Carcinoma of the breast. Occurence after treatment with melphalan for multiple myeloma.
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Biomedical subjects
Publications and source records attributed to R Bell.
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Complexes formed between labelled proteolytic enzymes (trypsin, subtilopeptidase A) and the alpha-macroglobulins of plasma are rapidly and selectively taken up by rabbit alveolar macrophages. The uptake occurs over a narrow zone of pH. Kinetics of the uptake is affected by temperature; in particular, incubation of macrophages at 37 degrees C before the addition of the labelled complex reduces the capacity to take up complexes. EDTA prevents the association of labelled complexes with macrophages, and can dissociate previously bound label. The effect of EDTA is reversed by the addition of calcium or magnesium or both. Iodoacetamide does not prevent the uptake of complexes but causes them to remain available for dissociation from the cells by EDTA. Incubation of complexes with macrophages at 37 degrees C with no iodoacetamide results in the appearance of trichloroacetic acid soluble products of the enzyme in the supernatant fluid. These observations indicate that the selective uptake of proteinase-alpha-macroglubin complexes by rabbit alveolar macrophages can be resolved into three phases: (1) membrane binding which depends upon divalent cations and is pH sensitive, (2) endocytosis inhibitable by iodoacetamide and (3) temperature-dependent hydrolysis of the contained labelled enzyme.
This experiment determined whether reaction to a novel stimulus was diminished in a dose-dependent fashion following 8 consecutive days of d-amphetamine administration. Thirty-two male rats were injected with saline, 0.5, 2.5, or 5.0 mg/kg of d-amphetamine (each N = 8). On the ninth day, all animals received saline injections and were tested (a) in the presence of a novel stimulus, or (b) in the absence of a novel stimulus. Reaction to the novel stimulus varied inversely with the dose of d-amphetamine which had been received during the drug administration period. This reduction in reaction to the novel stimulus did not seem to depend on (a) the level of amphetamine-induced sterotypy at the end of the drug administration period (b) general reduction of activity, or (c) interference by drug-conditioned responses.
Complexes of labelled proteinases (subtilopeptidase A, trypsin) with serum alpha 1-macroglobulin or alpha 2-macroglobulin are rapidly taken up in vitro by rabbit alveolar macrophages and peritoneal macrophages but not by mixed rabbit peripheral blood leukocytes. Enzyme, not bound to alpha 1- or alpha 2-macroglobulin, does not become associated with alveolar macrophages. Chemically inactivated subtilopeptidase A does not bind to alpha 1- or alpha 2-macroglobulin; chemically inactivated subtilopeptidase A in mixtures with alpha 1 - or alpha 2-microglobulin, does not interact with alveolar macrophages. Blocking experiments confirmed that the interaction of proteinase with alveolar macrophages is complex specific; uptake of labelled complex was prevented by the simultaneous addition of macroglobulin complexes formed with non-labelled subtilopeptidase A, subtilopeptidase B, trypsin or chymotrypsin but not by macroglobulin alone. The findings demonstrate a complex-specific interaction between proteinase-alpha-macroglobulin complexes and macrophages.
Proteinases in plasma bind largely to alpha1-antitrypsin and alpha-macroglobin. The latter is represented in humans by alpha2-macroglobulin and in the rabbit by alpha2-macroglobulin and alpha1-macroglobulin. There is a selective and rapid uptake of proteinase-macroglobulin complexes by rabbit alveolar macrophages. It was found that complexes of labelled trypsin or subtilopeptidase A with rabbit alpha1-antitrypsin do not become similarly associated with rabbit alveolar macrophages. Moreover, proteinase-alpha1-antitrypsin complexes failed to inhibit the uptake of labelled proteinase-macroglobulin complexes. Thus, the interaction with macrophages of proteinase-macroglobulin complexes represents a pathway of proteinase metabolism distinct from that involving proteinase bound to alpha1-antitrypsin.
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Characteristics relevant to cardiovascular disease, including anthropometry, arterial blood pressure, serum cholesterol levels, chest radiography and electrocardiography, were investigated in a survey of 843 men and women aged 35-54 years of African and Indian origin living in 2 communities in Guyana. Clinical experience suggested a high incidence of hypertension and a low incidence of ischaemic heart disease.Africans were taller and heavier than Indians but their other characteristics were, in general, similar except that their mean blood pressure levels and R amplitudes in certain ECG leads were consistently higher. Hypertension was common and was significantly correlated with obesity and, probably independently, with body size. Serum cholesterol levels, with mean values of about 200 mg/100 ml, were strongly correlated with factors associated with obesity in men but not in women. Cardiothoracic ratios, measured from chest films, were greater than values regarded as normal for Europeans because of a relative narrowness of thoracic diameters.Prevalence of S-T-segment and T-wave defects in ECGs classified by the Minnesota Code was as high as reported from communities where ischaemic heart disease is clinically more frequent. Hypertension, cardiac enlargement, obesity and cholesteraemia were more prevalent when defects involved lateral leads (I, aVL, V5 and V6) than in subjects with normal ECGs, suggesting that the majority of important abnormalities occurred primarily in the left ventricle and were probably related to hypertension rather than to coronary insufficiency without hypertension. Analysis of S-T and T-wave defects, both by blood pressure and by lead position, might show meaningful differences between populations which, by present methods of presentation, appear to have surprisingly similar prevalences of ECG abnormalities.
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