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Biomedical subjects

D G Marsh

Publications and source records attributed to D G Marsh.

At least 127 records · Page 7Linked to original sources
PubMed1981

Studies on allergoids from naturally occurring allergens. III. Preparation of ragweed pollen allergoids by aldehyde modification in two steps.

We have devised a new process for modifying heat-labile allergens, which employs a sequential "two-step" incubation at temperatures of 10 degree C and 30 degree to 32 degree C. This process was found to produce effective ragweed "allergoids" with low allergenicity and good immunogenicity, which makes them useful for the therapy of allergic humans. Modification with formaldehyde produced derivatives ("formallergoids") that were about 10-fold less allergenic in allergic humans (as measured by leukocyte histamine-release assay), and similarly or more immunogenic in guinea pigs, than glutaraldehyde-modified allergens ("glutarallergoids"). Further analysis by RAST inhibition showed that a ragweed formallergoid was sixfold less reactive than a glutarallergoid with a pool of human IgE antibodies. However, the formallergoid had retained the ability to induce a wide array of antibodies against native ragweed antigens, since rabbit anti-formallergoid serum was able to recognize at least 12 different ragweed antigens, including AgE. Gel-filtration experiments showed that both the formallergoid and glutarallergoid materials contained polymers having apparent molecular weights distributed around 260,000 and 230,000 daltons, respectively (approximate range 30,000 to 900,000 daltons). Our studies provide the immunochemical basis for the use of these allergoids in the therapy of allergic humans.

Aldehydes↗
PubMed1981

Antigens of Ambrosia elatior (short ragweed) pollen. I. Crossed immunoelectrophoretic analyses.

A crude extract of short ragweed pollen was obtained by extraction, centrifugation, dialysis and freeze-drying. Crossed immunoelectrophoresis, with a high-titer purified rabbit antibody fraction, revealed that the extract contained at least 52 antigens, of which 33 migrated toward the anode, 16 toward the cathode, and 3 toward both the anode and cathode. The electrophoretic precipitation pattern indicated a great deal of electrophoretic heterogeneity in several of the antigens. The overall distribution of apparent m.w. for 35 of the 52 antigens and the approximate m.w. for 19 identified antigens were determined by a combination of gel filtration and immunochemical analysis. Among antigens with m.w. weights less than or equal to 10,000, 8 of 10 were basic; on the other hand, all 5 identified antigens with m.w. above 40,000 were acidic. The apparent pI distribution for 30 antigens, and more precise pI values for 20 of 52 antigens, were determined by means of sucrose-gradient isoelectric focusing. The data obtained provide a reproducible reference system of considerable use in ragweed allergen chemistry and enable one to predict conditions for isolation of ragweed antigens.

Animals↗
PubMed1980

Correlation between lymphocyte responses and immediate hypersensitivity to purified allergens.

Seventy-nine unrelated subjects were selected for high allergic sensitivity to ragweed and/or grass pollens. Sensitivities to ragweed antigens E and Ra5 and rye grass group 1 were measured by intradermal skin testing and by histamine release in vitro. Lymphocyte responses were determined by incorporation of 3H-thymidine in vitro in the presence of antigen. Skin-test and histamine-release sensitivities were significantly correlated with lymphocyte response in the case of antigen E, but not for group 1 and Ra5. In addition, lymphocyte response to antigen E was significantly correlated with total serum IgE level. Six antigen E-sensitive individuals had marked delayed, but no immediate, reactions to Ra5 and almost all showed lymphocyte responses to Ra5. We conclude that immediate sensitivity and lymphocyte responses of allergic individuals to antigen E are significantly correlated, and that lymphocyte responses and delayed reaction to an antigen without immediate sensitivity or IgG antibody are possible even in allergic subjects.

Allergens↗
PubMed1980

Skin reactivity to purified pollen allergens in highly ragweed-sensitive individuals.

Five hundred twenty-five atopic patients were skin tested over a 12-mo period to several crude allergens with a puncture skin-testing technique utilizing a bifurcated needle originally developed for smallpox immunization. Of these, 122 were highly allergic to short ragweed pollen and were subsequently tested with a series of purified grass and ragweed allergens. Data of their reactivity to these allergens is presented, and the phenomenon that each patient has a unique "allergic fingerprint" to purified pollen allergens is shown. The puncture technique showed good correlation with quantitative intradermal skin titration and offered a definite advantage, because many allergens could be rapidly and accurately assayed with good patient compliance.

Adolescent↗
PubMed1979

Association of HLA antigens and total serum immunoglobulin E level with allergic response and failure to respond to ragweed allergen Ra3.

We have applied rigorous statistical analysis to human immune response and HLA data in allergic subjects having varying sensitivity to the minor ragweed allergen, Ra3. By using regression analysis on a series of subsets of Ra3 responders and nonresponders, we obtained data supporting the concept of discrete "responder" and "nonresponder" phenotypes. We found significant positive associations between Ra3 response and total serum IgE and the presence of HLA antigens of the A2 crossreacting group (A2 and A28), and significant negative associations with antigens of the A3 crossreacting group (A3 and A11). Our results suggest that alleles of the HLA-A locus may function either as immune response or immune suppressor genes or that such alleles are epistatic to the response or suppressor genes. Our data add further support to previous findings that HLA-associated specific IgE response is strongly influenced by genetic regulation of basal IgE level.

Allergens↗
PubMed1979

Ruptured thoracic aorta: evolving radiological concepts.

The chest roentgenograms of 18 patients with ruptured aortas were studied and the radiographic features tabulated. Fifteen patients survived to undergo angiography, and 14 aortograms were available for review. Distortion of the normal aortic contour and blurring of the aortic outline occurred on the initial chest film in each of the 18 cases. Obliteration of the medial left upper lung field and displacement of the superior vena cava to the right were observed in 16 and 15 films, respectively. Increased mediastinal width was not the most common noted abnormality. The mean mediastinal width on 100 cm anteroposterior supine chest film was 8.8 cm. One patient exhibited a mediastinal width within the normal range. Other frequently occurring abnormalities included opacification of the clear space between the aorta and pulmonary artery, obliteration of the distal aortic shadow, and tracheal shift to the right. At aortography nine patients demonstrated both linear radiolucent defects across the aorta and pseudoaneurysm formations, three patients showed only pseudoaneurysms, and two exhibited only linear radiolucent defects.

Adolescent↗
PubMed1977

Enhanced diagnostic power of exercise testing for myocardial ischemia by addition of postexercise left ventricular ejection time.

To improve both the sensitivity and specificity of the multistage treadmill test, postexercise systolic time intervals were prospectively studied in 73 patients with angina-like chest pain and normal resting ST-T segments. The decision to perform coronary angiography was made independent of the exercise test. Twenty-three patients had normal coronary arteries and 50 had more than 50 percent reduction of luminal diameter of one or more major coronary arteries. The systolic time intervals were measured before and 2,4,6,8 and 10 minutes after exercise. Of all the systolic time intervals, the 4 minute postexercise left ventricular ejection time proved most discriminating between normal subjects and those with coronary artery disease. The deviations of this interval from the normal regression with heart rate both before and after exercise were used to calculate the net delta left ventricular ejection time after exercise. A net increase of more than 31 msec represented 2 standard deviations above normal. Twenty-three (46 percent) of the patients with coronary artery disease had an abnormal net delta ejection time after exercise. Twenty-five (50 percent) had a positive electrocardiographic response with a 9 percent false positive rate. Thirteen (26 percent) had only a positive postexercise net delta ejection time so that a total of 76 percent of patients with coronary artery disease were identified. Thus, measurement of the postexercise net delta ejection time a simple and useful adjunct to multistage treadmill testing.

Adult↗
PubMed1977

Double diastematomyelia.

Double diastematomyelia was diagnosed in a 23-year-old woman. The spurs occurred at T2 and L3. To the authors' knowledge, such a wide separation of double spurs has not been reported previously and the high position of the T2 spur is rare.

Adult↗
PubMed1977

Cervical myelopathy complicating cerebral angiography. Report of a case and review of the literature.

Transverse cervical myelopathy, at C-6 level, followed injection of Renografin-60 into the right thyrocervical trunk during cerebral angiography. Review of the literature yielded only two cases in which attempted posterior fossa angiography resulted in cervical myelopathy. Two more cases were found. In one, cervical myelopathy occurred during aortography in a patient with coractation of the aorta, and in the other it followed mediastinal angiography. Summation of anoxia, hemorrhage, and cellular toxicity is responsible for spinal cord necrosis following arterial injection of contrast material.

Adult↗
PubMed1977

'Mapping' of postulated Ir genes within HLA by studies in allergic populations.

Analysis of specific IgE responses to highly purified allergens provides a particularly good model to study the genetics of human immune response. The use of this model is illustrated by studies of large populations of allergic individuals in terms of their HLA phenotype, basal total IgE level and specific IgE-mediated sensitivities to rye grass group I (Rye I) and to ragweed Ra3. We find significant associations between HLA-B8 and Rye I response and HLA-A2 and Ra3 response, which become more striking in those atypical allergic subjects who have low total IgE levels. Our studies point to the importance of genetic regulation of basal IgE level in determining specific IgE response. Also, they suggest possible approaches toward a tentative 'mapping' of postulated Ir genes based on the linkage disequilibrium existing within the HLA complex.

Antibody Formation↗