratio and the Q-SART in the foot, although 4 of 25 patients with an abnormal foot Q-SART had a normal E/I ratio. We conclude that the concordance of results of the SSR and Q-SART supports the combined use of these tests to uncover early distal sympathetic failure in diabetic neuropathy.

Adult↗
PubMed1989

Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer.

The distribution of iodine-131 (131I) labelled antibody to carcinoembryonic antigen (CEA) has been studied in 16 patients with colorectal cancer. Levels of tumour and normal tissue radioactivity were measured by serial gamma-camera imaging and counting of blood and urine. Maximum concentrations were found in tumour 8 h after administration and varied up to 9-fold in different patients. Higher levels were found on average in tumour than in any other tissue. Liver, lung and blood were the other tissues in which antibody was concentrated relative to the rest of the body. Antibody cleared from all these tissues over 1 week. Second antibody directed against the antitumour (first) antibody was given 24 h after first antibody in order to accelerate clearance from the blood. This increased the tumour to blood ratio but had little effect on other tissues. Cumulative radiation dose to tumour and normal tissue was estimated. In patients with the most efficient localisation the tumour to body ratio was 20:1 and tumour to blood ratio 5:1. This may be sufficient for effective therapy of cancer in patients selected for efficient antibody localisation. The data may be used to estimate the effect of different therapeutic strategies. For instance, in the time after second antibody administration the average tumour to blood ratio of radiation dose was 11:1, suggesting that two phase systems in which the therapeutic modality is given after a good tumour to normal tissue ratio is obtained may be effective for the majority of patients.

Antibodies, Neoplasm↗
PubMed1989

Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours.

Germ cell tumours (GCT) producing alpha fetoprotein (aFP) can be imaged by external scintigraphy after intravenous administration of radiolabelled antibody directed against aFP. Antibody imaging (AI) by this method was used in an attempt to guide surgical resection of deposits of drug-resistant or recurrent GCT. 30 patients with GCT and raised aFP in whom site of tumour was not known were investigated by AI and conventional imaging methods. All but one were heavily pretreated. Where tumour appeared localised, resection was attempted. Tumour was found in all sites positive by both AI and conventional imaging. AI produced false-positive results in one of 30 patients and false-negative results in 9 patients. Computerised tomography was false-positive in one case and false-negative in three. In these patients, AI gave true-negative and true-positive results, respectively. Of 11 patients with positive AI in whom resection was attempted, 6 achieved sustained complete response with up to 5 years follow-up. We conclude AI and conventional imaging methods to be complementary in selection for surgery of patients with drug-resistant or recurrent GCT.

Adult↗
PubMed1988

Diagnostic significance of octadeca-9,11-dienoic acid in cervical neoplasia.

The percentage molar ratio (%MR) of the 9,11 and 9,12 isomers of octadecadienoic acid was determined in cervical exfoliated cells from 148 subjects, of whom 27 had cytologically proven intraepithelial neoplasia and in cervical biopsy specimens from 43 subjects, of whom 24 had histologically diagnosed cervical intraepithelial neoplasia. The %MR in both cervical biopsy specimens and exfoliated cells did not significantly differ in subjects with or without cervical intraepithelial neoplasia. The measurement of the %MR of 9,11:9,12 octadecadienoic acid has no role in the detection of cervical intraepithelial neoplasia.

Female↗
PubMed1988

Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporin A.

Antibody targeted therapy of cancer results in anti-antibody production which prevents repeated treatment. Cyclosporin A (CsA) has been used to suppress this response in patients treated with a radiolabelled antibody to carcinoembryonic antigen (CEA). Patients with CEA producing tumours received a minimum of two courses consisting of an injection of radiolabelled antibody and CsA, 24 mg kg-1 day-1, for 6 days; each course was given at 2 week intervals. Two weeks after the completion of the second course the mean human antimouse antibody (HAMA) levels were 3.5 micrograms ml-1 (s.d. 2.7) in 3 patients receiving CsA and 1,998 micrograms ml-1 (s.d. 387) in 3 patients not receiving the drug. Clearance of antitumour antibody was accelerated and tumour localisation absent when HAMA levels exceeded 30 micrograms ml-1. With lower levels of HAMA in the CsA-treated patients, further antitumour antibody accumulated in the tumour after each dose. Further therapy with antitumour antibody and CsA lead to the development of HAMA, but this was less than 25% of the amount in patients not given CsA. In this preliminary study up to 4 times as many doses of antitumour antibody could be usefully given when CsA was used. This increases the potential for effective antibody targeted therapy of cancer.

Adult↗
PubMed1988

Quantitation in 131I-radioimmunotherapy using SPECT.

Quantitation from planar imaging and single photon emission computed tomography (SPECT) were compared in phantom studies and in patients receiving therapeutic doses of 131I-labelled anti-CEA. During the reconstruction of the data for SPECT quantitation attenuation correction and a correction for Compton scatter were used. The limitations of both methods were examined using the phantom studies and it was shown that practical SPECT quantitation could be achieved in patients given therapeutic doses of 131I-labelled anti-CEA, and furthermore, that SPECT appeared to give a more accurate estimate of the activity concentration.

Carcinoembryonic Antigen↗
PubMed1987

Relationship between tumour size and uptake of radiolabelled anti-CEA in a colon tumour xenograft.

The relationship between tumour size and the uptake of three radiolabelled anti-CEA localising antibodies (A5B7, 1H12 and PK2G) into a human colon tumour xenograft (MaWi) has been examined. For tumour weights greater than 100 mg (109-873 mg) there was a strong positive correlation between absolute uptake and tumour weight with mean uptakes per gram of 9.8 (r = 0.92), 5.0 (r = 0.93) and 5.3 (r = 0.94) for A5B7, 1H12 and PK2G respectively. For tumour weights below 100 mg (17-99 mg) the percentage uptake per gram (specific uptake) increased markedly reaching 80% of the injected dose for A5B7. The above phenomena could be modelled by representing uptake by the surface area of a sphere and tumour weight by its volume. Transformation of this model produced a linear relationship suitable for regression analysis of the experimental data. The slopes of the regression lines for the three antibodies were very close to that predicted by the model suggesting that their uptake into MaWi xenografts is proportional to surface area. The main discrepancy of the actual data was shown by the intercepts which relate to the variation in uptake between different antibodies. This model provides a possible means of correcting for the effect of tumour size when investigating the uptake of antibodies into xenografts.

Adenocarcinoma, Mucinous↗
PubMed1987

The clinical value of imaging with antibody to human chorionic gonadotrophin in the detection of residual choriocarcinoma.

Choriocarcinoma can be imaged by external scintigraphy after intravenous administration of radiolabelled antibody directed against human chorionic gonadotrophin (HCG). The purpose of this study was to investigate whether antibody imaging was sufficiently sensitive and specific to improve the selection of patients for surgical resection of localised deposits of drug resistant or recurrent choriocarcinoma. Eighteen patients with raised serum HCG concentrations in whom the site of tumour was not known were investigated by antibody imaging and conventional imaging methods. When the tumour appeared localised, resection was attempted. Tumour was found at all sites in which both antibody imaging and conventional imaging methods were positive. Antibody imaging gave false positive results in 2 of 18 patients and false negatives in 5. Computerised tomography was false positive in one case and false negative in 2. In these patients, antibody imaging gave true negative and true positive results respectively. Of 8 patients with positive antibody imaging in whom resection was attempted, 5 achieved sustained complete response with up to five years follow up. It is concluded that antibody imaging is useful in selection of patients for surgery in drug resistant or recurrent choriocarcinoma.

Antibodies↗
PubMed1987

Use of second antibody in radioimmunotherapy.

In this study, a second antibody was directed against the first antitumor antibody to accelerate clearance of the 131I-labeled first antibody and improve tumor to normal tissue ratios of radioactivity. The value of this method in improving the therapeutic index of radioimmunotherapy with 131I-antibody to CEA has been investigated in nude mice bearing xenografts of human colon carcinoma and in 5 patients with colorectal cancer. The xenografts did not become saturated with anti-CEA as the administered dose was increased to therapeutic levels. At these high dose levels, the second antibody increased tumor to blood ratios to a maximum of 155:1, 48 times the level in controls that did not receive the second antibody. In 5 patients given 50 mCi of anti-CEA, there was no significant toxicity with the second antibody; clearance of radioactivity was accelerated; and tumor imaging was enhanced. The second antibody appears to have the potential to improve the therapeutic index of radioimmunotherapy.

Animals↗
PubMed1986

Radioimmunolocalization and selection for surgery in recurrent colorectal cancer.

The value of radioimmunolocalization (RIL) of cancer depends on its performance in situations where the result determines the choice of management. A rise in serum carcinoembryonic antigen (CEA) values after apparently curative resection of colorectal cancer implies localized, resectable recurrence in some patients and widespread unresectable tumour in others. This study investigated the ability of RIL with radiolabelled antibody to CEA and a novel numerical method for analysis of results to determine the extent of disease in 31 patients with raised serum CEA but no physical signs of recurrence. Surgical exploration or conventional radiology later confirmed the presence of tumour in 94 per cent of sites which were positive by RIL. Negative RIL predicted the absence of disease in 53 per cent of patients. The investigation could discriminate between localized and disseminated disease and often performed better than conventional radiology. RIL appears useful in selection of patients for second look laparotomy.

Carcinoembryonic Antigen↗
PubMed1986

Standardizing clinical laboratory data for the development of transferable computer-based diagnostic programs.

The existence of systematic differences between test results obtained at different laboratories can compromise the development of generally accessible reference databases for interpretive pathology. We review approaches to the elimination of inter-laboratory bias from pathology test results through the use of standard unit transformations. A general transform procedure is described that will permit laboratories serving a common population to make use of reference data, decision rules, and computer-based interpretive programs developed around a larger clinical database than each of these test centers could amass for themselves.

Clinical Laboratory Techniques↗
PubMed1985

Laboratory accuracy in casting removable partial denture frameworks.

An attempt was made to compare the clinical accuracy of two types of cast metals used in the fabrication of removable partial dentures as they were prepared by commercial laboratories. No comparison of the metals could be made, because the discrepancies that were found were too gross and were related to technical error. Suprabulge clasps were placed in less undercut than prescribed. Infrabulge clasps were placed in more undercut than prescribed. The laboratories produced better accuracy when they were informed of the purpose of the cast frameworks than when the frameworks were made without the knowledge that their work would be tested. One laboratory produced better results than the other under similar conditions.

Chromium Alloys↗