Biomedical subjects
Publications and source records attributed to D G Marsh.
HLA typing and cutaneous testing for allergen sensitivity of 76 ragweed allergic patients confirmed previous findings of a significant association between sensitivity to ragweed allergen Ra5 and possession of one or other of the HLA-B7 cross-reacting group of antigens.
The effect of heparin in clinical anticoagulant doses on S-T segment and cardiac enzymes was studied in 18 patients with acute myocardial infarction by electrocardiogram and enzyme evaluation 1 hour and 24 hours after initial heparin infusion. Intestinal mucosa heparin was given by infusion, 10,000 units after the admission electrocardiogram, and 5,000 units every 6 hours. Data in the nine control and nine treated patients were statistically similar on admission. The electrocardiograph findings were improved, but not significantly, 1 hour after administration of heparin. At 24 hours of heparin therapy, the S-T deviations were reduced 64% (from 139 +/- 2.1 [standard error of the mean] to 50.5 +/- 1.2 mm); in control patients S-T deviations were reduced 21% (from 109 +/- 1.8 to 86 +/- 0.9 mm (t=2.9, P less than 0.019). At 24% hours electrocardiographic leads with 2 mm or more deviation were reduced 86% in heparin-treated patients and 28% in control subjects. Cardiac enzymes were comparably elevated at 24 and 48 hours in both groups, with no clear trend. It is concluded that heparin in anticoagulant doses reduces the 12 lead electrocardiographic pattern of injury without discernibly modifying cardiac enzymes. The question of heparin efficacy in acute myocardial ischemic injury, reopened by findings with large dose heparin in therapy in dogs and anticoagulant dose in this study, awaits further expanded investigation.
The principal radiological indication for thoracic aortography following blunt chest trauma has been a widened mediastinum on chest roentgenogram. The presence or absence of sixteen findings on 100 cm anteroposterior supine chest roentgenograms were noted and compared in 47 consecutive patients who underwent aortography following blunt thoracic trauma and 100 patients without trauma. On the basis of our data, we propose six radiological indications for thoracic aortography following chest trauma: mediastinum greater than 8 cm on 100 cm AP supine chest film; tracheal shift to the right; blurring of the normally sharp outline of the aorta; obliteration of the medial aspect of the apex of the left upper lobe; opacification of the clear space between the aorta and pulmonary artery; and depression of the left main bronchus below 40 degrees.
A new method of labelling short ragweed pollen antigens with carbon-14 is described. The known ragweed antigens AgE, Ra3, Ra5 and several other antigens are radiolabelled. These components are biologically active, have a high specific radioactivity and a long half-life.
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In order to study genetic and immunological features which might be important in the pathogenesis of asthma, forty-one ragweed allergic seasonal asthmatics were first matched with forty-one ragweed allergic nonasthmatics on the basis of similar total IgE levels. No significant differences were observed in their sensitivity to ragweed antigen E (measured by histamine release), or in their skin response to ragweed antigens E, Ra3 and Ra5. An increased frequency of HLA-B5 was observed in nonasthmatics as compared to asthmatics (P = 0-03). Although frequencies of HLA-A1 and B8 were also elevated in nonasthmatics and HLA-B40 in asthmatics, these differences were not significant. The forty-one asthmatic patients were than paired with forty-one nonasthmatics patients were then paired with forty-one nonasthmatics on the basis of leucocyte sensitivity to ragweed antigen E. Similar HLA differences were found which were non-significant. No significant difference in total IgE levels were found between the two groups. Whereas no differences in IgE synthesis or antigen sensitivity was found in the two populations, the frequency of HLA antigens needs further study in larger groups.
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Studies of the distribution of total serum immunoglobulin E levels in nonallergic and allergic populations defined a cut-off point between low and high immunoglobulin E at 95 U/ml, based on Mendelian recessive inheritance of high immunoglobulin E level. Subsequent investigations of the distribution of total serum immunoglobulin E levels in 28 allergic families confirmed the recessive hypothesis. The results of quantitative skin tests in eight families, performed with between five and eight highly purified grass and ragweed pollen allergens per family, demonstrate that the immunoglobulin E-regulating gene exerts a profound effect on specific immunoglobulin E-mediated sensitivity, often masking the effect of HL-A associated immune response genes.
A relatively small proportion (17 percent) of individuals highly allergic to ragweed were found to develop marked reaginic (immunoglobulin E-mediated) skin sensitivity to a minor ragweed pollen allergen Ra5 (molecular weight 5200). Sensitivity to Ra5 was significantly associated with the possession of a major histocompatibility antigen of the HL-A7 cross-reacting group. This appears to be the first evidence of a strong association between a specific immune response and a specific group of closely related HL-A antigens in man.
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