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Biomedical subjects

M A Shaughnessy

Publications and source records attributed to M A Shaughnessy.

At least 73 records · Page 4Linked to original sources
PubMed1985

Brief report: evaluation of polymerized ragweed extracts by intradermal end point titration, RAST inhibition, and parallel line bioassay.

We have evaluated six polymerized ragweed extracts on the basis of RAST inhibition, parallel line bioassay, and intradermal end point titration. The results of the parallel line bioassay and intradermal end point titration are highly correlated (r = 0.995, df = 2, p less than 0.01). Both intradermal end point titration (r = 0.973, df = 4, p less than 0.01) and parallel line bioassay (r = 0.985, df = 2, p less than 0.05) are highly correlated with RAST inhibition. We have evaluated the utility of intradermal end point titration as a quantitative assay of relative allergenicity of polymerized extracts. The between assay reproducibility was derived by comparing a reference polymerized ragweed extract against itself. The 99% confidence limits of relative allergenicity were 53% to 188% when four assays were used. This compares favorably to the published 99% confidence limits of the parallel line bioassay 60% to 166% when three assays were used. Intradermal end point titration is highly reproducible, is highly correlated with RAST inhibition or parallel line bioassay, and thus is an appropriate bioassay of allergenic activity.

Allergens↗
PubMed1984

Persistence of efficacy after a brief course of polymerized ragweed allergen: a controlled study.

Immunotherapy with PRW has been demonstrated to be safe and effective. To determine whether the efficacy would remain in successive ragweed seasons without further therapy, a trial was conducted comparing PRW to histamine placebo therapy in patients that had received courses of PRW previously. Those patients were also compared to previously untreated ragweed-sensitive patients. In a double-blind fashion, 21 previously treated patients were treated before the 1982 ragweed season with four injections of PRW therapy, whereas 21 previously treated patients were treated with four injections of placebo therapy. An additional control group of 21 previously untreated ragweed-sensitive patients received no injections. Daily symptom and medication score sheets were completed by patients each day of the ragweed season. Blocking antibody rose elevenfold with treatment (p less than 0.0001) in the PRW group. There was a statistically significant difference in symptom score mean between untreated patients (1007 +/- 174) and previously treated patients whether they received supplemental injections (554 +/- 180) (p less than 0.01) or whether they did not (650 +/- 168) (p less than 0.03). In summary the efficacy of 15 injections of PRW immunotherapy persists at least several years without need for supplemental immunotherapy.

Clinical Trials as Topic↗
PubMed1983

A solid-phase bead radioimmunoassay for specific IgE to ragweed antigen E.

A solid-phase bead radioimmunoassay has been developed for measuring IgE against antigen E (IgE-a-AgE) in serum. The patient's IgE is bound by monoclonal mouse anti-human IgE which is on the surface of a solid bead. Other immunoglobulin classes are not bound and can be washed away. Radiolabeled AgE is then added and is specifically bound by IgE-a-AgE. This assay is reproducible, and in contrast to specific IgE assays utilizing RAST methodology, it cannot be inhibited by specific antibody of other classes. Moreover, the solid-phase bead method does not utilize myeloma IgE. Finally, its results correlate well with those of a previously developed polystyrene tube method.

Allergens↗
PubMed1983

Polymerization of individual species of grass pollen allergens.

Six grass pollen allergens have been individually polymerized. We had previously polymerized mixed grass pollen allergens. However, since every patient does not react to every grass, we sought to polymerize individual grasses that could subsequently be mixed into a preparation based on a patient's skin reactivity. As demonstrated by Sepharose 4-B chromatography of individual grass monomers and polymers, all six grasses were polymerized. Polymerized grass preparations as compared with monomer preparations demonstrated a 10(3)- to 10(5)-fold reduction in allergenicity as determined by cutaneous end point titer. That grass polymer contains the great majority of clinically important allergenic determinants was demonstrated by the ability of polymer to inhibit 78% IgE binding against crude grass in a pool of untreated grass-sensitive patients. Its antigenic similarity to crude grasses is further shown by the ability of polymer to inhibit 85% of IgG binding against crude grass in a pool of patients treated with usual crude grass extracts.

Binding, Competitive↗
PubMed1983

Evaluation and standardization of polymerized ragweed extracts by chromatography, radioimmunoassay inhibition, and end point cutaneous titration.

The standardization procedures for polymerized ragweed (PRW) must evaluate activity of PRW with assessments that differ from those used for standard unmodified extracts. This is because PRW allergens are different from conventional ragweed extracts in that they are much greater in average molecular weight and much lower in allergenicity for equivalent immunogenicity. We have evaluated seven samples of PRW for three parameters: allergenicity as determined by cutaneous end point titration, molecular weight distribution as determined by Sephadex G-200 chromatography, and availability of antigen E (AgE) determinants as measured by the ability of an extract to inhibit AgE binding to antibody by using a modification of the Farr technique. The skin test titers and molecular weight profiles provide information as to the safety of a PRW preparation and antigen-binding inhibitory activity gives information about allergenicity and immunogenicity. Appropriate limits may be set for each of these parameters to standardize PRW for clinical use.

Allergens↗
PubMed1983

A double-blind histamine placebo-controlled trial of polymerized whole grass for immunotherapy of grass allergy.

Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG. They were randomly assigned to two groups based on skin test titrations to grass allergens. One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU, and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo. Daily symptom and medication score sheets were completed by all patients each day of the grass season. Blocking antibody rose ninefold in the IPG group (p less than 0.007) but was unchanged in the placebo group. There was no significant change in IgE against rye grass group I in either the IPG or the placebo group. Symptom-score mean in the IPG group was 217 +/- 71 (S.E.M.), statistically lower (p less than 0.02) than the mean in the placebo group 496 +/- 117 (S.E.M.). There were no systemic reactions and only minor local reactions. There was no change in routine laboratory tests in either group. Although two prior studies with grass allergen immunotherapy reported efficacy, these studies did not use symptom-score analysis. This is the first double-blind, histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation. IPG is a safe, clinically effective, and potentially cost-effective therapy for grass pollinosis.

Clinical Trials as Topic↗
PubMed1983

Airway response to leukotriene D4 in rhesus monkeys.

We studied the effect of leukotriene D4(LTD4) given by aerosol challenge on asthmatic and normal monkeys. The response to LTD4 occurred within 2 min., was prolonged at higher concentrations, was reversed by epinephrine, and more closely resembled an antigen response than a histamine response. Since LTD4 concentrations of 30-100 micrograms/ml produced a response similar to 2-20 mg/ml of histamine, the LTD4 was 300-900 times as potent as histamine on a molar basis. Thus, LTD4, which appears to reproduce an antigen-induced response in rhesus monkeys, may be a mediator of allergic asthma in these animals.

Airway Obstruction↗
PubMed1982

A double-blind, placebo-controlled trial of polymerized whole ragweed for immunotherapy of ragweed allergy.

Immunotherapy with polymerized ragweed (PRW) has been demonstrated to be safe and effective when compared with monomeric ragweed or untreated controls. To further establish the efficacy of PRW, a trial was conducted comparing PRW, placebo, and no treatment in ragweed-sensitive individuals. In a double-blind manner, 21 patients were treated before the 1981 ragweed season with 15 weekly injections of PRW totaling about 50,000 PNU and 1200 microgram antigen E, while 19 patients were treated with 15 weekly injections of a caramelized glucose and histamine placebo. An additional control group received no injections. Blood was drawn for IgE against ragweed antigen E (IgE-a-AgE) and for blocking antibody against AgE before treatment, after treatment (before season), and after season. In the untreated patients, blood was drawn before season and after season. Daily symptom score sheets were completed by patients each day of the ragweed season. Blocking antibody rose more than 40-fold with treatment (p = 0.0001) in the PRW group but was unchanged in the placebo group with treatment. IgE-a-AgE rose with PRW therapy. Clinical efficacy of PRW was again confirmed in this study. Symptom score mean in the PRW group was statistically lower than the mean in the placebo group (p = 0.022) and in the untreated group (p = 0.018). There were no systemic reactions and only minor local reactions during treatment. In summary, PRW is an improved form of immunotherapy.

Adult↗
PubMed1982

Skin infections and immunoglobulin A in serum, sweat, and saliva of patients recovered from poststreptococcal acute glomerulonephritis or acute rheumatic fever and their siblings.

Differences in hygienic habits and base-line secretory immunoglobulin (Ig) A which might have contributed to the prevalence of skin infections and/or absence of increased serum IgA values were sought in patients with poststreptococcal acute glomerulonephritis (nephritis) in contrast to patients with acute rheumatic fever in Trinidad by studying patients and their siblings after the patients had recovered from these diseases. The overall history of skin infections was similar at this time in all groups, although they had been much more common in patients with nephritis and their families at the time of acute illness. The recovered nephritis patients bathed slightly less often than the other individuals, used a cream or lotion after bathing rather than coconut oil, and tended to sweat less than the others, but none of these differences was statistically significant. Neither were significant differences demonstrated in amounts of IgA and IgG in serum and saliva of recovered nephritis patients and their siblings compared to recovered rheumatic fever patients and their siblings, while only small amounts of IgA and IgG were present in any sweat, and probably had been transuded rather than secreted. These studies suggest that the lower serum IgA titers in patients with nephritis compared to patients with rheumatic fever in Trinidad do not reflect basic differences in serum IgA or secretory IgA as measured in saliva, and that IgA is not secreted by the eccrine glands.

Adolescent↗
PubMed1982

Serum immunoglobulin A and antibody to M-associated protein in patients with acute glomerulonephritis or rheumatic fever.

Serum immunoglobulin A (IgA) was markedly increased in 80% of 50 patients with acute rheumatic fever in Trinidad in contrast to 20% of 63 patients with acute glomerulonephritis, whereas serum IgG was increased in nearly all of both groups. Since total antibody to M-associated protein (MAP) (assessed by complement fixation) is the only antibody as yet consistently found to be of higher titer in patients with acute rheumatic fever than in patients with acute glomerulonephritis in Trinidad, it was measured and the titers were related to serum levels of IgA. The titers of total antibody to MAP were greater than or equal to 40 in 58% of the rheumatic fever patients, 43% of the nephritis patients, and 8% of well school-children. However, its presence in rheumatic fever patients did not correlate directly with amounts of serum IgA present (r = 0.0507). Moreover, titers of total antibody to MAP related equally well to enzyme-linked immunosorbent assay indicated amounts of IgG antibody (r = 0.3939) and IgA antibody (r = 0.3054) to MAP in rheumatic fever patients but not in nephritis patients (r = 0.0301 for IgA antibody and 0.6909 for IgG antibody to MAP), whereas they related best to IgM antibody to MAP in the school-children (r = 0.4204).

Acute Disease↗
PubMed1982

Streptococcal neuraminidase and acute glomerulonephritis.

We examined the hypothesis that streptococcal neuraminidase may alter host serum immunoglobulin G so that autoantibodies are formed which lead to immune complexes and acute glomerulonephritis. We confirmed the observation that T-type 4 and T-type 12 streptococci (both associated with acute glomerulonephritis) are the most likely of many types studied to produce neuraminidase. However, we did not find this enzyme to be produced by any of 23 streptococcal strains isolated from patients with nephritis, whereas it was produced by two strains from patients with rheumatic fever and by one strain from a patient with scarlet fever. Also, we were unable to find direct or indirect evidence of increased neuraminidase activity in the sera of six patients with acute glomerulonephritis when they were compared with the sera of six patients with acute rheumatic fever and with those of six normal subjects.

Acute Disease↗
PubMed1980

Some immunofluorescent observations on factor VIII/von Willebrand factor in dogs.

Factor VIII/von Willebrand factor (vWF) was sought by immunofluorescence in or on canine platelets and blood vessels. None was found on normal canine platelets and little was present in normal canine arteries, veins and capillaries compared with normal human blood vessels. However, free granules of vWF were scattered in platelet-rich canine plasma and occasional granules appeared on small clumps of platelets when ristocetin or collagen was added to the plasma. When the same platelets were suspended in human plasma and ristocetin or collagen was added, more clumps were formed and more vWF (human) was associated with these clumps. When thrombin was added to canine platelets in either canine or human serum, more solid, small clumps of platelets were formed and stained with anti-vWF sera. When thrombin was added to canine platelets in either canine or human plasma, a single large clot was formed which stained brightly for vWF.

Animals↗
PubMed1979

Variations in serum complement following inulin infusion in man.

Complement levels were determined in 12 normal human volunteers while receiving intravenous infusions of inulin for determination of standard inulin clearances. Significant decreases in beta IC globulin and total hemolytic complement activity were observed when inulin was infused, but not following infusion of saline as a control. These effects were noted only when steady-state inulin levels were greater than 26 mg%, suggesting a dose-dependent response. No evidence of increased coagulation was noted as measured by fibrinogen and fibrin degradation products. Since C4 levels remained largely unchanged following inulin infusion, it was concluded that the results most likely occurred through activation of the alternate complement pathway.

Adult↗
PubMedDate not supplied

Clinical and immunologic outcome of 42 individuals with trimellitic anhydride-induced immunologic lung disease after transfer to low exposure.

The purpose of this study is to determine the clinical and immunologic status of trimellitic anhydride (TMA)-exposed employees who have had immunologic lung disease and who have been moved to lower-exposure jobs. In a case series design, 42 consecutive employees with TMA-induced immunologic lung disease were studied after they had been moved to low-exposure jobs for more than 1 year. Pulmonary symptoms were obtained by physician-administered questionnaire. Immunologic studies were performed using ELISA techniques. Spirometry and chest films were obtained annually. Employees with late asthma (n = 4), late respiratory systemic syndrome (LRSS) (n = 13), or both LRSS and asthma (n = 4) had improved symptoms, improved pulmonary functions, and lower IgE against TM-HSA. Fourteen of 21 employees with asthma had improved symptoms, improved pulmonary functions, and lower IgE against TM-HSA. The 7 who did not improve with transfer to low-exposure jobs did improve with transfer to jobs with no TMA exposure. There were no chest film findings in any group that were definitely related to TMA. Most individuals who develop TMA hypersensitivity syndromes improve with transfer to low- exposure jobs, but occasionally, individuals require transfer to a no-exposure job.

Adult↗
PubMedDate not supplied

Practices in cat and dog immunotherapy among allergists.

Allergists in each of four groups, board certified with academic affiliation (A), board certified without academic affiliation (B), non-board certified (NB), and previous trainees of our program (PT)--were queried as to their practices and philosophies in cat and dog epidermal immunotherapy (CDI) and pollen immunotherapy (PI). The four groups were similar in numbers of new patients seen and practices of PI. In several instances, with respect to CDI, however, the PT and A groups segregated from the B and NB groups. Most of B and NB allergists would administer CDI to a patient who refused to give up a pet, while most physicians in the PT or the A groups would not. Overall the number of patients placed on CDI was higher and the degree of efficacy was perceived as higher among the NB and B groups than in the PT or A groups.

Allergy and Immunology↗
PubMedDate not supplied

Soluble copolymers of yellow jacket, yellow hornet and white faced hornet with human albumin for venom immunotherapy.

Soluble polymers have been prepared by polymerizing human serum albumin (HSA) with either yellow jacket venom (YJV), yellow hornet venom (YHV) or white faced hornet venom (WFHV). The venom-albumin polymer preparations were fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase (2.4 x 10(5) daltons). Rabbits were immunized with either yellow jacket venom-albumin polymer (YJVAP), yellow hornet venom-albumin polymer (YHVAP) or white faced hornet venom-albumin polymer (WFHVAP). Rabbits immunized with venom-albumin polymer (VAP) produced IgG antibody to VAP and venom, as measured by enzyme-linked immunosorbent assay (ELISA). Experiments to demonstrate antigenic completeness and absence of new antigenic determinants in the polymer were performed using WFHVAP. IgG against WFHVAP was completely inhibited by a mixture of WFHV and HSA demonstrating the absence of new antigenic determinants in WFHVAP. IgG against WFHV in sera from patients receiving maintenance doses of WFHV immunotherapy was completely inhibited by WFHVAP, demonstrating antigenic completeness. We have previously described similar results with bee venom-albumin polymer and wasp venom-albumin polymer. We now conclude that VAP preparations of all five clinically relevant hymenoptera venoms have potential value in the treatment of hymenoptera anaphylaxis.

Animals↗
PubMedDate not supplied

Absence of nasal priming as measured by rhinitis symptom scores of ragweed allergic patients during seasonal exposure to ragweed pollen.

A priming effect, increasing responsiveness of the nasal mucosa as measured by nasal patency or resistance, has been reported to occur after nasal challenge on successive days. Because it has been suggested that the priming effect may be of clinical importance, we have studied whether such an effect occurs during natural pollen exposure as measured by symptom-medication scores in 29 patients with ragweed rhinitis. By Wilcoxon's signed rank test, we compared the symptom-medication scores of patients during two 7-day periods, one early in the season and one later, in which the weekly pollen count was approximately 250 grains/m3; we also compared an early and late period during which the weekly pollen count was approximately 500 grains/m3. There were no statistically significant differences in scores between early and late seasonal periods at the same pollen count. We conclude that the priming effect is not a clinically significant phenomenon during natural pollen exposure in allergic rhinitis patients.

Humans↗